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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.