Ann Lab Med 2018; 38(6): 545-554  https://doi.org/10.3343/alm.2018.38.6.545
Differences in Colistin-resistant Acinetobacter baumannii Clinical Isolates Between Patients With and Without Prior Colistin Treatment
Yu Jin Park, M.D.1, Duck Jin Hong, M.D.2, Eun-Jeong Yoon, Ph.D.3, Dokyun Kim, M.D.3, Min Hyuk Choi, M.D.1, Jun Sung Hong, Ph.D.3,4, Hyukmin Lee, M.D., Ph.D.3, Dongeun Yong, M.D., Ph.D.3, and Seok Hoon Jeong, M.D., Ph.D.3
1Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea; 2Department of Laboratory Medicine, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, UAE; 3Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University, Seoul, Korea; 4Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea
Corresponding author: Seok Hoon Jeong
https://orcid.org/0000-0001-9290-897X
Department of Laboratory Medicine, Research Institute of Bacterial Resistance, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea
Tel: +82-2-2019-3532
Fax: +82-2-2057-8926
E-mail: kscpjsh@yuhs.ac
Received: November 9, 2017; Revised: January 26, 2018; Accepted: June 8, 2018; Published online: November 1, 2018.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: The increasing morbidity and mortality rates associated with Acinetobacter baumannii are due to the emergence of drug resistance and the limited treatment options. We compared characteristics of colistin-resistant Acinetobacter baumannii (CR-AB) clinical isolates recovered from patients with and without prior colistin treatment. We assessed whether prior colistin treatment affects the resistance mechanism of CR-AB isolates, mortality rates, and clinical characteristics. Additionally, a proper method for identifying CR-AB was determined.
Methods: We collected 36 non-duplicate CR-AB clinical isolates resistant to colistin. Antimicrobial susceptibility testing, Sanger sequencing analysis, molecular typing, lipid A structure analysis, and in vitro synergy testing were performed. Eleven colistin-susceptible AB isolates were used as controls.
Results: Despite no differences in clinical characteristics between patients with and without prior colistin treatment, resistance-causing genetic mutations were more frequent in isolates from colistin-treated patients. Distinct mutations were overlooked via the Sanger sequencing method, perhaps because of a masking effect by the colistin-susceptible AB subpopulation of CR-AB isolates lacking genetic mutations. However, modified lipid A analysis revealed colistin resistance peaks, despite the population heterogeneity, and peak levels were significantly different between the groups.
Conclusions: Although prior colistin use did not induce clinical or susceptibility differences, we demonstrated that identification of CR-AB by sequencing is insufficient. We propose that population heterogeneity has a masking effect, especially in colistin non-treated patients; therefore, accurate testing methods reflecting physiological alterations of the bacteria, such as phosphoethanolamine-modified lipid A identification by matrix-assisted laser desorption ionization-time of flight, should be employed.
Keywords: Colistin, Population heterogeneity, Acinetobacter baumannii, Resistance, Lipid A analysis, Pathogenesis



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