Evidence-Based Medicine

Research Appraisals

Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.

Showing 20 appraisals

otherEvidence: Weak
55CEBM

European journal of hospital pharmacy : science and practice

A bibliometric analysis of the application trends of information technology in antimicrobial stewardship within hospitals

OBJECTIVES: This study uses bibliometric analysis to systematically map research trends, knowledge structure and evolution of information technology (IT) in hospital antimicrobial stewardship (AMS) over the last 20 years. METHODS: A Web of Science Core Collection search (2000-2025) yielded 258 English-language publications on IT applications in hospital AMS. A bibliometric analysis, utilising CiteSpace and Bibliometrix, quantitatively evaluated domain evolution through temporal analysis, network mapping, keyword clustering, burst detection and examination of highly cited publications. RESULTS: The bibliometric analysis reveals a fluctuating yet overall increasing trend in annual publications, peaking at 49 articles in 2024. The US (131 publications) and European nations demonstrate significant research output (centrality >0.2), with major collaborative networks coalescing around institutions including Harvard University and Imperial College London. Keyword analysis identifies 'AMS' as a core theme, closely associated with technological keywords such as 'machine learning (ML)', 'clinical decision support systems (CDSS)', 'electronic health records (EHR)' and 'artificial intelligence (AI)'. Emerging trends suggest a shift in research focus from foundational strategies to data-driven prediction of antimicrobial resistance (AMR) and precision interventions. Highly cited literature emphasises the integration of EHR and ML technologies for optimising prescriptions and predicting resistance patterns. CONCLUSIONS: IT-driven AMS research has shifted from empirical management to data science. Despite EHR integration, and ML and CDSS support, challenges remain in data standardisation, technical deployment and ethics. Future work must emphasise global collaboration, standardisation, design refinement and ethical guidelines, and provide clear algorithm explanations to enhance AMR mitigation.

26 June 2026

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observationalEvidence: Moderate
85CEBM

mSphere

Novel machine learning-based approach to identify viral biomarkers of human respiratory emissions from oral and nasal metagenomes

Humans spend approximately 90% of their lives in built environments, making virus transmission indoors a key determinant of health. Environmental sampling of respiratory viral pathogens is often challenging because of frequent non-detect measurements. Non-detect measurements do not differentiate between samples containing low or no pathogens from samples that simply lack respiratory expulsions altogether. This ambiguity can be resolved by scanning samples for a biomarker of human respiratory emissions. To do so, reliable biomarkers for environmental monitoring need to be identified. Ideal biomarkers are prevalent across individuals, abundant, and unique to the human respiratory tract. Here, we present a new machine learning-based approach to query for suitable biomarker candidates from publicly available metagenomes and apply it to identify viral biomarkers of healthy oral and nasal microbiomes. Twelve viral biomarker candidates were selected from 1,232 curated viral operational taxonomic units. The viral biomarker candidates had as much as 63% prevalence across respiratory metagenomes, and prevalence was further increased to 77%-81% by combining two or three biomarkers. Real-time PCR confirmed that these viral biomarkers were prevalent and abundant in nasal swabs and saliva samples. Notably, top candidate biomarkers remained stable and detectable through multiple lab purification steps, increasing confidence in their viral origins and demonstrating their suitability for environmental monitoring. These findings demonstrate that existing metagenomes can be used to identify effective biomarker candidates for environmental sampling.IMPORTANCEDeveloping non-pharmaceutical interventions to reduce virus transmission indoors relies on robust environmental monitoring methods. Monitoring viral pathogens is challenging because of frequent non-detect measurements that introduce uncertainty. For instance, a non-detect measurement could indicate either the absence of the pathogen or simply the lack of human respiratory activity and, thus, exposure. To aid in distinguishing these scenarios, this study identifies viruses from the human respiratory tract using publicly available sequencing data that can be incorporated into environmental monitoring as biomarkers of human respiratory activity. These viral biomarkers will improve indoor monitoring to help enact interventions to mitigate virus transmission. Furthermore, our approach to identify biomarkers from existing metagenomes can be adapted for future biomarker identification in any system.

28 May 2026

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otherEvidence: Moderate
80CEBM

Journal of chemical information and modeling

Machine Learning-Driven Simulations of the SARS-CoV-2 Fitness Landscape from Deep Mutational Scanning Experiments

Predicting protein variant effects is a key challenge in preparing for pathogenic viral strains, understanding mutation-linked diseases, and designing new proteins. Protein sequence-structure-function relationships are difficult to model due to complex allosteric and epistatic effects. To investigate efficient modeling strategies, we trained supervised machine learning (ML) models with deep mutational scanning (DMS) libraries of SARS-CoV-2 receptor binding domain (RBD) sequences labeled with angiotensin converting enzyme 2 (ACE2) binding affinity. These models demonstrate superior performance predicting combinatorial mutation effects compared to adding or averaging the effects of point mutations and exhibit strong extrapolative performance ranking omicron variants when training only near wild type (WT) variants. We characterize the RBD fitness landscape by combining ML with Markov Chain Monte Carlo simulations to predict evolutionary patterns from the WT sequence. These generate comparable sequence profiles to high-fitness sequences in DMS data and predict mutations in unseen omicron variants. These models provide insight into the relationship between RBD sequence elements and offer a new perspective on the use of DMS to predict emerging viral strains, which we anticipate will be applicable to other evolutionary prediction tasks. To facilitate application and future development of this strategy, we introduce Mavenets: https://github.com/SztainLab/mavenets.

27 May 2026

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observationalEvidence: Moderate
75CEBM

mSystems

Insects shape the cadaver decomposition microbiome and postmortem interval estimation accuracy

The breakdown and recycling of carrion is a crucial ecological process that largely relies on a community of necrophagous insects and microbes. Recent work has shown that a specialized microbial network, likely dispersed throughout the environment by insects, assembles during cadaver decomposition to break down flesh regardless of climate and geography. Because of their broad distribution and successional nature, decomposer microbes have been used in machine learning models to predict the postmortem interval (PMI) of human remains, an important contribution to the field of forensics. How factors such as an indoor environment, which alters insect activity, impact the composition of microbial communities decomposing human remains is unclear. Here, we investigate the effects of enclosed shelter on microbial community assembly and successional patterns during human decomposition and provide important considerations for PMI modeling. Compared to outdoor cadavers, we show that indoor cadavers experienced delayed colonization of key decomposer microbes over the course of decomposition due to restricted insect access. Consequently, machine learning models trained on outdoor cadavers frequently underestimated the PMI of cadavers decomposing indoors. Delayed colonization by blow fly maggots (Diptera: Calliphoridae) was correlated with higher PMI prediction errors, suggesting that insects are an important source of microbial decomposers that drive PMI model predictions. Incorporating microbial data from indoor cadavers and insect activity into PMI models significantly improved prediction capabilities for both indoor and outdoor decomposition environments. Ultimately, we demonstrate the important role insects play in the maintenance and distribution of microbes that help to recycle vertebrate remains.IMPORTANCEMicrobes are critical for the decomposition and recycling of organic matter. Recently, microbiome-based models have shown promising performance in estimating the postmortem interval (PMI). However, many deaths occur indoors, yet no studies have investigated the impact of enclosed shelter on the cadaver microbiome in a controlled setting. Here, cadavers were decomposed indoors, and we found that blow fly maggots serve as an important source of decomposer taxa that significantly alter the cadaver microbiome following infestation. Notably, PMI estimation models trained on outdoor data sets failed to accurately predict the PMI when insect colonization was delayed. We show that incorporating 16S rRNA amplicon data from cadavers decomposing indoors, along with environmental variables, significantly improves PMI estimates, suggesting a microbiome-based forensic tool may be feasible across decomposition environments. Importantly, this research demonstrates the critical ecological role insects play in the dispersal of specialized microbes that are involved in the breakdown and recycling of vertebrate remains.

22 May 2026

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Systematic ReviewEvidence: Moderate
65CEBM

Current allergy and asthma reports

Impact of IL-4/IL-13 Blockade with Dupilumab on the Microbiome in Type 2 Inflammatory Diseases: A Systematic Review

PURPOSE OF REVIEW: To systematically review current evidence on microbiota changes associated with dupilumab treatment across different anatomical sites in type 2 inflammatory diseases. RECENT FINDINGS: Fifteen studies were included, comprising two randomized trials and thirteen observational studies, mostly in atopic dermatitis, with fewer data in chronic rhinosinusitis with nasal polyps and NSAID-exacerbated respiratory disease. The skin was the most frequently investigated site, followed by the sinonasal tract and gut. Across skin studies, dupilumab was consistently associated with reduced Staphylococcus aureus, increased microbial diversity, and enrichment of commensal taxa. Sinonasal studies suggested shifts toward more eubiotic microbial communities. Gut evidence was limited, although one study suggested modulation of tryptophan metabolism-related pathways.  Dupilumab appears to exert compartment-specific and disease-dependent effects on the microbiome. The strongest evidence concerns the skin and sinonasal compartments, whereas gut microbiota changes remain poorly defined. Further prospective studies are needed to assess microbiota signatures as potential biomarkers of response.

