Notes from the Field: Large Cluster of Verona Integron-Encoded Metallo-Beta-Lactamase-Producing Carbapenem-Resistant Pseudomonas aeruginosa Isolates Colonizing Residents at a Skilled Nursing Facility - Chicago, Illinois, November 2016-March 2018.
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SUBMITTER: Clegg WJ
PROVIDER: S-EPMC6181260 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Metallo-?-lactamases (MBLs) are of increasing clinical significance; the development of clinically useful MBL inhibitors is challenged by the rapid evolution of variant MBLs. The Verona integron-borne metallo-?-lactamase (VIM) enzymes are among the most widely distributed MBLs, with >40 VIM variants having been reported. We report on the crystallographic analysis of VIM-5 and comparison of biochemical and biophysical properties of VIM-1, VIM-2, VIM-4, VIM-5, and VIM-38. Recombinant VIM variants were produced and purified, and their secondary structure and thermal stabilities were investigated by circular dichroism analyses. Steady-state kinetic analyses with a representative panel of ?-lactam substrates were carried out to compare the catalytic efficiencies of the VIM variants. Furthermore, a set of metalloenzyme inhibitors were screened to compare their effects on the different VIM variants. The results reveal only small variations in the kinetic parameters of the VIM variants but substantial differences in their thermal stabilities and inhibition profiles. Overall, these results support the proposal that protein stability may be a factor in MBL evolution and highlight the importance of screening MBL variants during inhibitor development programs.
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Project description:Surveillance data from Southern Ontario show that a majority of Verona Integron-encoded Metallo-β-lactamase (VIM)-producing Enterobacteriaceae are locally acquired. To better understand the local epidemiology, we analysed clinical and environmental blaVIM-positive Enterobacteriaceae from the area. Clinical samples were collected within the Toronto Invasive Bacterial Diseases Network (2010-2016); environmental water samples were collected in 2015. We gathered patient information on place of residence and hospital admissions prior to the diagnosis. Patients with and without plausible source of acquisition were compared regarding risk exposures. Microbiological isolates underwent whole-genome sequencing (WGS); blaVIM carrying plasmids were characterized. We identified 15 patients, thereof 11 with blaVIM-1-positive Enterobacter hormaechei within two genetic clusters based on WGS. Whereas no obvious epidemiologic link was identified among cluster I patients, those in cluster II were connected to a hospital outbreak. Except for patients with probable acquisition abroad, we did not identify any further risk exposures. Two blaVIM-1-positive E. hormaechei from environmental waters matched with the clinical clusters; plasmid sequencing suggested a common ancestor plasmid for the two clusters. These data show that both clonal spread and horizontal gene transfer are drivers of the dissemination of blaVIM-1-carrying Enterobacter hormaechei in hospitals and the aquatic environment in Southern Ontario, Canada.
| S-EPMC7596063 | biostudies-literature
Project description:Background:Verona Integron-encoded Metallo-β-lactamase-positive Pseudomonas aeruginosa (VIM-PA) can cause nosocomial infections and may be responsible for increased mortality. Multidrug resistance in VIM-PA complicates treatment. We aimed to assess the contribution of VIM-PA to mortality in patients in a large tertiary care hospital in the Netherlands. Methods:A focus group of five members created a scheme to define related mortality based on clinical and diagnostic findings. Contribution to mortality was categorized as "definitely", "probably", "possibly", or "not" related to infection with VIM-PA, or as "unknown". Patients were included when infected with or carrier of VIM-PA between January 2008 and January 2016. Patient-related data and specific data on VIM-PA cultures were retrieved from the electronic laboratory information system. For patients who died in our hospital, medical records were independently reviewed and thereafter discussed by three physicians. Results:A total of 198 patients with any positive culture with VIM-PA were identified, of whom 95 (48.0%) died. Sixty-seven patients died in our hospital and could be included in the analysis. The death of 15 patients (22.4%) was judged by all reviewers to be definitely related to infection with VIM-PA. In 17 additional patients (25.4%), death was probably or possibly related to an infection with VIM-PA. The level of agreement was 65.7% after the first evaluation, and 98.5% after one session of discussion. Conclusion:Using our assessment tool, infections with VIM-PA were shown to have an important influence on mortality in our complex and severely ill patients. The tool may be used for other (resistant) bacteria as well but this needs further exploration.
