title: Activity of a new antipseudomonal cephalosporin, CXA-101 (FR264205), against carbapenem-resistant and multidrug-resistant Pseudomonas aeruginosa clinical strains.
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 microg/ml) was determined for strains with high CXA MICs. The presence of acquired beta-lactamases was investigated by isoelectric focusing and PCR amplification followed by sequencing. Additional beta-lactamase genes were identified by cloning and sequencing. The CXA MIC50/MIC90 for the complete collection of carbapenem-resistant P. aeruginosa isolates was 1/4 microg/ml, with 95.3% of the isolates showing an MIC of <or=8 microg/ml. Cross-resistance with any of the antibiotics tested was not observed; the MIC50/MIC90 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 microg/ml produced a horizontally acquired beta-lactamase, including the metallo-beta-lactamase (MBL) VIM-2 (one strain), the extended-spectrum beta-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 microg/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.
authors.affiliation: Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta, C. Andrea Doria no. 55, 07014 Palma de Mallorca, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Juan
authors.forename: Laura
authors.initials: L
authors.lastname: Zamorano
authors.forename: José L
authors.initials: JL
authors.lastname: Pérez
authors.forename: Yigong
authors.initials: Y
authors.lastname: Ge
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D007525:Isoelectric Focusing; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D011552:Pseudomonas Infections / Q000382:microbiology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; C519491:ceftolozane; D001618:beta-Lactamases