18 May 2026

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Systematic ReviewEvidence: Moderate
75CEBM

African journal of reproductive health

Evaluation of the effects of probiotic supplementation on the ecology and inflammatory factors of female vaginal flora: a systematic review and meta-analysis

This meta-analysis systematically evaluated the effects of probiotic supplementation on vaginal microbiota and inflammatory factors in women. PubMed, Embase, Web of Science, CNKI, and Wanfang were searched from inception to January 2026 for randomized and controlled studies. Outcomes included vaginal pH, Nugent score, and inflammatory cytokines (IL-4, IL-6, IL-10, TNF-α). Fifteen studies were included. Compared with controls, probiotics did not significantly reduce IL-4, IL-6, IL-10, or TNFα levels, nor did they significantly improve Nugent score. However, probiotic supplementation significantly reduced vaginal pH (OR = 0.36, 95% CI: 0.15-0.89; P = 0.03), indicating improved maintenance of a weakly acidic vaginal environment. Sensitivity analyses showed generally stable results, although heterogeneity remained substantial for several outcomes. Overall, probiotics appear effective in modulating vaginal acid-base balance but show limited evidence for improving inflammatory cytokine profiles or restoring vaginal microbiota structure. Current data are insufficient to support routine probiotic use for optimizing vaginal microbiota and inflammatory status. Further high-quality, well-designed randomized controlled trials are required to clarify their clinical benefits. Cette méta-analyse a évalué de manière systématique les effets de la supplémentation en probiotiques sur le microbiote vaginal et les facteurs inflammatoires chez les femmes. Les bases de données PubMed, Embase, Web of Science, CNKI et Wanfang ont été consultées depuis leur création jusqu’en janvier 2026 afin d’identifier des études randomisées et contrôlées. Les critères de jugement comprenaient le pH vaginal, le score de Nugent et les cytokines inflammatoires (IL-4, IL-6, IL-10, TNF-α). Quinze études ont été incluses. Comparativement aux groupes témoins, les probiotiques n’ont pas réduit significativement les concentrations d’IL4, IL-6, IL-10 ou TNF-α, ni amélioré significativement le score de Nugent. En revanche, la supplémentation en probiotiques a significativement réduit le pH vaginal (OR = 0,36 ; IC à 95 % : 0,15–0,89 ; P = 0,03), indiquant un meilleur maintien d’un environnement vaginal faiblement acide. Les analyses de sensibilité ont montré des résultats globalement stables, bien qu’une hétérogénéité substantielle persiste pour plusieurs critères. Dans l’ensemble, les probiotiques semblent efficaces pour moduler l’équilibre acido-basique vaginal, mais les preuves restent limitées quant à leur capacité à améliorer les profils cytokiniques inflammatoires ou à restaurer la structure du microbiote vaginal. Les données actuelles sont insuffisantes pour recommander l’utilisation systématique des probiotiques dans l’optimisation du microbiote vaginal et du statut inflammatoire. Des essais contrôlés randomisés de haute qualité sont nécessaires pour confirmer leurs bénéfices cliniques.

16 May 2026

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Systematic ReviewEvidence: Moderate
80CEBM

Antimicrobial resistance and infection control

Time-related changes in bacterial air contamination of sterile covered items in operating rooms: a systematic review and meta-analysis

