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Antimicrob Agents Chemother. 2017 Feb 23;61(3). pii: e01268-16. doi: 10.1128/AAC.01268-16. Print 2017 Mar.

High-Dose Ampicillin-Sulbactam Combinations Combat Polymyxin-Resistant Acinetobacter baumannii in a Hollow-Fiber Infection Model.

Author information

1
Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA.
2
School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, New York, USA.
3
California Northstate University College of Pharmacy, Elk Grove, California, USA.
4
Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.
5
Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
6
Catholic University of Daegu, Hayang, South Korea.
7
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
8
Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA btsuji@buffalo.edu.

Abstract

Acinetobacter baumannii is emerging with resistance to polymyxins. In 24-h time-kill experiments, high-dose ampicillin-sulbactam in combination with meropenem and polymyxin B achieved additivity or synergy against 108 CFU/ml of two clinical A. baumannii isolates resistant to all three drugs (maximum reductions, 1.6 and 3.1 logs). In a 14-day hollow-fiber infection model, high-dose ampicillin-sulbactam (8/4 g every 8 h, respectively) in combination with meropenem (2 g every 8 h) and polymyxin B (1.43 mg/kg of body weight every 12 h with loading dose) resulted in rapid (96 h) eradication of A. baumannii.

KEYWORDS:

Acinetobacter; antibiotic resistance; antimicrobial combinations; meropenem; polymyxins; sulbactam; synergism

PMID:
28052852
PMCID:
PMC5328540
DOI:
10.1128/AAC.01268-16
[Indexed for MEDLINE]
Free PMC Article

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