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Project description:Inhibition of β-lactamases presents a promising strategy to restore the β-lactams antibacterial activity to resistant bacteria. In this work, we found that aromatic carboxyl substituted 2-triazolylthioacetamides 1a-j inhibited VIM-2, exhibiting an IC50 value in the range of 20.6-58.6 μM. The structure-activity relationship study revealed that replacing the aliphatic carboxylic acid with aromatic carboxyl improved the inhibitory activity of 2-triazolylthioacetamides against VIM-2. 1a-j (16 mg/mL) restored the antibacterial activity of cefazolin against E. coli cell expressing VIM-2, resulting in a 4-8-fold reduction in MICs. The isothermal titration calorimetry (ITC) characterization suggested that the primary binding 2-triazolylthioacetamide (1b, 1c, or 1h) to VIM-2 was a combination of entropy and enthalpy contributions. Further, the crystal structure of VIM-2 in complex with 1b was obtained by co-crystallization with a hanging-drop vapour-diffusion method. The crystal structure analysis revealed that 1b bound to two Zn(II) ions of the enzyme active sites, formed H-bound with Asn233 and structure water molecule, and interacted with the hydrophobic pocket of enzyme activity center utilizing hydrophobic moieties; especially for the phenyl of aromatic carboxyl which formed π-π stacking with active residue His263. These studies confirmed that aromatic carboxyl substituted 2-triazolylthioacetamides are the potent VIM-2 inhibitors scaffold and provided help to further optimize 2-triazolylthioacetamides as VIM-2 even or broad-spectrum MβLs inhibitors.
| S-EPMC7022493 | biostudies-literature
Project description:BackgroundAntibiotic resistance is often spread through bacterial populations via conjugative plasmids. However, plasmid transfer is not well recognized in clinical settings because of technical limitations, and health care-associated infections are usually caused by clonal transmission of a single pathogen. In 2015, multiple species of carbapenem-resistant Enterobacteriaceae (CRE), all producing a rare carbapenemase, were identified among patients in an intensive care unit. This observation suggested a large, previously unrecognized plasmid transmission chain and prompted our investigation.MethodsElectronic medical record reviews, infection control observations, and environmental sampling completed the epidemiologic outbreak investigation. A laboratory analysis, conducted on patient and environmental isolates, included long-read whole-genome sequencing to fully elucidate plasmid DNA structures. Bioinformatics analyses were applied to infer plasmid transmission chains and results were subsequently confirmed using plasmid conjugation experiments.ResultsWe identified 14 Verona integron-encoded metallo-ß-lactamase (VIM)-producing CRE in 12 patients, and 1 additional isolate was obtained from a patient room sink drain. Whole-genome sequencing identified the horizontal transfer of blaVIM-1, a rare carbapenem resistance mechanism in the United States, via a promiscuous incompatibility group A/C2 plasmid that spread among 5 bacterial species isolated from patients and the environment.ConclusionsThis investigation represents the largest known outbreak of VIM-producing CRE in the United States to date, which comprises numerous bacterial species and strains. We present evidence of in-hospital plasmid transmission, as well as environmental contamination. Our findings demonstrate the potential for 2 types of hospital-acquired infection outbreaks: those due to clonal expansion and those due to the spread of conjugative plasmids encoding antibiotic resistance across species.
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Project description:Multidrug-resistant Pseudomonas aeruginosa commonly causes serious nosocomial infections. In this study, a novel lytic bacteriophage belonging to a member of the family Podoviridae, YMC01/01/P52 PAE BP, which infects carbapenem-resistant Pseudomonas aeruginosa, was isolated and characterized. YMC01/01/P52 PAE BP genome was analyzed by whole-genome sequencing and putative function identification. The bacteriophage genome consists of a double-stranded linear DNA genome of 49,381 bp with a GC content of 62.16%.