BACKGROUND: There is still only limited evidence regarding how bacterial air contamination of sterile items changes over time in the operating room, even when protected by sterile covers. This review aimed to synthesize the available data to inform safe handling and preparation of sterile equipment. METHODS: A systematic search was conducted for controlled studies that assessed time-related bacterial contamination of covered sterile items in operating rooms and that reported the outcome as colony forming units (CFU) measured at two or more time points, generating distinct timelines. Six databases were searched from inception to 1 September 2025: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, CINAHL, the Cochrane Database of Systematic Reviews, Embase, and Web of Science. A meta-analysis was performed using linear regression with CFU as the dependent variable and time (minutes) as the independent variable. The review followed PRISMA guidelines and was registered in PROSPERO (CRD420251018280). RESULTS: Five timelines from four studies evaluating CFU counts yielded an R2 of 0.085, indicating that time explained 8.5% of CFU variation. Similarly, analysis of eight timelines from four studies assessing mean CFU values produced an R2 of 0.070, attributing 7% of variation to time. Neither analysis demonstrated a statistically significant linear association between time and CFU count (p = 0.176, CI: -1.319 < β < 4.863) or mean CFU values (p = 0.108, CI: 0.191 < β < 0.420) when sterile covers were used. Three additional timelines excluded from the meta-analysis showed mixed results: two indicated a positive association, while one showed no relationship. CONCLUSIONS: Time has only a modest impact on bacterial contamination of sterile items when protective covers are used, with minimal increases in CFU over different waiting periods. Clinically, this confirms that properly covered sterile items can be prepared in advance without compromising microbial safety, thus supporting efficient operating room organization and workflow. These findings reinforce the effectiveness of sterile covers as a key measure to reduce the risk of surgical site infections and ensure the safe handling of sterile equipment. Although covered storage appears safe, minimizing unnecessary waiting time, even with coverage, is good clinical practice.

15 May 2026

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Randomised Controlled TrialEvidence: Strong
65CEBM

JAMA

Intrawound Tobramycin Plus Vancomycin to Prevent Surgical Site Infection in Tibial Fractures: The TOBRA Randomized Clinical Trial

IMPORTANCE: Previous research has suggested that intrawound vancomycin powder reduces deep surgical site infections among patients with periarticular tibial fractures at high risk of infection. It is unknown whether the addition of tobramycin powder further decreases infection rates. OBJECTIVE: To compare whether the combination of tobramycin plus vancomycin vs vancomycin alone delivered as intrawound powder at the time of definitive fixation reduces deep surgical site infections. DESIGN, SETTING, AND PARTICIPANTS: Open-label, assessor-masked, randomized clinical trial conducted at 39 US trauma centers. Eligible patients were adults with an operatively treated periarticular tibial fracture (either tibial plateau or pilon) who met 1 of 3 criteria for elevated infection risk. Enrollment occurred between June 18, 2021, and December 12, 2024 (final follow-up, July 15, 2025). INTERVENTIONS: Intrawound tobramycin (1.2 g) plus vancomycin (1.0 g) powder vs intrawound vancomycin (1.0 g) powder delivered at the time of definitive fixation. MAIN OUTCOMES AND MEASURES: The primary outcome was a deep surgical site infection requiring surgical management within 182 days of definitive fracture fixation. Secondary outcomes included deep surgical site infections with pathogens that were gram-negative only, deep surgical site infections with at least 1 pathogen that was gram-positive, deep surgical site infections with polymicrobial cultures, deep surgical site infections with negative culture results, and cellulitis or skin infections treated only with antibiotics. RESULTS: Among the 1660 participants randomized, 1528 (mean age, 47.0 [SD, 14.3] years; 603 female [39.5%]; 925 male [60.5%]) were included in the primary analysis. Deep surgical site infections occurred in 51 of 753 participants (182-day probability, 7.4%) in the tobramycin plus vancomycin group and 47 of 775 participants (182-day probability, 6.6%) in the vancomycin alone group (hazard ratio, 1.11; 95% bayesian credible interval, 0.75-1.66; posterior probability of superiority, 29.7%). The threshold required for superiority was not reached for any secondary outcome. CONCLUSIONS AND RELEVANCE: Among patients with operatively treated periarticular tibial fractures at high risk of infection, adding intrawound tobramycin powder to vancomycin powder at the time of definitive fixation did not reduce deep surgical site infections compared with vancomycin powder alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02227446.

14 May 2026

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Systematic ReviewEvidence: Weak
70CEBM

BMJ open respiratory research

Prevalence and determinants of drug-resistant pulmonary tuberculosis in the MENA region: a systematic review and meta-analysis

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a constraining challenge for tuberculosis (TB) control worldwide. The Middle East and North African (MENA) region represents a significant part of the global MDR-TB burden. AIM: To estimate the pooled prevalence of MDR-TB and its determinants in the MENA region. METHODS: We searched for studies published in English and French on the subject up to 31 January 2026 on Web of Science, PubMed, Scopus and Cochrane, without time restriction. Original studies reporting data on the prevalence of MDR-TB in individuals living in the MENA region were selected. The meta-analysis was done using the random effects model considering the heterogeneity among the included studies and I 2 statistic was used to assess the heterogeneity. RESULTS: A total of 1239 articles were identified and 25 studies from 6 countries were included in this review. The prevalence of MDR-TB in the MENA region ranged from 0% (95% CI 0% to 4.1%) to 17.1% (95% CI 10.6% to 25.4%). The pooled prevalence was 3.54% (95% CI 2.18% to 5.72%) with a high heterogeneity, I2 =95.6%; 95% CI 94.4% to 96.5%. Previous exposition to TB treatment, HIV infection, smoking and the presence of comorbidities were the most reported associated factors. CONCLUSION: This review underscores the persistence of MDR-TB in the MENA region, suggesting insufficiency in TB control. Multisectoral interventions integrating strong prevention measures, standardised treatment protocols and measures to enhance treatment adherence should be implemented.

