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CORRESPONDENCE
Year : 2016  |  Volume : 34  |  Issue : 4  |  Page : 558-560
 

In vitro susceptibility of carbapenem-resistant Enterobacteriaceae to colistin: A hope at present


Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India

Date of Submission30-Sep-2016
Date of Acceptance25-Oct-2016
Date of Web Publication8-Dec-2016

Correspondence Address:
S Mohanty
Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.195381

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How to cite this article:
Mohanty S, Gaind R. In vitro susceptibility of carbapenem-resistant Enterobacteriaceae to colistin: A hope at present. Indian J Med Microbiol 2016;34:558-60

How to cite this URL:
Mohanty S, Gaind R. In vitro susceptibility of carbapenem-resistant Enterobacteriaceae to colistin: A hope at present. Indian J Med Microbiol [serial online] 2016 [cited 2017 May 24];34:558-60. Available from: http://www.ijmm.org/text.asp?2016/34/4/558/195381


Dear Editor,

The emergence of carbapenem-resistant Enterobacteriaceae (CRE), a rapidly evolving global public health dilemma, has necessitated the use of older classes of antimicrobial agents, such as colistin. In addition to an extremely rapid bactericidal activity, colistin also possesses a significant post-antibiotic effect against multidrug-resistant Gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae.[1] A previous study in our institute on P. aeruginosa and Acinetobacter spp. isolates had demonstrated 8.4% and 6.0% resistance, respectively.[2] This study was conducted to evaluate the in vitro activity of colistin against CRE, including the carbapenemase-producing as well as the non-carbapenemase-producing CRE.

The study, approved by the Institutional Ethical Committee, was conducted at the Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, a 1531-bedded Tertiary Care, Teaching and Referral Hospital in North India over a 3-year period from January 2011 to December 2013. Consecutive, non-repetitive carbapenem-resistant isolates of Escherichia coli and K. pneumoniae isolated from patients with clinically diagnosed bloodstream infections were included in the study. The resistance to carbapenems was detected by the disk-diffusion method and minimum inhibitory concentration (MIC) assays using ertapenem, meropenem and imipenem disks (HiMedia, Mumbai, Maharashtra, India) and Etests (bioMérieux, Marcy l'Etoile, France), respectively, and interpreted as per the CLSI 2012 recommendations.[3] The presence of carbapenemase genes (NDM-1, KPC, IMP, VIM, OXA-48 and OXA-181) was detected using previously published primers and standardised protocol with single polymerase chain reaction for each gene.[4],[5],[6],[7] The in vitro activity of colistin against these CRE isolates was determined by Etests (bioMérieux, Marcy l'Etoile, France) according to the manufacturer's guidelines. The MICs were interpreted following the European Committee on Antimicrobial Susceptibility Testing Criteria (≤2 and ≥4 µg/ml for susceptible and resistant, respectively).[8]

A total of 93 (24.03%) isolates were found to be CRE (59 K. pneumoniae, 34 E. coli) during the study period. Of these, 71 (76.3%) isolates comprising 45 K. pneumoniae and 26 E. coli were positive for at least one tested carbapenemase gene. These included NDM-1 in 61 (65.6%; 39 K. pneumoniae, 22 E. coli), OXA-48 in 23 (24.7%, 13 K. pneumoniae, 10 E. coli), OXA-181 in 22 (23.6%; 18 K. pneumoniae, 4 E. coli), VIM in 6 (6.4%; 4 K. pneumoniae, 2 E. coli) and KPC in 2 (2.1%; K. pneumoniae) isolates. [Table 1] shows the MICs of carbapenems and colistin in the CRE isolates, distributed into two groups as carbapenemase-producing and non-carbapenemase-producing CRE. All the CRE isolates were susceptible to colistin, with a similar profile of MIC range, MIC50 and MIC90 in both the groups. [Table 2] shows the distribution of colistin MIC among the CRE isolates. Maximum isolates (27.9%) demonstrated a colistin MIC of 0.38 µg/ml, followed by 0.094 µg/ml and 1.0 µg/ml (20.4%) each. These MIC values are well below the susceptible breakpoint of ≤2 µg/ml, indicating excellent in vitro activity of colistin against CRE isolates in India.
Table 1: Carbapenem and colistin minimum inhibitory concentrations in carbapenem-resistant Enterobacteriaceae

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Table 2: Distribution of colistin minimum inhibitory concentrations in carbapenem-resistant Enterobacteriaceae

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Similar to our study, a recent Global Surveillance Program study demonstrated a low prevalence of colistin resistance overall among Enterobacteriaceae; however, susceptibility rates varied between the carbapenemase-producing and non-carbapenemase-producing isolates and even among the types of carbapenemase producers.[9] The rate of colistin susceptibility was 98.4% overall, but it was reduced to 88.0% among 482 carbapenemase-positive isolates. Colistin susceptibility was higher among MBL-positive isolates (92.6%) than those positive for a KPC (87.9%) or OXA-48 (84.2%).[9] In China, the susceptibility rate for colistin was 92.7% among 82 CRE isolates.[10] However, 4 isolates (3 KPC-2 positive) showed high resistance to colistin, with MICs of >64 µg/ml for 3 isolates and 4 µg/ml for 1 isolate.[10] A previous Indian study on 44 NDM-1 positive Enterobacteriaceae isolates demonstrated 100% in vitro susceptibility to colistin.[11]

In conclusion, colistin has promised in vitro activity against CRE at present. However, recent reports of colistin resistance among CRE necessitate the use of colistin with extreme caution and care. Furthermore, the usefulness of combination therapy with other antimicrobials such as carbapenem or rifampicin in critically ill patients with multidrug-resistant Gram-negative infections should be kept in mind.

Financial support and sponsorship

We acknowledge the financial assistance received from the Indian Council of Medical Research, Government of India, for this work through an extramural research grant No. 5/3/10/2010-ECD-1.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Michalopoulos AS, Falagas ME. Colistin: Recent data on pharmacodynamics properties and clinical efficacy in critically ill patients. Ann Intensive Care 2011;1:30.  Back to cited text no. 1
    
2.
Mohanty S, Maurya V, Gaind R, Deb M. Phenotypic characterization and colistin susceptibilities of carbapenem-resistant of Pseudomonas aeruginosa and Acinetobacter spp. J Infect Dev Ctries 2013;7:880-7.  Back to cited text no. 2
    
3.
CLSI Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; 22nd Informational Supplement. CLSI Document M100-S22. Wyne, PA: Clinical and Laboratory Standards Institute; 2012.  Back to cited text no. 3
    
4.
Kothari C, Gaind R, Singh LC, Sinha A, Kumari V, Arya S, et al. Community acquisition of ß-lactamase producing Enterobacteriaceae in neonatal gut. BMC Microbiol 2013;13:136.  Back to cited text no. 4
    
5.
Siu LK, Huang DB, Chiang T. Plasmid transferability of KPC into a virulent K2 serotype Klebsiella pneumoniae. BMC Infect Dis 2014;14:176.  Back to cited text no. 5
    
6.
Miriagou V, Tzelepi E, Gianneli D, Tzouvelekis LS. Escherichia coli with a self-transferable, multiresistant plasmid coding for metallo-beta-lactamase VIM-1. Antimicrob Agents Chemother 2003;47:395-7.  Back to cited text no. 6
    
7.
Shanthi M, Sekar U, K A, Bramhne HG. OXA-181 beta lactamase is not a major mediator of carbapenem resistance in Enterobacteriaceae. J Clin Diagn Res 2013;7:1986-8.  Back to cited text no. 7
    
8.
European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters, Version 1.3. Växjö, Sweden: European Committee on Antimicrobial Susceptibility Testing; 2011.  Back to cited text no. 8
    
9.
Bradford PA, Kazmierczak KM, Biedenbach DJ, Wise MG, Hackel M, Sahm DF. Correlation of β-lactamase production and colistin resistance among Enterobacteriaceae isolates from a Global Surveillance Program. Antimicrob Agents Chemother 2015;60:1385-92.  Back to cited text no. 9
    
10.
Chen S, Hu F, Zhang X, Xu X, Liu Y, Zhu D, et al. Independent emergence of colistin-resistant Enterobacteriaceae clinical isolates without colistin treatment. J Clin Microbiol 2011;49:4022-3.  Back to cited text no. 10
    
11.
Chandran SP, Nagaraj S, Kalal BS, Muralidharan S, Macaden R. In-vitro susceptibility to colistin and tigecycline in New Delhi metallo-beta-lactamase-1 producing Enterobacteriaceae. Indian J Med Microbiol 2013;31:419-20.  Back to cited text no. 11
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