High-dose ampicillin-sulbactam combinations combat polymyxin-resistant Acinetobacter baumannii in a hollow-fiber infection model

Justin R Lenhard; Nicholas M. Smith; Zackery P. Bulman; Xun Tao; Visanu Thamlikitkul; Beom Soo Shin; Roger L Nation; Jian Li; Jurgen B Bulitta; Brian T Tsuji

doi:10.1128/AAC.01268-16

High-dose ampicillin-sulbactam combinations combat polymyxin-resistant Acinetobacter baumannii in a hollow-fiber infection model

Justin R Lenhard, Nicholas M. Smith, Zackery P. Bulman, Xun Tao, Visanu Thamlikitkul, Beom Soo Shin, Roger L Nation, Jian Li, Jurgen B Bulitta, Brian T Tsuji

Drug Delivery Disposition & Dynamics

Research output: Contribution to journal › Article › Research › peer-review

71 Citations (Scopus)

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.

Original language	English
Article number	e01268
Number of pages	6
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	3
DOIs	https://doi.org/10.1128/AAC.01268-16
Publication status	Published - 1 Mar 2017

Keywords

Acinetobacter
Antibiotic resistance
Antimicrobial combinations
Meropenem
Polymyxins
Sulbactam
Synergism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1128/AAC.01268-16

Cite this

Lenhard, J. R., Smith, N. M., Bulman, Z. P., Tao, X., Thamlikitkul, V., Shin, B. S., Nation, R. L., Li, J., Bulitta, J. B., & Tsuji, B. T. (2017). High-dose ampicillin-sulbactam combinations combat polymyxin-resistant Acinetobacter baumannii in a hollow-fiber infection model. Antimicrobial Agents and Chemotherapy, 61(3), Article e01268. https://doi.org/10.1128/AAC.01268-16

@article{a057c74650874bc295f1d8bd4db2015a,

title = "High-dose ampicillin-sulbactam combinations combat polymyxin-resistant Acinetobacter baumannii in a hollow-fiber infection model",

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",

author = "Lenhard, {Justin R} and Smith, {Nicholas M.} and Bulman, {Zackery P.} and Xun Tao and Visanu Thamlikitkul and Shin, {Beom Soo} and Nation, {Roger L} and Jian Li and Bulitta, {Jurgen B} and Tsuji, {Brian T}",

year = "2017",

month = mar,

day = "1",

doi = "10.1128/AAC.01268-16",

language = "English",

volume = "61",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "3",

}

TY - JOUR

T1 - High-dose ampicillin-sulbactam combinations combat polymyxin-resistant Acinetobacter baumannii in a hollow-fiber infection model

AU - Lenhard, Justin R

AU - Smith, Nicholas M.

AU - Bulman, Zackery P.

AU - Tao, Xun

AU - Thamlikitkul, Visanu

AU - Shin, Beom Soo

AU - Nation, Roger L

AU - Li, Jian

AU - Bulitta, Jurgen B

AU - Tsuji, Brian T

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - Acinetobacter

KW - Antibiotic resistance

KW - Antimicrobial combinations

KW - Meropenem

KW - Polymyxins

KW - Sulbactam

KW - Synergism

UR - http://www.scopus.com/inward/record.url?scp=85014072479&partnerID=8YFLogxK

U2 - 10.1128/AAC.01268-16

DO - 10.1128/AAC.01268-16

M3 - Article

AN - SCOPUS:85014072479

SN - 0066-4804

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 3

M1 - e01268

ER -

High-dose ampicillin-sulbactam combinations combat polymyxin-resistant Acinetobacter baumannii in a hollow-fiber infection model

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Cite this