Pharmacodynamic Effects of Sulbactam/Meropenem/Polymyxin-B Combination Against Extremely Drug Resistant Acinetobacter baumannii Using Checkerboard Information.
Microb Drug Resist
; 25(9): 1266-1274, 2019 Nov.
Article
em En
| MEDLINE
| ID: mdl-31216222
Aim: The aims of the study are to evaluate the activity of sulbactam, meropenem, and polymyxin B alone and in combination against six isolates of extremely drug resistant Acinetobacter baumannii and to determine dosing regimens that achieve a sufficient joint probability of target attainment (PTA) based on combination antimicrobial pharmacodynamics. Materials and Methods: The combinations were evaluated by the checkerboard method and were considered synergistic when the fractional inhibitory concentration index (FICI) ≤0.5. Pharmacodynamic analyses were carried out by evaluating dosing regimens that achieve ≥90% joint PTA at the percentage of time over a 24-h period wherein the free drug concentration is above the minimum inhibitory concentration (%fT> MIC) of 40% and 60% for meropenem and sulbactam, respectively, and 20 for the ratio of the area under the free drug concentration-time curve over MIC (fAUC/MIC) for polymyxin B. Results: For both polymyxin B-resistant and susceptible isolates, the addition of sulbactam in combination with meropenem and subinhibitory concentration of polymyxin B showed important synergistic activity (five isolates; FICI ≤0.281); the recommended dosing regimens were 2/4 g meropenem/sulbactam q8 hours and 0.5 mg/kg polymyxin B q12 hours. Conclusion: This in vitro study showed that sulbactam can significantly improve the action of meropenem and polymyxin B in OXA-producing A. baumannii isolates, especially when there are no new treatment options available for infections caused by these microorganisms.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimixina B
/
Sulbactam
/
Acinetobacter baumannii
/
Meropeném
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Microb Drug Resist
Assunto da revista:
MICROBIOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos