Colistin-heteroresistance in carbapenemase-producing Enterobacter species causing hospital-acquired infections among Egyptian patients

Mashaly, Ghada El-Saeed; Mashaly, Mervat

doi:10.1016/j.jgar.2020.11.019

Cited by 11 publications

(10 citation statements)

References 33 publications

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“…Patidar et al observed, 47% of Enterobacter were carbapenem-resistant in a study in India which is in accordance with our findings (24). Although our finding is lower than a study by Mashaly who reported carbapenem-resistance among Egyptian patients was 53% (25). This prevalence is also consistent with recent reports of surveillance studies of carbapenem resistance among patients with HAI caused by Gram-negative bacteria in Egypt (54.1%) (26) and in India (53.84%) (27).…”

Section: Discussionsupporting

confidence: 92%

Prevalence and Phenotypic Detection of Carbapenem-Resistant Enterobacter Species from the Clinical Specimens of a Tertiary Care Hospital in Bangladesh

Munny¹,

Shamsuzzaman

Hossain

et al. 2023

Update Dent. Coll. j

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Background: Carbapenem-resistant Enterobacter (CRE) is an emerging threat spread rapidly around the world in the past few years, posing substantial hazards to human health. Objective: The study was conducted to evaluate the prevalence of carbapenem resistance and to detect carbapenemase producers phenotypically from patients of a major tertiary care hospital, in Bangladesh. Methods: Prospective cross-sectional study was conducted from July 2018 to June 2019, at the Dhaka Medical College hospital. Patients admitted to different wards, and intensive care units, visited the outpatient department, and samples received in the microbiology department were included in this study. A total of 350 clinical samples were collected, inoculated, and incubated in accordance to the standard protocol. Identification was done using the standard biochemical method. Antimicrobial susceptibility testing of commonly used antibiotics including imipenem was done using Kirby Bauer disk diffusion method. All the clinical isolates of Enterobacter were screened for carbapenem resistance as per CLSI guidelines. Such strains were then subjected to phenotypic confirmation of carbapenemase production by the Modified Hodge test. All isolates that gave a positive screening test were further evaluated for Metallo-β lactamase (MBL) production. MBL was further detected by Combined Disc Test (CD) using a combination of Imipenem and Imipenem-EDTA and double disc synergy (DDS) test. Result: A total of 350 clinical specimens were analyzed, of which 224 (65.14%) isolates yielded growth. Among them, 28 (12.28%) Enterobacter were isolated of which 12 (42.86%) were found to be Imipenem resistant (14.25%) and were labeled 'Carbapenem-resistant Enterobacter" or CRE. Minimum inhibitory concentration (MIC) was determined among the carbapenem-resistant clinical isolates. Modified Hodge test (MHT) performed on the 12 carbapenem-resistant isolates showed 9 (75%) isolates to be carbapenemase enzyme producers. Nine out of twelve carbapenem-resistant isolates are Metallo-beta-lactamase producers detected by combined disc test (CDT) and eight (66.67%) MBL producers detected by DDS test. Conclusion: The finding from this study revealed a high prevalence of carbapenem resistance among isolated Enterobacter species in hospital settings as well as community levels. As there are limited treatment regimens, therefore, the timely and accurate detection of carbapenem-resistant Enterobacter species is essential for the clinical treatment and prevention of infections. Simple phenotypic methods like MHT can be used for the rapid detection of carbapenemases, and these are expected to be used routinely in clinical microbiology laboratories. Update Dent. Coll. j: 2023; 13(1): 17-22

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Section: Discussionsupporting

confidence: 92%

Prevalence and Phenotypic Detection of Carbapenem-Resistant Enterobacter Species from the Clinical Specimens of a Tertiary Care Hospital in Bangladesh

Munny¹,

Shamsuzzaman

Hossain

et al. 2023

Update Dent. Coll. j

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“…From the starting population, 105/115 (93.9 %) were susceptible to colistin with MICs ranging from 0.125 to 2 mg l −1 . Population analysis revealed that 14.8 % of isolates developed heteroresistance with MICs ranging from 0.25 to 2 mg l −1 although colonies from heteroresistance subpopulations were able to grow even in higher colistin concentrations (16 mg l −1 ) [23]. Based on our findings and the above studies, heteroresistance should be taken into account before administration of colistin.…”

Section: Discussionsupporting

confidence: 60%

Pharmacodynamics of colistin resistance in carbapenemase-producing Klebsiella pneumoniae: the double-edged sword of heteroresistance and adaptive resistance

