Detection of mcr-1 Gene in Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae From Human Urine Samples in Pakistan

Bilal, Hazrat; Hameed, Fareeha; Khan, Muhammad Asif; Khan, Sabir; Yang, Xingyuan; Rehman, Tayyab

doi:10.5812/jjm.96646

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…In the current study, 28(30.11%) studies reported the antibiotic-resistant genes in which the most prominent are ESBL and carbapenem-resistant bla NDM-1 and bla KPC-2 gene. Correspondingly, the mcr-1 gene is being reported from Pakistan [ 115 ]. Further molecular studies about the strain type, sequence type, and plasmid typing are required to better understand the resistant magnitude.…”

Section: Discussionmentioning

confidence: 99%

Antibiotic resistance in Pakistan: a systematic review of past decade

et al. 2021

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Background During the last six decades, extensive use of antibiotics has selected resistant strains, increasing the rate of fatal infectious diseases, and exerting an economic burden on society. This situation is widely accepted as a global problem, yet its degree is not well elucidated in many regions of the world. Up till now, no systemic analysis of Antimicrobial resistance (AMR) in Pakistan has been published. The current study aims to describe the antibiotic-resistance scenario of Pakistan from human samples of the last 10 y, to find the gaps in surveillances and methodology and recommendations for researchers and prescribers founded on these outcomes. Methods Original research articles analyzed the pattern of Antibiotic resistance of any World Health Organization (WHO) enlisted priority pathogens in Pakistan (published onward 2009 till March 2020), were collected from PubMed, Google scholar, and PakMedi Net search engines. These articles were selected based on predefined inclusion and exclusion criteria. Data about the study characteristics and antibiotic-resistance for a given bacterium were excluded from literature. Antibiotic resistance to a particular bacterium was calculated as a median resistance with 95% Confidence Interval (CI). Results Studies published in the last 10 y showed that Urinary Tract Infection (UTI) is the most reported clinical diagnosis (16.1%) in Pakistan. E. coli were reported in 28 (30.11%) studies showing high resistance to antibiotics’ first line. Methicillin-resistant Staphylococcus aureus (MRSA) was found in 49% of S. aureus’ total reported cases. Phenotypic resistance pattern has mostly been evaluated by Disk Diffusion Method (DDM) (82.8%), taken Clinical Laboratory Standards Institute (CLSI) as a breakpoint reference guideline (in 79.6% studies). Only 28 (30.11%) studies have made molecular identification of the resistance gene. blaTEM (78.94% in Shigella spp) and blaNDM-1 (32.75% in Klebsiella spp) are the prominent reported resistant genes followed by VanA (45.53% in Enterococcus spp), mcr-1 (1.61% in Acinetobacter spp), and blaKPC-2 (31.67% in E. coli). Most of the studies were from Sindh (40.86%), followed by Punjab (35.48%), while Baluchistan’s AMR data was not available. Conclusion Outcomes of our study emphasize that most of the pathogens show high resistance to commonly used antibiotics; also, we find gaps in surveillances and breaches in methodological data. Based on these findings, we recommend the regularization of surveillance practice and precise actions to combat the region’s AMR.

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Section: Discussionmentioning

confidence: 99%

Antibiotic resistance in Pakistan: a systematic review of past decade

et al. 2021

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“…Travel and trade can contribute to this spread; the spread of NDM-1, from Indian sub-continent region to Europe and United States highlights the global nature of this public health disaster [ 3 ]. Reports of high levels of antibacterial resistance [ 4 – 7 ] from hospitals as well as the community [ 8 , 9 ] in Pakistan, the fifth most populous country globally [ 10 ], places an additional burden on an overstressed and under resourced health care system. Circulating mobile genetic elements in bacterial species [ 5 , 7 , 11 ] that can transfer multidrug resistance genes within and between species have also been reported.…”

Section: Introductionmentioning

confidence: 99%

“…Reports of high levels of antibacterial resistance [ 4 – 7 ] from hospitals as well as the community [ 8 , 9 ] in Pakistan, the fifth most populous country globally [ 10 ], places an additional burden on an overstressed and under resourced health care system. Circulating mobile genetic elements in bacterial species [ 5 , 7 , 11 ] that can transfer multidrug resistance genes within and between species have also been reported. Further, the detection of extensively drug resistant (XDR) Salmonella Typhi from Hyderabad, Pakistan [ 12 ] reinforces concerns over the complex interaction between environment and anthropogenic activities in contributing towards emerging AMR.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial resistance among GLASS priority pathogens from Pakistan: 2006–2018

