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Journal of Clinical Microbiology Sep 2023rRNA gene Sanger sequencing is being used for the identification of cultured pathogens. A new diagnostic approach is sequencing of uncultured samples by using the... (Meta-Analysis)
Meta-Analysis
Direct 16S/18S rRNA Gene PCR Followed by Sanger Sequencing as a Clinical Diagnostic Tool for Detection of Bacterial and Fungal Infections: a Systematic Review and Meta-Analysis.
rRNA gene Sanger sequencing is being used for the identification of cultured pathogens. A new diagnostic approach is sequencing of uncultured samples by using the commercial DNA extraction and sequencing platform SepsiTest (ST). The goal was to analyze the clinical performance of ST with a focus on nongrowing pathogens and the impact on antibiotic therapy. A literature search used PubMed/Medline, Cochrane, Science Direct, and Google Scholar. Eligibility followed PRISMA-P criteria. Quality and risk of bias were assessed drawing on QUADAS-2 (quality assessment of diagnostic accuracy studies, revised) criteria. Meta-analyses were performed regarding accuracy metrics compared to standard references and the added value of ST in terms of extra found pathogens. We identified 25 studies on sepsis, infectious endocarditis, bacterial meningitis, joint infections, pyomyositis, and various diseases from routine diagnosis. Patients with suspected infections of purportedly sterile body sites originated from various hospital wards. The overall sensitivity (79%; 95% confidence interval [CI], 73 to 84%) and specificity (83%; 95% CI, 72 to 90%) were accompanied by large effect sizes. ST-related positivity was 32% (95% CI, 30 to 34%), which was significantly higher than the culture positivity (20%; 95% CI, 18 to 22%). The overall added value of ST was 14% (95% CI, 10 to 20%) for all samples. With 130 relevant taxa, ST uncovered high microbial richness. Four studies demonstrated changes of antibiotic treatment at 12% (95% CI, 9 to 15%) of all patients upon availability of ST results. ST appears to be an approach for the diagnosis of nongrowing pathogens. The potential clinical role of this agnostic molecular diagnostic tool is discussed regarding changes of antibiotic treatment in cases where culture stays negative.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Genes, rRNA; Meta-Analysis as Topic; Mycoses; Polymerase Chain Reaction; RNA, Ribosomal, 16S; RNA, Ribosomal, 18S; Sensitivity and Specificity; Systematic Reviews as Topic
PubMed: 37367430
DOI: 10.1128/jcm.00338-23 -
Nature Communications Aug 2023Microorganisms play essential roles in the health and resilience of cnidarians. Understanding the factors influencing cnidarian microbiomes requires cross study...
Microorganisms play essential roles in the health and resilience of cnidarians. Understanding the factors influencing cnidarian microbiomes requires cross study comparisons, yet the plethora of protocols used hampers dataset integration. We unify 16S rRNA gene sequences from cnidarian microbiome studies under a single analysis pipeline. We reprocess 12,010 cnidarian microbiome samples from 186 studies, alongside 3,388 poriferan, 370 seawater samples, and 245 cultured Symbiodiniaceae, unifying ~6.5 billion sequence reads. Samples are partitioned by hypervariable region and sequencing platform to reduce sequencing variability. This systematic review uncovers an incredible diversity of 86 archaeal and bacterial phyla associated with Cnidaria, and highlights key bacteria hosted across host sub-phylum, depth, and microhabitat. Shallow (< 30 m) water Alcyonacea and Actinaria are characterized by highly shared and relatively abundant microbial communities, unlike Scleractinia and most deeper cnidarians. Utilizing the V4 region, we find that cnidarian microbial composition, richness, diversity, and structure are primarily influenced by host phylogeny, sampling depth, and ocean body, followed by microhabitat and sampling date. We identify host and geographical generalist and specific Endozoicomonas clades within Cnidaria and Porifera. This systematic review forms a framework for understanding factors governing cnidarian microbiomes and creates a baseline for assessing stress associated dysbiosis.
