[Music] we turn now in our discussion of central nervous system infections to bacterial meningitis very serious infection indeed so we would define bacterial meningitis as an infection of the meninges of the coverings of the brain specifically the subarachnoid space and brain as well it's really a meningoencephalitis usually due to over any of a variety of blood-borne microorganisms now among the causes of acute meningitis actually viruses probably account for most cases of acute infection of the meninges but viral meningitis is generally a benign disease it's not terribly serious it's troubling for the patient but they get over the this kind of an infection but blood-borne bacteria can cause a life-threatening problem now when a physician can't tell which it is is it viral or is it bacterial then that physician would be prudent to start antibiotics just in case it is bacterial now among the bacteria that cause meningitis and there are many these are the top five streptococcus pneumoniae Neisseria meningitidis streptococcus agalactiae also known as Group B Strep Listeria monocytogenes and hemolysis influenza hemolysis influenza was the most common cause of meningitis in the past but because of we now have a vaccine against that particular organism am awfully influenza type B it is no longer the most common cause of meningitis now turning to the epidemiology we need to look at the causes of meningitis first among newborns and here Group B Strep strep agalactiae accounts for about 70% of the infections of the meninges followed by Listeria and by the pneumococcus from one month to two years of age look what is now top cause streptococcus pneumonia as I mentioned in the past it was a muffle us influenza but that has essentially vanished in developed countries Neisseria meningitidis and strep agalactiae follow behind from the age of two to the age of young adults Neisseria meningitidis causes about 60% of the cases of meningitis followed by the pneumococcus and Hamas influenza in adults the pneumococcus tops the list causing 60% with Neisseria meningitidis causing 20% and the others are relatively rare causes but by the age of 60 years plus the pneumococcus accounts for most cases of bacterial meningitis and Listeria moves up the list accounting for about 20% so let's look at the clinical features of bacterial meningitis newborns are a challenge for physicians because they do not have the classic findings that are talked about in meningitis for example newborns don't have generally a stiff neck there they may have fever but they may have no fever or they may have a low temperature so they have temperature instability newborns with meningitis are generally listless they are not responsive to their surrounding they may have an unusual kind of high-pitched cry which suggests a process going on in the brain they as expected would be fretful than lethargic they may not feed well they may not feed at all and the mothers may notice that they have a very weak suck so they're generally irritable and of course all newborns are jaundiced but newborns with meningitis may have unusually severe jaundice they may vomit they may have diarrhea and respiratory distress so a pediatrician evaluating a newborn it has to worry about meningitis in a baby with these kind of findings any of them and there's an indication to do a spinal tap and examine the cerebrospinal fluid if there's any suggestion of meningitis children from age 1 to 4 are a little easier to evaluate more than 90% of them are going to have fever 80 plus percent will be vomiting and stiff neck starts to present itself after about the year of 1 so those are the main findings in children 1 to 4 older children and adults are easier to diagnose virtually a hundred percent will have fever most of them have headache almost all of them will have meningismus which is the syndrome of having a stiff neck and this is an important point patients with viral meningitis they may complain of headache they may have fever they may even have a stiff neck but they're not out of it most patients with bacterial meningitis on the other hand have cerebral dysfunction when they are brought to a physician and they're usually brought to the physician they have confusion they had their head doesn't work and the classic findings are the findings of kernig and birds in ski sign now kerning sign it's often hard to remember it was for me when I was a student but the way I remember it now is k4 kernig k4 doing something with the knee so the patient is supine and you take the patient's leg and flex the leg like that and then extend the knee now in a patient who's awake extending the knee puts traction on the meninges and that causes pain going up and down the spine that would be a positive kernig sign now in a comatose patient they can't tell you whether they have pain but doing this maneuver and feeling resistance when you try to extend the knee is a positive kernig sign and a comatose patient birds in ski sign is where you have the patient lying supine and you flex the patient's neck and if the patient's hips involuntarily flex they have a positive Burzynski sign cranial nerve palsy x' are not as frequent they occur in a minority of patients with bacterial meningitis but they are an ominous sign because it usually means that there is involvement of the brain stem in every patient with Jada's they need to be searched carefully their extremities legs arms for a petechial rash because a petechial rash occurs primarily in meningococcal meningitis the meningitis due to Neisseria meningitidis but it can occur also in other forms of meningitis particularly pneumococcal meningitis in the in the presence of a splenectomy seizures are obviously a bad sign and indicate that that the meningitis is pretty far advanced as is hemiparesis so let's turn our attention to Neisseria meningitidis the incubation period is pretty abrupt and we're usually going to find this in young adults or kids and it's especially common in college age students who live in a dormitory setting or in a military barracks young people in the military barracks and this is an abrupt illness these patients will have fever they will have a stiff neck their blood pressure may be low and many of them probably 50% of them will have a rash which I'll point out shortly and it's absolutely essential to make this diagnosis because the fatality rate is between nine and twelve percent and up to 40% of the patients will have bacteria in the bloodstream so called meningococcemia the other thing is you can have meningococcemia without meningitis but we'll focus in this discussion on meningitis so with meningococcal Samiha and you can have meningitis with it you have fever and this petechial or purpura crash and I want to just stop for a minute and tell you about a patient I saw years ago in my training a little girl was brought into the emergency room and she was a little bit lethargic and she had a little bit of low-grade fever but otherwise was not that sick she did not have a stiff neck for example but anyway because we were concerned about her lethargy we decided that she needed to have a spinal tap so we did a spinal tap while she was in the emergency room and in those days we looked at the spinal fluid ourselves and we found that the spinal fluid was abnormal and we found all this out in about 30 minutes so when we recognized that the spinal fluid was abnormal we knew she had some form of meningitis so in the emergency room within 30 minutes of her arrival we gave her intravenous penicillin because we were very concerned about her having meningitis and I'm sad to say that four hours later her skin was covered with the lesions that I'm showing you right here and she died and the main point about it is that meningococcal meningitis is one of the causes of sudden death so it is essential to keep your antennae up for this particular illness the other thing about this rash is if you were to put your finger down on some of these spots they would not turn white under your finger you can also use a microscope slide and press down and you would find that these lesions do not go away with pressure so the smallest ones are petechiae and largest ones are really essentially bruises under the skin there ecchymosis and the point about this is this can develop over the course of hours it did in this little girl despite giving her antibiotics the main thing in the differential diagnosis of this rash there are other things that can do it I mentioned the pneumococcus but there's one other thing especially in the United States and it's called Rocky Mountain spotted fever which in itself has a 20% mortality so the physicians especially in this southeast like in North Carolina Virginia Georgia and those states in the southeastern United States where this is common this disease Rocky Mountain spotted fever is actually spread by tick bite and it's different than meningococcemia initially initially the lesions of Rocky Mountain spotted fever will Blanche when you press on them and over the course of several days they can look like this rash of meningococcemia so the pace with Rocky Mountain spotted fever is different but the bottom line is sometimes patients come in like this and you're not sure whether they have Rocky Mountain spotted fever or whether they have meningococcemia so what you do is you treat for both you would treat both illnesses and Rocky Mountain spotted fever the drug of choice is doxycycline I think that digression is important because these two diseases can really resemble each other both of them can come along with hypotension and both can result in multi organ failure in addition to the direct effects of meningococcemia adrenal infarction leading to adrenal insufficiency can contribute to the hypotension and shock this is called the water house Fredrickson syndrome so turning to another cause of bacterial meningitis is that of Group B streptococcus and most of the people who get this if their children have got it from some kind of middle ear disease otitis media or perhaps mastoid itis and for reasons that I'm not certain about but diabetics seem to get an an ordinate umber of infections due to Group B Strep dukakis and this disorder carries with a fairly high mortality at least in one series that I'm familiar with Listeria monocytogenes ordinarily looks like regular men and like the other men and Jiddah teas but occasionally it can present as a granulomatous kind of meningitis and the spinal fluid can look different we'll talk more about that later and then very rarely it can present as a Rumbo encephalitis in other words presenting as inflammation of the back of the brain and the brain stem with cranial nerve palsy x' cerebellar signs hemiparesis and altered consciousness' so this is a sneaky one and so you need to know that it it usually presents as a typical bacterial meningitis but can rarely show other things meningitis in the elderly is also a challenge it can present much more insidiously it can be sneaky most of the elderly that have it are lethargic most of them are out of it but many elderly patients have Alzheimer disease so it's a challenge to figure out what's causing the altered mental status occasionally an elderly person will have no fever and yet they will have meningitis most of them have fever but if they don't have fever that's a bad prognostic sign it's the most dramatic predictor of death on presentation if they have meningitis but no fever with it it suggests that the immune system is not very active they may or may not have signs of meningeal irritation like a stiff neck or kernig zorb radzinsky sign and remember a lot of elderly people have osteoarthritis of their cervical spine so they have a stiff neck even when they're feeling well so a stiff neck may be difficult to evaluate in an elderly person it's essential to get some spinal fluid in a patient who has meningitis and when you get some spinal fluid during the lumbar puncture you will note that the opening pressure is elevated when you microscopically examine the spinal fluid you will find that there are too many white cells now normally there should be no more than five white cells in spinal fluid and they should be all mono nuclear lymphocyte or round cells so it's abnormal if a spinal tap shows even one white cell that's a neutrophil so neutrophils are abnormal in