12 May 2026

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Systematic ReviewEvidence: Moderate
70CEBM

International health

Pneumonia in Ghana: prevalence, mortality and antimicrobial resistance-a systematic review and meta-analysis

Pneumonia is a major cause of morbidity and mortality in Ghana, especially among children <5 y of age and the elderly. However, comprehensive data on its prevalence and distribution remain limited. This systematic review addresses this gap by analysing the prevalence, regional variations, risk factors, antimicrobial resistance and mortality rates of pneumonia in Ghana. We searched PubMed, ScienceDirect, Web of Science and African Journals Online databases, including 21 studies with a total of 124 582 participants. A random-effects meta-analysis estimated pooled prevalence and subgroup differences based on age, region and participant type. Heterogeneity was assessed using the I2 test and meta-regression, with sensitivity analysis also conducted. Study quality was evaluated using standardized Joana Briggs Institute checklists for prevalence studies. The pooled prevalence of pneumonia in Ghana was 22.01%, with significant regional variations. The highest prevalence was observed in a study conducted in the Greater Accra and Northern regions (32.31%), while the lowest was in the Upper West (4.83%). The prevalence in children <5 y of age was 17.79%. Hospitalized patients had a higher prevalence (22.14%) than community children (21.49%). Streptococcus pneumoniae was the most common pathogen, with high resistance (>70%) to co-trimoxazole, gentamicin and tetracycline. Key risk factors included indoor air pollution and seasonal changes. The mortality rate for pneumonia was found to be 3.07%. This systematic review highlighted significant regional disparities, pathogen resistance patterns and environmental risk factors that shape the burden of pneumonia in Ghana, providing critical evidence for targeted public health strategies. The findings highlight avenues for future research, including environmental drivers of transmission, focusing on underreported regions and surveillance of antibiotic resistance of pathogens isolated from pneumonia patients.

11 May 2026

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Systematic ReviewEvidence: Moderate
70CEBM

Antonie van Leeuwenhoek

Faecalibacterium prausnitzii and Akkermansia muciniphila: driving the multiple sclerosis-a systematic review

The gut microbiota (GM) is a complex microbial ecosystem, and its alteration contributes to the development of several diseases including multiple sclerosis (MS). Progressive research concerning neurodegenerative diseases and GM reveals that GM dysbiosis has been linked to fostering the development and progression of MS. Among existing bacteria, F.prausnitzii and A.muciniphila are key species implicated in this disease. Thus, the present study systematically reviewed and synthesized the research on the involvement of F. prausnitzii and A. muciniphila in MS patients versus healthy individuals. We systematically searched PubMed, MEDLINE, EMBASE, and Web of Science databases for relevant published articles from January 2010 till January 2023. Out of 400 articles, 16 met the required criteria. The included research investigations originated from the US, Germany, Norway, Egypt, Iran, Brazil, China, the UK, and Romania. Most publications reported decreased levels of F. prausnitzii and increased levels of A. muciniphila in MS patients compared to controls. This review underscored the importance of the F. prausnitzii and A. muciniphila in MS, which could explain the chronic inflammation that characterizes this disease and not only help in understanding its etiology and progression but also open new avenues for the treatment strategies focusing on gut health. Moreover, understanding the role of F. prausnitzii and A. muciniphila could lead to novel biomarkers for early detection and progression monitoring MS.

