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Emerging Infectious Diseases Nov 2023We identified a novel ceftazidime/avibactam resistance mechanism in sequence type 11 Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae. Plasmid recombination...
We identified a novel ceftazidime/avibactam resistance mechanism in sequence type 11 Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae. Plasmid recombination and chromosomal integration formed a novel virulence plasmid and provided an additional promoter for bla, leading to bla overexpression and ceftazidime/avibactam resistance. Genetic rearrangement contributed to convergence of hypervirulence and ceftazidime/avibactam resistance.
Topics: Humans; Ceftazidime; Anti-Bacterial Agents; Klebsiella pneumoniae; Klebsiella Infections; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Microbial Sensitivity Tests
PubMed: 37877674
DOI: 10.3201/eid2911.230830 -
EcoSal Plus Dec 2023EcoCyc is a bioinformatics database available online at EcoCyc.org that describes the genome and the biochemical machinery of K-12 MG1655. The long-term goal of the... (Review)
Review
EcoCyc is a bioinformatics database available online at EcoCyc.org that describes the genome and the biochemical machinery of K-12 MG1655. The long-term goal of the project is to describe the complete molecular catalog of the cell, as well as the functions of each of its molecular parts, to facilitate a system-level understanding of . EcoCyc is an electronic reference source for biologists and for biologists who work with related microorganisms. The database includes information pages on each gene product, metabolite, reaction, operon, and metabolic pathway. The database also includes information on the regulation of gene expression, gene essentiality, and nutrient conditions that do or do not support the growth of . The website and downloadable software contain tools for the analysis of high-throughput data sets. In addition, a steady-state metabolic flux model is generated from each new version of EcoCyc and can be executed online. The model can predict metabolic flux rates, nutrient uptake rates, and growth rates for different gene knockouts and nutrient conditions. Data generated from a whole-cell model that is parameterized from the latest data on EcoCyc are also available. This review outlines the data content of EcoCyc and of the procedures by which this content is generated.
Topics: Escherichia coli; Escherichia coli K12; Databases, Genetic; Software; Computational Biology; Escherichia coli Proteins
PubMed: 37220074
DOI: 10.1128/ecosalplus.esp-0002-2023 -
Clinical Infectious Diseases : An... Aug 2023Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of...
BACKGROUND
Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort.
METHODS
Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture.
RESULTS
Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec.
CONCLUSIONS
Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.
Topics: Humans; Prospective Studies; beta-Lactamases; Escherichia coli; Bacterial Proteins; Carbapenem-Resistant Enterobacteriaceae; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 37154071
DOI: 10.1093/cid/ciad288 -
Journal of Microbiology, Immunology,... Feb 2024Carbapenem-resistant Klebsiella pneumoniae (CRKP) is capable of causing serious community and hospital-acquired infections. However, currently, the identification of...
BACKGROUND/PURPOSE
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is capable of causing serious community and hospital-acquired infections. However, currently, the identification of CRKP is complex and inefficient. Hence, this study aimed to develop methods for the early and effective identification of CRKP to allow reasonable antimicrobial therapy in a timely manner.
METHODS
K. pneumoniae (KP)-, K. pneumoniae carbapenemase (KPC)- and New Delhi metallo-β-lactamase (NDM)- specific CRISPR RNAs (crRNAs), polymerase chain reaction (PCR) primers and recombinase-aided amplification (RAA) primers were designed and screened in conserved sequence regions. We established fluorescence and lateral flow strip assays based on CRISPR/Cas13a combined with PCR and RAA, respectively, to assist in the detection of CRKP. Sixty-one clinical strains (including 51 CRKP strains and 10 carbapenem-sensitive strains) were collected for clinical validation.
RESULTS
Using the PCR-CRISPR assay, the limit of detection (LOD) for KP and the blaKPC and blaNDM genes reached 1 copy/μL with the fluorescence signal readout. Using the RAA-CRISPR assay, the LOD could reach 10 copies/μL with both the fluorescence signal readout and the lateral flow strip readout. Additionally, the positivity rates of CRKP-positive samples detected by the PCR/RAA-CRISPR fluorescence and RAA-CRISPR lateral flow strip methods was 92.16% (47/51). The sensitivity and specificity reached 100% for KP and blaKPC and blaNDM gene detection. For detection in a simulated environmental sample, 1 CFU/cm KP could be detected.
CONCLUSION
We established PCR/RAA-CRISPR assays for the detection of blaKPC and blaNDM carbapenemase genes, as well as KP, to facilitate the detection of CRKP.
