Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clini...
|Journal Title:||Antimicrobial Agents and Chemotherapy|
|Authors and Corporations:||, , , ,|
|In:||Antimicrobial Agents and Chemotherapy, 54, 2010, 2, p. 846-851|
|Type of Resource:||E-Article|
American Society for Microbiology
|Summary:||<jats:title>ABSTRACT</jats:title> <jats:p>The activity of the new cephalosporin CXA-101 (CXA), previously designated FR264205, was evaluated against a collection of 236 carbapenem-resistant <jats:italic>P. aeruginosa</jats:italic> 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<jats:sub>50</jats:sub>/MIC<jats:sub>90</jats:sub> for the complete collection of carbapenem-resistant <jats:italic>P. aeruginosa</jats:italic> 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<jats:sub>50</jats:sub>/MIC<jats:sub>90</jats:sub> 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 <jats:italic>P. aeruginosa</jats:italic> isolates, including MDR strains. Resistance was restricted to still-uncommon strains producing an acquired MBL or ESBL.</jats:p>|