Genomic epidemiology, antimicrobial resistance and virulence factors of Enterobacter cloacae complex causing community-onset bloodstream infections in a tertiary care hospital of Nepal
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ABSTRACT:
PROVIDER: PRJEB45230 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR5987090_1.fastq.gz | Fastqsanger.gz | |||
| ERR5987090_2.fastq.gz | Fastqsanger.gz | |||
| ERR5987100_1.fastq.gz | Fastqsanger.gz | |||
| ERR5987100_2.fastq.gz | Fastqsanger.gz | |||
| ERR5987110_1.fastq.gz | Fastqsanger.gz |
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Project description:The epidemic community-acquired methicillin-resistant S. aureus (CA-MRSA) clone USA300 has recently become a leading cause of hospital-associated bloodstream infections (BSI). Leveraging this recent introduction into hospitals and the limited genetic variation across the USA300 strains, we combined microbial comparative genomics with phenotypic analyses to discover adaptive mutations. USA300 isolates from BSI were found to have independently evolved single nucleotide variants in the transcriptional regulator sarZ. sarZ inactivation lead to altered expression of virulence factors, resulting in increased lethality in a murine model of BSI. Thus, USA300 strains can optimize their fitness in hospitals through evolution of higher virulence.
2022-10-08 | GSE185544 | GEO
Project description:ObjectivesCommunity-onset bloodstream infections (BSIs) caused by carbapenemase-producing Enterobacter cloacae complex (ECC) species are increasing internationally. This observation suggests that ECC are emerging pathogens, requiring for detailed understanding on their genomic epidemiology including transmission dynamics and antimicrobial resistance profiles.Patients and methodsWe performed WGS on 79 Enterobacter spp. isolated from the patients with clinically significant BSIs and admitted to emergency department of a major tertiary hospital in Nepal between April 2016 and October 2017.ResultsWe identified 5 species and 13 STs of ECC. Enterobacter xiangfangensis ST171, one of the globally emerging carbapenem resistant ECC clones with epidemic potential, was the most prevalent (42%). Phylogenetic analysis showed a large (>19 400 SNPs) core genome SNP distance across major STs, which was minimal (<30 SNPs) among the isolates of each prevalent ST, suggesting the relatively recent importation of major STs followed by local clonal expansions. Genomic evidence for resistance to all major antimicrobial classes except for colistin and macrolides was detected. A limited number of isolates also carried bla NDM-1 (n = 2) and bla OXA-48 (n = 1) carbapenemase genes. Virulence factors encoding siderophores (24%), T6SSD (25%) and fimbriae (54%) were detected.ConclusionsOur study highlighted that MDR ECC clones are important pathogens of BSIs in community. Though of low prevalence, carbapenem resistance observed in our ECC isolates raised concern about further community dissemination, underscoring the need for community surveillance to identify MDR ECC clones with epidemic potential.
| S-EPMC9155248 | biostudies-literature
Project description:Background:Treatment and prevention of wound infection continues to be a challenging issue in clinical settings of Nepal especially in the context of globally growing problem of antimicrobial resistance. Study on opportunistic pathogens and sensitivity to commonly prescribed local antimicrobial agents are cardinal to reduce the disease burden of wound infections. The aim of this study was to determine the prevalence and antimicrobial susceptibility pattern of methicillin resistant Staphylococcus aureus (MRSA) and extended spectrum ?-lactamase (ESBL) producing bacteria from wound infections of patients at a tertiary care hospital in Nepal. Methods:Pus specimens were processed using standard microbiological procedures. Antimicrobial susceptibility test was performed following the modified Kirby Bauer disc diffusion technique. Clinical information of patients was obtained from preformed questionnaire and hospital record. Results:One hundred eighty two pus specimens from wounds of different body parts: leg, hand, backside, abdominal part, foot, breast and chest, head and neck region were collected and analyzed; 113 bacterial isolates were isolated showing the overall bacterial growth rate of 62%, where the highest rate was among patients of ?10 years age group (82.1%). A higher rate (68.5%) of bacterial isolates were from inpatients (p?<?0.05). Among 116 bacterial isolates, Staphylococcus aureus was the most predominant bacteria (56.9%) followed by Escherichia coli (8.6%), coagulase negative staphylococci (7.8%), Acinetobacter spp. (5.2%), Klebsiella pneumoniae (5.2%), Pseudomonas aeruginosa (4.3%), Enterococcus spp. (4.3%), Citrobacter freundii (2.6%), Proteus vulgaris (1.6%) and P. mirabilis (0.9%). Both Gram positive (73.3%) and negative (78.8%) isolates showed high frequency of sensitive to gentamycin. Conclusion:Among S. aureus isolates, 60.6% were MRSA strains, whereas 40% of K. pneumoniae and 33.3% of C. freundii were ESBL producing bacteria followed by E. coli (25%). It is thus paramount to address the burden of silently and speedily increasing infections caused by drug resistant strains of MRSA and ESBL in Nepal.
| S-EPMC6174564 | biostudies-other
Project description:MultiSeq-AMR: an amplicon sequencing workflow for BSI diagnosis
| PRJEB82614 | ENA
Project description:Staphylococcus aureus, an important nosocomial pathogen, is frequently associated with infections in human. The management of the infections by it especially methicillin resistant ones is often difficult because methicillin resistant S. aureus is usually resistant to multiple antibiotics. Macrolide-lincosamide streptogramin B family of antibiotics is commonly used to treat such infections as an alternative to vancomycin.This study was conducted over the period of one and half year from November 2013-April 2015 in Microbiology laboratory of Nepal Medical College and Teaching Hospital, Kathmandu, Nepal to find the incidence of different phenotypes of MLSB resistance among S. aureus from clinical samples and their association with methicillin resistance. Two hundred seventy isolates of S. aureus were included in the study. Methicillin resistance was detected by cefoxitin disc diffusion method and inducible clindamycin resistance by erythromycin and clindamycin disc approximation test (D-test).Of the 270 clinical isolates of S. aureus, 25.1% (68/270) were MRSA. Erythromycin and clindamycin resistance was seen in 54.4% (147/270) and 41.8% (113/270) isolates respectively. Resistance to erythromycin and clindamycin were higher in MRSA as compared to MSSA (erythromycin-resistance: 88.2% Vs 39.1% and clindamycin-resistance: 79.4% Vs 41.8%). The overall prevalence of iMLSB and cMLSB phenotype was 11.48% (31/270) and 29.25% (79/270) respectively. Both iMLSB and cMLSB phenotypes predominated in MRSA strains.Detection rate of MRSA in our study shows the necessity to improve in healthcare practices and to formulate new policy for the control of MRSA infections. Clindamycin resistance in the form of iMLSB and cMLSB especially among MRSA emphasizes the need of D-test to be performed routinely in our set up while using clindamycin as an alternative choice to anti-staphylococcal antibiotics like vancomycin and linezolid in the treatment of staphylococcal infections.
| S-EPMC5504788 | biostudies-other
Project description:Background: Non-malaria febrile illnesses such as bacterial bloodstream infections (BSI) are a leading cause of disease and mortality in the tropics. However, there are no reliable, simple diagnostic tests for identifying BSI or other severe non-malaria febrile illnesses. We hypothesized that different infectious agents responsible for severe febrile illness would impact on the host metabololome in different ways, and investigated the potential of plasma metabolites for diagnosis of non-malaria febrile illness. </p> Methodology: We conducted a comprehensive mass-spectrometry based metabolomics analysis of the plasma of 61 children with severe febrile illness from a malaria-endemic rural African setting. Metabolite features characteristic for non-malaria febrile illness, BSI, severe anemia and poor clinical outcome were identified by receiver operating curve analysis. </p> Principal Findings: The plasma metabolome profile of malaria and non-malaria patients revealed fundamental differences in host response, including a differential activation of the hypothalamic-pituitary-adrenal axis. A simple corticosteroid signature was a good classifier of severe malaria and non-malaria febrile patients (AUC 0.82, 95% CI: 0.70-0.93). Patients with BSI were characterized by upregulated plasma bile metabolites; a signature of two bile metabolites was estimated to have a sensitivity of 98.1% (95% CI: 80.2-100) and a specificity of 82.9% (95% CI: 54.7-99.9) to detect BSI in children younger than 5 years. This BSI signature demonstrates that host metabolites can have a superior diagnostic sensitivity compared to pathogen-detecting tests to identify infections characterized by low pathogen load such as BSI. </p> Conclusions: This study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings.