Topics: Humans; Anti-Bacterial Agents; Klebsiella pneumoniae; CRISPR-Cas Systems; Microbial Sensitivity Tests; beta-Lactamases; Carbapenems; Carbapenem-Resistant Enterobacteriaceae; Klebsiella Infections
PubMed: 37963801
DOI: 10.1016/j.jmii.2023.10.010 -
The Journal of Hospital Infection Dec 2023Carbapenemase-producing Enterobacterales (CPE) cases increases every year in Denmark and the proportion of CPE-positive cases with a travel history decreases. Several... (Review)
Review
Carbapenemase-producing Enterobacterales (CPE) cases increases every year in Denmark and the proportion of CPE-positive cases with a travel history decreases. Several epidemiological links show transmission in Danish healthcare setting indicating infection prevention and control challenges and raising questions about the Danish CPE screening protocol. The aim of this review was to identify additional risk factors to those described in the Danish CPE-screening protocol in order to detect the Danish CPE-positive patients and thereby reduce the risk of transmission and outbreaks. A systematic literature search was conducted in PubMed, Embase and Cochrane Library during March 2022. A total of 1487 articles were screened, and 19 studies were included. Retrieved studies dealt with patients with laboratory-confirmed CPE (colonization and/or infection) and associated risk factors. Antimicrobial therapy, especially broad-spectrum antimicrobial agents, prior or current hospitalization of approximately one week in ICU and 20-28 days in other wards and travel history with or without hospitalization abroad were significant risk factors associated with CPE acquisition. Comorbidities and invasive procedures were identified as risk factors, but without identifying specific comorbidities or invasive procedures associated with risk for CPE-acquisition. This study suggests the need to develop an additional algorithm for CPE-screening in Denmark. In addition to risk-based screening on admission, screening of inpatients should be considered. The screening protocol might include screening of inpatients with comorbidities who are hospitalized >1 week in ICU or >3 weeks in other wards and who have previously received or currently are receiving antibiotic treatment. Further research is needed to develop a new CPE-screening algorithm.
Topics: Humans; Enterobacteriaceae Infections; Carbapenem-Resistant Enterobacteriaceae; Bacterial Proteins; beta-Lactamases; Gammaproteobacteria
PubMed: 37802236
DOI: 10.1016/j.jhin.2023.09.018 -
Emerging Microbes & Infections Dec 2023Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from... (Meta-Analysis)
Meta-Analysis Review
Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from ESBL-PE bacteremia is very important. The present systematic review and meta-analysis aimed to evaluate studies to determine predictors associated with ESBL-PE bacteremia mortality. We searched PubMed and Cochrane Library databases for all relevant publications from January 2000 to August 2022. The outcome measure was mortality rate. In this systematic review of 22 observational studies, 4607 patients with ESBL-PE bacteremia were evaluated, of whom 976 (21.2%) died. The meta-analysis showed that prior antimicrobial therapy (RR, 2.89; 95% CI, 1.22-6.85), neutropenia (RR, 5.58; 95% CI, 2.03-15.35), nosocomial infection (RR, 2.46; 95% CI, 1.22-4.95), rapidly fatal underlying disease (RR, 4.21; 95% CI, 2.19-8.08), respiratory tract infection (RR, 2.12; 95% CI, 1.33-3.36), Pitt bacteremia score (PBS) (per1) (RR, 1.35; 95% CI, 1.18-1.53), PBS ≥ 4 (RR, 4.02; 95% CI, 2.77-5.85), severe sepsis (RR, 11.74; 95% CI, 4.68-29.43), and severe sepsis or septic shock (RR, 4.19; 95% CI, 2.83-6.18) were found to be mortality predictors. Moreover, urinary tract infection (RR, 0.15; 95% CI, 0.04-0.57) and appropriate empirical therapy (RR, 0.39; 95% CI, 0.18-0.82) were found to be a protective factor against mortality. Patients with ESBL-PE bacteremia who have the aforementioned require prudent management for improved outcomes. This research will lead to better management and improvement of clinical outcomes of patients with bacteremia caused by ESBL-PE.
Topics: Humans; Enterobacteriaceae Infections; Enterobacteriaceae; Bacteremia; Sepsis; beta-Lactamases; Anti-Bacterial Agents; Retrospective Studies; Treatment Outcome
PubMed: 37219067
DOI: 10.1080/22221751.2023.2217951 -
Frontiers in Cellular and Infection... 2024The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to... (Review)
Review
The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to acquire mobile genetic elements such as plasmids, represent one of the most hazardous microorganisms. This phenomenon poses a serious threat to public health. Notably, the significance of tigecycline, a member of the antibiotic group glycylcyclines and derivative of tetracyclines has increased. Tigecycline is one of the last-resort antimicrobial drugs used to treat complicated infections caused by multidrug-resistant (MDR) bacteria, extensively drug-resistant (XDR) bacteria or even pan-drug-resistant (PDR) bacteria. The primary mechanisms of tigecycline resistance include efflux pumps' overexpression, genes and outer membrane porins. Efflux pumps are crucial in conferring multi-drug resistance by expelling antibiotics (such as tigecycline by direct expelling) and decreasing their concentration to sub-toxic levels. This review discusses the problem of tigecycline resistance, and provides important information for understanding the existing molecular mechanisms of tigecycline resistance in . The emergence and spread of pathogens resistant to last-resort therapeutic options stands as a major global healthcare concern, especially when microorganisms are already resistant to carbapenems and/or colistin.