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Background In 2018 Pakistan initiated its national antimicrobial resistance (AMR) surveillance aligned with Global Antimicrobial Surveillance System (GLASS). To complement this surveillance, we conducted a situational analysis of AMR rates among GLASS organisms in the country. Data from published studies and from antibiograms was compared and role of antibiograms as potential contributors to national AMR surveillance explored. Methods AMR rates for GLASS specified pathogen/antimicrobials combination from Pakistan were reviewed. Data sources included published studies (2006–2018) providing AMR rates from Pakistan (n = 54) as well as antibiograms (2011–2018) available on the Pakistan Antimicrobial Resistance Network (PARN) website. Resistance rates were categorized as follows: Very low: 0–10%, Low: 11–30%, Moderate: 30–50% and High: > 50%. Results Published data from hospital and community/laboratory-based studies report resistance rates of > 50% and 30–50% respectively to 3rd generation cephalosporins, fluoroquinolones and cotrimoxazole amongst Klebsiella pneumoniae and Escherichia coli. Carbapenem resistance rates amongst these organisms remained below 30%. High (> 50%) resistance was reported in Acinetobacter species to aminoglycosides and carbapenems among hospitalized patients. The evolution of ceftriaxone resistant Salmonella Typhi and Shigella species is reported. The data showed > 50% to fluoroquinolones amongst Neisseria gonorrhoeae and the spread of methicillin resistant Staphylococcus aureus (< 30%; 2008) to (> 50%; 2010) in hospital settings. Resistance reported in published studies aligned well with antibiogram data. The latter also captured a clear picture of evolution of resistance over the study period. Conclusion Both published studies as well antibiograms suggest high rates of AMR in Pakistan. Antibiogram data demonstrating steady increase in AMR highlight its potential role towards supplementing national AMR surveillance efforts particularly in settings where reach of national surveillance may be limited.

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“…However, in late 2015, the first plasmid-mediated colistin resistance gene, mobilized colistin-resistance ( mcr-1 ), was detected in China in pigs and humans; this initiated the post-antibiotic era, because all available antibiotic options were countered by bacterial resistance mechanisms [ 11 ]. Nowadays, carbapenem-resistant Enterobacterales harboring mcr have been reported worldwide [ 12 , 13 , 14 ]; therefore, colistin is alternatively used to cure those infections that lead to increases of the colistin resistance [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli

et al. 2022

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Before the emergence of plasmid-mediated colistin resistance, colistin was once considered the last drug of choice for infections caused by carbapenem-resistant bacteria. Currently, researchers are relentlessly exploring possible alternative therapies that could efficiently curb the spread of drug resistance. In this study, we aim to investigate the synergistic antibacterial activity of tetrandrine in combination with colistin against mcr-1-harboring Escherichia coli. We examined the antibacterial activity of tetrandrine in combination with colistin in vivo and in vitro and examined the bacterial cells by fluorescence, scanning, and transmission electron microscopy (TEM) to explore their underlying mechanism of action. We further performed a computational analysis of MCR-1 protein and tetrandrine to determine the interaction interface of these two molecules. We confirmed that neither colistin nor tetrandrine could, on their own, inhibit the growth of mcr-1-positive E. coli. However, in combination, tetrandrine synergistically enhanced colistin activity to inhibit the growth of E. coli both in vivo and in vitro. Similarly, molecular docking showed that tetrandrine interacted with the three crucial amino acids of the MCR-1 protein in the active site, which might inhibit MCR-1 from binding to its substrates, cause MCR-1 to lose its ability to confer resistance. This study confirmed that tetrandrine and colistin have the ability to synergistically overcome the issue of colistin resistance in mcr-1-harboring E. coli.

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Detection of mcr-1 Gene in Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae From Human Urine Samples in Pakistan

Cited by 9 publications

References 35 publications

Antibiotic resistance in Pakistan: a systematic review of past decade

Antibiotic resistance in Pakistan: a systematic review of past decade

Antimicrobial resistance among GLASS priority pathogens from Pakistan: 2006–2018

Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli

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