scholarly journals The Mobile Colistin Resistance Gene, mcr-1.1, Is Carried on IncX4 Plasmids in Multidrug Resistant E. coli Isolated from Rainbow Trout Aquaculture

2020 ◽  
Vol 8 (11) ◽  
pp. 1636
Author(s):  
Jouman Hassan ◽  
Razan Zein Eddine ◽  
David Mann ◽  
Shaoting Li ◽  
Xiangyu Deng ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Antimicrobial Stewardship ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Sequencing Analysis ◽  
Colistin Resistance ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Recent Emergence ◽  
The Status

Colistin, a last resort antibiotic, is important for controlling infections with carbapenem-resistant Enterobacteriaceae. The recent emergence of mobile-colistin-resistance (mcr) genes has threatened the effectiveness of colistin. Aquaculture is hypothesized to be a major contributor to the evolution and dissemination of mcr. However, data on mcr in aquaculture are limited. Here, the occurrence of mcr-1 was assessed in Rainbow Trout in Lebanon, a country with developing antimicrobial stewardship and an established use of colistin for medical and farming purposes. mcr-1 was detected in 5 Escherichia coli isolated from fish guts. The isolates were classified as multidrug-resistant and their colistin minimum inhibitory concentration ranged between 16 and 32 μg/mL. Whole genome sequencing analysis showed that mcr-1 was carried on transmissible IncX4 plasmids and that the isolates harbored more than 14 antibiotic resistance genes. The isolates belonged to ST48 and ST101, which have been associated with mcr and can occur in humans and fish. The mcr-1-positive E. coli persisted in 6-day biofilms, but there was a potential fitness cost. Given the status of infrastructure in Lebanon, there is a high potential for the dissemination of mcr via aquatic environments. Urgent actions are needed to control mcr and to enhance antimicrobial stewardship in Lebanon.

scholarly journals Molecular Detection of Colistin Resistance mcr-1 Gene in Multidrug-Resistant Escherichia coli Isolated from Chicken

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 97
Author(s):  
Md Bashir Uddin ◽  
Mohammad Nurul Alam ◽  
Mahmudul Hasan ◽  
S. M. Bayejed Hossain ◽  
Mita Debnath ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Agents ◽  
Catalytic Domain ◽  
Phylogenetic Analyses ◽  
Multidrug Resistant ◽  
Sequencing Analysis ◽  
Global Public Health ◽  
Colistin Resistance ◽  
E Coli ◽  
Chicken Feces

Zoonotic and antimicrobial-resistant Escherichia coli (hereafter, E. coli) is a global public health threat which can lead to detrimental effects on human health. Here, we aim to investigate the antimicrobial resistance and the presence of mcr-1 gene in E. coli isolated from chicken feces. Ninety-four E. coli isolates were obtained from samples collected from different locations in Bangladesh, and the isolates were identified using conventional microbiological tests. Phenotypic disk diffusion tests using 20 antimicrobial agents were performed according to CLSI-EUCAST guidelines, and minimum inhibitory concentrations (MICs) were determined for a subset of samples. E. coli isolates showed high resistance to colistin (88.30%), ciprofloxacin (77.66%), trimethoprim/sulfamethoxazole (76.60%), tigecycline (75.53%), and enrofloxacin (71.28%). Additionally, the pathotype eaeA gene was confirmed in ten randomly selected E. coli isolates using primer-specific polymerase chain reaction (PCR). The presence of mcr-1 gene was confirmed using PCR and sequencing analysis in six out of ten E. coli isolates. Furthermore, sequencing and phylogenetic analyses revealed a similarity between the catalytic domain of Neisseria meningitidis lipooligosaccharide phosphoethanolamine transferase A (LptA) and MCR proteins, indicating that the six tested isolates were colistin resistant. Finally, the findings of the present study showed that E. coli isolated from chicken harbored mcr-1 gene, and multidrug and colistin resistance. These findings accentuate the need to implement strict measures to limit the imprudent use of antibiotics, particularly colistin, in agriculture and poultry farms.

scholarly journals Mobile Plasmid Mediated Transition From Colistin-Sensitive to Resistant Phenotype in Klebsiella pneumoniae