Topics: Tigecycline; Anti-Bacterial Agents; Enterobacteriaceae; Humans; Drug Resistance, Multiple, Bacterial; Drug Resistance, Bacterial; Minocycline; Microbial Sensitivity Tests; Plasmids; Enterobacteriaceae Infections
PubMed: 38655285
DOI: 10.3389/fcimb.2024.1289396 -
Emerging Infectious Diseases Aug 2023After an increase in carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections and associated deaths in the neonatal unit of a South Africa hospital, we... (Review)
Review
After an increase in carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections and associated deaths in the neonatal unit of a South Africa hospital, we conducted an outbreak investigation during October 2019-February 2020 and cross-sectional follow-up during March 2020-May 2021. We used genomic and epidemiologic data to reconstruct transmission networks of outbreak-related clones. We documented 31 cases of culture-confirmed CRKP infection and 14 deaths. Two outbreak-related clones (bla sequence type [ST] 152 [n = 16] and bla ST307 [n = 6]) cocirculated. The major clone bla ST152 accounted for 9/14 (64%) deaths. Transmission network analysis identified possible index cases of bla ST307 in October 2019 and bla ST152 in November 2019. During the follow-up period, 11 new cases of CRKP infection were diagnosed; we did not perform genomic analysis. Sustained infection prevention and control measures, adequate staffing, adhering to bed occupancy limits, and antimicrobial stewardship are key interventions to control such outbreaks.
Topics: Infant, Newborn; Humans; Bacterial Proteins; Klebsiella pneumoniae; South Africa; Cross-Sectional Studies; Klebsiella Infections; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Disease Outbreaks; Sepsis; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 37486166
DOI: 10.3201/eid2908.230484 -
Journal of Global Antimicrobial... Dec 2023Carbapenem-resistant Enterobacterales (CRE) commonly cause hospital-acquired infections and hospital outbreaks worldwide, with an alarming increase in Africa,... (Review)
Review
OBJECTIVES
Carbapenem-resistant Enterobacterales (CRE) commonly cause hospital-acquired infections and hospital outbreaks worldwide, with an alarming increase in Africa, necessitating review of regional CRE epidemiological trends.
METHODS
A systematic review was conducted using PRISMA guidelines, searching PubMed, Scopus and Web of Science databases for studies describing CRE distribution, risk factors for CRE acquisition and clinical outcome of CRE infections in Africa.
RESULTS
One-hundred and sixty-nine studies were included, with the majority from North Africa (92/169, 54.4%). Most studies (136/169; 80.4%) focused only on infection, with a total of 15666 CRE isolates (97.4% clinical infection, 2.6% colonisation). The leading bacterial species included Klebsiella (72.2%), Escherichia coli (13.5%), and Enterobacter (8.3%). The most frequently detected carbapenemases were NDM (43.1%) and OXA-48-like (42.9%). Sequence types were reported in 44 studies, with ST101 and ST147 most commonly reported in K. pneumoniae, and ST410, ST167 and ST38 in E. coli. Previous antibiotic use, prior hospitalisation, surgical procedures, indwelling devices, intensive care unit admission and prolonged hospital stay, were the most frequent factors associated with CRE infection/colonisation. Crude mortality for CRE infection was 37%.
CONCLUSION
Although K. pneumoniae and E. coli remain the most frequent CRE in Africa, observed sequence types are not the commonly reported global 'high-risk' clones. The distribution of species and carbapenemases differs across African regions, while risk factors for CRE colonisation/infection, and patient outcomes are similar to those reported globally. There are limited data on CREs from parts of Africa, highlighting the need to strengthen epidemiologic surveillance programmes in the region.
Topics: Humans; Carbapenems; Escherichia coli; Enterobacteriaceae Infections; Carbapenem-Resistant Enterobacteriaceae; Klebsiella pneumoniae; Risk Factors
PubMed: 37879456
DOI: 10.1016/j.jgar.2023.10.008 -
Pharmacological Research Aug 2023Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known... (Review)
Review
Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.
Topics: Humans; Enterobacteriaceae; Noncommunicable Diseases; Gastrointestinal Microbiome; Inflammation; Microbiota
PubMed: 37460001
DOI: 10.1016/j.phrs.2023.106856