Topics: Animals; RNA, Ribosomal, 16S; Microbiota; Bacteria; Archaea; Anthozoa; Phylogeny
PubMed: 37580316
DOI: 10.1038/s41467-023-39876-6 -
The ISME Journal Jan 2024Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing... (Review)
Review
Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing microbial ecology. Since their first application for aerobic gammaproteobacterial methane oxidizers less than a decade ago, GEMs have substantially increased our understanding of the metabolism of methanotrophs, a microbial guild of high relevance for the natural and biotechnological mitigation of methane efflux to the atmosphere. Particularly, GEMs helped to elucidate critical metabolic and regulatory pathways of several methanotrophic strains, predicted microbial responses to environmental perturbations, and were used to model metabolic interactions in cocultures. Here, we conducted a systematic review of GEMs exploring aerobic methanotrophy, summarizing recent advances, pointing out weaknesses, and drawing out probable future uses of GEMs to improve our understanding of the ecology of methane oxidizers. We also focus on their potential to unravel causes and consequences when studying interactions of methane-oxidizing bacteria with other methanotrophs or members of microbial communities in general. This review aims to bridge the gap between applied sciences and microbial ecology research on methane oxidizers as model organisms and to provide an outlook for future studies.
Topics: Methane; Oxidation-Reduction; Aerobiosis; Metabolic Networks and Pathways; Models, Biological
PubMed: 38861460
DOI: 10.1093/ismejo/wrae102 -
Annals of Clinical Microbiology and... Jun 2022Klebsiella pneumoniae is a gram-negative pathogen common cause of nosocomial infections. Colistin is a last resort antibiotic to treat infections caused by K.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Klebsiella pneumoniae is a gram-negative pathogen common cause of nosocomial infections. Colistin is a last resort antibiotic to treat infections caused by K. pneumoniae. In recent years, the resistance rate to colistin has increased in K. pneumoniae. This study evaluated the prevalence of colistin resistance of K. pneumoniae isolates in Iran using a systematic review and meta-analysis.
METHOD
A systematic search was performed for relevant articles until August 2021 in the following database: PubMed, Scopus, SID and Google Scholar. The pooled prevalence of colistin resistance in clinical K. pneumoniae isolates analyzed using Comprehensive Meta-Analysis Software (CMA).
RESULTS
Finally, 19 articles with appropriate criteria were included in the meta-analysis. Our results showed 6.9% of the pooled prevalence of colistin resistance in clinical K. pneumoniae isolates in Iran. The results of subgroup analysis demonstrated increase resistance of colistin from 4.8%; (95% CI 1.5-13.9%) in 2013-2018 to 8.2%; (95% CI 3.4-18.6%), in 2019-2021. Also, the results of our study showed a strong association between the carbapenem producing K. pneumoniae and increased resistance to colistin.
CONCLUSIONS
This study showed a high prevalence of colistin resistance in K. pneumoniae isolates. It is recommended that regular evaluation be performed to control colistin resistance.
Topics: Bacterial Proteins; Colistin; Humans; Iran; Klebsiella pneumoniae; Microbial Sensitivity Tests; Prevalence
PubMed: 35765073
DOI: 10.1186/s12941-022-00520-8 -
JAMA Network Open Dec 2020Controversy remains regarding the transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
IMPORTANCE
Controversy remains regarding the transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
OBJECTIVE
To review current evidence on air contamination with SARS-CoV-2 in hospital settings and the factors associated with contamination, including viral load and particle size.
EVIDENCE REVIEW
The MEDLINE, Embase, and Web of Science databases were systematically queried for original English-language articles detailing SARS-CoV-2 air contamination in hospital settings between January 1 and October 27, 2020. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The positivity rate of SARS-CoV-2 viral RNA and culture were described and compared according to the setting, clinical context, air ventilation system, and distance from patients. The SARS-CoV-2 RNA concentrations in copies per meter cubed of air were pooled, and their distribution was described by hospital areas. Particle sizes and SARS-CoV-2 RNA concentrations in copies or median tissue culture infectious dose (TCID50) per meter cubed were analyzed after categorization as less than 1 μm, from 1 to 4 μm, and greater than 4 μm.
