Managing KPC infections in daily practice: when BLBLIs are interchangeable - and when they are not

Κlebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales infections are currently treatable with novel β-lactam-β-lactamase inhibitors (BLBLIs) combinations, but their optimal use in daily practice requires defining when ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB), and imipenem-cilastatin-relebactam (IMI-REL) are clinically interchangeable and when treatment should be individualized.

Contemporary surveillance and observational data support high activity of all three agents against confirmed KPC-producing Enterobacterales, providing a rationale for interchangeability in low-risk infections with source control and no recent BLBLI exposure. However, clinically relevant differences are increasingly recognized. CAZ-AVI resistance is most often linked to KPC variants, whereas reduced MER-VAB and IMI-REL susceptibility more frequently involves porin loss, reduced permeability, and increased β-lactamase expression. Pneumonia, high MICs, altered renal function, renal replacement therapy, prior BLBLI exposure, persistent colonization, immunocompromise, and delayed source control may narrow interchangeability.

BLBLI with KPC activity interchangeability is clinically reasonable only in selected, microbiologically confirmed, low-risk scenarios. In complex infections, therapy should be guided according to resistance mechanism, infection site, pharmacokinetics/pharmacodynamics (PK/PD) parameters, and host factors.