Meletiadis

Paranos

Tsala

et al. 2022

Journal of Medical Microbiology

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Introduction. The presence of heteroresistant subpopulations and the development of resistance during drug exposure (adaptive resistance) limits colistin’s efficacy against carbapenemase-producing Klebsiella pneumoniae (CP-Kp) isolates. Hypothesis/Gap statement. The pharmacokinetic/pharmacodynamic (PK/PD) characteristics of both types of colistin resistance against CP-Kp are unknown. Aim. We therefore studied the PK/PD characteristics of colistin resistance in an in vitro PK/PD model simulating clinical colistin exposures. Methods. Two K. pneumoniae clinical isolates, one non-CP-Kp and one CP-Kp, with colistin MICs of 0.5–1 mg l−1 at a final inoculum of 107 c.f.u. ml−1 were used in an in vitro PK/PD dialysis/diffusion closed model simulating 4.5 MU q12h and 3 MU q8h clinical dosing regimens. Heteroresistant (HRS, bacteria with stable high-level resistance present before drug exposure) and adaptive resistant (ARS, bacteria with reversible low-level resistance emerging after drug exposure) subpopulations were measured and optimal PK/PD targets for reducing both ARS and HRS were determined. Cumulative fractional response (CFR) was calculated with Monte Carlo simulation for 9 MU q24h, 4.5 MU q12h and 3 MU q8h clinical dosing regimens. Results. A 2–5 log10c.f.u. ml–1 decrease of the total bacterial population was observed within the first 2 h of exposure, followed by regrowth at 12 h. Colistin exposure was positively and negatively correlated with HRS and ARS 24–0 h c.f.u. ml–1 changes, respectively. An optimal PK/PD (~0.5log10 increase) target of 35 fAUC/MIC (the ratio of the area under the unbound concentration–time curve to the MIC) was found for reducing both HRS and ARS of high-level resistance (MIC >16 mg l−1). The 4.5 MU q12h regimen had slightly higher CFR (74 %) compared to the other dosing regimens. Conclusions. High colistin exposures reduced high-level adaptive resistance at the expense of selection of heteroresistant subpopulations.

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“… 23 Also, the well‐known heteroresistance phenomenon, mainly described in Enterobacter spp., could be presented in these isolates making it difficult to confront MICs interpretations because it likes to produce different MICs results. 24 , 25 This phenomenon has been well described in Enterobacte r spp. ; however, we observed it in K. pneumoniae , similar to those described by Fóldes et al 26 Additionally, the possibility of some technical mistakes associated with pipetting cannot be excluded, due to the fact that our study was performed under a routinary laboratory workflow.…”

Section: Discussionmentioning

confidence: 83%

“…Errors in MIC values of 2 μg/ml were not observed, but only 17 isolates were included 23 . Also, the well‐known heteroresistance phenomenon, mainly described in Enterobacter spp., could be presented in these isolates making it difficult to confront MICs interpretations because it likes to produce different MICs results 24,25 . This phenomenon has been well described in Enterobacte r spp.…”

Section: Discussionmentioning

confidence: 93%

Colistin resistance screening by 3 μg/ml colistin agar in Carbapenemase‐producing Enterobacterales

Soria-Segarra

Soria‐Segarra

Andrade‐Soriano³

et al. 2022

Clinical Laboratory Analysis

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Background In low‐ and middle‐income countries, the use of colistin in therapeutic regimens is common, to treat infections produced for Carbapenemase‐producing Enterobacterales (CPE) due to limited access to the recently discovered‐approved antibiotics. Furthermore, the technical limitations to perform colistin susceptibility tests make it difficult to assess the suitability of this treatment for each patient, as well as to monitor the rates of resistance. In the present study, we describe the use of agar dilution using a unique colistin concentration of 3 μg/ml to discriminate isolates with colistin resistance in CPE obtained from clinical samples. Methods Clinical Laboratory Standards Institute (CLSI) colistin broth microdilution method and dilution agar with a colistin concentration of 3 μg/ml were performed in 168 isolates of CPE obtained from clinical samples in Guayaquil, Ecuador. Broth microdilution was considered our gold standard using CLSI breakpoints as reference (≤2 μg/ml intermediate and ≥4 μg/ml resistant). Categorical agreement was defined as obtaining a reading within the same category with both methodologies. Results Isolates obtained from respiratory samples were the most prevalent (26.19%; n = 44). Klebsiella pneumoniae was the predominant specie (94.04%; n = 158). KPC‐like carbapenemase was present in all the isolates, and interestingly, colistin resistance was not mediated by MCR‐1 production. Categorical agreement between both methods resulted in 97.02%. Conclusion We propose the use of dilution agar with a colistin concentration of 3 μg/ml, as a valid method for screening colistin resistance in low‐ and middle‐income countries to monitor resistance and to perform epidemiological studies.

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Colistin-heteroresistance in carbapenemase-producing Enterobacter species causing hospital-acquired infections among Egyptian patients

Cited by 11 publications

References 33 publications

Prevalence and Phenotypic Detection of Carbapenem-Resistant Enterobacter Species from the Clinical Specimens of a Tertiary Care Hospital in Bangladesh

Prevalence and Phenotypic Detection of Carbapenem-Resistant Enterobacter Species from the Clinical Specimens of a Tertiary Care Hospital in Bangladesh

Pharmacodynamics of colistin resistance in carbapenemase-producing Klebsiella pneumoniae: the double-edged sword of heteroresistance and adaptive resistance

Colistin resistance screening by 3 μg/ml colistin agar in Carbapenemase‐producing Enterobacterales

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