2021 ◽  
Vol 12 ◽  
Author(s):  
Baoyue Zhang ◽  
Bing Yu ◽  
Wei Zhou ◽  
Yue Wang ◽  
Ziyong Sun ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Sequencing Analysis ◽  
Direct Repeats ◽  
Colistin Resistance ◽  
Health Crisis ◽  
Carbapenem Resistant ◽  
Resistant Phenotype ◽  
New Challenges

Multidrug-resistant bacteria, including carbapenem-resistant Klebsiella pneumoniae (CRKP), are becoming an increasing health crisis worldwide. For CRKP, colistin is regarded as “the last treatment option.” In this study, we isolated a clinical CRKP strain named as K. pneumoniae R10-341. Phenotyping analysis showed that this strain could transit from a colistin-sensitive to a resistant phenotype by inserting an IS4 family ISKpn72 element into the colistin-resistance associated mgrB gene. To investigate the mechanism of this transition, we performed genome sequencing analysis of the colistin-sensitive parental strain and found that 12 copies of ISKpn72 containing direct repeats (DR) are located on the chromosome and 1 copy without DR is located on a multidrug-resistant plasmid pR10-341_2. Both types of ISKpn72 could be inserted into the mgrB gene to cause colistin-resistance, though the plasmid-derived ISKpn72 without DR was in higher efficiency. Importantly, we demonstrated that colistin-sensitive K. pneumoniae strain transferred with the ISKpn72 element also obtained the ability to switch from colistin-sensitive to colistin-resistant phenotype. Furthermore, we confirmed that the ISKpn72-containing pR10-341_2 plasmid was able to conjugate, suggesting that the ability of causing colistin-resistant transition is transferable through common conjugation. Our results point to new challenges for both colistin-resistance detection and CRKP treatment.

scholarly journals First Report of the mcr-1 colistin Resistance Gene Identified in Escherichia coli Isolated from a Clinical Sample in Naples in 2020

2020 ◽  
Author(s):  
BIAGIO SANTELLA ◽  
CARLA ZANNELLA ◽  
CHIARA DEL VECCHIO ◽  
ANNALISA CHIANESE ◽  
VERONICA FOLLIERO ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Gene ◽  
Clinical Sample ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Colistin Resistance ◽  
Gram Negative ◽  
E Coli ◽  
Carbapenem Resistant

Abstract Background: The emergence of a novel plasmid-mediated colistin resistance mechanism, encoded by the mcr-1 gene, represents a major public health concern. The mechanism of resistance to colistin, mediated by plasmids, is a serious problem, both for its ability to be transferred to other species, and for infections caused by carbapenem-resistant Gram-negative, in which colistin is used as an antimicrobial drug of last line for the treatment of these infections. The present study highlights the first isolation and genetic evaluation of detecting plasmid-mediated resistance to colistin in a multidrug-resistant (MDR) Escherichia coli (E. coli) isolated from a clinical sample in the metropolitan city of Naples, Italy. Results: Colistin-resistant E. coli isolate was identified in August 2020 from the blood culture of a male patient with multiple comorbidities. The minimum inhibitory concentration (MIC) of colistin was 8 mg/L. In addition to colistin, the isolate was resistant to third-generation cephalosporins (cefotaxime and ceftazidime), penicillin (amoxicillin and piperacillin), aminoglycosides (gentamicin and tobramycin), and fluoroquinolones (ciprofloxacin and levofloxacin). However, it showed susceptibility to carbapenems (ertapenem, imipenem, and meropenem), tetracyclines (tigecycline), and piperacillin-tazobactam. The results of the PCR confirmed the presence of the mcr-1 resistance gene. Conclusion: This study confirms the presence of resistance to colistin mediated by the mcr-1 gene in a clinical isolate of E. coli. Although resistance to colistin caused by the mcr-1 gene is not common in our region, it should not be ignored. Therefore, further surveillance studies are recommended to monitor the spread of plasmid-mediated colistin resistance genes in Gram-negative MDR bacteria.