FINDINGS
Among 2284 records identified, 24 cross-sectional observational studies were included in the review. Overall, 82 of 471 air samples (17.4%) from close patient environments were positive for SARS-CoV-2 RNA, with a significantly higher positivity rate in intensive care unit settings (intensive care unit, 27 of 107 [25.2%] vs non-intensive care unit, 39 of 364 [10.7%]; P < .001). There was no difference according to the distance from patients (≤1 m, 3 of 118 [2.5%] vs >1-5 m, 13 of 236 [5.5%]; P = .22). The positivity rate was 5 of 21 air samples (23.8%) in toilets, 20 of 242 (8.3%) in clinical areas, 15 of 122 (12.3%) in staff areas, and 14 of 42 (33.3%) in public areas. A total of 81 viral cultures were performed across 5 studies, and 7 (8.6%) from 2 studies were positive, all from close patient environments. The median (interquartile range) SARS-CoV-2 RNA concentrations varied from 1.0 × 103 copies/m3 (0.4 × 103 to 3.1 × 103 copies/m3) in clinical areas to 9.7 × 103 copies/m3 (5.1 × 103 to 14.3 × 103 copies/m3) in the air of toilets or bathrooms. Protective equipment removal and patient rooms had high concentrations per titer of SARS-CoV-2 (varying from 0.9 × 103 to 40 × 103 copies/m3 and 3.8 × 103 to 7.2 × 103 TCID50/m3), with aerosol size distributions that showed peaks in the region of particle size less than 1 μm; staff offices had peaks in the region of particle size greater than 4 μm.
CONCLUSIONS AND RELEVANCE
In this systematic review, the air close to and distant from patients with coronavirus disease 2019 was frequently contaminated with SARS-CoV-2 RNA; however, few of these samples contained viable viruses. High viral loads found in toilets and bathrooms, staff areas, and public hallways suggest that these areas should be carefully considered.
Topics: Air Microbiology; COVID-19; Hospitals; Humans; Microbial Viability; Particle Size; RNA, Viral; SARS-CoV-2
PubMed: 33355679
DOI: 10.1001/jamanetworkopen.2020.33232 -
The Lancet. Microbe Nov 2021Bedaquiline is a crucial drug for control of rifampicin-resistant tuberculosis. Molecular drug resistance assays could facilitate effective use of bedaquiline and...
BACKGROUND
Bedaquiline is a crucial drug for control of rifampicin-resistant tuberculosis. Molecular drug resistance assays could facilitate effective use of bedaquiline and surveillance of drug resistance emergence. To facilitate molecular assay development, we aimed to identify genomic markers of bedaquiline resistance.
METHODS
In this systematic review and individual isolate analysis, we searched Europe PubMed Central and Scopus for studies published from the inception of each database until Oct 19, 2020, that assessed genotypic and phenotypic bedaquiline resistance in clinical or non-clinical isolates. All studies reporting on the assessment of variants in the four genes of interest (, , , and ) and phenotypic bedaquiline data in both clinical and non-clinical samples were included. We collated individual isolate data from eligible studies to assess the association between genomic variants with phenotypic bedaquiline resistance, using a standardised method endorsed by WHO. Risk of bias of the extracted data was independently assessed by two authors using the Quality Assessment of Diagnostic Accuracy Studies tool for clinical studies and Systematic Review Center for Laboratory Animal Experimentation tool for animal studies. The primary outcome was to identify mutations associated with resistance in four genes of interest (, , , and ); for each genomic variant, the odds ratio (OR), 95% CI, and p value were calculated to identify resistance markers associated with bedaquiline resistance. This study is registered with PROSPERO, CRD42020221498.
FINDINGS
Of 1367 studies identified, 41 published between 2007 and 2020 were eligible for inclusion. We extracted data on 1708 isolates: 1569 (91·9%) clinical isolates and 139 (8·1%) non-clinical isolates. We identified 237 unique variants in , 14 in , 28 in and 11 in . Most clinical isolates with a single variant reported in (229 [79%] of 287 variants), (14 [88%] of 16 variants), (32 [100%] of 32 variants), or (115 [98%] of 119 variants) were phenotypically susceptible to bedaquiline. Except for the 187G→C (OR ∞, [95% CI 13·28-∞]; p<0·0001) and 138_139insG (OR 6·91 [95% CI 1·16-47·38]; p=0·016) variants, phenotypic-genotypic associations were not significant (p≥0·05) for any single variant in , , and .