| S-EPMC3503104 | biostudies-literature
Project description:Passive samplers were deployed across Cleveland, OH and Chicago, IL to evaluate the spatial variability of airborne PCBs in urban areas. We measured SigmaPCB concentrations, the sum of 151 congeners or congener groups quantified using tandem mass spectrometry, spatial distributions, and congener profiles in two urban areas in the Great Lakes region. Mean SigmaPCB concentrations were significantly different between Cleveland (1.73 +/- 1.16 ng m(-3)) and Chicago (1.13 +/- 0.58 ng m(-3)) during the August 2008 sampling period. Mean congener profiles were compared with commercial Aroclor mixtures and found to be similar to Aroclor 1242 in Cleveland and similar to a mixture of 1242 and 1254 in Chicago. We observed large spatial variation in concentrations and weak or no significant autocorrelation between sites in both cities. "Hot spots" of high SigmaPCB concentrations were identified in both urban areas and the congener profiles at these locations were most strongly correlated to that of PCB Aroclor mixtures. Congener profiles showed important differences including the enrichment of dioxin-like congeners in Chicago.
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Project description: Not available
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Project description:ImportanceThere has been large geographic inequity in vaccination coverage across Chicago, Illinois, with higher vaccination rates in zip codes with residents who predominantly have high incomes and are White.ObjectiveTo determine the association between inequitable zip code-level vaccination coverage and COVID-19 mortality in Chicago.Design, setting, and participantsThis retrospective cohort study used Chicago Department of Public Health vaccination and mortality data and Cook County Medical Examiner mortality data from March 1, 2020, through November 6, 2021, to assess the association of COVID-19 mortality with zip code-level vaccination rates. Data were analyzed from June 1, 2021, to April 13, 2022.ExposuresZip code-level first-dose vaccination rates before the Alpha and Delta waves of COVID-19.Main outcomes and measuresThe primary outcome was deaths from COVID-19 during the Alpha and Delta waves. The association of a marginal increase in zip code-level vaccination rate with weekly mortality rates was estimated with a mixed-effects Poisson regression model, and the total number of preventable deaths in the least vaccinated quartile of zip codes was estimated with a linear difference-in-difference design.ResultsThe study population was 2 686 355 Chicago residents in 52 zip codes (median [IQR] age 34 [32-38] years; 1 378 658 [51%] women; 773 938 Hispanic residents [29%]; 783 916 non-Hispanic Black residents [29%]; 894 555 non-Hispanic White residents [33%]). Among residents in the least vaccinated quartile, 80% were non-Hispanic Black, compared with 8% of residents identifying as non-Hispanic Black in the most vaccinated quartile (P < .001). After controlling for age distribution and recovery from COVID-19, a 10-percentage point increase in zip code-level vaccination 6 weeks before the peak of the Alpha wave was associated with a 39% lower relative risk of death from COVID-19 (incidence rate ratio [IRR], 0.61 [95% CI, 0.52-0.72]). A 10-percentage point increase in zip code vaccination rate 6 weeks before the peak of the Delta wave was associated with a 24% lower relative risk of death (IRR, 0.76 [95% CI, 0.66-0.87]). The difference-in-difference estimate was that 119 Alpha wave deaths (72% [95% CI, 63%-81%]) and 108 Delta wave deaths (75% [95% CI, 66%-84%]) might have been prevented in the least vaccinated quartile of zip codes if it had had the vaccination coverage of the most vaccinated quartile.Conclusions and relevanceThese findings suggest that low zip code-level vaccination rates in Chicago were associated with more deaths during the Alpha and Delta waves of COVID-19 and that inequitable vaccination coverage exacerbated existing racial and ethnic disparities in COVID-19 deaths.
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential for rapid transmission in congregate settings. We describe the multidisciplinary response to an outbreak of coronavirus disease (COVID-19) in a large homeless shelter in Chicago, Illinois, USA. The response to the outbreak included 4 rounds of mass PCR testing of all staff and residents and subsequent isolation of persons who tested positive for SARS-CoV-2. We further describe the dynamics of the shelter outbreak by fitting a modified susceptible-exposed-infectious-recovered compartmental model incorporating the widespread SARS-CoV-2 testing and isolation measures implemented in this shelter. Our model demonstrates that rapid transmission of COVID-19 in the shelter occurred before the outbreak was detected; rates of transmission declined after widespread testing and isolation measures were put in place. Overall, we demonstrate the feasibility of mass PCR testing and isolation in congregate settings and suggest the necessity of prompt response to suspected COVID-19 outbreaks in homeless shelters.
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