scholarly journals Emergence of mobilized colistin resistance-1 in multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province in China: a multicentre study

2021 ◽  
Author(s):  
Yi Li ◽  
Wenjuan Yan ◽  
Qi Zhang ◽  
Nan Jing ◽  
Youhua Yuan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Ethylenediaminetetraacetic Acid ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Henan Province ◽  
Close Monitoring ◽  
Colistin Resistance ◽  
E Coli ◽  
Carbapenem Resistant

Abstract Background The increased clinical use of polymyxin led to the emergence of polymyxin-resistant strains, especially those carrying plasmid-borne mobilized colistin resistance (mcr) gene variants. In this study, we aimed to evaluate the prevalence and characteristics of polymyxin-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province, China. Methods A total of 16 polymyxin-resistant isolates among 2301 E. coli and K. pneumoniae isolates collected in 6 local hospitals in the Henan province were studied. The isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the minimum inhibitory concentrations (MICs) were determined using the microbroth dilution technique. Polymyxin-resistant isolates were further analysed for mcr-1 and carbapenemase-mediated resistance using the modified carbapenem inactivation method, the ethylenediaminetetraacetic acid-modified carbapenem inactivation method, and polymerase chain reaction. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed to disclose the phylogenetic relationships of the polymyxin-resistant isolates. The clinical characteristics of patients infected with the polymyxin-resistant isolates were also retrospectively analysed. Results 5/1499 (0.3%) and 11/802 (1.4%) E. coli and K. pneumoniae isolates, respectively, were polymyxin-resistant. The MICs of polymyxin were in the range of 4–64 µg/mL and all of the 16 polymyxin-resistant isolates were susceptible to tigecycline. Additionally, four of the five E. coli polymyxin-resistant isolates were mcr-1 positive; one of them was also carbapenem-resistant, carrying blaNDM−5. Conversely, only 1/11 K. pneumoniae isolates was mcr-1 positive, while 9 polymyxin-resistant isolates were also carbapenem-resistant (PRCRKP), carrying blaKPC−2 but not mcr-1. MLST results showed that the five E. coli isolates belonged to four sequence types (STs), including ST2, ST132, ST632, and ST983, while all PRCRKP isolates belonged to ST11. However, all 16 isolates showed different PFGE types using a genetic similarity of ≥ 95%. Furthermore, 33.3% (5/15) of the patients carrying polymyxin-resistant K. pneumoniae isolates showed a history of polymyxin use, and 10/15 (66.7%) patients displayed good clinical outcomes. Conclusion The polymyxin resistance rate of K. pneumoniae was slightly higher than that of E. coli in the Henan province; however, mcr-1 was only detected in one K. pneumoniae isolate. Thus, close monitoring is needed to prevent and control the spread of PRCRKP.

scholarly journals Genomic Features of MCR-1 and Extended-Spectrum β-Lactamase-Producing Enterobacterales from Retail Raw Chicken in Egypt

2021 ◽  
Vol 9 (1) ◽  
pp. 195
Author(s):  
Mustafa Sadek ◽  
José Manuel Ortiz de la Rosa ◽  
Mohamed Abdelfattah Maky ◽  
Mohamed Korashe Dandrawy ◽  
Patrice Nordmann ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Food Samples ◽  
Colistin Resistance ◽  
Gene Encoding ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Resistance Trait ◽  
Severe Infections ◽  
Positive Isolate