spinal fluid there are some exceptions because of the pace of meningococcal meningitis the patient may not have had time to develop much in the way of white cells this little girl that I told you about had just one or two neutrophils in her spinal fluid and in infants under four weeks of age they may not have white cells in the spinal fluid of that magnitude now if they have white cells there is a neutrophil predominance more than 80% are neutrophils once again the exceptions to that would be a newborn where they had the cause being something like e-coli they may not have a neutrophil predominance and also with Listeria now if you remember the name of Listeria is Listeria monocytogenes and that implies that the organism can cause meningitis with mononuclear cells in the spinal fluid so that's where it got that name here is a last example in tuberculosis meningitis you also find lymphocytosis rather than neutrophil predominance now obviously when you get some spinal fluid you're gonna culture it and you'll get a positive culture in about 80 percent of individuals unless they've been given antibiotics and think how many patients go to the physician and get empirical antibiotics for fever you know I wonder what's up with that but that may obscure the diagnosis of bacterial meningitis and the cultures may be negated or reduced to 60 or 70% positive if antibiotics have been given it's also important to measure the spinal fluid glucose you'll find that the spinal fluid glucose is lower than it's supposed to be it'll be usually less than 40 milligrams per deciliter and at least 60% of individuals and if you compare the spinal fluid glucose to the serum glucose it's less than 31 percent of the corresponding serum glucose and oftentimes it's less than 18 milligrams per deciliter it's usually very low and if it's that low it's going to be highly predictive of bacterial meningitis the protein is usually elevated sometimes quite elevated to 500 milligrams per deciliter and a Gram stain of spinal fluid is essential and it you'll find that it's positive it'll predict what you need to treat with in sixty to ninety percent of patients you can choose antibiotics on the basis of the Gram stain findings we also contest for bacterial antigens and the best use of it is when somebody's been given prior antibiotics the bacterial antigens may still be around even though the bugs have been partially killed and so it's used when the Gram stain is negative unfortunately it's not particularly helpful to do bacterial antigens in urine or serum in patients with bacterial meningitis now if we compare these findings to viral meningitis in the latter you would find normal glucose levels not so high protein levels and lymphocyte ik predominance now I did mention that the spinal fluid should be examined and everybody who's got a suspicion of meningitis but there are certain physical findings that may have make you delay doing a lumbar puncture because if the patient has evidence of increased intracranial pressure you may kill them with a lumbar puncture because if they have markedly elevated intracranial pressure if you do a lumbar puncture and relieve some of that pressure below they may actually herniate and so the herniation can kill them so what you need to do is if you think there's clinical evidence of an increased intracranial pressure you need to verify that with imaging and so you have to delay there for your examination of spinal fluid where you find gram positive diplococci along with a lot of neutrophils is it Hamas influenza a very plea of Orphic gram negative Kaka bacillus or is it that classic Neisseria meningitidis or is it Listeria monocytogenes which are small gram positive rods and the value of the Gram stain is that it suggests an etiology before your cultures come back the cultures may not come back for up to 72 hours so if you've got an idea what to treat with the Gram stain you can design your antibiotic regimen unfortunately the Gram stain is less useful if the patient has received antibiotics and it may be negative one thing it doesn't change is is the spinal fluid formula the protein still up the white count is still up the glucose is still low that doesn't usually change with antibiotics blood cultures are positive in a large number of patients but as you could imagine the blood cultures are often negative if antibiotics have been given so blood cultures are useful when a spinal tap is contraindicated so you have evidence that the patient has increased intracranial pressure you got in cultures from somewhere and so getting them from the blood if you get an organism you know what to treat there are some rapid tests that we can do on spinal fluid the one that was in vogue when I was training was the latex agglutination this is no longer used because of the number of false positives we now use immuno chromatographic tests which are rapid they can be done in less than two minutes and give you an idea of what to treat for example in a study showing 450 specimens of cerebral spinal fluid a hundred and twenty two of them had streptococcus pneumoniae in them and the they were identified by culture in 87 individuals and 35 were identified by PCR but the bottom line was that all the patients that had streptococcus pneumoniae were positive so this immuno chromatographic test had a sensitivity in this study of a hundred percent it's probably not quite that good but it's pretty good and we can also do PCR targeting the 16s ribosomal RNA gene which is highly conserved among bacteria so you can demonstrate that the patient has a bacterial meningitis with PCR it's a little more labor-intensive and it's not available immediately but in a study of 206 CSF specimens tested 17 pathogens were identified by either culture PCR and three of them were culture negative but PCR positive so it's showing great promise so the rapid tests ultimately have a sensitivity of about a hundred percent and a specificity of more than 95 percent but we still need more studies dealing with these rapid tests so how do you manage bacterial meningitis if the Gram stain is negative in other words you're not sure what you're treating well you would have to