Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients.
Carbapenemase- and extended-spectrum β-lactamase-producing Enterobacterales, as well as
carbapenemase-producing Pseudomonas and Acinetobacter spp., are common MDR pathogens. New
antibiotics and combinations have been developed to address this threat. Clinical trial findings support several combinations, notably
ceftazidime-avibactam (CZA, a
cephalosporin-β-lactamase inhibitor combination), which is effective in treating complicated
urinary tract infections (cUTI), complicated
intra-abdominal infections and hospital-acquired and
ventilator-associated pneumonia caused by GNBs. Other clinically effective combinations include
meropenem-vaborbactam (MVB),
ceftolozane-tazobactam (C/T) and
imipenem-
relebactam (I-R).
Cefiderocol is a recent
siderophore β-
lactam antibiotic that is useful against cUTIs caused by
carbapenem-resistant Enterobacterales (CRE) and is stable against many β-lactamases.
Carbapenem-resistant Enterobacterales are a genetically heterogeneous group that vary in different world regions and are a substantial cause of
infections, among which Klebsiella pneumoniae are the most common. Susceptible CRE
infections can be treated with
fluoroquinolones,
aminoglycosides or
fosfomycin, but alternatives include CZA, MVB, I-R,
cefiderocol,
tigecycline and
eravacycline. Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are increasingly common pathogens producing a range of different carbapenemases, and
infections are challenging to treat, often requiring novel
antibiotics or combinations. Currently, no single agent can treat all MDR-GNB
infections, but new β-
lactam-β-lactamase inhibitor combinations are often effective for different
infection sites and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel β-
lactam approaches for treatment of MDR-GNB
infections.