Colistin is considered as a last resort agent for treatment of severe infections caused by carbapenem-resistant Enterobacterales (CRE). Recently, plasmid-mediated colistin resistance genes (mcr type) have been reported, mainly corresponding to mcr-1 producers. Those mcr-1-positive Enterobacterales have been identified not only from human isolates, but also from food samples, from animal specimens and from environmental samples in various parts of the world. Our study focused on the occurrence and characterization of mcr-1-positive Enterobacterales recovered from retail raw chicken in Egypt. From the 345 retail chicken carcasses collected, a total of 20 samples allowed to recover mcr-1-positive isolates (Escherichia coli, n = 19; Citrobacter freundii, n = 1). No mcr-2- to mcr-10-positive isolate was identified from those samples. The colistin resistance trait was confirmed for all those 20 isolates with a positivity of the Rapid Polymyxin NP (Nordmann-Poirel) test. Minimum inhibitory concentrations (MICs) of colistin for all MCR-1-producing isolates ranged between 4 and 16 μg/mL. Noticeably, 9 out of the 20 mcr-1-positive isolates produced an extended-spectrum β-lactamase (ESBL), respectively producing CTX-M-9 (n = 2), CTX-M-14 (n = 4), CTX-M-15 (n = 2), and SHV-12 (n = 1). Noteworthy, the fosA4 gene encoding resistance to fosfomycin was found in a single mcr-1-positive E. coli isolate, in which both genes were located on different conjugative plasmids. The pulsed-field gel electrophoresis (PFGE) patterns were identified, corresponding to 10 different sequence types (STs), highlighting the genetic diversity of those different E. coli. Whole-genome sequencing revealed three major types of mcr-1-bearing plasmids, corresponding to IncI2, IncX4, and IncHI2 scaffolds. The occurrence of MCR-1-producing multidrug-resistant Enterobacterales in retail raw chicken is of great concern, considering the possibility of transmission to humans through the food chain.

scholarly journals Emergence of colistin resistance in multidrug-resistant Klebsiella pneumoniae and Escherichia coli strains isolated from cancer patients

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Mai M. Zafer ◽  
Hadir A. El-Mahallawy ◽  
Asmaa Abdulhak ◽  
Magdy A. Amin ◽  
Mohamed H. Al-Agamy ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Cancer Patients ◽  
Clonal Diversity ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Global Public Health ◽  
Colistin Resistance ◽  
E Coli ◽  
Recent Emergence

Abstract Background Colistin resistance is mainly driven by alterations in the Gram-negative outer membrane lipopolysaccharides and is caused, in most cases, by mutations in mgrB gene. However, the recent emergence of plasmid-encoded colistin resistance among Enterobacteriaceae strains represents a serious threat to global public health. In this paper we have investigated the rates of colistin resistance and the underlying mechanisms in 450 Klebsiella pneumoniae and Escherichia coli isolates obtained from cancer patients in Egypt. Methods Colistin susceptibility and minimum inhibitory concentrations were determined according to the European Committee on Antimicrobial Susceptibility Testing, by broth microdilution, and by E-test. The mcr-1, mcr-2 and mgrB genes were detected by PCR and then sequenced. Clonal diversity in colistin-resistant K. pneumoniae was evaluated by multilocus sequence typing. Results Forty (8.8%) colistin-resistant isolates, including 22 K. pneumoniae and 18 E. coli, were isolated over 18 months. Of these, 50% were carbapenem-resistant, out of which nine were blaOXA-48 and seven blaNDM-1 positive. The mechanisms of colistin resistance could be revealed only in three of the 40 resistant strains, being represented by mcr-1 in one blaNDM-1-positive E. coli strain and in one K. pneumoniae ST11 and by mgrB mutations, detected in one K. pneumoniae isolate. None of the studied isolates harbored mcr-2. Conclusions Our results demonstrate a high frequency of colistin resistance in enterobacterial strains isolated from cancer patients, but a low prevalence of the most well known resistance mechanisms.

scholarly journals Analysis of β-Lactamase Resistance Determinants in Enterobacteriaceae from Chicago Children: a Multicenter Survey

2016 ◽  
Vol 60 (6) ◽  
pp. 3462-3469 ◽  
Author(s):  
Latania K. Logan ◽  
Andrea M. Hujer ◽  
Steven H. Marshall ◽  
T. Nicholas Domitrovic ◽  
Susan D. Rudin ◽  
...  
Keyword(s):  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Outpatient Setting ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Plasmid Replicon ◽  
Multicenter Survey ◽  
Potential Impact