treat for all pathogens that might be present so on a patient from the age of one month to 50 years of age you're going to be using ampicillin ceftriaxone and vancomycin and notice that we're adding a corticosteroid with that dexamethasone and the main reason for dexamethasone is to reduce the amount of inflammation that is present because the inflammation causes increased intracranial pressure and may cause some of the irreversible damage that happens because of the inflammatory response in the cerebrospinal fluid now there are I've listed there the alternatives for you in patients that can't cannot take cephalosporins or ampicillin and that would be mare open em plus vancomycin again plus dexamethasone now if the patient has had some neuro surgery or a cochlear implant or some head trauma then we need to think about what bugs could cause meningitis there and we're thinking staph we're thinking gram-negative rods so the treatments going to be vancomycin to cover methicillin-resistant staph and cefepime which is an anti Pseudomonas fourth generation cephalosporin or ceftazidime a third generation which covers Pseudomonas and so that's what we're thinking empirically and alternatively we would use once again meropenem a carbapenem plus vancomycin there's not evidence of whether you should use corticosteroids in this setting but many patients who had a neurosurgical procedure or trauma are already getting dexamethasone so now what if you do have a positive Gram stain let's say streptococcus pneumoniae what's recommended is vancomycin plus ceftriaxone plus dexamethasone now why vancomycin plus ceftriaxone there are some pneumococci that are relatively resistant to ceftriaxone not very common but vancomycin would be expected to cover that small percentage of pneumococci not susceptible alternatively once again we're turning to meropenem or moxifloxacin a fluoroquinolone plus dexamethasone all right what if your Gram stain shows you evidence of a gram-negative organism like ma feliss influenza or Pseudomonas aeruginosa sometimes h flu can be elongate and resemble other gram-negative rods and so the Gram stain doesn't give you certainty so you're going to have to treat for both and an anti Pseudomonas F Allah sporran will cover both H flu and Pseudomonas but in this case because there may be a few percentage that are not covered by these cephalosporins you would add gentamicin at least until you get the results of your cultures back and alternatively you would use once again meropenem a fluoroquinolone plus dexamethasone alright if you're pretty sure the patient has that bad meningococcal meningitis then the treatment of choice in babies newborns is actually cefotaxime and cefotaxime and ceftriaxone are very very similar third-generation cephalosporins bug wise but because a newborns liver is not mature they may not handle ceftriaxone which is partially excreted by the liver very well so you use cefotaxime for newborns everybody else would get ceftriaxone plus dexamethasone and the reason for ceftriaxone is that you can give it once a day or twice a day at the most and alternatively it would be penicillin the meningococcal still is completely susceptible to penicillin G or ampicillin or moxifloxacin if patients cannot tolerate a beta lactam the empirical treatment for a patient suspected of having Listeria on Gram stain would be ampicillin in fact the organism is more susceptible to ampicillin than it is penicillin G + gentamicin for synergism alternatively they can receive trim sulfa meropenem and questionably this new agent called Len a solid but because of some lack of certainty we add to that and because of this this organism is a little bit slow to grow because it's intracellular and more difficult to treat we usually treat this for 21 days Listeria meningitis now if it's Staphylococcus we're going to use vancomycin empirically because of the possibility of methicillin-resistant Staph aureus if we think it's a streptococcus then like Group B Strep for example that would be ampicillin plus gentamicin in a newborn an infant's and it would be penicillin in adults alternatively if they can't take a beta lactam it would be vancomycin now what if a patient has visited a doctor's office or is brought to a private physicians office and the private physician feels like they have meningitis well of course they've got to transfer them to a hospital there may be valuable time wasted and so if a private physician happens to have the availability of giving intravenous ampicillin or penicillin then he or she should do that I'll just give the medication empirically because of the danger of death with delay now the infectious disease Society of America guidelines I will now summarize for you if you have a patient with a suspicion of bacterial meningitis and you have for example a patient who's immunocompromised has a history of papilledema focal neurologic deficit or there's going to be some kind of delay in therapy then that produces an algorithm and you go down one side if the answer is yes and on the other side of the answer's no so they do not have any of these you would go ahead and get blood cultures you would do a lumbar puncture immediately you would give dexamethasone and any empirical antibiotics you've got your cultures cooking and then you would get the spinal fluid analyzed if the findings are consistent with bacterial meningitis you would continue therapy so that is if the patient has no immuno compromised no history of central nervous system disease no papilledema no focal neurologic deficit and you've been able to tap them immediately on the other hand if the answer to that question is yes then there's going to be a delay you can't tap them immediately so you've got to get your blood cultures you go ahead and give them dexamethasone and empirical antibiotics now there may be delay in x-ray well you don't want the patient to be waiting an x-ray and not have been given antibiotics so that's why you give them empirical antibiotics and then send them off to x-ray if their head CT scan shows no evidence of increased intracranial pressure you can now analyze their spinal fluid a spinal tap can be done [Music] you