New Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria in Lung Transplantation: Clinical Evidence, Safety, and PK/PD Properties.

Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) and Pseudomonas aeruginosa are leading causes of morbidity and mortality after lung transplantation (LuTx). We reviewed the pharmacology, clinical evidence, and safety of five agents potentially active against MDR-GNB in LuTx recipients (LUTR): ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and cefiderocol. Literature from the last 10 years was reviewed for data on activity spectrum, efficacy in LUTR and adverse events. Ceftolozane/tazobactam and ceftazidime/avibactam were the most studied, providing high cure rates for difficult-to-treat Pseudomonas (DTR-PA) and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, respectively. Meropenem/vaborbactam offers reliable coverage of KPC strains, while imipenem/relebactam is an interesting option for imipenem-non-susceptible Pseudomonas spp. Cefiderocol exhibits the broadest in vitro spectrum, including metallo-β-lactamase producers. Across agents, pharmacokinetic variability, augmented renal clearance, and extracorporeal support can compromise target attainment; prolonged or continuous infusion is preferred. Collectively, these antibiotics expand the therapeutic armamentarium against MDR-GNB in LUTR, allowing pathogen-directed, toxicity-sparing regimens. Nonetheless, prospective LuTx-focused studies are needed to optimise their use in such a peculiar setting.