KPC-33 emergence and strain-dependent fitness observed in longitudinal Klebsiella pneumoniae study

Ceftazidime–avibactam is a therapeutic option for infections caused by KPC-producing Klebsiella pneumoniae, but exposure can select for KPC variants. A longitudinal observational study in Antimicrobial Agents and Chemotherapy examined 35 clonally related ST11 isolates from eight hospitalized patients during clinical follow-up. Researchers combined whole-genome sequencing, susceptibility testing, in vitro competition assays, enzyme kinetics and transcriptomics to investigate within-host evolution and the fitness consequences of KPC-33.

KPC-33 was the most frequently detected variant, appearing in longitudinal isolates from four of seven patients treated with ceftazidime–avibactam. It was also identified in the patient who had not received the drug; other variants appeared sporadically. Compared with KPC-2, KPC-33 showed reduced catalytic turnover and altered substrate affinity. Its competitive fitness varied substantially between strains rather than showing a consistent, pronounced deficit. Higher-fitness strains generally had limited transcriptional changes, whereas lower-fitness strains showed broader transcriptional remodeling.

These findings suggest that the fitness consequences of KPC-33 depend on strain background and may relate to transcriptional remodeling. Detection in an unexposed patient also cautions against attributing every occurrence to direct drug exposure. The small cohort and laboratory fitness measurements limit clinical interpretation; the available abstract provides no quantitative susceptibility results or treatment outcomes, and full text was unavailable for assessment.