Transcript for:
Understanding Antibiotic Mechanisms and Resistance

what's up ninja nerds in this video today we're going to be talking about antibiotics and there is so much to talk about it is insane here's what i really want you guys to do i'm telling you it will really benefit you if you do this go down the description box below click on the link to our website when you get to the website download the illustrations for this video it is going to be crucial have the one where we have everything on the whiteboard where it's not filled out and then have the key where everything is already filled out and follow along we'll do it together and then i urge you guys antibiotics are tough there's so much to remember keep going through those and keep testing yourself trying to fill everything in multiple times until you fill it out on your own without having to look at the key i'm urging you guys to please do this this is a lot to cover it'll be hard to remember everything but i think i organized it in a way that will help you guys to remember so let's talk about antibiotics all right so let's talk about how antibiotics work against bacteria particularly their mechanism of action how do they kill or reduce the actual growth of gram positive gram negative bacteria anaerobic bacteria atypical bacteria how do they do that and so i think the way that we can categorize this is based upon the structure of the bacteria there's different components of the actual bacteria the first one that is important is the cell wall so the cell wall is made up of peptidoglycans and it's cross-linked by these different types of tetrapeptides there's a lot of proteins that work in that area called like penicillin binding proteins or trans peptidases as you can call them if we can inhibit some of the enzymes that either synthesize peptidoglycan layers within the cell wall that'll inhibit the cell wall synthesis and if we don't have the cell wall the bacteria won't have the ability to divide properly and also it's susceptible to things leaking in and out of the cell introducing the opportunity for bacterial death now there's two ways within the cell wall synthesis one is we can decrease the peptidoglycan synthesis i'll say okay so we can actually just reduce the synthesis of peptidoglycans and there's two antibiotics that i want you to remember that are qualified within that category the first one is vancomycin the second one that you may not have actually heard about too often because we only really use it in like acute cystitis is phosphomycin so phosphomycin okay so that's one type of actual category of antibiotics that work to inhibit the cell wall synthesis of the actual bacteria by inhibiting the peptidoglycans that are the component of that actual cell wall the other thing is we can actually reduce the cross-linking so the cross-linking via the tetrapeptides of the peptidoglycans is crucial because this helps to stabilize the actual cell wall and if you reduce the cross-linking via the penicillin binding proteins you then reduce the ability of the cell wall to be synthesized and this is susceptible now to bacterial cell death there is a plethora of antibiotics within this category of reducing the cross-linking let's talk about these the first one that i want you to remember is your natural penicillins and there's two types of penicillins that i want you to remember the first one is your penicillin g this comes in the im or the iv form the other one is your penicillin v this is more of the p.o form okay the next group so you have your natural penicillins penicillin g penicillin v the anti-staphylococcal penicillins is how i like to remember these so this would be a couple different ones you have what's called oxacillin which is going to be in an iv form you have naphthalene which is another type of iv form and then you have the only po form which is dicloxacillin okay so these are the different groups for that one the next group that i want you guys to remember is the amino penicillins the amino penicillins are very interesting and this consists of primarily amoxicillin and ampicillin now we'll talk about these later but certain types of bacteria have developed resistance against the actual penicillinase bacteria penicillinase so they'd actually develop these different types of enzymes certain bacteria called beta-lactamases which break down the beta-lactam ring of the penicillins that's what these are called your beta-lactams they can break them down and render the antibiotic ineffective so what happens is we often take these these drugs that are penicillinase like susceptible and we add on something called a beta lactamase inhibitor that we'll talk about over there we commonly add on amoxicillin plus something called clavillonate to make amoxicillin clavillon also known as augmentin or ampicillin plus what's called sulbactum which is ampicillin sulbactum also known as unison so that is the group here natural penicillins anti-staphylococcal penicillins and aminopenicillins the next one here is your anti-pseudomonal penicillins very very commonly utilized drug category here you'll see this so many times utilized in the hospital and this is called pipicillin now pippericillin is a really interesting one because there is some types of resistance from certain types of bacteria they have what's called beta-lactamase inhibitors you can actually utilize them so they are beta-lactamases you can use an inhibitor with this actual drug here it's called tazobactum and so commonly we never give pepperocillin by itself we give it what's called pipracillin tazobactum also known as zosim and so commonly this will also get added to a beta-lactamase inhibitor which we'll talk about all right that's our penicillins again we're all talking about this whole category here we actually put them in the category called beta-lactams it's just the structure of the actual penicillin or the beta-lactams they have like a ring and that beta-lactam ring is the important component to a lot of these drugs here your penicillins your cephalosporins your carbopenems and your monobactins all right the next group within your betalactams is your cephalosporins and there is actually five generations of cephalosporins and as we go down you'll see they have they go from gram-positive coverage to more gram-negative coverage as you go down but we'll get into that when we get into antibiotic coverage in the spectrum but for the first generation cephalosporins i want you to remember here for these you have something called cefazolin and this is an interesting drug also known as anceph and the other one is cephalexin cephalexin these are the two primary antibiotics that you'll utilize second gen to be honest with you i don't think i've ever seen them utilize i don't know what happened to these dang things but your second gen are going to be something like cephaclor sufoxetin cephotin but again not too commonly utilized to be honest with you third generation cephalosporin are the workhorse of antibiotics to be honest with you these are utilized pretty heavily with the big one being ceftriaxone it's a pretty solid agent cefotaxine and to be honest with they don't see this one too commonly utilized but ceftriax on a big one and then another one that's also commonly utilized is called ceftazidime so it's ceftazadine so again first gen cephalexin and cephazolam pretty commonly utilized drugs second generation cephalus of oxatin cephotene not too commonly utilized third gen big workhorses especially ceftriaxone and ceftasidine your fourth generation is primarily going to be with something called cephepeme and your fifth generation if you've got heavy pockets because this is extremely expensive drug is called cephtaryline okay so again that covers the cephalosporins for the beta active so we got our natural penicillins anti-staphylococcal amino and anti-pseudomonal and then we got our first through fifth generation cephalosporins all a part of this beta-lactam group which reduces the cross-linking of peptidoglycans the one that reduced the synthesis is vanco and phospho there's two more categories here these are called your carbapenems these antibiotics they're like taking a grenade and just throwing it into a pool back here they'll kill anything but these are really broad agents and so you can remember these by the mnemonic dime so you have what's called dory penum you have what's called emmy penum you have something called marrow penum and then you have something called urtra penum these are beast agents the last one is a monobactin and this is actually called astrinum and really the claim to fame for this antibiotic is really just if you have those penicillin allergic patients but it's also a super broad agent gram negative coverage and sometimes pseudomonas as well but this would be a lot of your beta-lactams and again remember your beta-lactams they're pretty intense drugs your natural penicillins anti-staphylococcal amino anti-pseudomonas penicillins is a good way to categorize these your first through fifth generation cephalosporins your carbapenums and your monobactums now vancophospho out of these i would remember vanco vanco's a really good glycopeptide and again it inhibits the pipettor glycogen synthesis for the last thing here before we actually go through all the other antibiotics is we have to talk about this thing called beta-lactamase innovators so some bacteria very nasty bacteria have the ability to produce a very interesting enzyme so naturally we have a protein called a penicillin binding protein and this is the one that actually synthesizes the peptidoglycan layer right it helps to be able to take the names and the nags that make up the peptidoglycan layer and cross link them via the tetrapeptide connections we can utilize antibiotics and what these antibiotics do let's imagine here is your antibiotic what it'll do is it'll bind to the penicillin binding protein and inhibit it so it can't synthesize the cell wall or cross link them what happened is we actually developed these bacteria these nasty little bacteria they actually produced an enzyme they developed a resistance mechanism where they produce something called a beta lactamase and what this beta-lactamase does is it takes the beta-lactam antibiotics and inhibits them now these are actually they actually break the brady beta-lactam ring if they break the beta-lactam ring they no longer combine to the penicillin binding proteins they're no longer able to inhibit the penicillin binding proteins they don't inhibit the peptidoglycan synthesis and cross-linking and now the bacteria can continue to survive so what we need is we need drugs that can actually break the beta-lactamase a particular enzyme and that way these beta-lactams can actually still bind to the penicillin binding protein so what are the drugs that are going to work to inhibit this beta lactamase what are those drugs these are the ones that we add on so we can remember them by clavulanate so clavillonate is a really interesting one we add this to amoxicillin you remember which one that was for the beta lactose it was your amino penicillin the other one is we can utilize something called sulbactim and sulbactin we add on to ampicillin do you remember that one that's another amino penicillin this actually becomes augmentin this actually becomes unison the other one is pepercillin do you remember we added with that tazobactum so tazobactum and again we add the tasobactum onto pippericillin and the last one here not too commonly thought about but it's a newer one it's called avibactum and avibactum is added on to ceftazidime do you remember which of the actual cephalosporins cephtazidine was it was a third generation cephalosporin so when we talk about the beta-lactamase inhibitors what they're doing is they're inhibiting the beta-lactamase so that the beta-lactaman antibiotic can inhibit the penicillin binding protein so that it can reduce the cross-linking of the peptidoglycan layer allowing for the bacteria to still be able to die so that's a pretty cool mechanism for these antibiotics all right so we covered the cell wall synthesis inhibitors with the beta-lactams like glycopeptide like vancomycin and we talked about the beta-lactamase inhibitors let's keep going through all the other antibiotics and their mechanism of action all right knows a lot we're going to cover a lot i really urge you guys use our table of contents in the video we have all the different chapters that i urge you guys to go through maybe go through mechanism of action take a little break get a snack review it and then go on to the next part which will be the bacterial coverage or the antibiotic spectrum of specific antibiotics so let's talk about the next type of antibiotics which alter the cell membrane so if you remember if your cell wall which is the peptidoglycan layer with the tetrapeptides cross-linking them we talked about the drugs that work on that we now have drugs that can actually alter the cell membrane the inner cell membrane the integrity of it can be thrown off there are certain drugs here we don't commonly utilize them but one of them would be daptomycin so daptomycin is an interesting drug and what it does is it actually creates these little pumps if you will so it creates these little efflux pumps in the cell membrane so imagine it kind of plugs in these little efflux pumps which allows for things like potassium to move out of the cell and maybe other types of ions and water to move into the cell and this can actually produce bacterial like cell lysis so adaptomycin may be one of those and it creates these little efflux pumps which inhibits the membrane integrity makes it a little bit more porous and it increases the permeability of the bacteria so that's one particular thing the other one lord have mercy if you ever have to utilize this drug but it's called polymixins these are intense drugs you really don't ever want to have to utilize these but these are good for multi-drug resistant types of bacteria as a salvage therapy like you have no other antibiotic that's going to treat these patients they're resistant to everything this is kind of like the one last resort that you can throw in there now how polymixin's work is it's a very interesting type of drug it's like a cationic like detergent if you will and so what it does is it actually increases the permeability of the cell membrane as well but again it kind of acts like this like very interesting types of cationic detergent molecule which will bind with the actual cell membrane and increase the permeability of the cell membrane allowing for things to be able to move in or out of the bacteria increasing the risk of bacterial cell lysis so a pretty interesting type of drug all right so we got our cell membrane integrity inhibitors remember daptomycin creates efflux pumps for potassium and then polymixins are your really interesting cationic detergents that bind to the cell membrane and increase the permeability of the cell membrane all right the next drugs work particularly not on the cell wall not on the cell membrane but they work on these little metabolic pathways inside the cell that are crucial for dna and rna synthesis and this is your folic acid pathway you know folic acid you start off bacteria use something called para aminobenzoic acid and then they get taken inside of the bacteria and then they get converted via specific enzymes into something called dihydrofolate and then through more mechanisms they get converted to something called tetrahydrofolate and then from this this tetrahydrofolate can be utilized to can be put into mrna or rna and it can also be utilized to make dna so it's very important for nucleotide synthesis so what if we utilize drugs to inhibit the synthesis of dihydrofolate or tetrahydrofolate and we have those drugs that can inhibit these particular mechanisms and if you inhibit this you reduce the synthesis of tetrahydrofolate and reduce the synthesis of dna and rna and now the bacteria can't divide so you know there's very interesting terminology that sometimes you have to utilize these cell wall synthesis inhibitors they kill bacteria they blow these suckers up so when we use the term kill these are called bacteriocidal agents they kill bacteria they blow them up the cell membrane integrity they alter the permeability and increase the risk of blowing the bacteria up so they kill bacteria but this one it doesn't really do anything to kill the bacteria it just reduces the growth or the division of the bacteria that's called bacteriostatic so this one it actually reduces the actual growth and so we refer to this one as a bacteriostatic agent now there's two drugs we actually utilize them in combo so this is called your sulfonamides and so we usually use like so your sulfonamides the most commonly utilized one is called sulfur methoxazole we commonly use the abbreviation smx this one will particularly inhibit the conversion of paraminal benzoic acid into dihydrofolate okay so you can remember this one's the for that first step then from there the second step which is inhibiting the conversion of dihydrofolate to tetrahydrofoil which reduces the synthesis of nucleotides is the other drug called trimethoprim and this inhibits that second step we commonly give these in combo trimethoprim and sulfur methoxazole this is also known as bactrum and so this is a very commonly utilized drug as well so these ones will inhibit the folic acid synthesis pathway but we know which ones kill kill and then reduce growth okay the next one's your dna integrity so they alter the dna integrity these are really like interesting agents so one of these is actually called metronidazole so metronidazole is a pretty interesting agent can kill a lot of anaerobes some like really like weird types of pathogens as well but metronidazole works to be able to create a lot of what's called reactive oxygen species so it increases the formation of something called your reactive oxygen species like free radicals and that can actually produce damage to the bacteria can actually produce like breaks within the dna strands and if you produce breaks within the dna strain it can actually lead to complete like destruction of the dna and then now the bacteria doesn't have the ability to completely like survive and so this can actually kill bacteria the other one is called nitropharantoid and nitropharantone is also another one that can actually increase the formation of reactive oxygen species of free radicals which again can produce damage to dna they can actually damage your rna and they can even inhibit some of the protein synthesis pathways as well so when we talk about dna integrity metronidazole nitropharantoid again these are the ones that are really particularly producing a lot of reactive oxygen species free radicals which are producing damage to dna rna and proteins okay the next group we're not going to really talk about it too much in this video we'll talk about it in another video on anti-mycobacterial drugs so drugs that work against tuberculosis but there's drugs that actually inhibit the rna polymerase you see this cute little red little blue enzyme they inhibit what's called the rna polymerase enzyme and this is called your rifampin so this is one of the commonly utilized drugs that we give in patients who have tuberculosis so we're not going to talk too much about that one let's move on to the next one that we do utilize a lot unfortunately and this developed a lot of resistance so there's another one that inhibits this enzyme here this pink enzyme so we already have how this one inhibits this particular process and we have how the mrna synthesis rifampin inhibits this process and then we talked about how the dna integrity metronidazole nitrofrancoin inhibit the actual they destroy the dna they destroy the actual rna and some of the proteins but the next one is we can utilize drugs that inhibit the dna gyrase or topoisomerase type 4 enzyme and what this drug does is so topoisomerases they could actually help to be able to maintain the topology of the the dna so what they do is they produce little nicks within the dna allow for it to unwind whenever there's a lot of like super coils and then they allow for it to unwind and then they link it back up together once you relieve the super coils what if we activated the actual cutting part of this enzyme and it just chops and chops and chops and never re-ligates it then you just chop the actual dna up into pieces and this is a terrible situation but it's good whenever we want to get rid of bacteria so this types of drugs that i want you to remember here are what's called your fluoroquinolones so these are called jor fluro quinolones and there's a bunch of that actually part of this category so there's our first generations and the primary commonly utilized one for the first gens is going to be ciprofloxacin and then you have your second gens also known as your respiratory fluoroquinolones and this is your levofloxacin your gemifloxacin and then the last one is moxifloxacin so these are going to be the fluoroquinolones and they inhibit the dna gyrus they inhibit the actual topoisomerase enzyme and so it produces a multiple well particularly they inhibit the the actual ligating the annealing portion of it and then they increase the activity of the cutting portion the nucleus portion and it just fragments and fragments and fragments the dna into pieces so now you don't have any dna to be able to allow for the bacteria to survive so again this one will kill all right so it's a bacteriocyte agent all right we come on to the ones that inhibit the protein synthesis so you know that dna we utilize rna polymerases to make rna particularly mrna mrna binds with the ribosomes particularly which types of ribosomes and bacteria your 50s and your 30s ribosomal subunits and then from the mrna we make proteins well what if we utilize particular antibiotics that inhibit the protein synthesis so particularly some will act on the 50s ribosomal subunit and some will inhibit at the 30s ribosomal subunit what are those drugs glad you asked all right so for the 50s ribosomal subunit the big one is your macrolides so your macrolides this actually is going to be particularly it'll be your something called a zythromycin you have something called erythro mycin and you have chlorithro mycin so these are your macrolides pretty good one is the azithromycin which will be the more commonly utilized ones the other ones that are kind of like scattered there's no like very specific like category for these well there is but i think it's easier just remember the name of these for these ones you have something called clindamycin the other one is called chloramphenicol now chloramphenicol is not superly commonly utilized it's more in the low-income countries and then the last one is lynasolid now what's important to remember for these drugs is all of them inhibit the 50s ribosomal subunit which inhibits protein synthesis which proteins are important for being able to allow for certain replication functions and growth of the cell so these do not kill they actually reduce growth so they are called bacteriostatic agents so these reduce growth they don't blow the bacteria up they just reduce them from being able to grow all right so the next one is your 30s ribosomal subunits again these are inhibiting the actual 30s ribosomal subunit inhibiting protein synthesis will they kill will they reduce growth a little bit of both and i'll talk about which ones do that and which ones don't so for these your aminoglycosides and tetracyclines for the aminoglycosides i want you to remember primarily three so tobramycin is a is a good one amy casein is a pretty good one and gentomycin is a pretty good one as well okay for the tetracyclines there is doxycycline and tetracycline that's really it you can consider minocycline but we don't really use that too often maybe for like acne for the propriano bacterium but really i would just primarily remember doxycycline and if you want to add another one in there you can remember tetracycline but primarily the one that is worth remembering is your doxycycline now we can't just consider this whole group to kill or blow up cells and then some to be able to reduce growth one of them actually reduces growth and one of them kills so the ones that actually kill is going to be your amino glycosides where's my maroon marker here this one's good here all right so this one this group will kill and this one will reduce the growth so the tetracyclines are the bacteriostatic and then your aminoglycosides will kill okay now that we covered the mechanism of action which took forever now we're going to cover the bacterial coverage of the spectrum of these antibiotics alright guys so now we're going to move into the next chapter which is going to be the bacterial coverage of these antibiotics now there's a lot of ways of looking at this i personally think this is the easiest way to remember which antibiotics cover which types of bacteria and i also think it's more clinically like representative because a lot of the times you learn in school here's the antibiotic here's the bacteria that that antibiotic covers oftentimes in the clinical world and i think an easier way to remember is you either start patients on empiric antibiotic therapy and we'll talk about that for common infections and you base it upon what the most likely pathogen is and then what you do is you get cultures and from those cultures once the cultures come back they tell you which type of bacteria was showed up in the culture and then you utilize the actual bacteria that covers that pathogen very specifically and so i think it's a little bit easier to remember and it's more clinically applicable so what i'm going to do first is i'm going to talk about here's the pathogen here's the gram-positive gram-negative anaerobe atypical bacteria that came back from the culture what's the best antibiotics that cover this without being too broad and then after that we'll talk about what are the empiric antibiotic therapy the common regimens for very common infections and then how we tailor back based upon what the actual culture shows us okay so the first thing is gram-positive bacteria there's a lot of different types of gram-positive bacteria but the most common ones that you'll see on your exam or in the clinical world is going to be these so misa is what's called your methicillin sensitive staphylococcus aureus there's a couple antibiotics that work relatively well against this without being too broad and so the ones that i would want you guys to remember is think about first your your beta lactams if you will okay so the first ones that i want you guys to remember within the betalactin but your penicillin category is the anti-staphylococcal penicillins right so those ones will be very very good so i want you to remember your anti staphylococcal penicillins so do you guys remember what these were your naphcillin your oxacillin and your dicloxacillin these are going to be good against your methicillin sensitive staphylococcus aureus then you go into your cephalus more so keep going through the mechanism of action in your head so the next one is is there any other types of penicillins no is there any cephalosporins oh yeah the first generation cephalosporin is a really good one so your first gen cephalosporins are going to be very very good against your misa so this is your cephalexin keflex cephalexin or cefazolin these are very very good against these and then the other one that you can add into this category as well if you continue to keep going through in your head you can go through all the other ones and think about okay what else is there in the cephalosporins nothing else is really good against it do bactrim no bactrim not really what about your fluoroquinolones fluorquinolones are actually decent against misa so you can also add in your fluoroquinolones as well to cover some of the misses species if you go down to the other ones doxycycline no tetracyclines macrolides no so this would be the big ones that i would remember for your misa is going to be your anti-staphylococcal penicillins your first gen cephalosporins and your fluoroquinolones okay for your mrsa these are nasty like bugs these are usually your nosocomial infections so these are the ones that you get from like multi-drug resistant types of situations like in the hospital and so mrsa methicillin-resistant staphylococcus aureus there's only a specific types of antibiotics that cover these so again go through it in your head any of the penicillins no any of the actual generation cephalosporins actually the fifth generation cephalosporin it's called ceftaryline this one will actually cover your mrsa all right what about the um vanco or fossilmycin vanco is actually a really good agent that covers it so then we have vancomycin okay what about your full gasoline inhibitors like your trimethylamine sulfate oxal this one actually does cover mrsa so your trimethoprim sulfamethoxazole will cover it metronidazole nitrofarantoin no fluoroquinolones no what else can i go on to my next one which are going to be like my macrolides macrolides won't cover it we'll clean to cover it clinda covers it so clindamycin will cover it chloramphenicol will not cover it lynasalid will cover it and then if we continue to keep going on here then we go on to the next part which is your amino glycosides none of the aminoglycosides cover tetracyclines the only one is doxycycline now there is one other one that i want to talk about but it's a very interesting one it was going back to the cell membrane integrity inhibitors that was your daptomycin daptomycin does cover mrsa but you have to be very careful it only covers it on the skin or right-sided endocarditis it will not cover any type of lung infection due to mrsa because it gets inactivated by the surfactant in the lungs so daptomycin really the only mrsa coverage you'll get is some skin soft tissue infections and some right sided infective endocarditis due to mrsa so that would be your mrsa so your misa anti-staphylococcal so your naphthalene oxacillin and in your diet clocks first gen and cephalozone cephalexin and then fluoroquinolones but these would definitely be the best mrsa all of these and again go in that order all right so for the strep pneumonia there's a bunch of different antibiotics that we can utilize for these ones so think about your penicillins let's put them in a group here just i think it's easier so your penicillins penicillin itself penicillin g this would actually cover this one so you can cover this one with penicillin and then another type of beta-lactam that i want you guys to remember is your aminopenicillins you remember those amoxicillin and ampicillin plus the beta-lactamase inhibitors gives you a little bit of coverage against those with the resistance so the other one here will actually just continue on penicillin you can also consider your amino penicillins your amino penicillins are actually pretty good here your anti-staphylococcal not too much and then if we go into the cephalosporins i would actually consider really more of like your third gen cephalosporins will actually be pretty good i wouldn't actually forget those and again that's your your cef triaxone so cephalosporins for this one if you continue to go down here carpet venoms that's way too broad monobactine's way too broad the other ones that i would actually consider and if you go into dapto no you know polymixon's heck no bactrum bactrim's not too good at covering strep pneumonia fluoroquinolones will cover strep dumo so you can actually consider your fluoroquinolones as well so moxifloxus and levofloxacin if we were to go into the next ones and you actually consider some of the macrolides macrolides have some benefit i think there's becoming a lot of resistance out there against it but you can consider macrolides and then the other one is clindamycin so clindamycin will also cover these um not so much so for the nasality not so much for for the chloramphenicol and then your aminoglycosides not really and then again on top of that your tetracycline's not really as well so these would be the primary ones for strep pneumo if you had out of all of these which ones would you pick to be the best ones i would say your penicillin your amino penicils and your third gen cephalosporins would be the best ones these ones down here fluoroquinolones are okay mackerel is a lot of resistance cleaned up becoming a lot of resistance as well all right for the strep a and b so this is your group a strep so this is your streptococcus pyogenes and then your streptococcus agueleciae which is your strep b these ones again some of the similar agents here so penicillin will also cover this one your amino penicillins will also cover this one now for the cephalosporins not really the third gin it'd be more of your first gen cephalosporins so your first gen cephalosporins especially cephalexin that one will also cover this one as well and then again if you continue to keep going through carbopenum is way too broad monobacter's way too broad if you go into bacterium bactrim will actually cover these so you can add in trimethoprim sulfur methoxazole dapto way too way not to specifically for mrsa polymixins heck no if you go on to fluoroquinolones fluoroquinolones not too great against the strep a and b so i wouldn't really like consider those if you go on to your macrolides macrolides somewhat beneficial again there is becoming a lot of resistance against these and then again if you go into clindamycin clindamycin's not too bad as well so these would be the primary ones that i would consider for the patients who have strep a and b all right your enterococcus species your enterococcus you have enterococcus ficalis fecium there's a lot of these suckers here the amino penicillins tend to be the best for this one so i'd primarily remember you can consider penicillin so if you really wanted to you can consider penicillin you can consider your amino penicillins i would really consider these first okay and then the other one that you can consider as an add-on because it concentrates well particularly within the urine so it's good against utis due to enterococcus i'll add a little side note on to that is your nitropharantoid so nitropharantome will cover those in terracocca species but primarily because it concentrates well in the urine that would be the primary area you wouldn't use this for any other infections except for urinary tract infections due to enterococcus the last one here is listeria monocytogenes this is a heck of a pathogen and to be honest with you amino penicillins would be the best one ampicillin amoxicillin plus clavilani so you can cover your amino penicillins and again i would really consider whenever you add on these amino penicillins consider the resistance so sometimes if we add on amino penicillins it might not be enough to just have amoxicillin or ampicillin by itself sometimes you may have to add on their beta-lactamase inhibitor same thing for the enterococcus and listeria you may have to add on the beta-lactamase inhibitor and the last one of the listeria is bactrim trimethoprim sulfamethoxazole okay the last thing that i want to talk about is vancomycin so let's say that you have a patient who you think you've treated for any of these gram-positive infections they either are penicillin allergic or they're super resistant to all of these pathogens vancomycin will be the best one for that agent okay so if i have a patient who is penicillin allergic and on top of that they have resistance to the above gram-positive pathogens vancomycin will be your best agent it'll cover any one of these with the exception of vancomycin resistant staphylococcus aureus you'll have to use other agents for that one or vancomycin resistant enterococcus so sometimes certain these two bacteria enterococcus and staphylococcus aureus can become resistant we call that vre for vancomycin-resistant enterococcus and vancomycin resistant staphylococcus aureus as well but that's going to be the gram positive coverage so if you had a patient had an infection you treated them with broad spectrum it was from the lungs and it came back oh their infection was very specifically streptococcus pneumonia you can utilize one of these agents and peel back on the other ones oh their skin infection came back as missa and not mrsa start them on one of these agents okay so that's how you peel them back the next one is the monsters which is your gram negative coverage so now we move on to our gram negative coverage so when we talk about gram negative i think the easiest way to remember these we're going to do them in groups just like we did with the misa the mrsa strep the enterococcus