INTERPRETATION
Absence of clear genotypic-phenotypic associations for bedaquiline complicates the development of molecular drug susceptibility tests. A concerted global effort is urgently needed to assess the genotypic and phenotypic drug susceptibility of isolates, especially in patients who have received unsuccessful bedaquiline-containing regimens. Treatment regimens should be designed to prevent emergence of bedaquiline resistance and phenotypic drug susceptibility tests should be used to guide and monitor treatment.
FUNDING
Research Foundation Flanders, South African Medical Research Council, Department of Science and Innovation - National Research Foundation, National Institute of Health Institute of Allergy and Infectious Diseases, and Doris Duke Charitable Foundation.
Topics: Animals; Antitubercular Agents; Data Analysis; Diarylquinolines; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Multidrug-Resistant
PubMed: 34796339
DOI: 10.1016/s2666-5247(21)00175-0 -
Cancer Medicine Sep 2023The relationship between commensal microbiota and lung cancer (LC) has been studied extensively. However, developing replicable microbiological markers for early LC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between commensal microbiota and lung cancer (LC) has been studied extensively. However, developing replicable microbiological markers for early LC diagnosis across multiple populations has remained challenging. Current studies are limited to a single region, single LC subtype, and small sample size. Therefore, we aimed to perform the first large-scale meta-analysis for identifying micro biomarkers for LC screening by integrating gut and respiratory samples from multiple studies and building a machine-learning classifier.
METHODS
In total, 712 gut and 393 respiratory samples were assessed via 16 s rRNA amplicon sequencing. After identifying the taxa of differential biomarkers, we established random forest models to distinguish between LC populations and normal controls. We validated the robustness and specificity of the model using external cohorts. Moreover, we also used the KEGG database for the predictive analysis of colony-related functions.
RESULTS
The α and β diversity indices indicated that LC patients' gut microbiota (GM) and lung microbiota (LM) differed significantly from those of the healthy population. Linear discriminant analysis (LDA) of effect size (LEfSe) helped us identify the top-ranked biomarkers, Enterococcus, Lactobacillus, and Escherichia, in two microbial niches. The area under the curve values of the diagnostic model for the two sites were 0.81 and 0.90, respectively. KEGG enrichment analysis also revealed significant differences in microbiota-associated functions between cancer-affected and healthy individuals that were primarily associated with metabolic disturbances.
CONCLUSIONS
GM and LM profiles were significantly altered in LC patients, compared to healthy individuals. We identified the taxa of biomarkers at the two loci and constructed accurate diagnostic models. This study demonstrates the effectiveness of LC-specific microbiological markers in multiple populations and contributes to the early diagnosis and screening of LC.
Topics: Humans; Lung Neoplasms; Gastrointestinal Microbiome; Microbiota; Databases, Factual; Biomarkers
PubMed: 37676050
DOI: 10.1002/cam4.6503 -
Global epidemiology of antimicrobial resistance in commensal Neisseria species: A systematic review.International Journal of Medical... Apr 2022Commensal Neisseria species (spp). represent an important reservoir of antimicrobial resistance genes for pathogenic Neisseria spp. In this systematic review, we aimed... (Review)
Review
BACKGROUND
Commensal Neisseria species (spp). represent an important reservoir of antimicrobial resistance genes for pathogenic Neisseria spp. In this systematic review, we aimed to assess the antimicrobial susceptibility of commensal Neisseria spp. and how this has evolved over time. We also aimed to assess if commensal Neisseria spp. showed intrinsic resistance to four antimicrobials - penicillin, azithromycin, ceftriaxone and ciprofloxacin.
METHODS
Pubmed and Google Scholar were searched following the PRISMA guidelines. Articles reporting MICs of commensal Neisseria spp. were included according to inclusion/exclusion criteria, and the quality of the articles was assessed using a pre-designed tool. Individual and summary measures of penicillin, azithromycin, ceftriaxone and ciprofloxacin MICs were collected. Additional data was sought to perform a comparison between the MICs of pathogenic and commensal Neisseria spp.
RESULTS
A total of 15 studies met our criteria.We found no evidence of intrinsic AMR in commensal Neisseria spp. We did find evidence of an increasing trend in MICs of commensal Neisseria spp. over time for all antimicrobials assessed. These findings were similar in various countries. Eight additional studies were included to compare pathogenic and commensal Neisseria spp.
