Carbapenem Resistance - KPC

A 61-year-old patient with a history of liver transplant two months ago presents with secondary bacterial peritonitis. The patient presented to the emergency room with hypotension and sepsis. He was initially empirically started on meropenem. Blood cultures grew Citrobacter freundii, and the multi-plex PCR assay identified a KPC gene. A common characteristic of KPCs is 3rd/4th generation cephalosporin and carbapenem resistance.

KPC enzymes are a broad class with numerous variants and variable susceptibility patterns. Within the USA, these variants are KPC 1-3, which have the potential of being susceptible to plazomicin, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, colistin/polymyxin, omadacyline, and eravacycline. The local hospital susceptibility patterns showed that meropenem/vaborbactam had higher susceptibility within KPC isolates. Meropenem/vaborbactam, imipenem/relebactam, and ceftazidime/avibactam are the antibiotics that would produce high serum concentrations to treat potentially septic patients with systemic bloodstream infections.

KPC Overview

KPCs fall into the Class A ambler classification, which has high carbapenem resistance, contrary to OXA, which typically shows lower carbapenem MIC values. There are numerous variants within KPCs, which some lead to higher level resistance within different antibiotics. Typically, these resistance mechanisms will be combined with outer porin membrane mutations that correlate with that resistance. Specifically, looking at the antimicrobials that would be the best utilized in the situation of KPC, it is essential to distinguish the difference in each antimicrobial. If the patient has a delineated KPC infection where no other gene is involved, meropenem/vaborbactam has a slight edge over competitors based on the IDSA panel 2022. In this review, some KPC isolates were resistant to ceftazidime/avibactam. Other options include cefiderocol, imipenem/cilastatin/relebactam, plazomicin, ceftazidime/avibactam, and eravacycline. It is also essential to recognize that many older antimicrobials retain activity against KPC, including sulfamethoxazole/trimethoprim, colistin, polymyxin, and tigecycline.

References

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