Irreproducible and Uninterpretable Polymyxin B MICs for Enterobacter cloacae and Enterobacter aerogenes

Landman, David; Salamera, Julius; Quale, John

doi:10.1128/jcm.02129-13

Cited by 71 publications

(58 citation statements)

References 30 publications

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“…isolates). This observation suggests that the failure of the BD Phoenix system to detect colistin resistance in those isolates could be related to a heteroresistance phenotype (defined by the presence of two subpopulations exhibiting different susceptibilities to colistin) [14]. The skipped wells observed during the MIC determination of those isolates by the BMD method are mainly for dilutions comprised between 0.125 and 4 mg/l.…”

Section: Discussionmentioning

confidence: 97%

Comparison of methods for detection of plasmid-mediated and chromosomally encoded colistin resistance in Enterobacteriaceae

Jayol

Nordmann

Lehours

et al. 2018

Clinical Microbiology and Infection

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Objectives: Because of the emergence of plasmid-mediated (mcr-1 and mcr-2 genes) and chromosomally-encoded colistin resistance, reliable methods for detecting colistin resistance/susceptibility in routine laboratories are required. We evaluated the respective performances of the BD Phoenix automated system, the newly-developed Rapid Polymyxin NP test and the broth microdilution (BMD) reference method to detect colistin resistance in Enterobacteriaceae, and particularly those producing MCR-1 and MCR-2.Methods: Colistin susceptibility of 123 enterobacterial clinical isolates (40 colistinsusceptible and 83 colistin-resistant isolates) was tested with the Phoenix automated system, the Rapid Polymyxin NP test and the BMD method. Molecular mechanisms responsible for plasmid-mediated and chromosomally-encoded colistin resistance mechanisms were investigated by PCR and sequencing.Results: Considering BMD as a reference method, the Phoenix system failed to detect ten colistin-resistant isolates (one Escherichia coli, one Klebsiella pneumoniae, seven Enterobacter spp., and one Salmonella enterica). The Rapid Polymyxin NP test failed to detect the same single E. coli isolate. Those two latter methods detected the sixteen E. coli, K. pneumoniae and S. enterica isolates producing the plasmid-encoded MCR-1 and MCR-2. Conclusion:The Phoenix system and the Rapid Polymyxin NP test are reliable techniques for detecting plasmid-mediated MCR-1 and MCR-2-related colistin resistance. However, a high rate of false susceptibility was observed with the Phoenix system, indicating that susceptibility results obtained with that system should be confirmed by BMD method. By contrast, the Rapid Polymyxin NP test showed a good agreement with the BMD method and results were obtained rapidly (within two hours). The BMD method should be performed if MIC values are needed.

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Section: Discussionmentioning

confidence: 97%

Comparison of methods for detection of plasmid-mediated and chromosomally encoded colistin resistance in Enterobacteriaceae

Jayol

Nordmann

Lehours

et al. 2018

Clinical Microbiology and Infection

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“…This phenomenon might be caused by heteroresistant subpopulations for Enterobacter spp. (69). In parallel, "skip well" isolates of P. aeruginosa have been found to have increased expression of the pmrAB, phoQ, and arn genes related to changes in the LPS structure, reducing the potential binding sites of polymyxins (74).…”

Section: Dilution Methodsmentioning

confidence: 95%

“…However, studies including larger numbers of resistant isolates reported high rates of false susceptibility (up to 32%) for Gram-negative rods compared to those with dilution methods (69,70,78,83). The Etest method may fail to detect resistance to colistin even when isolates exhibit high MICs by dilution methods (70,83).…”

Section: Nonautomatic Systems (I) Dd Test (Kirby-bauer Procedure)mentioning

confidence: 99%

“…Polymyxin susceptibility testing is now a major challenge, as human infections with colistin-resistant Gram-negative bacteria are associated with higher patient mortality (68). The difficulties in testing susceptibility to polymyxins are diverse, including poor diffusion of polymyxins into agar, the inherent cationic properties of polymyxins, the occurrence of heteroresistance to polymyxins in many species, and the lack of a reliable reference method that may allow reliable comparisons of commercial tests (69,70).…”

Section: Methods For Susceptibility Testingmentioning

confidence: 99%

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Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

2017

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SUMMARY Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.