and listeria so for the gram negative coverage there's a big group of bacteria i couldn't fit them all out i tried to come up with the easiest kind of mnemonic they actually used this in the first aid book for the usmle step one but it's hens peck so you can remember this by homophilus influenza enterobacter neseria gonorrhea and meningitidis seratia proteus like mirabilis e coli for the ec and klebsiella okay so haemophilus influenza enterobacter neseria seratia proteus e coli and klebsiella what types of antibiotics will cover these this is a huge one because it's a pretty common like type of infection for certain types of common infections that we'll talk about later but for the first one here is go through again your penicillins any of those penicillins not the first like natural penicillins aminopenicillins not too bad they can cover some of these so if you add on here amino penicillins they will cover all of these with the exception that they will not cover the enterobacter they will not cover serratia for these ones and they will not cover nessaria so in this case they will not cover the uh enterobacter and the necessary and they will not cover serratia for the amino penicillins so this would be again your amoxicillin plus clavilani or your ampicillin plus the sulbactum then you go into the other one so then continue down the penicillins anti-staphylococcal no anti-pseudomonal penicillins those ones are actually pretty good they have a very very significant broad coverage so if you considered your anti-pseudomonal penicillin this would definitely be a good one so this would be your pipracillin tazobactum all right go to the next ones your car your generally your cephalosporins so any of the cephalosporins first generation heck no well actually that's not necessarily true your first generation cephalosporins they actually can cover some of these they will only cover the peck portion so they'll only cover the proteus they'll cover the e coli and they'll cover the klebsiella the second generation third generation and fourth generation will cover all of these so you can actually consider your second through fourth gen these will actually cover all of them the next one is you move on to your carbopenums again carbohydrate boom that blow up everything so carbohydrates you can always put down to pretty much cover every single type of bacteria okay do you guys remember this the dime dory penum imma penemeropenum and urjapenum monobactums will cover these as well the monobactums will also cover these now the monobactums on in this situation here are pretty good the next one is if we continue to go through so keep keep moving through you got your adapto no vanco no poly mix and poly mexicans will cover everything so if you had to add this one on for the last one yes poly mixins will also cover it if you continue to move on into the fluoroquinolones fluoroquinolones will also cover this pretty well as well so you can definitely add in your fluoroquinolones and then if you move into your macrolides no clinda no chloramphenicol no lynasalidno aminoglycosides aminoglycosides will also cover these as well the one thing i would try to remember though is for your fluoroquinolones and your aminoglycosides these don't cover the nesaria as well so this one will not cover the nasseria and this one will not cover necessarily as well so these would be the primary agents to remember here for these and then again if you add on doxycycline or your tetracyclines they don't cover as much of these as well so this would be the primary antibiotics that would cover the hemophilus influenza enterobacter neseria seratia proteus e coli and klebsiella amino penicillins with the exception of anterobacter serratia and nyseria your anti-pseudomonal penicillins like percentage of bacterium first gens they only cover the pec portion second to fourth gen they'll cover all of them carbopenums particularly if you had to remember any of these the third gen will be the best one because that will specifically cover necessarily meningitis your carbopenes will cover these your monobactins will cover these your fluoroquinolone glycosides they will just not cover the nasseria species okay so we got the hens peck ones now we move on to the really nasty organisms remember how we had mrsa that was a type of nosocomial infection well your pseudomonas and acetate needle bacter are also some really nasty nosocomial types of gram-negative bacteria so pseudomonas originosa this is probably one of the big big big ones so let's keep going down that list any of the penicillins penicillin no aminopenicillin aminopenicillin will only cover the asynetobacter so if you put in these the aminopenicillins just realize it will not cover the pseudomonas it only covers the acetobacter if you continue to go down anti-staphylococcus no anti-pseudomonas penicillins heck yes peppercilantazobactum so you can consider the anti-pseudomonal penicillins like your pipercylentazobactum cephalosporins any of the first heck no second no third only one of the third generation cephalosporins will cover pseudomonas do you guys know so only one of the third gen and this is the ceftazidine so ceftazidime the fourth gen will definitely cover it and your fourth gen is going to be cephepine okay move through carbipenems do they cover pseudomonas yes monobactums do they cover it yes they just don't cover acetobacter so your carbapenems will cover all of these and your monobactums will cover all of these except for no acetobacter okay continue to go on trimethylsulfoxazole no fluoroquinolones here's the thing for fluoroquinolones they actually do consider these to cover the pseudomonas specifically your cipro and your levo but this is mainly for something called double coverage of pseudo and it's not really backed by a lot of evidence so they say that you can take one of these other agents that covers pseudomonas and add on a fluoroquinolone like ciproflox and levofloxacin for double coverage but it's not really heavy you know balanced inside of the actual evidence so they're not really good for monotherapy against uh pseudomonas but they can be somewhat considered as an add-on for double coverage of pseudomonas if you're considering it but there's not a lot of evidence to back that up okay then we continue to go down any of the macrolides any of the clinda any of the chloramphenicol um any of the other ones particularly no not really so then the last one here would be your aminoglycosides and your tetracyclines do any of those aminoglycosides will cover the pseudomonas so you can consider aminoglycosides one of the things to consider though for the aminoglycosides is they're not super good at covering the asynetobacter though so they will not cover the acid needle bacter as well but they will cover the pseudomonas and the last one is that like last one where you ain't got no other agent and like the patients like near death and they have no other antibiotic you can cover these you can add on the poly mixins so poly mixins is kind of like that last resort it's that salvage therapy so yes you could also consider this one to cover your pseudomonas and ace needle bacter all right so we got our hens pec hemophilus your enterobacter neseria seratia proteus e coli cleb and now we got the pseudomonas and acetobacter let's come down and talk about two other gram negatives that i need you guys to remember that being espl species and then the last one is called stenotrophomonas all right so let's talk about espls so what types of antibiotics will cover the espl well what the heck is an espl so it's an extended spectrum beta-lactamase bacteria so these are bacteria that have beta-lactamases that are so broad they can actually make a lot of antibiotics that we've just talked about for gram negatives not work so pretty much a lot of your beta-lactase so if you think about it think about for example the hens peck and then the pseudomonas a lot of similarities right amino penicillins won't work anti pseudomonas penicillins won't work thirds gens won't work fourth gens won't work carbopenems actually are remember boom that'll blow up everything fluoroquinolones these aren't even good at the extended spectrum aminoglycosides is not a beta-lactam so we can add that one on and remember i told you poly mixins will blow up everything so because of that we're really only left with carbapenems aminoglycosides and polymixins and then one last thing which there has been some literature to support so for these i remember karmapenums i'd remember your aminoglycosides i'd remember your polymixins now here's the one thing that there's actually been some research against you can take a third generation cephalosporin like ceftazidine and you can add on a beta-lactamase inhibitor like avibactum and this may have enough coverage to break down some of these extended spectrum beta-lactamase bacteria now the question is what are some of these bacteria it's a lot of the ones that we talked about really so i would really remember your enterobacters so you're in pterobactericie this is some big ones that have some extended spectrum your e coli your klebsiella is a huge one my friends so don't forget these these are really some of those bacteria that have developed a lot of resistance via these extended spectrum betalactamases that we need very specific antibiotics to cover okay the last one here is the stenotrophomonas so stenotrophomonas i really want you guys to remember for specifically for this one your ant so go through your penicillins do any of the penicillins cover this one the only penicillin to cover this one is the anti-pseudomonas penicillin which one's that one piparcillin plus you have to add the taseobactin to that one so your anti pseudomonal penicillins the other one to remember here for this guy is if you go through um is your polymixins polymixons cover everything this is a really nasty pathogen so polymixons would kind of be a big one to add on here and then believe it or not it's just a random one bactrim so trimethoprim sulfamethoxazole will also cover your stenotrophomonas so this will be a lot of your gram negative coverage i know there is a lot there again i encourage you to sit down write them all out with me write them out on your own and keep doing it it's a lot of work but we're gonna get there let's move on to the uh atypicals and anaerobes so the next one is your anaerobic coverage so i like to help to remember this is can't breathe perfectly fresh air so for the can't breathe perfectly fresh air you can remember this by claustridium so the clostridium species clostridium perfringens clostridium difficile clostridium uh botulinum clostridium uh tetani so there's a lot of different clostridial species the next one is bacterioides so bacterioides for jealous p for pepto streptococcus f for fuso bacterium and a for actinomyces so again these are your anaerobic bacteria again clostridium bacteroides peptostreptococcus fusibacterium and actinomycetes what are the antibiotics that will cover your anaerobes so the ways i like to remember this is first off i like to remember above the diaphragm there's a very specific set of antibiotics that cover these and then the ones below the diaphragm and then we'll cover the ones that just hit everything and again those obviously you know carbohydrates are going to be a part of it so let's cover these so if it's above the diaphragm clindamycin has been shown to be the primary one that will cover some of the anaerobes that are above the diaphragm now for the ones below the diaphragm so your gi infection so this would be above the diaphragm and the skin so any parts of the skin and above the diaphragm so here we'll put diaphragm and skin metronidazole is not really good against the skin infections that are anaerobic so like your decubitus ulcers from diabetics that have like um so decubitus ulcers or like the diabetic foot ulcers that are polymicrobial that have probably some gram positive and anaerobes in them then clintomics will be the better one for that one but for the ones that are below the diaphragm so your git infections some of the pelvic infections that's going to be your metronidazole so let's put that down here metronidazole so this will be for the actual pathogens that are below the diaphragm okay so git infections the ones that if you're not trying to be specific and you just want to hit everything gram negatives and anaerobes it'll just hit everything it's karbapenums and your anti-pseudomonal penicillins like pepperocidal taseobactin those are again they're bombs you just throw them in they kill everything so this will be your carbapenems and then last but not least is your anti-pseudomonal penicillins now i'm going to add in just a little kind of thing here there is a questionable effect of fluoroquinolones being effective against some types of anaerobics there is some literature that is suggesting that there's a lot of resistance so i'd be very careful it is mentioned in the textbooks as a potential coverage for anaerobics especially like cipro that's the primary one so ciprofloxacin but there is some question if it's actually good enough to be able to cover that okay the seed differs so when you're peeing out your butthole what is the bacteria that's causing that that's the clostridium difficile it's one of the types of clostridium for the anaerobes but the types of antibiotics that we utilize to cover this one is very specific we already talked about one of them so c diff it's affecting the git so the colon right so you get pseudomonas colitis so which one is below the diaphragm to cover that one metronidazole so metronidazole will actually cover the c diff but there's one other one which is just like you're like what the heck where'd this one come from it's vancomycin but not the iv form the po form so vancomycin the po form will actually cover c diff so those are the two options that i want you to remember for that specific and rope all right let's come down and talk about the atypical coverage so they don't really fit well within the gram positive the gram negative the anaerobe they're just some random wonky ones that may be possibly get tested on so i want you guys to know these so this is mcl mycoplasma chlamydia lesionella these are very specific types of atypical bacteria that there's very specific antibiotics that cover all right so go through the list again any of the penicillins cover this one not really your bactrim cover this one or dapto or phospho or polymixins no fluoroquinolones cover this one the fluoroquinolones actually do cover these especially if it's lesionell it's actually the preferred agent so for the fluoroquinolones i would actually remember that these are actually preferred especially if lesionella is the type it's preferred okay then go on to the next part go into your macrolides macrolides do cover these pretty well actually so macrolides will definitely be one to consider the other thing here is chloramphenicol does that one cover it yes it does except for the last one so chlor and phenical this will not cover the legionella so if you have legionella not preferred but again this is more of like the low-income countries that will be utilized and then the next thing is what about your linasalidno what about clinda no what about your aminoglycosides no what about your tetracyclines yes doxycycline preferred so doxycycline is really good one because it'll cover all of these really well so these will be the agents that will cover your atypical types of bacteria mycoplasma chlamydia and lesionella okay the other ones are your tick-borne bacteria so this covers all of them except for babesiosis do you guys remember all of these sons of guns here borrelia burgdorferi rickettsia ricatzia erlickia anaplasma all of these guys cover multiple types of these tick-borne illnesses so again berylia causes lymes rickettsia rickettsia causes rocky mountain spot of fever earlykia causes erlichiosis and anaplasma causes anaplasmosis these can be covered very well okay so if you go through here some of these are similar so the big one here that i want you guys to remember is going to be doxycycline so doxycycline is the preferred agent for all of your tick-borne illnesses and here we'll just put them as abbreviations borrelia burgdorferi rickettsia rickettsia likiosis and anaplasmosis except for babesiosis that's not the treatment for these ones so doxycycline is one chlorine finical will be the one for like those low-income countries and then a little side note to remember here especially for borrelia burgdorferi if it becomes disseminated so it actually causes like meningitis it causes bilateral facial nerve palsy it causes like an av block the preferred agent for that is cephtriaxone especially if it's cns because ceftriaxone has good cns penetration so it's the preferred agent for cns infections especially for beryllium or dorphy so it might be a little add-on that they throw at you okay the last thing to remember here is treponema politum this is a spirochete so this is actually the thing that causes syphilis so in this disease which ones do we utilize penicillin is actually the preferred it's a penicillin g and then if that's not an option or they have an allergy you can consider doxycycline so to be honest with you if you don't know which one to pick for the atypicals you notice a common trend among all these doxycycline tends to be the best for your atypicals okay that covers the anaerobe that covers the atypical coverage and that covers the bacterial coverage of all these antibiotics now what we have to move on to in the next chapter here is we have to talk about what are the actual empiric antibiotic therapies for common infections so i have no idea what the actual bacteria is i just have a suspicion of what it is based upon the infection that they have what are the antibiotics i'm going to throw at them then when the cultures come back and they tell me which type of bacteria it is i know which antibiotic to pick that's best suited for the bacteria now let's talk about that now all right guys so now let's talk about the empiric antibiotics for common infection so you have a patient who comes in they have pneumonia right you diagnose it based upon the clinical features of pneumonia and the radiographic evidence of pneumonia so you have concern for pneumonia you have to discern if it's a community acquired versus a