CONCLUSION
The MICs of commensal Neisseria spp. appear to be increasing in multiple countries. Surveillance of MICs in commensals could be used as an early warning system for antimicrobial resistance emergence in pathogens. Our findings underline the need for antibiotic stewardship interventions, particularly in populations with high antimicrobial consumption.
Topics: Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Drug Resistance, Bacterial; Gonorrhea; Humans; Microbial Sensitivity Tests; Neisseria; Neisseria gonorrhoeae
PubMed: 35231823
DOI: 10.1016/j.ijmm.2022.151551 -
Clinical Microbiology and Infection :... Dec 2022The intestinal microbiome provides a reservoir for antibiotic resistance genes (ARGs). The neonatal microbiome is more susceptible to disturbance from external factors... (Review)
Review
BACKGROUND
The intestinal microbiome provides a reservoir for antibiotic resistance genes (ARGs). The neonatal microbiome is more susceptible to disturbance from external factors than the established microbiome in later life.
OBJECTIVES
In this review, we systematically summarize studies which investigated the intestinal resistome in neonates.
DATA SOURCES
MEDLINE and Embase databases were searched.
STUDY ELIGIBILITY CRITERIA
We included original studies which investigated ARGs in stool or rectal swabs in neonates using molecular diagnostics.
METHODS OF DATA SYNTHESIS
Two authors independently extracted data, which were summarized in tables.
RESULTS
Our search identified 2701 studies, of which 23 (22 cohorts) were included. The studies show that the neonatal intestine harbours a high abundance and variety of ARGs, even in the absence of direct antibiotic exposure. The most commonly found ARGs confer resistance to aminoglycosides, β-lactams, macrolides, tetracyclines, or multidrug resistance. There is evidence that ARGs can be transferred from mothers to neonates. Interestingly, however, compared to mothers, neonates are reported to have a higher abundance of ARGs. One likely reason for this is the bacterial phylogenetic composition with a high abundance of Gammaproteobacteria in neonatal stool. Factors that have been associated with a higher abundance of ARGs are intrapartum and neonatal antibiotic use. Breastfeeding and neonatal probiotic use have been associated with a lower abundance of ARGs. Antibiotics during pregnancy, delivery mode, or sex are reported to have little effect. However, this might be because studies were underpowered and because it is difficult to account for effect modifiers.
CONCLUSIONS
The neonatal intestine seems to have a lower colonization resistance, which could make it easier for antibiotic-resistant populations to establish themselves. Future studies will help in the development of evidence-based interventions to modulate the abundance of ARGs in neonates, for example, by the use of pre- and probiotics and bacteriophages.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Phylogeny; Drug Resistance, Microbial; Anti-Bacterial Agents; Bacteria; Intestines
PubMed: 35868586
DOI: 10.1016/j.cmi.2022.07.014 -
Brazilian Journal of Microbiology :... Jun 2024In South Africa, basic healthcare centres treat sexually transmitted infections (STIs) using a syndromic approach. In line with Preferred Reporting Items for Systematic... (Review)
Review
In South Africa, basic healthcare centres treat sexually transmitted infections (STIs) using a syndromic approach. In line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a complete study of all randomised controlled trials and surveillance data relevant to N. gonorrhoeae antibiotic resistance was conducted. To discover papers published between 2002 and 2022, searches were undertaken using PubMed, EMBASE and any other relevant databases. This systematic review extracted a total of 463 articles published between 2002 and 2022 from a variety of online research sources. Seven South African provinces were represented in the studies that were assessed. Mpumalanga and the North West Province did not have any studies that described the identification and monitoring of antimicrobial resistance (AMR). This study presents data obtained from a comprehensive analysis of 2140 isolates, in which we examined the presence of one or more antibiotic resistance. Our findings revealed that out of these samples, 1891 isolates exhibited antimicrobial properties; tetracycline was the antimicrobial resistance that was found the most often (30%), followed by ciprofloxacin (19%) and penicillin (17%). The mean of the isolates was 143, the upper 95% mean was 243, and the standard deviation (SD) was 181.6. All microbiological identification and susceptibility testing processes must be standardised and improved so national organisations can monitor AMR. The nation's health community must address all identified areas of concern to avoid AMR.
Topics: South Africa; Neisseria gonorrhoeae; Gonorrhea; Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 38662152
DOI: 10.1007/s42770-024-01281-6