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Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Stra...
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| Zeitschriftentitel: | Antimicrobial Agents and Chemotherapy |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | Antimicrobial Agents and Chemotherapy, 54, 2010, 2, S. 846-851 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
|
| Schlagwörter: |
| author_facet |
Juan, Carlos Zamorano, Laura Pérez, José L. Ge, Yigong Oliver, Antonio Juan, Carlos Zamorano, Laura Pérez, José L. Ge, Yigong Oliver, Antonio |
|---|---|
| author |
Juan, Carlos Zamorano, Laura Pérez, José L. Ge, Yigong Oliver, Antonio |
| spellingShingle |
Juan, Carlos Zamorano, Laura Pérez, José L. Ge, Yigong Oliver, Antonio Antimicrobial Agents and Chemotherapy Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains Infectious Diseases Pharmacology (medical) Pharmacology |
| author_sort |
juan, carlos |
| spelling |
Juan, Carlos Zamorano, Laura Pérez, José L. Ge, Yigong Oliver, Antonio 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.00834-09 <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> Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant <i>Pseudomonas aeruginosa</i> Clinical Strains Antimicrobial Agents and Chemotherapy |
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| title |
Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_unstemmed |
Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_full |
Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_fullStr |
Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_full_unstemmed |
Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_short |
Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_sort |
activity of a new antipseudomonal cephalosporin, cxa-101 (fr264205), against carbapenem-resistant and multidrug-resistant
<i>pseudomonas aeruginosa</i>
clinical strains |
| topic |
Infectious Diseases Pharmacology (medical) Pharmacology |
| url |
http://dx.doi.org/10.1128/aac.00834-09 |
| publishDate |
2010 |
| physical |
846-851 |
| description |
<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> |
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| description | <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> |
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| spelling | Juan, Carlos Zamorano, Laura Pérez, José L. Ge, Yigong Oliver, Antonio 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.00834-09 <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> Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant <i>Pseudomonas aeruginosa</i> Clinical Strains Antimicrobial Agents and Chemotherapy |
| spellingShingle | Juan, Carlos, Zamorano, Laura, Pérez, José L., Ge, Yigong, Oliver, Antonio, Antimicrobial Agents and Chemotherapy, Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains, Infectious Diseases, Pharmacology (medical), Pharmacology |
| title | Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_full | Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_fullStr | Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_full_unstemmed | Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_short | Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| title_sort | activity of a new antipseudomonal cephalosporin, cxa-101 (fr264205), against carbapenem-resistant and multidrug-resistant <i>pseudomonas aeruginosa</i> clinical strains |
| title_unstemmed | Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains |
| topic | Infectious Diseases, Pharmacology (medical), Pharmacology |
| url | http://dx.doi.org/10.1128/aac.00834-09 |