hospital acquired pneumonia right and based upon that that kind of gives you an idea of which kind of pathogens are the most likely cause of their pneumonia so for a community acquired pneumonia you usually think about strep pneumo as the big one hemophilus influenza maybe morex celicate or alice right so you can think about again i remember strep pneumo haemophilus influenza morex electoralis and then i think about my atypicals right so i think about lesionella mycoplasma chlamydia ammonia right in those situations i need to think about which types of antibiotics will cover my strep pneuma primarily and my atypicals so one of those that covers both of them that cover strep pneumo is my fluoroquinolones and then the other thing is that fluoroquinolones also cover all the types of atypicals especially preferred for lesionella so if i wanted to with one antibiotic and done fluoroquinolones would kind of be the ideal one to go here so i would pick like a fluoroquinolone the respiratory fluoroquinolones okay the other thing here is if i wanted a little bit of a better coverage maybe to give me some of the coverage of strep pneumo as well as hemophilus influenza morexella and then i have another agent that's really more targeted to the atypicals like doxycycline or a macrolide then i could use that plus something that would give me the strep pneumo and some of the gram negative coverage what's that ceftriaxone a very specific beta-lactam so i would pick something like a beta-lactam and the preferred agent as the betalactim is going to be ceftriaxone so i remember ceftriaxone again you're going to see out of all these antibiotics that we have there's very specific ones that are most commonly utilized and then add on to that either a macrolide plus or sorry or doxycycline or doxycycline these would be the agents that i would pick so for cap community acquired pneumonia monotherapy fluoroquinolone or a beta-lactam plus a doxy or a macrolide for the hospital acquired pneumonia now on the other hand you're thinking about nasty multi-drug resistant type of pathogens you're talking about the pseudomonas you're talking about mrsa so for this situation here you're talking about mrsa so you need to have coverage for mrsa and you're talking about pseudomonas so you need to think about all the antibiotics that'll cover mrsa and the ones that will cover pseudomonas remember all those that's the preferred one for for mrsa vancomycin so that'll be the first one for your for your mrsa coverage so vancomycin and then for your peppers sorry for your pseudomonas i already gave you the answer but you could have a bunch of drugs here so you could pick your anti pseudomonal penicillins which is your pipper cylinder tazobactin you could also pick ceftazity you could pick cefepime you could even pick an aminoglycoside right so these are the options that you could add here so it would be a vancomycin plus one of these to give you your pseudomonas coverage the more commonly utilized one is going to be anti-pseudomonopenizing and cefapine okay that'll cover your pneumonia so once you have them come in you treat them with these particular antibiotics for your cat do these get some cultures and then once you get the cultures and they come back oh it was only strapped pneumo then you can peel back some of the other antibiotics and only utilize the ones that will cover your atypicals or your strep pneumo if you end up getting a hap you end up starting them on the worst case bacteria mrsa pseudomonas then you get the cultures back and then they come back and they say oh it wasn't even merc it was misa oh then i can get rid of vanco i can get rid of the pseudomonal coverage and i can only target the missus species which i can use something like naphthalene oxacil oxacyline dicloxacillin or cefazolins cephalaxin something like that or even potentially like a fluoroquinolone so in those situations that's how i would go about targeting these now the next thing is your git infection so this includes like cholecystitis cholangitis appendicitis diverticulitis pancreatic walled off necrosis peritonitis and intra-abdominal abscess anything that you can think of git wise there's a lot of things that we have to cover but most specifically for the git you think about your gram negative rods the hens peck so with particular emphasis on enterobactericie e coli klebsiella and then for the other thing you have to consider is your anaerobic infections so all those anaerobes so the clostridium species the bacteroides the fusibacterium the peptostreptococcus and the actinomycetes you have to cover those so i need gram negative and anaerobe coverage now to think about this which one is the boom blows up everything we'll cover every gram negative and every anaerobe there's the karba pendums and then your anti-pseudomonal penicillins are also pretty good there because they'll cover anaerobes and gram negatives by themselves so the ones i would consider for these is going to be your carbapenems that would be a monotherapy there or your anti-pseudomonal penicillins because they'll cover you all your gram negatives and your anaerobes now if you're trying to do double coverage like you actually have two agents where you want to be a little bit less intense with these nasty agents because they're really intense they're great drugs but they're super broad you can consider something like a double coverage where you add on metronidazole which is for anaerobic infections below the diaphragm and then you have something that covers a gram negative so i would cover let's put metronidazole plus metronidazole plus metronidazole plus so metronidazole plus a fluoroquinolone like cipro would actually be not a bad idea because that also gives a little bit anaerobic coverage metronidazole plus ceftriaxone which gives a good gram-negative coverage against collab e coli and enterobacter and metronide is all placefein because that also gives a good coverage and even gives you some pseudomonas coverage as well so those would be the types of antibiotics that i would cover for a gram-negative and anaerobic infection okay so commonly it's usually you'll see the the third option here or the fourth option and if you really want to carbon pendulums will cover it all okay the next thing is your skin and soft tissue infections for the skin and soft tissue infections there's two types of pathogens that i want you to remember you're going to see staphylococcus aureus and strep a as the streptococcus pyogenes but there's two types there's the misa and the mrsa for the staph aureus so for misa and strep a i want you to know the po and iv version so if you have someone with a cellulitis or they have an abscess or they have some type of like nasty like skin infection soft tissue infection what do i cover them with well the first thing is if they have miss and strep a and i want to cover them with po versions then i would consider which one was the coverage for the missa it was the anti-staphylococcal so diclox so diclox was the only like really po one um that would cover the misa and the strep a okay what are some other agents that i could utilize it was the first generation cephalosporins which one was those cephas nolan is pretty much iv so cephalexin would be the other one or cephalexin okay if i want to cover more of an iv form then i could use all the other ones so nafcillin or oxicillin or i could utilize which one for the first generation cephalosporins cefazolin another cool thing about cefazolin which is actually interesting since we just talked about anaerobes is there's actually some literature that suggests that these can be used as a post-surgical prophylaxis so if somebody has like their abdomen open they get a surgery of any kind um any kind of like post-surgical process you can give them a couple doses of cefazolin and it's actually been shown to be pretty good at post-exposure like treatment of a prevention of bacterial infections and it actually has anaerobic coverage cefazolin but anyway the next thing is your mrsa infection so mrsa so these won't work for mrsa so i need to know what things will cover mrsa but let's know the po versions and then what's the iv versions so the po versions is going to be things like particularly if you had for these i would actually consider something like bactrim like trimethoprim sulfamethoxazole the other one that i would consider something like doxycycline or clindamycin because these will cover both your mrsa and your strep a if you're going po form for the iv form the preferred agents are going to be your vancomycin okay the vancomycin will be the preferred agent for this and if you've got heavy pockets and you can consider like ceftaroline but vancomycin be the primary one okay so the next thing is if we have the urinary tract infection so the utis we have to think about what if it's actually due to a pilo what if it's due to an acute cystitis so the most common pathogens particularly for a pilot or for an acute cystitis are particularly going to be those pec organisms so again you're going to think about the proteus mirabilis your e coli your klebsiella and then don't forget your enterobacter so your enterobacter are going to be some of those as well so same thing pec and enterobacter okay so for these i want to know which kinds of antibiotics are going to cover me for pyelonephritis especially against the pec and the enterobacter well the big one that i would think about is ceftriaxone the third generation cephalosporin is an obvious one here definitely can't go wrong with this one so ceftriaxone is a pretty good one here the other one that i would also consider here is going to be a fluoroquinolone particularly ciprofloxacin this one's also pretty good can i also give you some coverage against these organisms as well the other one that you could potentially consider against these is something in the lines of like a amino penicillin amino penicillins may not be too bad they don't cover your enterobacter very well but they would cover some of the proteus the e coli and the klebsiella so you can consider something like an amino penicillin particularly ampicillin but these would be some of the agents that you can consider for the pyelonephritis for the acute cystitis so this is primarily of the bladder this would be particularly in your pec in your enterobacter but there's a very subset of antibiotics very specific to these so trimethoprim sulfamethoxazole would be one if they're like not pregnant nitropharan tone is usually good for also known as macro bit is good for like post coital prophylaxis against certain types of utis another one that you can consider here is phosphomycin and then lastly is if a second lyden agent it would be like ciprofloxacin so this would be more of your second line agent because there is a lot of resistance out there to get this drug so these would be the agents that you would consider for a patient for acute societies now the last situation is what if the patient has a complicated uti so it's a complicated uti meaning that they got some nasty pathogens in this bad boy they got something like pseudomonas they got something like mrsa or they have something like enterococcus and these situations now we have to broaden up our coverage a little bit so i have to think primarily about the pseudomonas what's going to cover that pseudomonas really well so the pseudo i got to think about any kind of anti-pseudomonal drug so this would be again think about your piperacillin so we'll put piptazo that's your anti-suitable penicillin you can think about cefepime you can think about an aminoglycoside maybe even ceftazidim something of that nature um the other thing that you can consider here is what else for the complicated utis especially for the mrsa if you're definitely concerned about mrsa and enterococcus because they have like their chronic foley so they have like a chronic and dwelling foley then you can consider something like vancomycin and then again for some of these you can even potentially consider like an amino penicillin but amino penicillins wouldn't really um actually amino penicillins would particularly be against the enterococcus so amino penicillins would really be primarily against the enterococcus if it came back it was definitely enterococcus the amino penicillins would actually be beneficial against this one you can even consider carbapenems but that's way too broad i wouldn't go ahead with a carbohydrate okay that's our uti so we covered pneumonia git infections skin soft tissue urinary tracts what about bone and joint particularly like septic arthritis or maybe even like an osteomyelitis in those situations you want to think primarily about mrsa because it's off the skin right so it spreads from the skin into the actual boner joint so if you want to think about mrsa coverage what's the best antibiotic for mrsa especially iv which you're going to need vancomycin if you also have to think about this one here add this one into the list it's a tricky one so nesarius this okay so naserio gonorrhea especially in this situation sometimes patients can get some nasty like sexually transmitted infections and it can actually spread to the actual joint so for this one you want to consider something like a ceftriaxone if you have concern for this okay and the last thing is pseudomonas pseudomonas is a pretty nasty one especially like diabetics um so you want to think about any kind of pseudomonal penicillin a pseudomonal drug so specifically for these cefepime and ceftaz are a little bit better in comparison to your pipercellontesobactum okay that would cover our bone joint uti skin soft tissue our pneumonias and git infections let's now come down here and talk about meningitis and then some bloodstream infections like uh clabsis and sepsis all right my friends now let's move on to cns infection so now we're talking about like meningitis a really nasty meningitis if a patient comes in they've got symptoms of energized photophobia headache they got neck stiffness they got fevers all the above and you're considering is this a community acquired meningitis so they actually developed what types of pathogens here likely you want to think about strep pneumo you want to think about homophilus influenza and you want to think about nesaria meningitidis okay these are the primary community acquired meningitis infections so you have to think about what kind of things are going to cover your strep pneumonia your hemophilus and uranus area so the best things to consider in these situations here is actually going to be vancomycin because that'll cover a lot of your strep pneumo okay especially if there's any resistance situations here and then ceftriaxone because that'll also be a really good one because it has the best cns penetration remember good cns penetration for ceftriaxone now the other thing that's a benefit to this one is that you also get coverage of the hemophilus influenza and the necessary meningitis the last thing that you can consider is ampicillin and the only reason i would add this one on is the concern for listeria so if you're concerned for listeria the patient is greater than 60 years of age or 50 years of age actually some literature says they're immunocompromised like they have hiv the transplant something like that or their little baby then you can consider the addition of ampicillin because you're trying to cover for listeria if not if they don't have a lot of those risk factors you don't really need to add on ampicillin okay so that your community acquired meningitis now hospital acquired they had a neurosurgical procedure they had a hemicraniactomy they had a evd they had some type of thing where we opened up the skull or we did some type of surgery mucked around near the meninges and we introduced a pathogen that's in the hospital nasty stuff into the actual meninges that's mrsa and pseudomonas so what do we give for those infections that we're concerned about if we think it's mrsa my friends we give vanco and sometimes even linaselli is actually a decent one as well for the other one we're concerned about pseudomonas because this is a a nosocomial infection episode taser bacterium not too good at penetrating into the actual meninges cefepime is and unfortunately can actually cause encephalopathy and seizures too but cephepim is a pretty good one that i would actually consider here and if you really need another one that penetrates well but it also can cause neurotoxicity and seizures carbopenes as well but i would go with cephepene primarily for this one okay now we move on to the bloodstream infections you have a patient who's coming in they're coding you have to throw in an emergent crash line and you don't do it sterily or you do do it sterily whatever it may be sometimes you actually do a sterile procedure you put in an ig you put in a subclavian line whatever it is and you perform it sterile what are the pathogens that are on the skin that actually may move along the actual length of the catheter or the actual needle and get into the bloodstream along that catheter what's the big one to think about mrsa staphylococcus aureus you can get things like um staphylococcus epidermidis but that's more like not a concerning one i wouldn't be too worried about that one i'd be worried about mrsa okay so if i'm concerned about that definitely think about that one so in a patient who has a bloodstream infection they got fever they got hypotension they got a leukocytosis in those situations and you're thinking about oh they got a line in think about that as a potential source of their infection and so i got to cover the possibility if this is mrsa which is the most likely one because of where the actual pathogens would have a route into then i would consider something like vancomycin now the times where i would add on a plus or minus for the actual gram negatives so any kind of gram negative that you can think about why i would think about this with the femme lines so if you have a femoral central line what's that right near right near the booty hole so a lot of opportunity for gram-negative bacteria to hop onto that area if they're pooping if they're having like incontinence and moving along the length of that catheter into the actual bloodstream so in those situations like you have like a a non-sterile line or a crash femme line or fem line in general think about this as a potential opportunity and then you'll add on the things that will give you the gram negative coverage what's the best one really that'll cover your gram negatives your pseudomonas i'd say peppercilantazobactum okay so for this one you want to consider piptazo okay and that's your anti-pseudomonal penicillin i just don't want to write it out my arms are getting weak okay the next one is sepsis you have a bloodstream infection and you actually are concerned a patient comes in you have no idea what's going on to them they are tachycardic they're hypotensive they're fibra they've got a blasting white count you have them on pressers you have them on fluids you have them intubated you're doing everything to be able to keep this patient alive but they have a sepsis of unknown etiology there's always the classic antibiotics that you start them on and that's vancomycin to cover mrsa and any other kind of gram-positive infection and then the other one is your pipercelantazobactum to cover any kind of gram-negative pseudomonas acetynobacteria extended spectrum beta-lactamases anaerobes because it's just a broad agent if you don't want to use that one what was the other one boom carbopenums so those are the agents that i would think about if for any gram positive that you're trying to cover for especially mrsa is vanco and then if it's the other ones for your gram negs or anaerobes and i'm talking any of them what was the ones that covered almost every dang gram negative in almost every anaerobe possible pseudomonas per the anticipated penicillin like piptazo and the carbopenums okay i know this was a lot take the time now to go back review it keep writing it down and trying to go through this stuff a couple times let's now take a break do that and move on to the next big beast to tackle and that is the adverse effects and contraindications lots to talk about let's get there all right guys so we have covered so far up to this point the mechanism of action we covered the bacterial coverage we covered empiric antibiotic particularly for common infections now we move on to the next chapter which is the adverse effects and contraindications as if it wasn't enough to remember all the actual bacterial coverage of these antibiotics now we got to remember their adverse effects and there is a lot of them i think the best way to do this is to take the big common adverse effects and then group which antibiotics particularly cause these adverse effects and then we'll talk about some of the other types of random ones that don't really fit within these categories super well and we'll get into those a little bit all right so first things first neurotoxicity so this can look a couple different ways it can look like seizures it can look like myoclonus it can look like encephalopathy it can even cause some really weird situations here we'll talk about another one called serotonin syndrome but what are some of these actual types of antibiotics that cause neurotoxic effects in other words they penetrate into the actual central nervous system and cause adverse effects big ones to remember are your penicillins your cephalosporins are also going to be really good ones okay the other one is your carbipenums these are are really big offenders especially at high dosages the other ones that i want to remember is your polymixins so mixins are also another one and then last but not least is your lenasa lid now linaselid i have to add a little side note here it actually produces something called serotonin syndrome and it can also cause peripheral neuropathy now the reason why this isn't important was because linaselid can actually and work against those monoamine oxidase inhibitors and help to increase the level of serotonin with inside of the synapses which can produce a serotonin syndrome so for penicillins cephalosporins carbipenums really you can just remember all your beta-lactams really and then after that polymixins and linasa litter for the neurotoxic drugs for your pancytopenia same thing penicillins tend to be a big one they can work particularly by maybe causing pancytopenia and on top of that they also may induce a little bit of a hemolytic anemia to talk about a little bit later but penicillins can be one cephalosporins are one now your carbapenel is not so much so the other ones that i want you guys to remember here is going to be if you continue to kind of go down through the wheel of all these antibiotics that we've been going through any of the other beta-lactams carbophenomenas no monobactins no vanco no phosphomycin no dapto no polymixins um not too much maybe a little bit of uh the actual kind of effect there but not too much not worth mentioning bactrim yes bactrim actually can produce um some panzero penis so trimethoprim sulfamethoxazole then you go into the next one's metronidazole nitrofarantoin no you go into your fluoroquinolones no you move into your macrolides no you move into your clinda chloramphenicol chloramphenicol can actually cause some pancytopenia so i'd remember that one as well chloramphenicol and then lynasolid linaseali can also suppress your bone marrow as well so these are the ones that i would remember penicillin cephalosporin bactrum chloramphenicol and linaselid now the respiratory failure is an interesting one for respiratory failure what you want to remember here is going to be polymixin so polymixins can actually cause respiratory failure and then the other one here is going to be pulmonary fibrosis due to nitrofarantone so nitroforantone that we use pretty much for a lot of those urinary tract infections can actually cause pulmonary fibrosis so it actually cause fibrosis which can lead to respiratory failure okay let's come down now and talk about these other kind of ones here nephrotoxic ototoxics and things that can actually exacerbate myasthenia gravis all right so now the next thing is nephrotoxic agents so these things that actually cause kidney injury so ones that actually cause direct kidney injury that we'll talk about those last but the ones that actually work through an indirect mechanism they produce kind of something called acute interstitial arthritis by a kind of like a hypersensitivity reaction so we'll talk about a little bit later but basically you exposed to the drug your immune system cells produce antibodies like ige and igg antibodies and these kind of molecules actually lead to inflammation around the kidney tubules and cause acute interstitial nephritis which can cause an acute kidney injury the ones that i want you to remember for that one is your penicillins your cephalosporins and then the last one here is your bactrum so your trimethoprim sulfamethoxazole all of these is a category can cause acute interstitial nephritis the ones that cause direct nephrotoxic destruction though are going to be your aminoglycosides and don't forget this one vancomycin these ones will actually cause direct nephrotoxic effects so big big ones to monitor in these patients ototoxic just take the two ones that we just talked about aminoglycosides and vancomycin bring them down so aminoglycosides can cause ototoxic effect and vancomycin can cause ototoxic effects especially if combined with aminoglycosides myasthenia gravis so myasthenia gravis is basically again it's that whenever patients produce antibodies that are against like the nicotinic receptors that are present on the muscle cells the skeletal muscles right where we can actually have particular drugs that can worsen the myostinia gravis and put them into a crisis and so the big ones to remember for this one is going to be your fluoroquinolones your aminoglycosides your macrolides and then last but not least your clindamycin so these ones would probably stay away from if a patient has myasthenia gravis and you don't want to put them into a mycenaean crisis all right so that's the ones for again nephrotoxic ototoxic and then worsening the mystery graphics let's go back up and talk about the other ones particularly the teratogenic medications all right so the next thing is teratogenic medications meaning that you should not give these to patients because they have the risk of causing particular types of destructive effects to the baby during the actual gestational period so avoid these medications and so the big ones that i definitely think are worth remembering here are going to be a couple different drugs so if we go through all the penicillins they're all safe the beta lactams are safe vancomycin's safe bactrim i would actually kind of avoid that one the reason why is bactrim trimethoprim sulfamethoxazole has been shown to be able to produce something called kernicterus so it can actually cause a lot of um unconjugated types of bilirubin to accumulate within like the cerebellum the brain stem and then like the uh particularly some of the actual basal ganglia structures which can cause a lot of like neurotoxic effects so that's one particular one that i would stay away from um if you go through the other ones like metronidazole nitrofarantone not so much then if you go into your fluoroquinolones fluoroquinolones there actually is particularly like contraindications against those less than 18 years of age because it can produce a lot of cartilaginous damage and arthropathies so that's one particular drug that i would also consider like fluoroquinolones to kind of just stay away from um then if you move on from there you move into um your 50s ribosomal inhibitors so macrolives are pretty safe clinda is relatively safe chloramphenicol i would actually kind of avoid as well especially in certain situations so chloramphenicol one of the problems with this drug is it can produce something called gray baby syndrome and you're like what the heck so this is important in like the glucoronate reaction so you know there's an enzyme called udp glucose glucuronasal transferase and what it does it produces puts a glucaronic molecule on certain types of drugs during the biotransformation process if they have a deficiency in that enzyme then they don't glucoroni uh put a glucoronidal on chloramphenicol and so we have lots of these metabolites of chloramphenicol which can produce kind of a gray ash and appearance of the baby and also cause significant hypotension tachyarrhythmias and produce cardiovascular collapse and even respiratory failure in these babies so avoid chloramphenicol the nasal lid is actually relatively okay if you go into your aminoglycosides those are not too bad and then the other one that i would also consider is your tetracyclines like doxycycline that's a big one as well so i would also consider doxycycline maybe avoid that one as well just because of the risk particularly for this one um this one can also potentially cause a lot of teratogenic effects as well so these are some of the big ones that i would actually say to avoid in a patient who has again who is pregnant and uh you don't want to actually cause some type of teratogenic effect the next thing is your disulfiram reaction so disulfiram reactions are basically whenever someone takes a medication and combines with alcohol they can actually develop like nasty like nausea vomiting like exorcist level vomiting like flushing hypotension tachycardia a lot of problematic issues with this and the big one to remember for the disulfiram reaction i'm actually gonna get rid of the other one because i think this one's the more important one remember i don't want you guys get too confused is metronidazole so do not forget metronidazole the other one if you really want to remember it it's the third generation cephalosporin ceftriaxis has been shown to be able to produce this as well but again i focus more particularly on disulfiram reaction metronidazole the other one is qt prolongation with the increased risk of producing something called torso's deployment so you know if you actually increase your qt interval you increase the risk of something called torsades to points which is a nasty type of polymorphic ventricular tachycardia that can quickly defibrillate break down into ventricular fibrillation so i would also be careful for this one the two particular drugs that you want to remember for this one is your fluoroquinolones and your macrolides so fluoroquinolones and your macrolides are going to be the big ones for this one okay so now that we got these let's move on to the next group here which is your cyp 450 inhibitors let's talk about these all right so the next thing is your cyp-450 inhibitor so what are the particular drugs that can actually work so you know whenever you have cyp-450 molecules these are basically particular enzymes that are going to work to take a drug and undergo a biotransformation process so to be able to kind of add on a little intermediate metabolite that makes this molecule a little bit more polar and allow for it to be able to exert its effects okay if we give particular drugs like cyp we give some of these other antibiotics they can act like inhibitors and if they act like inhibitors what happens is they actually reduce the metabolism of the drug and that causes the concentrations of the actual drug to be a lot higher within bloodstream producing more negative connotations of that drug and so the big ones to remember for this one are going to be your fluoroquinolones your macrolides and your trimethoprim sulfamethoxazole so these are the ones that can actually kind of increase the concentrations of the drug because they can inhibit the cyp-450 and enzyme which doesn't allow for it to be able to get converted into like this metabolite form and so because of that now this drug concentration is a lot higher and it has the ability to presume more negative effects so for example if i took this with like warfarin which is designed to be able to cause a patient to thin out their blood right anticoagulant now if i give it with these medications it can actually increase the concentration of the warfarin within the bloodstream and produce a potential increased risk of bleeding so that's a thing to consider all right the next thing is your hemolytic anemia so hemolytic anemia is uh particularly the destruction of your red blood cells and there's a lot of particular drugs that work at this level too the big thing to remember is if you remember for the thrombocytopenia there was penicillins and cephalosporins these actually cause like hypersensitivity reactions which can lead to kind of a a coombs positive coombs test which actually can be positive on these patients so they'll have anemia you can check their ldh you can check their haptoglobin there may be some evidence of hemolysis and then you check their coombs test and it's actually positive and so for these patients i would remember penicillin encephalosporins that these can actually produce a positive coombs test the other ones that i actually would remember here specifically exacerbate our worst in our produce a hemolytic crisis in patients with g6 pdh deficiencies and so this one's i would remember trimethoprim sulfamethoxazole fluoroquinolones and nitropharantone these can actually worsen your g6pdh deficiency and produce a kind of a hemolytic event or hemolytic crisis so i would remember these the last one here to add on is phototoxicity so if exposed to the sun it can actually cause a lot of rashes and kind of skin burning effect and i would remember for this one is doxycycline and trimethoprim sulfamethoxazole all right my friends we talked about the most common types of like adverse effects as groups based upon the type of problem that they have let's now come for some of like the little more nuanced types of adverse effects or contraindications of each individual kind of drug class and we'll talk about one more thing which is the c diff all right let's get in there all right so now let's talk about just some extra adverse effects that i want you guys to remember in case it comes up for your exam so penicillins are there anything else besides what we talked about over here with the neurotoxic effects the pancytopenia particularly the nephrotoxic effects we talked about its effects particularly within um the hemolytic anemias as well are there any other kind of things that we should talk about particularly for this one i would remember uh the hypersensitivity reaction that it can actually produce is anaphylactic shock so because of that you actually get exposed let's say at some point in time to penicillin right what happens is your immune system responds to that and produces like different types of antibodies like ige antibodies and then what happens that can get plugged into like different mast cells and let's say in the future you get exposed to penicillin again now you have these particular antibodies on the mast cells when they're exposed to them they can start producing massive amounts of histamines and bradykinins and things of that nature and this can hit the lungs this can hit the skin this can obviously cause particulate like nasty bronchial constriction bronchospasm it can produce respiratory failure can produce a lot of like rashes and heaves and it can even cause the point where you can actually become hypotensive and lead to anaphylactic shock so those are things to consider particularly for the penicillin is the anaphylactic shock effect for cephalosporins on the other hand the other things that i would actually add on to this one is particularly it's been shown by some type of mechanism whether it be the absorption whether it be destroying the bacteria whether it be working directly on the liver enzymes but it's been shown to potentially produce a vitamin k deficiency so if you can actually produce a vitamin k deficiency what happens is is it inhibits the ability to be able to make particular types of coagulation proteins procoagulants and so you might have a higher risk of being able to potentially bleed the other thing is that it's been shown very interesting especially with ceftriaxone is it can produce an increased risk of a biliary sludge you're like what the heck is that it can increase the risk of like cholecystitis especially ceftriaxone and the last thing is that particularly whenever you use cephalosporins and in combo with aminoglycosides this can really increase an acute kidney injury and have a very nasty nephrotoxic effect okay so penicillins remember big thing for this one is anaphylaxis and then for cephalosporins don't forget the vitamin k deficiency the biliary sludge especially with