2016-03-17 | MTBLS315 | MetaboLights
Project description:AimAlthough carbapenem is the last-resort drug for treating drug-resistant Gram-negative bacterial infections, prevalence of carbapenem-resistant bacteria has substantially increased worldwide owing to irrational use of antibiotics particularly in developing countries like Nepal. Therefore, this study was aimed to determine the prevalence of carbapenemase-producing K. pneumoniae and to detect the carbapenemase genes (blaNDM-2 and blaOXA-48) in at a tertiary care hospital in Nepal.Materials and methodsA hospital-based cross-sectional study was carried out from June 2018 to January 2019 at the Microbiology Laboratory of Annapurna Neurological Institute and Allied Sciences, Kathmandu, Nepal. Different clinical samples were collected and cultured in appropriate growth media. Biochemical tests were performed for the identification of K. pneumoniae. Antibiotic susceptibility testing (AST) was performed by the Kirby-Bauer disc diffusion method. The modified Hodge test (MHT) was performed to detect carbapenemase producers. The plasmid was extracted by the modified alkaline hydrolysis method. Carbapenemase-producing K. pneumoniae were further confirmed by detecting blaNDM-2 and blaOXA-48 genes by PCR using specific forward and reverse primers followed by gel electrophoresis.ResultsOut of the total 720 samples, 38.9% (280/720) were culture positive. K. pneumoniae was the most predominant isolate 31.4% (88/280). Of 88 K. pneumoniae isolates, 56.8% (50/88) were multi-drug resistant (MDR), and 51.1% (45/88) were MHT positive. Colistin showed the highest sensitivity (100%; 88/88), followed by tigecycline (86.4%; 76/88). blaNDM-2 and blaOXA-48 genes were detected in 24.4% (11/45) and 15.5% (7/45) of carbapenemase-producing K. pneumoniae isolates, respectively.ConclusionThe rate of MDR and carbapenemase production was high in the K. pneumoniae isolates. Colistin and tigecycline could be the drug of choice for the empirical treatments of MDR and carbapenemase-producing K. pneumoniae. Our study provides a better understanding of antibiotic resistance threat and enables physicians to select the most appropriate antibiotics.
| S-EPMC8474737 | biostudies-literature
Project description:Resistance to antibiotics, biofilm formation and the presence of virulence factors play important roles in increased mortality associated with infection by staphylococci. The macrolide lincosamide streptogramin B (MLSB) family of antibiotics is commonly used to treat infections by methicillin-resistant isolates. Clinical failure of clindamycin therapy has been reported due to multiple mechanisms that confer resistance to MLSB. This study aims to find the incidence of different phenotypes of MLSB resistance and biofilm production among staphylococci. A total of 375 staphylococci were isolated from different clinical samples, received from two tertiary care hospitals in Nepal. Methicillin resistance was detected by cefoxitin disc diffusion method and inducible clindamycin resistance by D test, according to CLSI guidelines. Biofilm formation was detected by the tissue culture plate method and PCR was used to detect ica genes. Of the total staphylococci isolates, 161 (42.9%) were Staphylococcus aureus, with 131 (81.4%) methicillin-resistant strains, and 214 (57.1%) isolates were coagulase-negative staphylococci, with 143 (66.8%) methicillin-resistant strains. The overall prevalence of constitutive MLSB (cMLSB) and inducible MLSB (iMLSB) phenotypes was 77 (20.5%) and 87 (23.2%), respectively. Both iMLSB and cMLSB phenotypes predominated in methicillin-resistant isolates. The tissue culture plate method detected biofilm formation in 174 (46.4%) isolates and ica genes in 86 (22.9%) isolates. Among biofilm producing isolates, cMLSB and iMLSB phenotypes were 35 (20.1%) and 27 (15.5%), respectively. The cMLSB and iMLSB were 11 (12.8%) and 19 (22.1%), respectively, in isolates possessing ica genes. Clindamycin resistance in the form of cMLSB and iMLSB, especially among MRSA, emphasizes the need for routine D tests to be performed in the lab.
