Carbapenemase-producing Klebsiella pneumoniae: (when) might we still consider treating with carbapenems?

Abstract

Infections caused by carbapenemase-producing Klebsiella pneumoniae (CPKP) are increasing in frequency worldwide. CPKP isolates exhibit extensive drug resistance phenotypes, complicate therapy, and limit treatment options. Although CPKP isolates are often highly resistant to carbapenems, a proportion of these have relatively low MICs for carbapenems, raising the question of whether this class of agents has any therapeutic potential against CPKP infections. Results from animal studies and patient outcome data indicate that carbapenems retain meaningful in vitro activity against CPKP isolates with carbapenem MICs of ≤ 4 mg/L. Accumulating clinical experience also suggests that the therapeutic efficacy of carbapenems against CPKP isolates with MICs of ≤ 4 mg/L is enhanced when these agents are administered in combination with another active antibiotic. The results of human pharmacokinetic/pharmacodynamic studies are in line with the above observations; it is highly probable that a high-dose/prolonged-infusion regimen of a carbapenem would attain a time above the MIC value of 50% for CPKP isolates with MICs up to 4 mg/L, ensuring acceptable drug exposure and favourable treatment outcome. The analyses summarized in this review support the notion that carbapenems have their place in the treatment of CPKP infections and that the currently proposed EUCAST clinical breakpoints could direct physicians in making treatment decisions.