Multidrug-resistant (MDR)Enterobacteriaceaeinfections are increasing in U.S. children; however, there is a paucity of multicentered analyses of antibiotic resistance genes responsible for MDR phenotypes among pediatricEnterobacteriaceaeisolates. In this study, 225 isolates phenotypically identified as extended-spectrum β-lactamase (ESBL) or carbapenemase producers, recovered from children ages 0 to 18 years hospitalized between January 2011 and April 2015 at three Chicago area hospitals, were analyzed. We used DNA microarray platforms to detect ESBL, plasmid-mediated AmpC (pAmpC), and carbapenemase type β-lactamase (bla) genes. Repetitive-sequence-based PCR and multilocus sequence typing (MLST) were performed to assess isolate similarity. Plasmid replicon typing was conducted to classify plasmids. The median patient age was 4.2 years, 56% were female, and 44% presented in the outpatient setting. The majority (60.9%) of isolates wereEscherichia coliand from urinary sources (69.8%). Of 225 isolates exhibiting ESBL- or carbapenemase-producing phenotypes, 90.7% contained ablagene. The most common genotype was theblaCTX-M-1group (49.8%); 1.8% were carbapenem-resistantEnterobacteriaceae(threeblaKPCand oneblaIMP). Overall, pAmpC (blaACT/MIRandblaCMY) were present in 14.2%. The predominantE. coliphylogenetic group was the virulent B2 group (67.6%) associated with ST43/ST131 (Pasteur/Achtman MLST scheme) containing theblaCTX-M-1group (84%), and plasmid replicon types FIA, FII, and FIB.K. pneumoniaeharboringblaKPCwere non-ST258 with replicon types I1 and A/C.Enterobacterspp. carryingblaACT/MIRcontained plasmid replicon FIIA. We found that β-lactam resistance in children is diverse and that certain resistance mechanisms differ from known circulating genotypes in adults in an endemic area. The potential impact of complex molecular types and the silent dissemination of MDREnterobacteriaceaein a vulnerable population needs to be studied further.

scholarly journals In vitro activity of antimicrobial peptide CDP-B11 alone and in combination with colistin against colistin-resistant and multidrug-resistant Escherichia coli

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin S. Witherell ◽  
Jason Price ◽  
Ashok D. Bandaranayake ◽  
James Olson ◽  
Douglas R. Call
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Minimal Media

AbstractMultidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including Escherichia coli #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (mcr-1). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against E. coli #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of E. coli #0346. CDP-B11 with colistin inhibits the growth of E. coli #0346 at ≥ 10× lower colistin concentrations compared to colistin alone in Mueller–Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25 μg/mL) compared to colistin alone (2.5 μg/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2 h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-resistant infections.

scholarly journals 166. Activity of a Novel β-lactamase Inhibitor QPX7728 Combined With β-lactams Against st258 klebsiella Pneumoniae and st131 escherchia Coli Isolates Producing β-lactamases

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S212-S213
Author(s):  
Mariana Castanheira ◽  
Jill Lindley ◽  
Timothy B Doyle ◽  
Andrew P Davis ◽  
Olga Lomovskaya
Keyword(s):  
Multidrug Resistant ◽  
Chemical Diversity ◽  
Sequencing Analysis ◽  
E Coli ◽  
Escherchia Coli ◽  
Global Spread ◽  
Encoding Genes ◽  
Center Research ◽  
Lactamase Inhibitor ◽  
Research Grant

