Molecular ß-Lactamase Characterization of Aerobic Gram-Negative Pathogens Recovered from Patients Enrolled in the Ceftazidime-Avibactam Phase 3 Trials for Complicated Intra-abdominal Infections, with Efficacies Analyzed against Susceptible and Resistant Subsets.
Antimicrob Agents Chemother
; 61(6)2017 06.
Article
en En
| MEDLINE
| ID: mdl-28348155
ABSTRACT
The correlation of the clinical efficacy of ceftazidime-avibactam (plus metronidazole) with that of meropenem was evaluated in subjects infected with Gram-negative isolates having characterized ß-lactam resistance mechanisms from the complicated intra-abdominal infection (cIAI) phase 3 clinical trials. Enterobacteriaceae isolates displaying ceftriaxone and/or ceftazidime MIC values of ≥2 µg/ml and Pseudomonas aeruginosa isolates with ceftazidime MIC values of ≥16 µg/ml were characterized for extended-spectrum-ß-lactamase (ESBL) content. Enterobacteriaceae and P. aeruginosa isolates with imipenem and meropenem MIC values of ≥2 and ≥8 µg/ml, respectively, were tested for carbapenemase genes. The primary efficacy endpoint was clinical cure at test of cure (TOC) among the members of the microbiologically modified intention-to-treat (mMITT) population. A total of 14.5% (56/387) and 18.8% (74/394) of patients in the ceftazidime-avibactam and meropenem arms had isolates that met the MIC screening criteria at the baseline visit, respectively. CTX-M variants alone (29.7%; 41/138) or in combination with OXA-1/30 (35.5%; 49/138), most commonly, blaCTX-M group 1 variants (79/90; 87.8%), represented the ß-lactamases most frequently observed among Enterobacteriaceae isolates. Among the patients infected with pathogens that did not meet the screening criteria, 82.2% showed clinical cure in the ceftazidime-avibactam group versus 85.9% in the meropenem group. Among patients infected with any pathogens that met the MIC screening criteria, clinical cure rates at TOC were 87.5% and 86.5% for the ceftazidime-avibactam and meropenem groups, respectively. Ceftazidime-avibactam had clinical cure rates of 92.5% to 90.5% among patients infected with ESBL- and/or carbapenemase-producing Enterobacteriaceae strains at the baseline visit, while meropenem showed rates of 84.9% to 85.4%. The ceftazidime-avibactam and meropenem groups had cure rates of 75.0% and 86.7%, respectively, among patients having any pathogens producing AmpC enzymes. The efficacy of ceftazidime-avibactam was similar to that of meropenem for treatment of cIAI caused by ESBL-producing organisms. (This study has been registered at ClinicalTrials.gov under registration no. NCT01499290 and NCT01500239.).
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Plantas_medicinales
Asunto principal:
Beta-Lactamasas
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Infecciones Intraabdominales
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Bacterias Aerobias Gramnegativas
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Antibacterianos
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos