|Year : 2018 | Volume
| Issue : 4 | Page : 587-589
Deciphering polymyxin B minimum inhibitory concentration from colistin minimum inhibitory concentration and vice versa: An analysis on 156 carbapenem-resistant Enterobacteriaceae isolates
Bijayini Behera, Jayanti Jena, Punyatoya Kar, Srujana Mohanty, Ashoka Mahapatra
Department of Microbiology, AIIMS, Bhubaneswar, Odisha, India
|Date of Web Publication||18-Mar-2019|
Dr. Bijayini Behera
Associate Professor, Department of Microbiology, AIIMS, Bhubaneswar - 751 019, Odisha
Source of Support: None, Conflict of Interest: None
The susceptibility determination to polymyxins (colistin and polymyxin B) remains a challenge for clinical microbiology laboratories. We evaluated the minimum inhibitory concentration (MIC) of both antimicrobials by the broth microdilution method in a selected subset of 156 carbapenem-resistant Enterobacteriaceae (CRE) isolates. Good concordance between polymyxin B and colistin MIC values was obtained, and there was 98% categorical agreement in CRE isolates. Future large-scale multicentre study is needed to draw conclusion if the MIC of colistin can be used to extrapolate the MIC of polymyxin B and vice versa.
Keywords: Broth microdilution method, carbapenem-resistant Enterobacteriaceae, Colistin, Minimum inhibitory concentration, polymyxin B
|How to cite this article:|
Behera B, Jena J, Kar P, Mohanty S, Mahapatra A. Deciphering polymyxin B minimum inhibitory concentration from colistin minimum inhibitory concentration and vice versa: An analysis on 156 carbapenem-resistant Enterobacteriaceae isolates. Indian J Med Microbiol 2018;36:587-9
|How to cite this URL:|
Behera B, Jena J, Kar P, Mohanty S, Mahapatra A. Deciphering polymyxin B minimum inhibitory concentration from colistin minimum inhibitory concentration and vice versa: An analysis on 156 carbapenem-resistant Enterobacteriaceae isolates. Indian J Med Microbiol [serial online] 2018 [cited 2019 Sep 16];36:587-9. Available from: http://www.ijmm.org/text.asp?2018/36/4/587/254392
| ~ Introduction|| |
The rising clinical usage of polymyxins (polymyxin B and colistin) in the era of multidrug-resistant and extensively drug-resistant (MDR and XDR) Gram-negative pathogens demands an accurate and timely determination of in vitro susceptibility testing. Polymyxin B and colistin belong to the same antimicrobial class and share the same spectrum of activity, still they have been compared to chalk and cheese rather than peas in a pod due to their differences in pharmacokinetics and pharmacodynamics. The susceptibility testing for both these drugs remains a challenge for clinical laboratories due to difficulties in the performance, reproducibility and accuracy of available methods., Disc diffusion, E test and commercial methods such as Vitek 2 are not reliable in determining polymyxin susceptibility, and broth microdilution (BMD) is endorsed by the Clinical and Laboratory Standards Institute (CLSI) as well as the European Committee on Antimicrobial Susceptibility Testing (EUCAST) as the reference method to determine the polymyxin minimum inhibitory concentrations (MICs). There is limited literature on head-to-head comparison between MIC values of polymyxin B and colistin in carbapenem-resistant Enterobacteriaceae (CRE) isolates. The present study was undertaken to evaluate the MIC of polymyxin B and colistin in a selected subset of CRE isolates obtained from ICU and general ward settings of a tertiary care teaching and referral hospital and to evaluate if the MIC of one antimicrobial can be used to extrapolate the MIC of other.
| ~ Materials and Methods|| |
A total of 156 nonduplicate CRE isolates recovered from various clinical samples such as urine, endotracheal secretion, bronchoalveolar lavage (BAL), pus and blood during 2017–2018 were included in this study. This included Escherichia More Details coli (n = 99), Klebsiella pneumoniae (n = 55) and Enterobacter spp. (n = 2). The sample-wise distribution of CRE isolates is given in [Table 1].
|Table 1: Sample-wise distribution of carbapenem-resistant Enterobacteriaceae isolates|
Click here to view
Pure substance of colistin sulphate and polymyxin B sulphate 1MU was obtained from commercial sources (catalogue number C4461, P1004, Sigma Aldrich Corporation, St. Louis, MO. USA). MICs of colistin and polymyxin B against CRE isolates were determined using the BMD method according to the CLSI guidelines. Drug concentrations ranging from 0.25 μg/ml to 32 μg/ml were tested. E. coli ATCC 25922 (MIC of 0.25–2 μg/mL), Pseudomonas aeruginosa ATCC 27853 (MIC of 0.5–4 μg/mL) and intrinsically polymyxin-resistant Proteus mirabilis and Serratia marcescens were taken as negative and positive internal controls, respectively. Interpretative breakpoints for colistin susceptibility are currently available from the EUCAST. CLSI currently does not have colistin or polymyxin B breakpoints for Enterobacteriaceae but have published colistin epidemiological cutoff values for E. coli, K. pneumoniae, Raoultella ornithinolytica, Enterobacter aerogenes and Enterobacter cloacae. The CLSI recommendation does not provide susceptible, intermediate or resistant interpretation but classifies isolates as either wild type or non-wild type (wild type ≤2 μg/mL and non-wild type ≥4 μg/mL).
| ~ Results|| |
As per EUCAST established breakpoints (susceptible/resistant) of colistin for Enterobacteriaceae (≤2/>2 μg/mL), (95/99) 95.9% and (97/99) 97.9% of E. coli were susceptible to colistin and polymyxin B, respectively. The corresponding percentages for K. pneumoniae were (51/55) 92.7% and (49/55) 89%, respectively. As per CLSI MIC-based classification of wild type or non-wild type, (96/99) 96.9% and (98/99) 98.9% of E. coli were susceptible to colistin and polymyxin B, respectively. The corresponding percentages for K. pneumoniae for wild type and non-wild type were (51/55) 92.7% and (49/55) 89%, respectively, the results being similar to EUCAST. As per the EUCAST and CLSI criteria, there were categorical agreements in (97/99) 97.9% and (54/55) 98.1% of E. coli and K. pneumoniae isolates, respectively.
Of the 99 isolates of E. coli, 72 isolates had exactly the same polymyxin B and colistin MIC. Of the rest 27 E. coli isolates, 5 isolates had higher colistin MIC (3 isolated more than 2 fold dilutions and 2 isolates more than 1 fold dilution) and 22 isolates had higher polymyxin B MIC. Of the 55 isolates of K. pneumoniae, 28 isolates had exactly the same polymyxin B and colistin MIC. Of the rest 27 K. pneumoniae isolates, 4 isolates had higher colistin MIC and 23 isolates had higher polymyxin B MIC. The MIC variation and corresponding MIC values of polymyxin B and colistin is detailed in [Table 2] and [Table 3].
|Table 2: Differences in minimum inhibitory concentration values between polymyxin B and colistin among carbapenem-resistant Enterobacteriaceae isolates (n=156)|
Click here to view
|Table 3: Number of carbapenem-resistant Enterobacteriaceae isolates (n=156) with corresponding polymyxin B and colistin minimum inhibitory concentration values|
Click here to view
| ~ Discussion|| |
Our study has shown good concordance between polymyxin B and colistin MIC values and 98% categorical agreement in CRE isolates. Two isolates of E. coli were polymyxin sensitive (MIC 1 μg/ml) but resistant to colistin (MIC 4 μg/ml) and 1 isolate of K. pneumoniae was colistin sensitive but resistant to polymyxin B. Colistin displayed higher potency compared to polymyxin B in both E. coli and K. pneumoniae despite more clinical usage of colistin in clinical settings. Several previous studies have addressed the MIC discrepancies between these two antimicrobials, mostly in non-fermentative Gram-negative bacilli and have found polymyxin B to be more potent than colistin.,,, In one study by Carrilho et al. which evaluated colistin MIC in 27 carbapenem- and polymyxin B-resistant isolates, 11 (41%) isolates were susceptible to colistin (P < 0.001). Polymyxin B MIC ranged from 4 ug/mL to 64 ug/mL and colistin MIC ranged from 0.5 ug/mL to 64 ug/Ml. In another large-scale study by Gales et al. involving 6311 E. coli and 4177 Klebsiella spp, 55.0 and 53.2% of strains, respectively, displayed a colistin MIC twofold lower than polymyxin B in susceptible isolates, but polymyxin B was slightly more potent than colistin against strains with decreased susceptibility to either polymyxin.
| ~ Conclusion|| |
Our study has shown good categorical agreement between the two antimicrobials and justifies the MIC determination of either polymyxin B or colistin and extrapolating the MIC of the other for determining susceptibility. However, as the present study is a single-centre in vitro study with a small number of isolates, large multicentre study is needed to draw conclusion if the MIC of colistin can be used to extrapolate the MIC of polymyxin B and vice versa.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Bakthavatchalam YD, Pragasam AK, Biswas I, Veeraraghavan B. Polymyxin susceptibility testing, interpretative breakpoints and resistance mechanisms: An update. J Glob Antimicrob Resist 2018;12:124-36.
Nation RL, Velkov T, Li J. Colistin and polymyxin B: Peas in a pod, or chalk and cheese? Clin Infect Dis 2014;59:88-94.
Bakthavatchalam YD, Veeraraghavan B. Challenges, issues and warnings from CLSI and EUCAST Working Group on Polymyxin Susceptibility Testing. J Clin Diagn Res 2017;11:DL03-4.
Clinical and Laboratory Standards Institute. Methods for Dilution of Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard. 11th
ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
European Committee on Antimicrobial Susceptibility Testing. Clinical Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 8.1. European Committee on Antimicrobial Susceptibility Testing; 2018.
Clinical and Laboratory Standards Institute. Performance Standard for Antimicrobial Susceptibility Testing. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
Tam VH, Chang KT, Abdelraouf K, Brioso CG, Ameka M, McCaskey LA, et al.
Prevalence, resistance mechanisms, and susceptibility of multidrug-resistant bloodstream isolates of Pseudomonas aeruginosa
. Antimicrob Agents Chemother 2010;54:1160-4.
Hawley JS, Murray CK, Griffith ME, McElmeel ML, Fulcher LC, Hospenthal DR, et al.
Susceptibility of Acinetobacter
strains isolated from deployed U.S. Military personnel. Antimicrob Agents Chemother 2007;51:376-8.
Ko KS, Suh JY, Kwon KT, Jung SI, Park KH, Kang CI, et al.
High rates of resistance to colistin and polymyxin B in subgroups of Acinetobacter baumannii
isolates from Korea. J Antimicrob Chemother 2007;60:1163-7.
Gales AC, Jones RN, Sader HS. Contemporary activity of colistin and polymyxin B against a worldwide collection of gram-negative pathogens: Results from the SENTRY antimicrobial surveillance program (2006-09). J Antimicrob Chemother 2011;66:2070-4.
Carrilho CM, Prina DM, Grion CM, Cardoso LT, Oliviera LM, Santos LC, et al
. MIC Difference Between Colistin and Polymyxin B: Are These Drugs Interchangeable in the Treatment of Carbapenem Resistant Enterobacteriacea
Infections. Presented at ESCMID Conference on Testing MD Gram negatives; Copenhagen, Denmark; 2015.
[Table 1], [Table 2], [Table 3]