Affiliation:
1. Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta, Instituto Universitario de Investigación en Ciencias de la Salud, Palma de Mallorca, Spain
2. Calixa Therapeutics, San Diego, California
Abstract
ABSTRACT
The activity of the new cephalosporin CXA-101 (CXA), previously designated FR264205, was evaluated against a collection of 236 carbapenem-resistant
P. aeruginosa
isolates, including 165 different clonal types, from a Spanish multicenter (127-hospital) study. The MICs of CXA were compared to the susceptibility results for antipseudomonal penicillins, cephalosporins, carbapenems, aminoglycosides, and fluoroquinolones. The MIC of CXA in combination with tazobactam (4 and 8 μg/ml) was determined for strains with high CXA MICs. The presence of acquired β-lactamases was investigated by isoelectric focusing and PCR amplification followed by sequencing. Additional β-lactamase genes were identified by cloning and sequencing. The CXA MIC
50
/MIC
90
for the complete collection of carbapenem-resistant
P. aeruginosa
isolates was 1/4 μg/ml, with 95.3% of the isolates showing an MIC of ≤8 μg/ml. Cross-resistance with any of the antibiotics tested was not observed; the MIC
50
/MIC
90
of CXA-101 was still 1/4 when multidrug-resistant (MDR) strains (42% of all tested isolates) or AmpC-hyperproducing clones (53%) were analyzed. Almost all (10/11) of the strains showing a CXA MIC of >8 μg/ml produced a horizontally acquired β-lactamase, including the metallo-β-lactamase (MBL) VIM-2 (one strain), the extended-spectrum β-lactamase (ESBL) PER-1 (one strain), several extended-spectrum OXA enzymes (OXA-101 [one strain], OXA-17 [two strains], and a newly described OXA-2 derivative [W159R] designated OXA-144 [four strains]), and a new BEL variant (BEL-3) ESBL (one strain), as identified by cloning and sequencing. Synergy with tazobactam in these 11 strains was limited, although 8 μg/ml reduced the mean CXA MIC by 2-fold. CXA is highly active against carbapenem-resistant
P. aeruginosa
isolates, including MDR strains. Resistance was restricted to still-uncommon strains producing an acquired MBL or ESBL.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
85 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