Colistin-Resistant Enterobacteriaceae Carrying the mcr-1 Gene among Patients in Hong Kong.
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ABSTRACT:
SUBMITTER: Wong SC
PROVIDER: S-EPMC4994376 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
Publications
Colistin-Resistant Enterobacteriaceae Carrying the mcr-1 Gene among Patients in Hong Kong.
Wong Sally C Y SC Tse Herman H Chen Jonathan H K JH Cheng Vincent C C VC Ho Pak-Leung PL Yuen Kwok-Yung KY
Emerging infectious diseases 20160901 9
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Project description:Stool samples from 38 travelers returning from India were screened for extended-spectrum cephalosporin- and carbapenem-resistant Enterobacteriaceae implementing standard selective plates. Twenty-six (76.3%) people were colonized with CTX-M or DHA producers, but none of the strains was colistin resistant and/or mcr-1 positive. Nevertheless, using overnight enrichment and CHROMagar Orientation plates supplemented with colistin, four people (10.5%) were found to be colonized with colistin-resistant Escherichia coli One cephalosporin-susceptible sequence type 10 (ST10) strain carried a 4,211-bp ISApl1-mcr-1-ISApl1 element in an IncHI2 plasmid backbone.
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Project description:The spread of the plasmid-mediated colistin resistance gene, mcr-1, into carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates poses a significant threat to global health. Here we report the identification of three mcr-1-harboring carbapenem-resistant Escherichia coli strains, collected from three patients in two provinces in China. Our results show that mcr-1-harboring CRE strains have started to spread in different hospitals in China. In addition, this report presents the first description of chromosomal integration of mcr-1 into a carbapenem-resistant E. coli strain.
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Project description:Limited data are available on temocillin susceptibilities in Enterobacteriaceae from Asian countries where antimicrobial resistance is prevalent. The in vitro activities of temocillin and 15 commonly used antimicrobials against 613 non-duplicate blood (n = 310) and urine (with clinically significant bacteriuria; n = 303) isolates of Enterobacteriaceae from patients who attended 3 out of 7 clusters of public hospitals of the Hospital Authority, Hong Kong, during 2015/2016 were tested. Minimum inhibitory concentrations (MICs) were determined by Clinical and Laboratory Standards Institute (CLSI) microbroth dilution (agar dilution with fosfomycin). For temocillin, MICs were also obtained using the British Society of Antimicrobial Chemotherapy (BSAC) microbroth dilution method and interpreted using the BSAC breakpoints. Overall, 93.0% (570) isolates were susceptible to temocillin using BSAC systemic breakpoint (≤8 mg/L) and all except 2 isolates were susceptible using the urinary breakpoint (≤32 mg/L). The extended spectrum beta-lactamase (ESBL) positivity rate was 23.2% (118 out of 508 E. coli, Klebsiella spp., Proteus spp.). Temocillin resistance rate to ESBL-positive isolates was 16.1% using the systemic breakpoint of ≤8 mg/L (MIC50 and MIC90 were 8 mg/L and 16 mg/L respectively). Two isolates (1 E. coli, temocillin MIC 64 mg/L, 1 Klebsiella sp., MIC 32 mg/mL) were resistant to meropenem and possessed the NDM-5 and KPC-2 genes respectively. Other susceptibility rates were: amoxicillin/clavulanate (59.1%), trimethoprim/sulfamethoxazole (62.5%), ciprofloxacin (71.5%), ceftriaxone (75.4%), nitrofurantoin (76.4%), gentamicin (78.3%), cefepime (81.1%), ceftazidime (83.5%), piperacillin/tazobactam (86%), colistin (88.8%), tigecycline (89.4%), fosfomycin (92.8%), ertapenem (99.0%), amikacin (99.2%) and meropenem (99.7%). Temocillin may be a useful alternative for the treatment of infections caused by ESBL and multi-drug-resistant Enterobacteriaceae in Hong Kong, particularly as resistance rates to ciprofloxacin, nitrofurantoin and piperacillin/tazobactam are high.
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Project description:Colistin is one of the last-line antimicrobial agents against life-threatening infections. The distribution of the colistin resistance gene mcr-1 has been reported worldwide. However, most studies have focused on the distribution of mcr-1-positive bacteria in humans, animals, food, and sewage; few have focused on their distribution in natural environments. We conducted a large spatial survey of mcr-1-positive Escherichia coli at 119 sites in 48 rivers, covering the entire island of Taiwan. We investigated the relationship between the livestock or poultry density in the surveyed riverine area and the number of mcr-1-positive E. coli in the river water. We then sequenced and characterized the isolated mcr-1-positive plasmids. Seven mcr-1 positive E. coli were isolated from 5.9% of the sampling sites. The mcr-1-positive sites correlated with high chicken and pig stocking densities but not human population density or other river parameters. Four of the mcr-1-positive E. coli strains harbored epidemic IncX4 plasmids, and three of them exhibited identical sequences with a size of 33,309 bp. One of the plasmids contained identical 33,309 bp sequences but carried an additional 5711-bp transposon (Tn3 family). To our knowledge, this is the first demonstration that mcr-1-carrying IncX4 plasmids can contain an insertion of such transposons. All mcr-1-positive isolates belonged to phylogenetic group A and harbored few known virulence genes. This study showed a positive relationship between the number of mcr-1-positive sites and high livestock and poultry density. The sequencing analyses indicated that the epidemic plasmid in the mcr-1 isolates circulates not only in humans, animals, and food but also in the associated environments or natural habitats in Taiwan, suggesting that the surveillance of antibiotics-resistance genes for livestock or poultry farm quality control should include their associated environments.
