Expert opinion on drug metabolism & toxicology · 2026
An update on beta-lactam-beta-lactamase inhibitor combinations for the treatment of carbapenem-resistant Gram-negative pathogens.
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Karaiskos Ilias, Gkoufa Aikaterini, Kyriazopoulou Evdoxia, Polyzou Eleni, Rapti Vasiliki, Ioannidis Konstantinos, Chrysanthopoulou Evangelia, Athanassa Zoe, Akinosoglou Karolina, Poulakou Garyphalia, Study Group of the Hellenic Group for the Combat of Antimicrobial Resistance in Critically Ill Patients of the Hellenic Society of Chemotherapy
Аннотация
INTRODUCTION: Carbapenem-resistant Gram-negative bacteria represent a major global health threat driven by diverse β-lactamase enzymes, particularly KPC, metallo-β-lactamases, and OXA-type carbapenemases, leading to limited treatment options and high mortality. The development of novel β-lactam/β-lactamase inhibitor (BLBLI) combinations has significantly improved outcomes in resistant infections by restoring β-lactam activity against key resistance mechanisms, primarily among Enterobacterales.
AREAS COVERED: This expert review summarizes the pharmacology, clinical efficacy, and safety of approved and emerging BLBLIs, including ceftolozane-tazobactam, cefepime-enmetazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, aztreonam-avibactam, and sulbactam-durlobactam. Emphasis is placed on activity against carbapenem-resistant Enterobacterales, difficult-to-treat Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii. Evidence derives from clinical trials, real-world studies, and pharmacokinetic/pharmacodynamic (PK/PD) analyses from major databases (PubMed, Scopus, Web of Science) from inception through January 2026, focusing on dosing optimization and outcomes.
EXPERT OPINION: BLBLIs have transformed the management of KPC-producing infections, markedly reducing mortality compared with legacy therapies. However, their impact is threatened by the rising prevalence of metallo-β-lactamases and the persistent therapeutic gap in carbapenem-resistant A. baumannii. Future success will depend on next-generation inhibitors with broader enzyme coverage, optimized dosing strategies guided by PK/PD principles, and robust antimicrobial stewardship to preserve long-term efficacy.
AREAS COVERED: This expert review summarizes the pharmacology, clinical efficacy, and safety of approved and emerging BLBLIs, including ceftolozane-tazobactam, cefepime-enmetazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, aztreonam-avibactam, and sulbactam-durlobactam. Emphasis is placed on activity against carbapenem-resistant Enterobacterales, difficult-to-treat Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii. Evidence derives from clinical trials, real-world studies, and pharmacokinetic/pharmacodynamic (PK/PD) analyses from major databases (PubMed, Scopus, Web of Science) from inception through January 2026, focusing on dosing optimization and outcomes.
EXPERT OPINION: BLBLIs have transformed the management of KPC-producing infections, markedly reducing mortality compared with legacy therapies. However, their impact is threatened by the rising prevalence of metallo-β-lactamases and the persistent therapeutic gap in carbapenem-resistant A. baumannii. Future success will depend on next-generation inhibitors with broader enzyme coverage, optimized dosing strategies guided by PK/PD principles, and robust antimicrobial stewardship to preserve long-term efficacy.