Abstract Background ST258 K. pneumoniae and ST131 E. coli clones are considered vectors for the global spread of multidrug resistance. We evaluated the activity of β-lactams in combination with QPX7728, a novel β-lactamase inhibitor active against all β-lactamase classes, against a collection of 210 isolates belonging to these clones collected from a worldwide surveillance study. Methods A total of 118 ST258 K. pneumoniae and 92 ST131 E. coli (single loci variant also included) were susceptibility tested by reference broth microdilution against various β-lactams ± QPX7728 and comparator agents. All isolates were screened for β-lactamases using whole genome sequencing analysis. Results All β-lactam agents had limited activity against 118 ST258 K. pneumoniae (1.7–7.6% susceptible). Among these, 104 carried carbapenemase-encoding genes: 66 KPC variants, 20 NDM and 17 OXA-48-like. One isolate carried 2 carbapenemases. The addition of QPX7728 at 4 mg/L or 8 mg/L lowered the MICs for cefepime (MIC50/90, 0.25/1 mg/L and MIC50/90, 0.12/0.5 mg/L), ceftolozane (MIC50/90, 0.5/ > 32 mg/L and MIC50/90, 0.25/16 mg/L), ertapenem (MIC50/90, 0.12/2 mg/L and MIC50/90, 0.06/0.5 mg/L), and meropenem (MIC50/90, 0.06/0.5 mg/L and MIC50/90, 0.03/0.12 mg/L; Table). QPX7728 at 4 mg/L reduced the ceftibuten (MIC50/90, 0.25/8 mg/L) or tebipenem (MIC50/90, 0.12/2 mg/L) MICs for ST258 isolates. E. coli ST131 carried mainly CTX-M variant (85 isolates), but 6 isolates harbored carbapenemases. Carbapenems were the only β-lactams displaying > 80.0% activity against ST131 E. coli, followed by piperacillin-tazobactam (79.3% susceptible). Only 5.4%and 41.3% ST131 isolates were susceptible to cefepime and ceftibuten, respectively. MIC50/MIC90 values for these agents with QPX7728 were ≤ 0.015/≤ 0.015 mg/L for cefepime and ≤ 0.015/0.06 mg/L for ceftolozane with the inhibitor at 8 mg/L and ≤ 0.015/0.03 mg/L for ceftibuten with the inhibitor at 4 mg/L. Conclusion QPX7728 lowered the MICs for all agents tested to clinically achievable levels when tested against isolates multidrug resistant belonging to important clones responsible to the dissemination of KPC, CTX variants, and metallo-β-lactamases. The development of this broad β-lactamase inhibitor should be pursued. Table 1 Disclosures Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Jill Lindley, Allergan (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Olga Lomovskaya, PhD, Qpex Biopharma (Employee)

scholarly journals Risk Factors for and Mechanisms of COlistin Resistance Among Enterobacterales: Getting at the CORE of the Issue

2021 ◽  
Author(s):  
John P Mills ◽  
Laura J Rojas ◽  
Steve H Marshall ◽  
Susan D Rudin ◽  
Andrea M Hujer ◽  
...  
Keyword(s):  
Case Control Study ◽  
Clinical Isolates ◽  
Colistin Resistance ◽  
E Coli ◽  
The Core ◽  
Increased Risk ◽  
Recent Emergence ◽  
Enterobacter Species ◽  
Ann Arbor ◽  
Control Study

Abstract Background Despite the recent emergence of plasmid-mediated colistin resistance, the epidemiology and mechanisms of colistin-resistant Enterobacterales (CORE) infections remain poorly understood. Methods A case-case-control study was conducted utilizing routine clinical isolates obtained at a single tertiary health system in Ann Arbor, MI. Patients with CORE isolates from January 1st 2016 to March 31st 2017 were matched 1:1 with patients with colistin-susceptible Enterobacterales (COSE) and uninfected controls. Multivariable logistic regression was used to compare clinical and microbiologic features of patients with CORE and COSE to controls. A subset of available CORE isolates underwent whole genome sequencing to identify putative colistin resistance genes. Results Of 16,373 tested clinical isolates, 166 (0.99%) were colistin-resistant, representing 103 unique patients. Among 103 CORE isolates, 103 COSE isolates, and 102 uninfected controls, antibiotic exposure in the antecedent 90 days and age > 55 years were predictors of both CORE and COSE. Of 33 isolates that underwent WGS, a large variety of mutations associated with colistin resistance were identified, including 4 mcr-1/mcr-1.1 genes and 4 pmrA/B mutations among 9 Escherichia coli isolates; 5 mgrB and 3 PmrA mutations among 8 Klebsiella pneumoniae isolates. Genetic mutations found in Enterobacter species were not associated with known phenotypic colistin resistance. Conclusions Increased age and prior antibiotic receipt were associated with increased risk for patients with CORE, and for patients with COSE. Mcr-1, pmrA/B, and mgrB were the predominant colistin resistance-associated mutations identified among E. coli and K. pneumoniae, respectively. Mechanisms of colistin resistance among Enterobacter species could not be determined.

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