ceftriaxone and then if you combine these with aminoglycosides they have an increased net for toxic effect all right let's move on now talk about vanco adapto all right so with vancomycin there's a couple extra things that i want you guys to remember so particularly for this one not only does it cause net for toxic and ototoxic effects but the other thing is it can also cause like especially if you push a little bit too fast it can cause phlebitis so it can really kind of burn whenever you push it into the vessel's iv here's the other thing if you push it too quickly you can cause something called red man syndrome so red man syndrome is whenever you push it too quickly it causes like a really nasty redness red rash to become super itchy it can lead to muscle spasms and it can even precipitate precipitate hypotension so this is one of the big things to consider if you push vancomycin too quickly it can cause a phlebitis and it can also cause red man syndrome like redness itchiness muscle spasms hypotension even a little bit of tachycardia the last thing to consider is it can also produce something called dress so this is kind of a drug related eosinophilic kind of like systemic reaction and so the classic kind of tetrad for this one is the patient has fevers they have a rash they have an increase in their eosinophils you see the red eosin acid with a telephone shaped nucleus and then they can also have lymphadenopathy so this is another particular thing to think about especially in patients with vancomycin the next one dapto please don't forget this one if you're utilizing this to treat a patient who has some type of like mrsa infection of the skin or a right-sided infective endocarditis for daptomycin it's been shown to be able to cause destruction of the actual muscle cells so what is this called rhabdo myolysis okay that's a big one so don't forget that one consider checking like a ck enzyme on these these patients okay so we talked about our penicillin or cephalosporins our vanco are dapto let's move on to the other ones so doxycycline so this is part of the grip of your tetracyclines is there any other additional effects i want you guys remember this one especially if a patient is taking doxycycline they should take it with a good amount of water and they should try to stay upright for a little bit the reason why is if it gets stuck inside the esophagus can actually cause like destruction of the esophageal tissue and it can cause what's called pill induced esophagitis so a big one to think about for this one especially like this one and like your bisphosphonates and stuff like that this is the big ones so don't forget pill induced esophagitis the other thing is this sucker loves like calcium and so it can love to bind to the calcium in the teeth especially little babies that can cause like teeth discoloration so the other one to remember here is especially in like children is really try to avoid this one because it can actually cause like staining of the teeth like the teeth discoloration macrolides you can remember the mnemonic for the adverse effects by macro so m is for motility dysfunction so the git there is potentially like some git dysfunction so alteration within the motility dysfunction a for arrhythmias you guys remember what it did prolong your qt interval increase the risk of testosterone points and increase the risk of v fib c for cholestasis so it can actually increase the risk of stasis of biliary flow the other thing is it can do r so rash and the last thing is oh this is kind of a stretch eosinophilia so i can increase the number of your eosinophils all right so big thing here doxy pill induce esophagitis teeth discoloration for macrolides remember macro motility dysfunction arrhythmias cholestasis rash and eosinophilia all right let's talk about clinda and lynasolid all right so the next one is clindamycin so with clindamycin one of the big things for this guy is it can cause c diff all right so we know that clindamycin definitely increases the risk of c diff so we can add clindamycin into the c diff column here right so clinda is there any other drugs that have actually been shown to be able to have a high risk of clostridium difficility really you can consider any antibiotic but with the most prominent ones to watch out for and to consider especially if you put a patient on antibiotic and they really develop really really nasty diarrhea and acute leukocytosis things of that nature then you can consider oh is it c diff so clinda is a big one but the other one to think about is carbapenem so anytime you put somebody on this like monster of an antibiotic you better consider that they have an increased risk of c diff the other one is trimethoprim sulfur methoxazole your third and fourth generation cephalosporins and the other one to consider here is your fluoroquinolones so these are the ones that i would really really be concerned about if a patient has seed if you started them on one of these antibiotics and developed some really nasty rip roaring diarrhea possibility that they have c dip with these antibiotics okay the last one that i want you to remember as a very specific thing is linaselli so we know that this one also caused like neurotoxicity like the serotonin peripheral neuropathy pancytopenia the other thing for this one it's been shown to cause lactic acidosis so because of that it works through particular mechanisms which increases the productive production of lactic acid so if you increase the production of lactic acid you can cause a lactic acidosis especially if you stay on this truck for a long period of time so if you're approaching like 10-14 days there is an increased risk of lactic acidosis with this drug all right we covered the most common ones for this column let's finish it off with fluoroquinolones and bactrim all right my friends almost there fluoroquinolones is there any additional like adverse effects that we should remember for this one so another thing to remember for this one is it can actually affect your glucose levels and believe it or not it can do both things it can cause hypoglycemia or hyperglycemia but that's not as the significant of the importance that i would want you to remember the other thing is it's been shown especially in children less than 18 years of age is to potentially cause destruction of cartilage so it can kind of cause like an arthropathy and so that's another big thing that's why i should be kind of like avoided in like young children or patiently patients who are actually growing so you know teratogenic in that effect so i remember that it also can cause like an arthropathy especially in patients less than 18 years of age the other thing that it can actually do is it can actually increase the risk of tendon rupture especially the achilles tendon so we can actually cause an achilles tendon rupture now with this tendon rupture the big thing that i would consider in these is maybe trying to avoid this in a patient who's greater than 60 years of age or who is on steroids like prednisone because that also can weaken the tendon a little bit so you throw them on fluoroquinolones they're greater than 60 and on steroids oh boy get ready for attendant rupture so that's the big thing with fluoroquinolones hyper hypoglycemia arthropathy and children less than 18 years of age and don't forget tendon rupture in those greater than 60 years of age or on steroids the last thing is bactrim so what can it do it can also cause hyperkalemia so it can also bump up your potassium so it can cause hyperkalemia all right we talked about the adverse effects the contraindications of these medications now the last thing is guess what bacteria are so intelligent they've tried to come up with ways that they can make themselves resistant to antibiotics let's talk about those mechanisms all right so now we're going to move on to the next chapter here which is talking about the mechanisms of antibiotic resistance if you haven't already take a little break again go review everything we've talked about with the mechanism of action the bacterial coverage the empiric antibiotics the adverse effects and contraindications now we're going to talk about how these tricky little bacteria have figured out a way to develop resistance against certain types of antibiotics and there's four particular mechanisms okay so normally when an antibiotic works it has to be able to get into the bacteria bind onto a target site and try to accumulate in high concentrations inside of the bacteria binding onto its target site and then there's particular enzymes that are working to be able to try to inactivate the actual antibiotic all right so those are the ways that antibiotics work as they try to get into the cell accumulate into the cell bind onto their target sites and exert their effects generally we want them to be able to evade the inactivation by enzymes that's the way that they should work what if the actual bacteria have figured out a way to reduce the actual permeability of the antibiotics so now antibiotics are supposed to be able to work to get into the bacterial cell to exert its effects by binding onto the target site what if the bacteria figured out a way to work against particular antibiotics to reduce the permeability of these antibiotics coming into the cell so now there's less of the actual antibiotics getting into the bacteria now they can't accumulate as well that's one particular mechanism the other mechanism is that we can reduce their accumulation by reducing permeability or causing them to get pushed out of the bacterial cell so now on top of that we figure out ways for these dang bacteria to push the antibiotic out of the bacterial cell reducing the amount of the antibiotic inside of the cell so if you think about it you reduce the permeability by letting less of them come in or you push them out of the cell via increased efflux the result of both of these things is that there is a decreased amount of the antibiotic accumulating with inside of the cell that means less of it is available to bind onto the target site and exert its effects which types of antibiotics target these i'm sorry which types of bacteria have actually developed in resistance to specific antibiotics via these mechanisms for decreased permeability this is the only way i remember these dang things is vat b so vat b is vancomycin amino aminoglycosides tetracyclines like doxy and then b is going to be for beta lactams okay this is the only way that i can remember so what happens is if certain bacteria have developed resistance to these antibiotics by reducing their entry into the bacterial cell they've also developed resistance to particular antibiotics by pushing them out of the cell what are the ones for this one you can remember and this is the only way i remember it i'm not trying to be mean but fat m okay so fluoroquinolones aminoglycosides tetracyclines again like doxy and then the last one here is going to be your macrolides okay these are the two mechanisms by which we reduce the amount of accumulation of the drug inside of the bacterial cell now the other ways that we can reduce the effectiveness of these antibiotics through resistance mechanisms is we can reduce their binding to the actual target site so you know some of the antibiotics are supposed to be able to bind onto dna bind onto protein like the ribosomal subunits supposed to bind onto specific proteins inside of the cell wall so whatever it may be they're supposed to bind to a particular protein and exert their effect on it now particular bacteria have reduced or altered their target site maybe they change an amino acid sequence maybe they change a particular structural morphology of a protein to where now the actual antibiotic can't bind to it anymore but they alter their ability of the antibiotic to bind to them and inhibit them there is many different drugs that do this so now you get the antibiotic inside now the antibiotic can't even bind to these dang target sites because they're altered in some particular way if you had a change in their morphology a chain in their amino acid sequence or something else that's binding to them preventing them from being able to be bound by the antibiotic what are the ones for this one again it's just the way i remember it but i remember fat bvm lt so fluoroquinolones aminoglycosides tetracyclines like doxy bvm so again i remember my beta lactams vancomycin and then m for macrolides and then lt so linaselid and then trimethoprim sulfamethoxazole so this is the ones that are going to reduce the actual binding of the antibiotic to their particular target sites again reducing the ability of the antibiotic to exert its effect now the bacteria is resistant it doesn't die or it doesn't stop growing the other thing is again normally the antibiotics are supposed to be able to not be broken down by the actual enzymes they're supposed to be able to evade the inactivation by particular enzymes what if we make these enzymes super inactivating enzymes we increase the production of carbopentaminases beta-lactamases a bunch of different types of enzymes that now can go and phosphorylate or can actually destroy or acetylate or phosphorylate all these different types of things that they can do to inactivate these antibiotics so now these antibiotics are going to be inactivated by these particular enzymes beta lactamases carbopenemasis other different types of enzymes that actually phosphorylate or inactivate the actual molecule what are these i remember bam so b for beta lactams okay and again this is obviously your beta lactamases are going to be those enzymes the other one is aminoglycosides again this is particularly via phosphorylation acetylation methylation reactions and the last one is your macrolides so these are the particular ways that these actual bacteria have developed resistance to antibiotics they either reduce the concentration of the drug inside of the bacteria by reducing its permeability vat b or pushing it out of the bacteria fat m it also reduces the binding of the antibiotic to the target side by changing the structure of the actual target site changing an amino acid having something bind to that actual target site and therefore inhibiting its ability to bind with the antibiotic remember fat bvm lt or we have particular enzymes that we produce that inactivate or destroy the actual antibiotic and render it ineffective the classic one is your beta lactamases that's why beta lactams are very very susceptible to this and then aminoglycosides via they transfer phosphorylate acetylate different types of molecules onto these and inactivate them or macrolides okay now that we've talked about this the mechanisms what i need to do is go in a little bit deeper so now bacteria have developed a resistance but how do more and more and more bacteria continue this transmission this further growth of resistance so in other words how does one bacteria that we have develop these mechanisms to become resistant to an antibiotic and then therefore pass that on to other bacteria let's talk about that next all right so what are the ways that we can actually see this transmission of antibiotic resistance in other words how does one bacteria that maybe becomes resistant to an antibiotic via reducing permeability pushing the antibiotic out changing the structure of its target site that actually the antibiotics supposed to bind to or producing enzymes that break down the actual antibiotic how does it pass it on to other bacteria and so it's via a vertical gene transfer or a horizontal gene transfer so it's kind of like a horizontal type of way that we can pass this on or a vertical way and we'll talk about what that means so the horizontal transfer of resistance is via three particular mechanisms so the horizontal transfer from one bacteria to another bacteria okay this would be something called transformation so let's say that you have a bacteria that is a really nasty bacteria okay and what happens is it gets destroyed and when it gets destroyed it releases out some of the dna or rna inside of it that's really really nasty and what brings about the opportunities to maybe change the permeability of the bacterial cell increase the efflux of the antibiotic out of the bacterial cell change the actual target of the protein that the antibiotics supposed to bind to or increase the activation of increase the formation of inactivating enzymes okay that's in that dna that it encodes those particular mechanisms what happens is you take a bacteria who doesn't have that ability to do any of those things it's susceptible to antibiotics it takes up this actual bacteria this other nasty dna rna from this harmful bacteria takes it up and now it gains the ability to be able to produce any of these mechanisms that's one that's called transformation the other mechanism is you take one bacteria and you connect it to another bacteria via a sex pilus and this mechanism which we can do this is called conjugation so what is this called this is called conjugation so in this actual bacteria here you have something called a plasmid and this plasmid may have on it a particular kind of dna sequence that allows for it to encode particular proteins or enzymes that then can reduce permeability increase efflux of the drug out change its target site or increase the formation of activating enzymes and pass that on to this bacteria who now has that that's called conjugation the other mechanism is we can have something where we can pass on this dna or rna material via something called a bacteriophage so via something called a bacteriophage so this bacteriophage contains in it some type of dna rna material that carries the ability to produce maybe specific protein enzymes that reduce permeability increase efflux change the target site or produce inactivating enzymes and we can pass that on to this person onto this bacteria here and what is this mechanism at which we pass this genetic material off to another bacterial cell via horizontal gene transfer this is called transduction so these would be some of the mechanisms by horizontal gene transfer conjugation transduction transformation the other way is let's say now this bacteria has inside of it this dna or rna or any kind of ability to produce resistance to particular antibiotics now what it can do is it can pass it through what's called vertical gene transfer in other words it goes through