25 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
80CEBM

PloS one

Impact of prophylactic oral azithromycin during labor on Azithromycin Resistance (AMR) in nasal Staphylococcus aureus and Streptococcus pneumoniae in women and infants in the multi-country Azithromycin Prevention in Labor Use Study (A-PLUS)

BACKGROUND: Prophylactic oral azithromycin vs. placebo reduced maternal, but not neonatal, mortality/sepsis in the A-PLUS Randomized Trial. While prophylactic intrapartum azithromycin reduces maternal mortality/sepsis, it may promote antimicrobial resistance (AMR) in commensal bacteria,. METHODS: Randomly selected women and their infants participating in A-PLUS were enrolled in a longitudinal cross-sectional sub-study to assess the presence of azithromycin resistance in selected bacteria in nasal cultures. Staphylococcus aureus and Streptococcus pneumoniae were cultured on selective agar, then azithromycin-containing agar to select for azithromycin resistant bacteria, identified biochemically. Azithromycin susceptibility was assessed by E-test. Nasal cultures were collected from women and infants between August 11, 2021 and September 18, 2023 during labor/day 1, day 7, 6 weeks, and 3, 6 and 12 months after delivery. RESULTS: The study enrolled 911 women and 915 liveborn infants at 8 sites in 7 countries. Azithromycin resistance in S aureus was higher and azithromycin susceptibility was lower in women receiving azithromycin compared with those receiving placebo on day 7 (P < 0.001), 6 weeks (P < 0.001) and 3 months (P = 0.009) after delivery. Azithromycin resistance in S aureus was also higher and azithromycin susceptibility was lower 6 weeks after delivery (P < 0.001) in infants born to women receiving azithromycin, Azithromycin resistance in S. pneumoniae was too sparse to interpret. CONCLUSIONS: There was an increase in prevalence of azithromycin resistance (or reduction in azithromycin susceptibility) in commensal nasal S. aureus between day 7, 6 weeks and 3 months in women exposed to azithromycin vs. placebo and only at 6 weeks in infants exposed to azithromycin vs. placebo. These differences between the azithromycin and placebo groups were no longer detected at 6 and 12 months post-partum in the women and after 6 weeks through 12 months in the infants.

20 Apr 2026

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diagnosticEvidence: Moderate
85CEBM

PloS one

upsML: A high-accuracy machine learning classifier for predicting Plasmodium falciparum var gene upstream groups

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the hypervariable var gene family, is central to malaria pathogenesis, influencing both disease severity and immune evasion. Classifying var genes into upstream groups (upsA, upsB, upsC, upsE) is important for understanding parasite biology and clinical outcomes, but remains challenging, especially with partial sequences, such as the DBLα tag or RNA-Seq assemblies. We developed upsML, a machine-learning-based classifier trained on 2,530 curated var genes, to accurately assign upstream groups based on sequence features from different partial gene regions. We compared seven methods, including support vector machines, random forests, XGBoost, and HMMER models. Several models in upsML achieve accuracies of 83% for DBLα-tag sequences and 92% for full-length PfEMP1 sequences, thereby significantly outperforming existing tools. Additionally, we developed a model to distinguish internal from subtelomeric var genes, which we applied to a global collection of P. falciparum genomes, revealing a higher frequency of internal var genes in Asia. upsML is available at https://github.com/sii-scRNA-Seq/upsML, providing a robust and efficient resource for large-scale var gene analysis. It can classify var genes from 20 genomes in under one second.

17 Apr 2026

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Systematic ReviewEvidence: Strong
85CEBM

Water research

Representation of urban and rural contexts in the application of wastewater surveillance for antimicrobial resistance: A systematic review.

Wastewater surveillance (WWS) can reveal community health trends through targeted monitoring of sewage. Given concerns regarding the global dissemination of drug-resistant infections, there is growing integration of antimicrobial resistance (AMR) in WWS infrastructure. However, most WWS has focused on highly urbanized sewersheds in resource-rich areas, which may exacerbate disparities in disease burdens and clinical datasets. This work presents both a systematic and scoping review of current published WWS efforts targeting antimicrobial resistance (AMR), with the aim to quantify and compare applied monitoring efforts capturing rural vs. urban areas and lower-income vs. higher-income countries. Of the 2,873 deduplicated manuscripts identified through a systematic search of four databases, 454 examined untreated domestic sewage and were characterized via a brief scoping review. Of these, 48 articles included an explicit focus on monitoring for population health surveillance, and were subject to methodological data extraction and risk of bias assessment. Sampling trends observed in the scoping and systematic review were similar. Only 13-19 % of scoping review sampling sites were classified as rural, and 44 % were located within lower- or middle-income countries (LMICs). Few articles examined AMR within unsewered communities. While analytical methods were similar across income brackets, rural monitoring efforts were more reliant on culture-based techniques than urban efforts. Monitoring in rural sites and LMICs were typically part of multi-site campaigns and featured less longitudinal sampling. Overall, methodological inconsistencies rendered a meta-analysis infeasible. The combined lack of research in rural and low-income areas indicates that key at-risk communities for circulation of AMR are an oversight.

17 Apr 2026

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Systematic ReviewEvidence: Weak
60CEBM

Infection and immunity

Maternal influences on oral microbiome development and implications for early childhood health: a systematic review

A deeper understanding of how maternal-infant interactions shape the establishment and diversification of the oral microbiome could have significant clinical applications; however, relatively few studies emphasize early maternal-infant microbial connections. This systematic review provides a longitudinal analysis of oral microbiome development from birth to five years, focusing on the relationship between maternal and infant microbiomes. We conducted a systematic search (June 2025) using keywords "mother," "children," "oral microbiome," and "longitudinal" across PubMed, Cochrane Library, and Embase. Twelve studies fulfilled the inclusion criteria: longitudinal design, healthy mother-child dyads, saliva sample collection, and relevant age range. We excluded review articles, non-English publications, and studies with overlapping data. Results were synthesized by developmental stage and topic. Overall, current literature agrees that the mother is an important source of exposure for initial colonization of the newborn's oral microbiome. Several studies indicated that the oral microbiome at birth is diverse and unspecialized, composed mostly of maternally derived strains. Rapid selection occurs over the first few weeks, as the relative abundances of typical oral bacterial species increase. Throughout the first year, increases in diversity strengthen the resemblance between infant and maternal microbiomes. The microbiome appears to stabilize around 3-5 years. In conclusion, maternal-infant connections play a significant role in influencing oral microbiome development during the first 5 years of life. This review highlights the need for future studies to incorporate larger, longitudinal designs with metadata and advanced tools to clarify the roles of delivery mode, tooth eruption, and parental lifestyle habits in shaping early oral microbiome development.

17 Apr 2026

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Systematic ReviewEvidence: Moderate
55CEBM

Biology of reproduction

The relationship between seminal microbiome and male reproductive wellness: a systematic review

The seminal microbiome, which is composed of different types of bacteria in semen and seminal plasma, has a significant impact on male reproductive health by changing the quality of semen and fertility. Previously regarded as sterile, the male reproductive tract contains microbes originating from the gastrointestinal tract, reproductive organs, and external sources such as sexual partners. Dysbiosis alters sperm parameters, triggers inflammation and oxidative stress, and is associated with conditions such as infertility, HPV infection, prostatitis, prostate cancer, and azoospermia. This systematic review adhered to the PRISMA 2020 guidelines (with 2025 extensions for reproducibility) and examined studies from PubMed, Scopus, and Science Direct (2015-2025, with prior context), concentrating on human, in vitro, and rodent models. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes are among the most important phyla. Beneficial genera, such as Lactobacillus, improve sperm motility, concentration, and DNA integrity, whereas dysbiotic taxa, such as Prevotella, Pseudomonas, and Ureaplasma, are associated with declines. Sexual activity facilitates bidirectional microbial transfer, modifying diversity and fostering the dysbiosis. Inflammatory cytokines, reactive oxygen species, and metabolic disruptions are all involved in this process. Changes that are specific to a disease, such as higher levels of Fusobacterium in HPV-positive samples, worsen the situation. This review highlights how the microbiome alters sperm function and causes infertility. Standardized methods and long-term studies are needed to prove causality. Probiotics and other therapeutic interventions show promise in restoring balance and boosting fertility.

16 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
70CEBM

Cell host & microbe

VIBRANT: A phase 1 randomized trial of multi-strain vaginal L. crispatus live biotherapeutic products in people with bacterial vaginosis

Bacterial vaginosis (BV) is characterized by high microbial diversity. High recurrence rates following antibiotics may stem from poor recolonization by protective Lactobacillus species. This phase 1 randomized trial in the United States and South Africa evaluated two vaginally delivered live biotherapeutic products (LBPs) containing multiple Lactobacillus crispatus strains. After metronidazole treatment for BV, participants received either a placebo or 3 or 7 days of active LBPs. LBP strains were detected by metagenomics in 66.1% (47/71) of participants in the active arms in the first 5 weeks. Among those, nearly half (49%, 23/47) remained colonized at 12 weeks despite the short initial treatment course. Participants were most often colonized by one of three component strains, with no geographic differences in strain colonization observed. LBPs were safe, acceptable, and well tolerated, with no serious adverse events (AEs) reported. These results provide a foundation for the development of transformational interventions aimed at optimizing the vaginal microbiome.

