Colistin and anti-Gram-positive bacterial agents against <i>Acinetobacter baumannii</i>

Liu, Bin; Liu, Youning; Di, Xiuzhen; Zhang, Xin; Wang, Rui; Bai, Yan; Wang, Jin

doi:10.1590/0037-8682-0081-2014

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Major Articles • Rev. Soc. Bras. Med. Trop. 47 (4) • Jul-Aug 2014 • https://doi.org/10.1590/0037-8682-0081-2014 copy

Colistin and anti-Gram-positive bacterial agents against Acinetobacter baumannii

Authorship SCIMAGO INSTITUTIONS RANKINGS

Introduction

Acinetobacter baumannii has attained an alarming level of resistance to antibacterial drugs. Clinicians are now considering the use of older agents or unorthodox combinations of licensed drugs against multidrug-resistant strains to bridge the current treatment gap. We investigated the in vitro activities of combination treatments that included colistin with vancomycin, norvancomycin or linezolid against multidrug-resistant Acinetobacter baumannii.

Methods

The fractional inhibitory concentration index and time-kill assays were used to explore the combined effects of colistin with vancomycin, norvancomycin or linezolid against 40 clinical isolates of multidrug-resistant Acinetobacter baumannii. Transmission electron microscopy was performed to evaluate the interactions in response to the combination of colistin and vancomycin.

Results

The minimum inhibitory concentrations (MICs) of vancomycin and norvancomycin for half of the isolates decreased below the susceptibility break point, and the MIC of linezolid for one isolate was decreased to the blood and epithelial lining fluid concentration using the current dosing regimen. When vancomycin or norvancomycin was combined with subinhibitory doses of colistin, the multidrug-resistant Acinetobacter baumannii test samples were eradicated. Transmission electron microscopy revealed that subinhibitory doses of colistin were able to disrupt the outer membrane, facilitating a disruption of the cell wall and leading to cell lysis.

Conclusions

Subinhibitory doses of colistin significantly enhanced the antibacterial activity of vancomycin, norvancomycin, and linezolid against multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii ; Colistin; Combination; Linezolid; Multidrug-resistant; Vancomycin

Antimicrobial agent	MIC₅₀^§ § MIC50: minimum inhibitory concentrations for 50% of the organisms;	MIC₉₀^¶ ¶ MIC90: minimum inhibitory concentrations for 90% of the organisms.	% R^ %R: percent resistant.
Colistin^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	0.25	0.5	0.0
Amikacin^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	64	> 256	100.0
Ceftazidime^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	128	> 256	95.0
Cefepime^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	64	> 256	97.5
Levofloxacin^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	64	> 256	100.0
Rifampicin^† † breakpoint not available (N/A);	4	16	N/A
Gentamicin^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	256	> 256	100.0
Piperacillin/tazobactam^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	256/4	> 256/4	92.5
Tigecycline^‡ ‡ United States of America-Food and Drug Administration (USA-FDA) breakpoints were applied when available (Tygacil® package insert, 2012); Tigecycline: susceptible ≤ 2 µg/ml, resistant ≥ 8µg/ml;	1	2	0.0
Imipenem^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	64	128	100.0
Meropenem^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	32	256	100.0
Minocycline^* * According to criteria published by the Clinical and Laboratory Standards Institute (CLSI) in 2013;	4	16	72.4
Sulbactam^† † breakpoint not available (N/A);	16	32	N/A

Agent	Alone				Combination
Agent	MIC range	MIC₅₀^* CT: colistin; VA: vancomycin; NVA: norvancomycin; LZD: linezolid;	MIC₉₀^† * MIC50: minimum inhibitory concentrations for 50% of the organisms;	%S^‡ † MIC90: minimum inhibitory concentrations for 90% of the organisms;	MIC range	MIC₅₀^* CT: colistin; VA: vancomycin; NVA: norvancomycin; LZD: linezolid;	MIC₉₀^† * MIC50: minimum inhibitory concentrations for 50% of the organisms;	%S^‡ † MIC90: minimum inhibitory concentrations for 90% of the organisms;
CT	0.125–0.5	0.25	0.5	100.0	0.0625–0.25	0.125	0.25	100.0
VA	> 256	> 256	> 256	0.0	1–32	2	32	52.5
NVA	> 256	> 256	> 256	0.0	1–32	4	32	42.5
LZD	> 256	> 256	> 256	0.0	8–64	32	64	0.0

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[1] Address: Dr. Youning Liu. Dept. of Respiratory Diseases/Chinese PLA General Hospital. 28 Fuxing Rd., 100853 Beijing, China. Phone: 86 10 6693-7908; Fax:86 10 6693-7166. e-mail:iamicehe@163.com