binary fission so it undergoes a binary fission process it actually replicates and it produces two daughter bacteria that now have within it the dna material or rna material that allow for it to be also resistant to particular types of antibiotics isn't that cool so these are the ways that these actual bacteria have developed resistance to antibiotics via conjugation mechanisms transduction mechanisms transformation mechanisms or once they've gathered all of this material they can pass it on to their actual daughter cells through binary fission or vertical transfer process okay now the question is these bacteria all have the ability to do this what actually increases these particular dna sequences rna sequences to undergo these particular mutations and produce resistance in the first place what triggers this what are the risk factors for antibiotic resistance and you know what it is it's often due to patients who get sick they go to the hospital in the hospital you have patients who are super super sick and in the hospital they develop some nasty multi-drug resistant pathogens there so anytime you go to the hospital there is always a risk of these really nasty multi-drug resistant pathogens that's one particular way so if you go to the hospital there's obviously an opportunity to catch something like mrsa something like pseudomonas something like ace needle bacter the other problematic issue here is that so again if you go to hospital you could be exposed to any of these and that's a problematic issue the other one it happens to be sometimes unfortunately for clinicians we like to over prescribe medications like antibiotics when it's not really necessary and so if we have a patient who has like a viral infection they don't really need an antibiotic and we put them on an enematic anyway we increase the opportunity for resistance to become available because now this person's been exposed to an antibiotic and their body can then create again their bacteria can create a way to become resistant to that antibiotic so trying to be able to prevent over prescription of antibiotics so over prescribing this is a big one and the last one here is a son of a gun the last one here is a little calo chicken you know we like to eat beef and all these other different types of things that we like to impregnate some of these things with antibiotics unfortunately some of the actual meats that we eat we're then ingesting those meats that now have particular antibiotics that were used in that meat and now we've been exposed to them and now our actual bacteria can develop ways to become resistant to it so also it can be via certain types of antibiotics in food products that we become exposed to and then again now we develop some resistance to antibiotics so these are a lot of the factors that can increase the resistance to antibiotics these are the mechanisms of which you get antibiotics and become resistant and this is the way we can take one bacteria and then pass on the ability from multiple other bacteria to develop resistance antibiotics it's just a terrible thing so i guess the question is is now we know that bacteria can develop a lot of resistance to antibiotics through many different mechanisms and a lot of the risk factors are here they have a lot of opportunity for transmission how do we as a clinician figure out which antibiotic is best particularly utilized for a very specific pathogen we already talked about that right the bacterial coverage of very specific pathogen well here's the thing some of these pathogens may develop resistance to the antibiotics that we talked about so how do we know what is the best antibiotic for this pathogen that they haven't developed resistance to it yet and that's we're going to talk about next there's these different methods that people figured out to talk about antibiotic susceptibility all right so when we talk about antibiotic susceptibility it's really saying okay we have a patient let's say that they come in they have an infection there's an obvious infection whether it be let's say pneumonia we think that it's a community-acquired pneumonia or acquired demonic we start them on the imperial antibiotics and we get cultures we get sputum cultures once we get those sputum cultures we'll obviously grow and see what kind of bacteria they grow and then which antibiotics would be best suited for them okay then we could do the same thing with skin soft tissue if the nasty skin soft tissue infection you have an abscess you take a sample from that you culture it send it off see what kind of bacteria come back what antibiotics are best suited for that one same thing you take a urinary urine culture because you have a patient with a uti you start treating them with either whether it's acute cystitis pyelonephritis or complicated uti and then again you start figuring out what kind of actual bacteria comes back from your culture and the last thing is you have like blood cultures you think somebody's septic or they have a concern for a clabsi then in those situations you can again take the actual blood culture sorry them on particular antibiotics or whatever you think the actual most common pathogen is and then from there once you get the actual uh cultures back and you figure out which antibiotics are best you can particularly target it right so the whole point is you're getting cultures you're going to be grabbing cultures whether this is sputum cultures whether this is uh skin cultures whether this is urine cultures whether this is blood cultures once you do that you take again treat them with the empiric antibiotic therapy we talked about over there what happens is you take the bacteria and you grow them right and you see which types of bacteria grow and then again once you kind of figure out oh it grew back klebsiella okay let's just say let's say that you had a patient with pneumonia the pathogen that it actually grew is klebsiella pneumonia okay from there you want to say okay klebsiella pneumonia was the one that grew so you had a gram-negative rod klebsiella pneumonia was the particular pathogen that grew on the culture from the sputum the next thing you have to figure out is okay which antibiotics would be best for this well i know any of those gram negative ones so part this is a part of the hens peck one right so i know really any of those would be best suited for that do you guys remember the hens pack ones they said the amino penicillins would be an okay one we said that the third generation cephalosporins would be good ones the fourth generation cephalosporins these are carbapenems monobactins we even went in to say like potentially fluoroquinolones aminoglycosides so a lot of these different ones would cover klebsiella but out of all of those antibiotics that we could pick from we want to know which one is the best and that's dependent upon what we do is we maybe there's a bunch of different methods there's what's called the broth micro dilution and macro dilution the kirby bauer method and all these different ways that we can do it like this diffusion so you know one of them i think is the coolest one it's the old school way is you would take the bacteria and what you would do is you would introduce antibiotics onto this let's say here is an antibiotic here was an antibiotic here's an antibiotic you would see how much like bacteria died around the antibiotic and that would actually determine like your minimum inhibitory concentration you could do this for a lot of different ways you could do with the kirby bower method you could do with micro dilution macro dilution a lot of different things but the whole point is is what this tells us is it tells us what's called the minimum inhibitory concentration the mic so what is the minimum amount of the actual drug that is needed to be able to kill the particular bacteria and it tells us which types of bacteria are susceptible to specific antibiotics that would cover it so again think about everything that would cover klebsiella there's a plethora of drugs right sometimes you have no idea which one to pick you'd want to prefer more of the narrow one not go super broad but what if the actual bacteria has developed resistance to it how do we know so what you do is you do these methods again the broth micro dilution macrolide dilution the kirby bower method but again the whole point is you expose the actual bacteria to multiple drugs and figure out which one of these had the best coverage which one when the actual bacteria was susceptible to or which one of these antibiotics the bacteria was resistant to or which one of these antibiotics was the bacteria kind of like ah it's kind of like in between that is the best way to be able to pick the perfect antibiotic that will cover the bacteria very well and so for example let's say you had a patient you have a sputum culture okay you have a patient who comes in they have pneumonia you start them on antibiotics whether it's a cap or a hap you get the sputum culture it comes back when the sputum culture comes back with klebsiella pneumonia maybe you had them on let's say let's say you had them on ceftriaxone and doxycycline but it comes back and they have klebsiella and ammonia and you weren't covering it particularly well from there you have to figure out okay which one of the antibiotics would be best well i can do anyone within the hens pec category but out of that hens pet category which one would the actual bacteria be very susceptible to resistant to or intermediate to and so let's say that we did that we took the klebsiella we grew it we'd found that out and then we actually exposed it to multiple antibiotics and when we did that then we found that ceftriaxone there was susceptibility to it so if you say give ceftriaxone it's actually pretty good ceftazine there was resistance to the klebsiella so we can't use this one pipercellon taste of bacterium there was susceptibility to it so if you want to you can use this one maripenum there was susceptibility to it gentamicin there was resistance to it levofloxacin there was resistance to it ampicillin soul bacterium let's just say for the heck of it just to have another one there was intermediate coverage out of all of these which ones do i not pick it's obvious don't give them ceftasidine because it's not going to cover it because it's resistant to it based upon the susceptibility testing which we did with microdilution macro dilution kirby bower method don't give them gentamicin because there's resistance to it don't give them levofloxane because it's resistance to it and i would even avoid ampicillin sulbactin because it's intermediate pick something else or if you really really like this drug give a higher dose than you usually need to to cover it but if that's the case i would just avoid these and this one and stick with either ceftriaxone piper cell and taser bacteripenum now if you're between these which one of these would you pick try to pick the one with the narrow coverage so you don't have too much broad coverage because remember pip tazo is a super broad agent not really necessary to go super broad meripenem not really necessary to go super broad i would just go with ceftriaxone it's not crazy crazy broad and i think it would be a good choice so again you have options here but which one you're going to pick and this is obviously more of a provider preference but you could pick ceftriaxone pipercellantasabactum and meropenem because these are the ones that the klebsiella pneumonia which we grew out from the sputum culture and we tested against multiple antibiotics these were the ones that the actual bacteria was susceptible to and would actually kill the bacteria that's the ones that i would pick so i hope that made sense now you would think that we're done but we're not i really want you guys to understand this information antibiotics is a lot take a little break review everything but get ready because now i want to test your knowledge to the max and i want to see how much of this you guys remember so let's do some practice problems some some cases and see if you guys can put this stuff together all right let's get into it all right guys let's do some cases and put to practice everything that we talked about on the whiteboard so it's gonna be pretty systematic all right 65 year old male past medical history myasthenia recent ons recently on steroids for that for an exacerbation presented to eddy with fever shortness of breath productive cough chest x-ray shows a nice right low bar infiltrate and a cvc with leukocytosis definitely seems that this patient has pneumonia right so the way that their actual clinical features present definitely pneumonia so the question is is that they have a pneumonia this is usually not hospital acquired because they weren't in the hospital they were coming to the emergency department so this is definitely a community acquired pneumonia so the pathogens that you want to be concerned about for community acquired are strep pneumone atypicals is the most common ones so that being said what kind of antibiotics would i start this patient on for a community acquired pneumonia empirically then i can get cultures figure out what the pathogen is and then narrow it down to that specific pathogen well i'm going to cover for strep new and atypical so i can do something like ceftriaxone if you guys remember that one which was the beta-lactam third generation plus a macrolide or doxycycline or i could do something like a monotherapy fluoroquinolone like moxie foxes and which covers strep pneumo and atypicals especially legionella if you guys remember so that would be my options to start off with then i would get cultures if i get my cultures back and then i say okay i'm going to give you a call in a couple days when your cultures come back and then what we'll do is we'll may you know modify your antibiotic regimen potentially and then you get it back and it comes back just strep pneumo okay well we don't really need that atypical coverage then so you know with this situation here doxycycline is not a great strep pneumo coverage macrolides will cover you know strep pneumos after action will cover strep pneumonia solely your first gens fluoroquinolones will cover you know your your strep pneuma as well aminopenicillins to some degree they're not too great you have to give a really high dose amoxicillin to hit the lungs but that's another option clindamycin's a decent one so these are some of the options that you could consider so these would be the ones that i consider so we already talked about amoxicillin but you have to bring a pretty high dose some first third gen cephs macrolides clinda and fluoroquinolones but the one thing that you got to be careful of is remember when you prescribe an antibiotic you have to be thinking about what are the adverse effects and what would be a contraindication and be prescribing this one well this basically is myasthenia gravis let's say that i start them off on just fluoroquinolone by itself ah do you guys remember what the adverse effect of fluoroquinolones are it is exacerbates myasthenia gravis that's not good so we don't want to be giving this medication but you know what else does that clindamycin does that um and and aminoglycosides will do that so i think it's important to be able to consider that um you probably would want to stay away from a fluoroquinolone consider something like a i'd say like more likely a first or third gen cephalosporin um you don't want to give clinda you wouldn't want to give fluoroquinolones if you give amoxicillin you just got to give a high dose macrolides even i'd be careful with that one too in this situation so it can exacerbate mycenia that's potentially a contraindication but guess what else is a contraindication tendon rupture with greater than 16 steroids this patient's greater than 60 and they're just on steroids so they have very high risk of an achilles tendon rupture so just things to be considering and again remember that they prolong the qt they cause the cyp450 inhibition they can also have a pretty high risk of c diff and cause hyper and hypoglycemia so things to consider i think the other thing that's important to think about is like what are the ways that bacteria develop resistance because a lot of the problems with fluoroquinolones is that they are becoming there's a lot of bacteria that are developing resistance to this in certain areas so it's important remember those mechanisms it was the decreased permeability efflux pumps altering the target site and then creating a lot of inactivating enzymes so if you guys remember i said it was that b fat m fat bvmlt and then bam so it's wherever the f is so fat m so e flux bumps and fat bv mlt that would be again within the altering the target binding size so they create eflux pumps and then alter the target binding site to be able to reduce the effectiveness and the efficacy of the fluoroquinolones all right i hope that made sense alright so the next one case study two we got a patient who presents the ed feverfang flank pain nausea vomiting diarrhea they got a cbc it shows the leukocytosis their ua shows white blood cell casts leukocyte esterase nitrates are positive there's more than 100 white cells per housefill unit on the ua and they have a lot of bacteria in their urine so this definitely seems like based upon their symptoms they have a symptomatic urinary tract infection particularly pilonephritis based upon some of the exam findings and the laboratory findings so i have a patient with an acute pyelonephritis so you guys got to remember for empiric antibiotic coverage of a you know a pyelonephritis what were the options do you guys remember one is you can consider ceftriaxone you can consider a fluoroquinolone and even aminoglycosides aren't a bad idea as well so these would be the things i would consider amino penicillins if you're going to give this you want to give particularly ampicillin just because of the imiv it would give a better penetration so these are options that i could consider a fluoroquinolone ceftriaxone or aminopenicils but i would consider ampicillin particularly over amoxicillin all right you get the urine cultures because you're going to start them on empiric antibiotics but you want to make sure that you're covering the correct bacteria so you get a culture when you get the culture it comes back with enterococcus well there's only a certain amount