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Project description:To investigate whether introduction of colistin into the clinical settings selected colistin-resistant CRE, we performed molecular epidemiological study of 1868 CRE strains collected from different geographical locales in China during the period 2014-2019. 1755 (96.18%) isolates carried the carbapenemase genes blaKPC and blaNDM; 14 Escherichia coli isolates (0.75%) carrying mcr-1 and blaNDM (MCR-CREC) were also identified. Importantly, the number and relative prevalence of MCR-CREC isolates increased from 5 (0.41%) to 9 (1.38%) after introduction of polymyxin into clinical practice. Consistently, results of genetic analysis indicated that MCR-CREC strains collected before December 2017 were genetically diverse, yet those collected after that date exhibited more closely related genetic profiles, indicating that specific MCR-CREC strains were rapidly selected as a result of increased usage of colistin in clinical settings. The resistance level of MCR-CREC isolates to colistin increased after the introduction of polymyxin into clinical use with the MIC to colistin from <2 mg/L in 80% strains to 2 mg/L in 100% strains. Further dissemination of MCR-CREC strains, which exhibit resistance to the last-line drugs of carbapenems and colistin, is expected to pose a severe threat to human health.
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Project description:Of 48 bacteria belonging to the family Enterobacteriaceae tested from urban sludge samples, one Escherichia coli isolate was resistant to colistin and possessed the resistance marker gene mcr-1 found for the first time from Bangladesh. The colistin resistant E. coli was multidrug resistant showing resistance to 11 different antibiotics tested.
| S-EPMC5738163 | biostudies-literature
Project description:BackgroundHuman fecal carriage of Enterobacteriaceae possessing mobilized colistin resistance genes (mcr-1 and mcr-2) remains obscure in Hong Kong. As part of routine surveillance on emerging antibiotic resistance, we conducted a prospective study on this topic in a regional hospital in Hong Kong.MethodsFrom October 31 to November 25, 2016, all fecal specimens submitted for routine analysis were included in this surveillance study. These comprised 672 consecutive routine fecal specimens collected from 616 individuals. Fecal specimens were screened for colistin-resistant Enterobacteriaceae by culture-based method, and the presence of mcr-1 and mcr-2 genes in resistant isolates was identified by polymerase chain reaction and Sanger sequencing. Whole genome sequencing (WGS) of mcr-1-possessing Escherichia coli strains was facilitated using Illumina® MiSeq® followed by sequence analysis with appropriate bioinformatics tools.ResultsFourteen mcr-1-positive E. coli strains were isolated from 14 separate individuals (2.08% of total fecal specimens), with 9 of them being asymptomatic, healthy clients coming for health assessment. No mcr-2-possessing Enterobacteriaceae was identified. Colistin minimum inhibitory concentrations of these mcr-1-positive isolates ranged from 2 to 4 μg/mL. All these isolates were susceptible to carbapenems with 2 being extended spectrum β-lactamase producers. WGS data revealed that these isolates belonged to at least 12 different sequence types (STs) and possessed diversified plasmid replicons, virulence and acquired antibiotic resistance genes. Further study on an E. coli ST201 strain (Pasteur scheme) revealed coexistence of 47,818-bp IncP-1 and 33,309-bp IncX4 types of mcr-1 plasmids, which was a combination of stability and high transmissibility.ConclusionsTo the best of our knowledge, this is the first study on human fecal carriage of Enterobacteriaceae possessing mcr-1 and mcr-2 genes in Hong Kong. Our data further revealed asymptomatic carriage of mcr-1-possessing Enterobacteriaceae by both patients and healthy individuals. This is alarming considering wide diversity and high transmissibility of mcr-1 plasmids, which potentially facilitate emergence of pan-drug-resistant bacteria in future infection. This also highlights the importance of surveillance on emerging antibiotic resistance, especially for patients under intensive care.
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Project description:We report a SCCmec II, ST39 methicillin-resistant Staphylococcus aureus isolate from pigs that harboured toxic-shock syndrome toxin gene (tsst-1). The gene was located in a rare pathogenicity island SaPI68111, which also carried enterotoxin genes that can cause fatal infections. Pigs may potentially serve as a reservoir for MRSA dissemination.
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Project description:Colistin is considered the last-line antimicrobial for the treatment of multidrug-resistant gram-negative bacterial infections. The emergence and spread of superbugs carrying the mobile colistin resistance gene (mcr) have become the most serious and urgent threat to healthcare. Here, we discover that silver (Ag+), including silver nanoparticles, could restore colistin efficacy against mcr-positive bacteria. We show that Ag+ inhibits the activity of the MCR-1 enzyme via substitution of Zn2+ in the active site. Unexpectedly, a tetra-silver center was found in the active-site pocket of MCR-1 as revealed by the X-ray structure of the Ag-bound MCR-1, resulting in the prevention of substrate binding. Moreover, Ag+effectively slows down the development of higher-level resistance and reduces mutation frequency. Importantly, the combined use of Ag+ at a low concentration with colistin could relieve dermonecrotic lesions and reduce the bacterial load of mice infected with mcr-1–carrying pathogens. This study depicts a mechanism of Ag+ inhibition of MCR enzymes and demonstrates the potentials of Ag+ as broad-spectrum inhibitors for the treatment of mcr-positive bacterial infection in combination with colistin.
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Project description:Resistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistant Enterobacteriaceae isolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.
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