Ampicillin-sulbactam against Acinetobacter baumannii infections: pharmacokinetic/pharmacodynamic appraisal of current susceptibility breakpoints and dosing recommendations.
J Antimicrob Chemother
; 79(9): 2227-2236, 2024 Sep 03.
Article
en En
| MEDLINE
| ID: mdl-39031073
ABSTRACT
BACKGROUND:
Sulbactam dosing for Acinetobacter baumannii infections has not been standardized due to limited available pharmacokinetics/pharmacodynamics (PK/PD) data. Herein, we report a comprehensive PK/PD analysis of ampicillin-sulbactam against A. baumannii pneumonia.METHODS:
Twenty-one A. baumannii clinical isolates were tested in the neutropenic murine pneumonia model. For dose-ranging studies, groups of mice were administered escalating doses of ampicillin-sulbactam. Changes in log10cfu/lungs relative to 0 h were assessed. Dose-fractionation studies were performed. Estimates of the percentage of of time during which the unbound plasma sulbactam concentrations exceeded the MIC (%fTâ>âMIC) required for different efficacy endpoints were calculated. The probabilities of target attainment (PTA) for the 1-log kill plasma targets were estimated following clinically utilized sulbactam regimens.RESULTS:
Dose-fractionation studies demonstrated time-dependent kill. Isolates resistant to both sulbactam and meropenem required three times the exposures to achieve 1-log kill; median [IQR] %fTâ>âMIC of 60.37% [51.6-66.8] compared with other phenotypes (21.17 [16.0-32.9] %fTâ>âMIC). Sulbactam standard dose (1 g q6h, 0.5 h infusion) provided >90% PTA up to MIC of 4 mg/L. Sulbactam 3 g q8h, 4 h inf provided greater PTA for isolates with sulbactam-intermediate susceptibility (8 mg/L, 100% versus 86% following the standard dose). Despite the higher exposure following 3 g q8h, 4 h inf, PTA was ≤57% among sulbactam-resistant/meropenem-resistant isolates.CONCLUSION:
Sulbactam standard dose is a valuable regimen across sulbactam-susceptible isolates while the high-dose extended-infusion provides additional benefit against sulbactam-intermediate isolates. Given that most of the sulbactam-resistant A. baumannii isolates are meropenem-resistant, high-dose prolonged-infusion regimens are not expected to be effective as monotherapy against infections due to these isolates.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por Acinetobacter
/
Pruebas de Sensibilidad Microbiana
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Sulbactam
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Acinetobacter baumannii
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Ampicilina
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Antibacterianos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos