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.
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.
- Castanheira M, Doyle TB, Kantro V, et al. Meropenem-Vaborbactam Activity against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals during 2016 to 2018. Antimicrob Agents Chemother 2020; 64(2)
- Pfaller MA, Huband MD, Mendes RE, et al. In vitro activity of meropenem/vaborbactam and characterisation of carbapenem resistance mechanisms among carbapenem-resistant Enterobacteriaceae from the 2015 meropenem/vaborbactam surveillance programme. Int J Antimicrob Agents 2018; 52(2): 144-50
- Johnston BD, Thuras P, Porter SB, et al. Activity of Imipenem-Relebactam against CarbapenemResistant Escherichia coli Isolates from the United States in Relation to Clonal Background, Resistance Genes, Coresistance, and Region. Antimicrob Agents Chemother 2020; 64(5).
- Alosaimy S, Jorgensen SCJ, Lagnf AM, et al. Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections. Open Forum Infect Dis 2020; 7(3): ofaa051
- Zhang R, Yang L, Cai JC, Zhou HW, Chen GX. High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression. J Med Microbiol. 2008 Mar;57(Pt 3):332-337. doi: 10.1099/jmm.0.47576-0. PMID: 18287296.
- Yao Y, Falgenhauer L, Falgenhauer J, et al. Carbapenem-Resistant Citrobacter spp. as an Emerging Concern in the Hospital-Setting: Results From a Genome-Based Regional Surveillance Study. Front Cell Infect Microbiol. 2021 Nov 11;11:744431. doi: 10.3389/fcimb.2021.744431. PMID: 34858870; PMCID: PMC8632029.
- Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America Antimicrobial-Resistant Treatment Guidance: Gram-Negative Bacterial Infections. Infectious Diseases Society of America 2022; Version 1.1. Available at https://www.idsociety.org/practice-guideline/amr-guidance/. Accessed 6, February, 2023.