hello and welcome everyone today we will present carbapenam resistance interacter the idsa guidelines so enterobacteria that is carop resistance is a cause of thousands of deaths annually worldwide it is defined by CDC as inro bacteria SE that is resistant to at least War carop antibiotic or producing a carbapenam enzyme C refers to organisms resistant to meropenam or imenom or inact producing carbapenam enzymes CR is characterized into carbapenam producing and non-c carbapenam producing groups now what is this non-carb producing it is a result from amplification of non- carbapenam bacum genes with concurrent disruption of the outer membrane protein so this results in a resistance to carop penams prevalence is very high that is 35 to 60% of CR cases in us are carbapenam producing based on the CDC definition and the common caropines are the kpcs that is cpal Anon carames New Delhi bames that is ndms Verona integron encoded metal metobala that is whims imum hydrolyzing metalo IMS Oxys Lenas that is oxa 48 like caropines now importance of isolating this in treatment is important because considering carbapenam is our important goto antibiotic for sepsis and broad spectrum resistant to this organism is going to change our acific therapy in case of isolation of these organisms now the diagnostic test that can be done to find kopam resistance is pheny typic testing ing which is the inactivation method of differentiating between carop penam and the non-carb producing CR molecular texting can also help us in this now there's a strong recommendation that all clinical labs to perform kopam phenotyping or genotyping to inform optimal treatment decisions so the guidelines what is the preferred treatment approach for infections caused by intacct isoated with carop pmus to meropenam and imum susceptible while it is resistant to arenum in those cases what should we do in that case you can go for extended infusion of meropenam and imum and the standard infusion dose can also be used and is may be considered reasonable if the patient has uncomplicated cystitis now consider severity and infection site for isolate susceptible to meropenam but not imum the treatment decision should consider the severity of the patient illness and infection thre for instance meenum would be suitable for urinary tract infection but not so for a complex intraabdominal infection avoid using meropenam vacum imum cilastatin rectum and for arenum resistance but meropenam and imum susceptible infection as they are likely do not offer significant benefit beyond the extended infusion of the meropenam and emenim next is what is the preferred antibiotic for treatment of uncomplicated cystitis due to CR in these cases we can go for nitrofen Primo self metool cusine or lyine we can also go for Alternatives like aminoglycosides oral phosphomycin colistin septo aaum meropenam vacum imum cilastatin rectum and seip seid call now the rational for preferring these options is these options are effective in C citis and aminoglycosides a single dose is usually effective against cystitis next is the preferred antibiotic for treatment of Pyon nephritis and complicated UTI now in these cases you can go for primary supr self methods resolve if the B bacteria is susceptible or cof flosin or leosin or you can go for sepm aaum meropenam vacum imum ctin reum sidol even aminoglycosides can be considered in this group of infections next is the preferred treatment for infection outside of UTI by C where the results are not not available or negative so in that cases special consideration should be done for patients recent medical care in areas with high prevalence of metacom is producing organisms previously identified with such organisms preferred treatment will be SEP iaum with asonam or seol as a monotherapy now rational is 35% of in us C isolates are carry main carop Gene that is bla KPC BL NDM like that seism aaum is effective against most kpcs and oxa 48 meropenam vacum and imum C is active against C producing kpcs but not oxa activity against metalo balacas producers the preferred agents lack activity against betalactamases thus sepid derol is if you're using a single therapy sepol is an alternative however you can reserve it for more challenging infections tetracycline or herbacy can be used as an alternative it's effective for infections not involving the bloodstream or the UTI Effectiveness is independent of carop presence or type advisory for extended infusions with carbapenam is against you do not use extended Ed infusions of carop in these type of infections increased mortality and nephrotoxicity risks can be present so it is advised not to use extended carbapenams in case of C now what is the preferred antibiotic for treatment of infection outside UTI by C if KPC production is present now it a specific KPC if KPC is specifically present then meropenam vacum sep AUM is the second choice imum catin rectum is the third choice now meropenam vacum and all the others are associated with r clinical outcomes compared to polymixin based treatment now there is limited clinical data where direct treatment have been compared so meropenam vacum resistance is still there but it is very low now there is also limited data with imum cast and reum but in Pro activity and clinical experience suggest that it is likely to be effective sepid derol continues to be an alternative but to be used only in case of very severe infections pgy and herbacy are alternatives where the infection is not in the bloodstream or unine next is the type of antibiotics for treatment of infection outside of UTI caused by C in NDM producing in these cases septim aaum asonam is the preferred treatment sepol monotherapy is second observational Studies have shown 30 days mortality with sep iopen asonam combination with other regimens so showing clear clinical benefit of these combination now patient should be monitored for liver enzyme elevation when you're using this kind of combination now in cases where sep as is not a viable option considered asonam with meropenam vacum or imum C racum this combination therapy is effective as long as there is no oxa type carbapenam present now pgy and herbacy are recommended alternatives for NDM producing infections these alternatives are suitable for infection not involving UTI or bloodstream the effectiveness of these Alternatives is not dependent on the type of carop present now next is the preferred antibiotic for treatment of infection outside the urinary tract where oxa 48 is the producing organism here clearly SE seasum aaum is the drug of choice sepid derol comes second now again the meropenam vacum and imum ctin rectum do not have activity against oxa 48 and they are not recommended in these infections sepol is to be used in case of these infections but to be used as a reserved drug the alternatives are tgy or herbacy as they can have activity against oxop producing organisms as well the next is the likelihood of emergence of resistance of these new agents to CR now the resistance to seum aaum arises by mutation in the bla KPC Gene while the meropenam bacum and imum CEST reum the primarily resistance is coming from permeability and E flux which also is associated with the increase in the BL KPC Gene copy numbers now the resistance to sepol has various mechanisms like iron Transport Systems change in ampc bet aimus increase in NDM expression now estimated resistance is 10 to 20% for seum aaum and 3% for meropenam vacum now clinical implication is a should be repeated for new bacum in certain cases and alternative agents may be considered if resistance emerges now what is the role of tetracycline derivatives for the treatment of infection caused by CR now tety are not recommended for treatment of urinary tract or bloodstream infections because the concentration is not adequate now tetracycline derivatives are effective regardless of the type of carop pames making them extremely suitable for other type of for all types of C infections now they have a rapid tissue distribution and resulting in uh now tety derivatives are considered for intraabdominal skin and soft tissue osteomylitis respiratory infection when the optimal dozing is being given and antimicrobial recommendation for TG cycling is the most uh published experience and high dose tetracycline may be helpful to reduce mortality remember the dose is 200 Mill loading and 100 milligram BD uh herbacy generally lower mic's against C compared to tgy limited clinical trial and post marketing data Minocycline can be used but again very limited data and we are not yet sure of the susceptibility omad dark cycling should not be used not recommended so what is the role of combination of antibiotic therapy in treatment of infection with C so when you are giving combination antibiotics how we should give regarding the role of polymixin we will do a separate video on that we have skipped polymixin and colistin in the management of C over here but as of the recommendations of idsa goes chistin may not be preferred in C so if you're giving a combination therapy then what is a rational the rational for giving a Mona therapy is empirical combination can ensure initial treatment and includes active agent for patients with the risk of C now the concerns about combination therapies prolonged use of the second agent can result in an increase antibiotic Associated adverse effects and there are lack of comparative data between uh the combination versus monotherapy now observational Studies have shown a similar 30-day mortality with sepm abum alone compared to sepm abum the second agent for KPC producing infections now expert panel advises against Comin ation usage of c and only the preferred bacum to be used in a monotherapy because the second is not really shown till now to be of any benefit other than adding to the complications thank you for your patience we will continue with this particular series with other set of organisms thank you