| S-EPMC8702181 | biostudies-literature
Project description:The burden of antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs) is largely unknown. Here, we evaluate attributable mortality of AMR infections in Indonesia. We used routine databases of the microbiology laboratory and hospital admission at Dr. Wahidin Sudirohusodo Hospital, a tertiary-care hospital in South Sulawesi from 2015 to 2018. Of 77,752 hospitalized patients, 8,341 (10.7%) had at least one blood culture taken. Among patients with bacteriologically confirmed bloodstream infections (BSI), the proportions of patients with AMR BSI were 78% (81/104) for third-generation cephalosporin-resistant (3GCR) Escherichia coli, 4% (4/104) for 3GCR plus carbapenem-resistant E. coli, 56% (96/171) for 3GCR Klebsiella pneumoniae, 25% (43/171) for 3GCR plus carbapenem-resistant K. pneumoniae, 51% (124/245) for methicillin-resistant Staphylococcus aureus, 48% (82/171) for carbapenem-resistant Acinetobacter spp., and 19% (13/68) for carbapenem-resistant Pseudomonas aeruginosa. Observed in-hospital mortality of patients with AMR BSI was 49.7% (220/443). Compared with patients with antimicrobial-susceptible BSI and adjusted for potential confounders, the excess mortality attributable to AMR BSI was -0.01 (95% CI: -15.4, 15.4) percentage points. Compared with patients without a BSI with a target pathogen and adjusted for potential confounders, the excess mortality attributable to AMR BSI was 29.7 (95%CI: 26.1, 33.2) percentage points. This suggests that if all the AMR BSI were replaced by no infection, 130 (95%CI: 114, 145) deaths among 443 patients with AMR BSI might have been prevented. In conclusion, the burden of AMR infections in Indonesian hospitals is likely high. Similar large-scale evaluations should be performed across LMICs to inform interventions to mitigate AMR-associated mortality.
| S-EPMC10021607 | biostudies-literature
Project description:The presence of Donor-Specific anti-HLA Antibodies (DSA) is associated with an increased risk of both acute and chronic antibody-mediated rejection (AMR) in kidney allografts. AMR has remained challenging in kidney transplantation and is the major cause of late allograft loss. However, not all patients with DSA develop AMR, leading to the question of whether this represents accommodation, if other protective mechanisms exist or if this is actually a state of pre-rejection. Clinical and histological features, and gene expression profiles of kidney biopsy and blood samples of donor-specific antibody (DSA)+ patients without rejection were compared to antibody-mediated rejection (AMR) patients to elucidate the mechanisms involved in prevention of AMR. Of the 71 DSA+ patients, 46 had diagnosis of AMR and 25 did not show rejection. 50 DSA- patients without rejection were used as control. A subgroup of patients with available biopsy (n=61) and blood samples (n=54) were analyzed by microarrays. Both, DSA+/AMR+ and DSA+/AMR- biopsies showed increased expression of gene transcripts associated with cytotoxic T, natural killer cells, macrophages, interferon-gamma and rejection compared to DSA- biopsies. Regulatory T cell transcripts were up-regulated in DSA+/AMR+ and B cell transcripts in DSA+/AMR- biopsies. Whole blood gene expression analysis showed increased immune activity in only DSA+/AMR+ patients. There were no differentially expressed tolerant genes studied (n=14) in the blood or biopsy specimens of DSA+/AMR- patients. During a median 36 months follow-up, 4 DSA+/AMR- patients developed AMR, 12 continued to have DSAs but 9 lost DSAs. Gene expression profiles did not predict the development of AMR or persistence of DSAs. These results indicate increased immune activity in DSA+/AMR- biopsies despite lack of histologic findings of rejection. All clinically indicated kidney transplant biopsies performed at our institution after January 2009 were reviewed and 263 patients with anti-HLA antibody testing at the time of biopsy were identified. There were 71 DSA+ and 192 DSA- patients (Figure 1). Of the 71 DSA+ patients, 46 had biopsy diagnosis of acute AMR (n=9) or chronic AMR (n=37), and 25 had normal histopathology or minimal non-specific interstitial fibrosis/tubular atrophy (IFTA). Of the 192 DSA- patients, 50 patients with normal histology and/or mild non-specific IFTA were used as a control group. Clinical and histopathological findings of these 3 groups (DSA+/AMR+, DSA+/AMR- and DSA-) were analyzed. A subgroup of patients who were enrolled in the Institutional Review Board-approved âImmune Monitoring Studyâ who had clinically indicated biopsy (n=61) and whole blood samples (n=54) stored were used for genomic analysis. Twenty-eight biopsy and blood samples from DSA+/AMR+ patients, 13 biopsy and 14 blood samples from DSA+/AMR- patients, and 20 biopsy and 12 blood samples from DSA- patients, were available for microarray analysis.
2013-08-23 | E-GEOD-50084 | biostudies-arrayexpress