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Activity of a new antipseudomonal cephalosporin, CXA-101 (FR264205), against carbapenem-resistant and multidrug-resistant Pseudomonas aeruginosa clinical strains.
Antimicrob Agents Chemother. 2010 Feb; 54(2):846-51.AA

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+Show Affiliations

Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta, C. Andrea Doria no. 55, 07014 Palma de Mallorca, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19933793

Citation

Juan, Carlos, et al. "Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), Against Carbapenem-resistant and Multidrug-resistant Pseudomonas Aeruginosa Clinical Strains." Antimicrobial Agents and Chemotherapy, vol. 54, no. 2, 2010, pp. 846-51.
Juan C, Zamorano L, Pérez JL, et al. Activity of a new antipseudomonal cephalosporin, CXA-101 (FR264205), against carbapenem-resistant and multidrug-resistant Pseudomonas aeruginosa clinical strains. Antimicrob Agents Chemother. 2010;54(2):846-51.
Juan, C., Zamorano, L., Pérez, J. L., Ge, Y., & Oliver, A. (2010). Activity of a new antipseudomonal cephalosporin, CXA-101 (FR264205), against carbapenem-resistant and multidrug-resistant Pseudomonas aeruginosa clinical strains. Antimicrobial Agents and Chemotherapy, 54(2), 846-51. https://doi.org/10.1128/AAC.00834-09
Juan C, et al. Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), Against Carbapenem-resistant and Multidrug-resistant Pseudomonas Aeruginosa Clinical Strains. Antimicrob Agents Chemother. 2010;54(2):846-51. PubMed PMID: 19933793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activity of a new antipseudomonal cephalosporin, CXA-101 (FR264205), against carbapenem-resistant and multidrug-resistant Pseudomonas aeruginosa clinical strains. AU - Juan,Carlos, AU - Zamorano,Laura, AU - Pérez,José L, AU - Ge,Yigong, AU - Oliver,Antonio, AU - ,, AU - ,, Y1 - 2009/11/23/ PY - 2009/11/26/entrez PY - 2009/11/26/pubmed PY - 2010/3/5/medline SP - 846 EP - 51 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 54 IS - 2 N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/19933793/Activity_of_a_new_antipseudomonal_cephalosporin_CXA_101__FR264205__against_carbapenem_resistant_and_multidrug_resistant_Pseudomonas_aeruginosa_clinical_strains_ L2 - https://journals.asm.org/doi/10.1128/AAC.00834-09?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -