Affiliation:
1. Basilea Pharmaceutica International Ltd., P.O. Box, Basel CH-4005, Switzerland
Abstract
ABSTRACT
BAL30072 is a new monocyclic β-lactam antibiotic belonging to the sulfactams. Its spectrum of activity against significant Gram-negative pathogens with β-lactam-resistant phenotypes was evaluated and was compared with the activities of reference drugs, including aztreonam, ceftazidime, cefepime, meropenem, imipenem, and piperacillin-tazobactam. BAL30072 showed potent activity against multidrug-resistant (MDR)
Pseudomonas aeruginosa
and
Acinetobacter
sp. isolates, including many carbapenem-resistant strains. The MIC
90
s were 4 μg/ml for MDR
Acinetobacter
spp. and 8 μg/ml for MDR
P. aeruginosa
, whereas the MIC
90
of meropenem for the same sets of isolates was >32 μg/ml. BAL30072 was bactericidal against both
Acinetobacter
spp. and
P. aeruginosa
, even against strains that produced metallo-β-lactamases that conferred resistance to all other β-lactams tested, including aztreonam. It was also active against many species of MDR isolates of the
Enterobacteriaceae
family, including isolates that had a class A carbapenemase or a metallo-β-lactamase. Unlike other monocyclic β-lactams, BAL30072 was found to trigger the spheroplasting and lysis of
Escherichia
coli
rather than the formation of extensive filaments. The basis for this unusual property is its inhibition of the bifunctional penicillin-binding proteins PBP 1a and PBP 1b, in addition to its high affinity for PBP 3, which is the target of monobactams, such as aztreonam.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
183 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献