of antibiotics that cover this do you guys know which one out of all of these would be the best for enterococcus coverage because remember it was a gram-positive bacteria and this was amino penicillins so aminopenicillins would definitely be pretty good at covering your enterococcus we said nitropharantome but that's more particularly for in the bladder so cystitis would be better for coverage for that one and then vancomycin is another one especially if they're resistant but not for the vancomycin resistant enterococcus but again i would say amino penicillins are good and then vancomycin is another option for that one so this would be the the best situation for that okay now i guess the question is is when you put a patient on an immunopenicillin like ampicillin what are the potential things that you have to watch out for and it's very common it's always acute interstitial nephritis some type of like you know a pancytopenia a rash maybe some type of like hypersensitivity reaction and neurotoxicity like reducing threshold for seizures so these are big things to be considering okay uh again what are the mechanisms that bacteria have developed to become resistant to amino penicillins well one of them we already know again we'll talk about this if you guys remember the mechanism of action oh real quick what is the mechanism of action of amino penicillins do you guys remember it works against the cell wall uh particularly reducing the cross-linking so it's reducing cell wall synthesis by preventing the cross-linking of the uh cell wall peptidoglycans okay but bacteria have developed a resistance that so again you got to go again with this one it's a beta lactam so you go vat b fat m fat bvmlt and then bam so pretty much the when you think about that that b that would be one so the first thing is it can reduce permeability fat m doesn't work on the e flux pumps fat bvmlt does work on altering the target binding site bam works on um potentially increasing the inactivating enzyme so it's three of those particular things that it works on just not the efflux bumps okay so that would be the way now one of these that's the most prominent one the one that we think about a lot is that it really increases the inactivating enzymes so because of that these are your beta lactamases so they break down the beta-lactam ring in amino penicillin rendering it ineffective and not being able to bind to the penicillin binding protein so we need a drug that we can combine with ampison in the case that this enterococcus has developed resistance to the amino penicillins we should add something on to that to break to bind onto the beta lactamases so that the amino penicillin can continue to work so what are the things that i can add to a beta-lactamase to make it more effective i'm sorry add to the amino penicillins to make it more effective against the beta-lactamases that that bacteria produces and you guys remember there was the beta-lactamase inhibitors such as clavillonate which combines with amoxicillin to make augmentin um and then you have sulbactum that combines with ampicillin to make unison and then if you wanted to remember there's the taseobacter with pipper cell and to make zosin and then there is the combination of avibactum and ceftazidime and that's going to be a combo that you know you don't commonly utilize unless you're like an infectious disease per you know expert but that would be the general ones that we would do here so that's perfect that works out well to kind of understand that stuff all right case study three a 35-year-old male presents the e.d with red edematous and painful cellulite so the right forearm some induration and it's spreading over the the right elbow um now so we definitely see like some just like some pretty good spread of a really nasty looking cellulitis so with that being said what is the empiric coverage for cellulitis assuming that this is like you know an outpatient one that we can continue to monitor they don't really look septic appearing they don't need to be observed in the hospital it's not that diffuse so we can kind of prescribe them an antibiotic send them home but you know if we have to we can get cultures and stuff like that if but there's nothing really to culture there's no abscess or anything so with this i'm just going to start covering for missa as the most common misa and streptococcus a or strep-paya genes so with that being said what are the pathogens what are the types of antibiotics that would cover that very well the misa and the strep a well the first thing to remember for the missa was your anti-staphylococcal penicillins so naphthalene oxacillin dicloxacillin out of all of those the only one that's po is the diclox and then the first generation cephalosporins like cefazolin and sep kefla encephalexin and they're really the primary one that's po is the cephalexin so if i'm gonna send this patient home with po meds it's either gonna be cephalexin or dicloxacillin okay now if i let's say for whatever reason they start to get worse right they don't get any better the cellulitis isn't improving even after i start them on a couple days of um keflax or cephalexin and they're still getting worse it's not getting any better which antibiotics do i consider now well now i'm wondering was it misa or is it mrsa now because maybe the diclox or the catholics isn't working particularly against the nasty types of pathogen that i think it is and it's a mrsa type and that's cephalax and diclox are just not going to hit it so i'm thinking it's mrsa what kind of antibiotics cover mrsa but i still think that this patient doesn't need to be in the hospital receiving iv medications yet do you guys remember so start thinking through them with starting with your betalactams and working your way through the mechanism of action so first thing if you really wanted to you can go through cephteraline i would not kind of go with that one i would avoid that one then you go to the next thing which is going to be vancomycin that's iv i wouldn't go with vancomycin just yet then we go to trimethoprim sulfamethoxazole that's definitely one didn't go to the metronidazole nitrofrancoin no fluoroquinolones no then you go to your macrolides doxycycline will actually cover community acquired mrsa um linaselid will cover it clendamycin will cover it and then if you go into the next part which is the aminoglycosides and the uh there's no amino glycosides that will cover that as well and again macrolides don't cover it tetracycline is the doxycycline will so for these i would say trimethoprim sulfamethoxazole clindamycin uh lynnae's lid would be another option doxycycline would be another option so these would be some things that i would consider for mrsa coverage okay now let's say that you put them on trimethoprim sulfoxazole okay you put them on that and they continue to get worse so it's not enough now the infection is really really bad and it's just it's becoming more systemically involved because now they're starting to have fevers rigers and they're starting to kind of like look a little septic in that situation they're probably going to require iv antibiotics which antibiotic would be best when it comes to this now vancomycin that begs the question though if i put someone on one of these drugs like trimethoprim sulfamethoxazole or you know i put them on vancomycin what are some of the things that i got to watch out for so adverse effects of bactrim is pancytopenia that's one hemolytic anemia particularly because it can worsen the g6pdh deficiency okay the other thing here is acute interstitial nephritis teratogenic it can actually increase the amount of the unconjugated bilirubin like and that can lead to kernicterus in babies it's a cyp450 inhibitor it also has the ability to cause phototoxicity so if you're exposed in the sun it can cause some rashes and then it can also bump your k and cause hyperkalemia same concept here what if i put them on vancomycin what do i got to watch out for it can hit the kidneys especially if you are a little bit super therapeutic on that can cause nephrotoxicity it can cause ototoxicity especially if combined with an aminoglycoside it can really burn when you infuse it so it can cause some phlebitis and uncomfortable kind of feeling there and then if you infuse it way too quickly it can lead to something called red man syndrome where they have rash muscle spasm itching paritis they have hypotension tachycardia so these things to consider and then dress so they can develop fevers they can develop lymphadenopathy they can develop some really like nasty eosinophilia so i would watch out for that one as well all right now the question i think that comes is again what are the mechanisms the bacteria have developed as a way to become resistant to particular antibiotics such as vancomycin well think about it again you got to go vat b fat m fat bv mlt and then bam so the v particularly for vancomycin was in the first one which was going to be decreasing the permeability and then it also was going to be in the third one which is altering the target binding site so with that being said i only think that it's going to alter the target binding site and again it will also decrease permeability okay so those are particular ways and this is especially significant when you have bacteria such as mrsa it can become resistant to vancomycin so we see like a vancomycin resistant staphylococcus aureus and then you can also have enterococcus become resistant to vancomycin we call that vancomycin resistant in pterococcus and then that's a that's a rough situation all right last case here for you guys 66 year old female in icu on the ventilator for the past three days develops an increasing speed and production hypoxia fevers and then nasty infiltrate on her chest x-ray definitely seems like pneumonia but she's been in the hospital for at least three days that's more than two days so this is a hospital-acquired pneumonia so what are the two pathogens i've got to think about i think about staphylococcus mursa sorry mrsa and then pseudomonas originosa so what are the actual best like commonly utilized antibiotic combo that you'll see most of the time in the hospital that covers mrsa that's vancomycin or lynasalid and then what covers the pseudo there's so many you could obviously go through them that you can give the ceftazidime the cephepem the pippercellentazobactum um there there's like a neverending amount of these um you can consider even like polymixins if you really had to that's more of a salvage therapy though um again trimethoprimocyloxis all know metronidazole nitrofanto and no fluoroquinolones those are more for your double coverage so those are very specific for double coverage it wouldn't be a monotherapy macrolides will not cover it clinda will not linnae's lid will not chloramphenicol will not aminoglycosides will cover um pseudomonas and then your um tetracyclines won't cover it as well so with that being said i would put them on i think the most commonly utilized one is vancomycin and peppercilantaseobactum so that would be the empiric regiment then i would get cultures from their sputum and i would see what it grows it grows pseudo so it would be all those ones that we just literally named so ceftasidium cifipim oh yeah this is going to forget about these carbopenums these are super broad remember boom it'll blow every bacteria up monobactins aminoglycosides fluoroquinolones only as a double coverage not as a monotherapy and polymixins as a salvage therapy when they're just resistant to everything okay so that would be this kind of process here so i'd start them on that and then i would get rid of the vancomycin once i got this pseudomonas back the next question is what are the adverse effects though aminoglycoside so we've talked about a lot of these but let's say that you know we decide to just keep them on percentages of bacterium but we're considering aminoglycosides and we just got to have a discussion about why would we not pick aminoglycosides and it's because of the adverse effects of it right um nephrotoxicity so they can really hit the kidneys pretty well they're ototoxic they can worsen myasthenia gravis and they are teratogenic so again things to consider i'm not to be honest they don't really ever use aminoglycosides but they're they're out there if you ever need them but one of the things that's interesting i think out of out of aminoglycosides and i think this is probably a really interesting reason as to why we don't use them that often they're just really never toxicity is a pretty rough thing with this one but when you think about this drug what are the mechanisms that a bacteria develop resistance to watch this it's the a in all of these right so you have vat b fat uh fat m fat bvmlt and then bam do you notice something bacteria develop all the mechanisms of resistance to the sucker so that's one of the nasty things about this one but it is a good drug if it's absolutely necessary in situations like infective endocarditis due to a prostatic valve or you know some of the urinary tract infections it's it's decent okay all right that would be the adverse effects there now we're not done unfortunately this patient develops a complication um all right so we have i'm sorry we have another patient i thought this was the same one my bad so you have a 46 year old male who's an icu status post large intracranial hemorrhaging on the ventilator develops high fevers hypotension tachycardia intense leukocytosis and is now started on vasopressors so this sounds like sepsis i mean it does all right so we got a patient who's definitely probably developed a hospital acquired pneumonia and then it's seeded into the bloodstream because now they have fevers they have hypotension they have tachycardia they have a white cell count and now they're started on vasopressors so now they're becoming hypotensive that's requiring basal pressure support definitely sounds like a septic shock patient in septic shock we assume that this patient is a septic due to two bugs one mrsa second pseudo what do we start them on same thing we just started before for the vap vancomycin and peppercilantase of bacterium those are the commonly utilized ones we get cultures in this patient we're going to get sputum cultures and blood cultures because they're pretty sick right so we get blood culture sputum cultures and it comes back as extended spectrum beta-lactamase klebsiella which antibiotic is best in this situation remember this is a nasty bug when you get those extended spectrum beta-lactamase bacteria they are really really nasty so which antibiotics will cover these there's not very many carbopenems blows everything up right what else aminoglycosides and polymixins would probably be about what you're going to get for these so that would pretty much be it here oh and then yeah i forgot about this one ceftazidime and avibactum that's a more of an infectious disease specialist who can give this one because if you remember extended spectrum beta-lactamase bacteria like e coli cleb you know some of the entire bactericie they develop such a significant extended spectrum beta lactamase that it's really hard for them to be able to respond to ceftasidine you remember your third your fourth generation cephalosporins and even someone like pippercontazobactum so you have to add on this thing avibactum and it might be enough to be able to knock out some of the betalactamases and allow ceftazidime to penetrate and kill the bacteria such as cleb so these would be your options now you're looking at these and you start considering which one you're going to put the patient on carbo venoms will probably be your best option out of all of these but you can consider the last one ceftaz and have you backed him if you have an infectious disease consultant on board but i think one of the things to think about is we haven't talked about these since you know carbopenums are a betalactim cephtazidim is a big lactone aminoglycosis we already talked about its adverse effects what will be the downside of polymixins one is their neurotoxic so they can really induce seizures nephrotoxic is another really nasty thing about these and respiratory failure so with this patient already having a likely vap i don't know i probably wouldn't go as far as to put them on this drug just because of how nasty it is but again it's an option if you have no nothing else to do for the patient so unfortunately the patient needed to get an evd their bleed was so big that their pressures inside their skull was increasing and we needed to be able to drain because the blood started pushing into their ventricles now and now they have some ivh and we need to put an evd to start sucking some of the blood out of those ventricles because they're starting to get hydro hydrocephalus when that happens and you get the evdn they end up developing a meningitis now because of the evd that was inserted and so they developed a hospital acquired meningitis what are the nasty types of bugs that you have to be thinking about for this one one is mrsa the other one is pseudomonas right so that's the primary thing so in this situation you start them on vancomycin but you need something that's going to penetrate the this central nervous system so cefepimesim seems to be a little bit better ceftazine is another option percentage of bacterium doesn't have this great of a central penetration so that one i would kind of maybe hold off on so i would start the vancomycin or lineage lid to cover the mrsa and then i would start them on something for the pseudo so cefepime or ceftazidim or something of that nature and wait till the cultures come back when i get the cultures back it reveals a really weird combo for some odd reason in this patient they have mrsa but they have nessaria meningitidis you're like what the heck all right well they have this i'm going to start them on vancolinaselid for the mrsa but i need something that's going to penetrate the central nervous system that's got good coverage against necessary do you guys remember third gen cephalosports ceftriaxone would be your best all right and that's what you start them on all right i know this was a lot i hope this lecture made sense i really hope that you guys enjoyed this and antibiotics have really become a little bit easier to grasp now um as always i love you thank you and until next time [Music] you