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“…Poor reliability and repeatability of colistin susceptibility testing for Enterobacter cloacae and Enterobacter aerogenes were first reported in 2013 (24). For some isolates, a higher number of heteroresistant colonies was detectable when the isolate was cultured in relatively higher polymyxin B concentrations.…”

Section: Discussionmentioning

confidence: 99%

Colistin and Polymyxin B Susceptibility Testing for Carbapenem-Resistant and mcr -Positive Enterobacteriaceae: Comparison of Sensititre, MicroScan, Vitek 2, and Etest with Broth Microdilution

et al. 2017

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Colistin and polymyxin B remain part of the last line of antibiotics for multidrug-resistant Gram-negative bacteria, such as carbapenem-resistant Enterobacteriaceae. Current joint EUCAST-CLSI recommendations are for broth microdilution (BMD) to be performed for MIC testing of colistin. Commercial susceptibility testing methods were evaluated and compared against the reference BMD, using a susceptibility breakpoint of Յ2 mg/liter for both colistin and polymyxin B. Seventy-six Enterobacteriaceae were included, of which 21 were mcr-1 positive (18 Escherichia coli isolates, 2 Klebsiella pneumoniae isolates, and 1 Enterobacter aerogenes isolate). Rates of essential agreement (EA) of colistin test results between BMD and Vitek 2, Sensititre, and Etest were 93.4%, 89.5%, and 75.0%, respectively. Rates of EA of polymyxin B test results between BMD and Vitek 2, Sensititre, and Etest were 96.1%, 96.1%, and 48.7%, respectively. A positive MIC correlation with a categorical agreement of Ͼ90% was achieved for Sensititre (colistin Spearman's ϭ 0.863, and polymyxin B Spearman's ϭ 0.877) and Vitek 2 (polymyxin B [only] Spearman's ϭ 0.8917). Although a positive MIC correlation (Spearman's ϭ 0.873) with the reference method was achieved for colistin testing with Vitek 2, categorical agreement was Ͻ90%, with very major error rates of 36%. Correlation with the Etest MIC was lower, with very major error rates of 12% (colistin) and 26.1% (polymyxin B). MicroScan (colistin) categorical agreement was 88.2%, with a very major error rate of 4%. Colistin MICs for 15 of the 21 mcr-1-positive isolates were Ͼ2 mg/liter, and polymyxin MICs for 17 of them were Ͼ2 mg/liter by broth microdilution. The use of a lower breakpoint of Յ1 mg/liter further improves detection of mcr-1 for all testing methods. However, further data on the correlation between MICs and clinical outcome are required to determine the most suitable breakpoint to guide clinical management.KEYWORDS colistin, polymyxin B, susceptibility testing, mcr-1 M ultidrug-resistant organisms (MDROs) represent a progressive burden on health care systems globally. Carbapenem-resistant Enterobacteriaceae (CRE) are now reported worldwide. CRE infections are difficult to treat, and there are limited options available. The polymyxins (colistin and polymyxin B) are antibiotics which are used for treating infections with CRE. Polymyxins initially fell out of favor among clinicians due to concerns over high rates of nephrotoxicity and neurotoxicity (1). In recent years, the use of polymyxins has been on the rise, with increasing rates of CRE infection.

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Irreproducible and Uninterpretable Polymyxin B MICs for Enterobacter cloacae and Enterobacter aerogenes

Cited by 71 publications

References 30 publications

Comparison of methods for detection of plasmid-mediated and chromosomally encoded colistin resistance in Enterobacteriaceae

Comparison of methods for detection of plasmid-mediated and chromosomally encoded colistin resistance in Enterobacteriaceae

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

Colistin and Polymyxin B Susceptibility Testing for Carbapenem-Resistant and mcr -Positive Enterobacteriaceae: Comparison of Sensititre, MicroScan, Vitek 2, and Etest with Broth Microdilution

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