11 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
75CEBM

Cell host & microbe

Vaginal microbiota impacts of a Lactobacillus crispatus live biotherapeutic and predictors of colonization in randomized controlled trial

Bacterial vaginosis (BV) affects >25% of women worldwide and often recurs after standard-of-care metronidazole (MTZ) treatment. LACTIN-V, a live biotherapeutic product (LBP) containing Lactobacillus crispatus strain CTV-05, significantly reduced recurrent BV in a phase 2b clinical trial, but efficacy was incomplete. Here, we characterize microbiota and immune effects using multi-omics and define correlates of treatment success. By week 12, an L. crispatus-dominant microbiota was achieved in 30% of LBP recipients compared with 9% of placebo recipients (benefit ratio: 3.31; p < 0.005). This is primarily due to CTV-05, but native L. crispatus strains are also present and increase over time. Inflammatory cytokines decrease in both arms after MTZ but return to baseline in placebo recipients. Successful L. crispatus colonization is associated with pre-MTZ microbiota, baseline inflammatory profiles, post-MTZ bacterial load, and clinical and behavioral variables. These findings elucidate LBP microbiota effects and identify predictors of treatment success, informing improved intervention strategies to advance women's health.

11 Apr 2026

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otherEvidence: Moderate
80CEBM

Microbiology spectrum

PneumoWiki: a pan-genome-based database for the pathogen Streptococcus pneumoniae

UNLABELLED: The Gram-positive bacterium Streptococcus pneumoniae is a major human pathogen that exhibits more than 100 different capsular serotypes and considerable genomic variability. S. pneumoniae is also an important model organism for basic and biomedical research, with a number of strains with different characteristics being used. To address this, we have created the manually curated pan-genome database PneumoWiki (https://pneumowiki.med.uni-greifswald.de) that integrates genomic data of 43 S. pneumoniae strains with various aspects of functional annotation. All data relating to a specific gene and gene product are compiled on a Gene page. In addition to the gene and protein sequences and annotation from NCBI RefSeq, this includes, for example, data on gene expression, protein function, and localization. The information is supplemented with links to the data sources as well as to other databases and relevant literature. The basic concept of PneumoWiki is the interlinked presentation of pan-genome-based and strain-specific information. Therefore, register tabs with strain names at the top of the Gene pages allow switching between orthologous genes and the corresponding pan-genome page. The pan-genome gene pages contain a summary with functional information and the occurrence of the gene, an ortholog table for the 43 S. pneumoniae strains, a multiple-strain genome viewer as well as a protein sequence alignment. PneumoWiki was developed as a user-friendly tool and is available free of charge. The data collected in PneumoWiki are accessible via various download options. Overall, PneumoWiki is a resource for the research community that supports the analysis and interpretation of experimental data and, in particular, enables the integration of the knowledge available for different S. pneumoniae strains. IMPORTANCE: Databases that integrate and curate the large amounts of genomic data and functional information available for well-studied organisms play an increasingly important role in many areas of life sciences, including infection research. Streptococcus pneumoniae is a major human pathogen associated with high morbidity and mortality rates. The species exhibits high variability in its genome sequence, and a number of strains with different characteristics are used in pneumococcal research. We created the wiki-type database PneumoWiki to provide researchers with curated, up-to-date information on a range of pneumococcal genomes, focusing on the individual genes and encoded proteins and their functional annotation. The key feature of PneumoWiki is the pan-genome approach, which allows combining information of individual strains, thereby supporting the analysis of experimental data and comparisons between studies using different strains. In this way, the database becomes a valuable research tool that can contribute to a better understanding of pneumococcal physiology.

10 Apr 2026

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otherEvidence: Moderate
55CEBM

Clin Dermatol

Gonorrhea.

Neisseria gonorrhoeae, a Gram-negative intracellular pathogen, causes gonorrhea. Although usually sexually transmissible, it can be acquired by direct inoculation. Untreated gonococcal infections have deleterious impacts, including adverse pregnancy outcomes, ectopic pregnancy, infertility, and even blindness. Extended-spectrum cephalosporins remain the mainstay of therapy, and gonococcal culture is essential to determine susceptibility to these agents. Antimicrobial resistance is a global public health concern, and a few new agents are in the pipeline. Gonorrhea control programs rely on health education, access to diagnostic testing (where possible), effective therapy, and partner notification. Introducing inexpensive, sensitive, and specific point-of-care tests will aid antimicrobial stewardship efforts in countries using the syndromic management approach. Targeted vaccination of higher-risk populations with cross-protective outer membrane vesicle-based meningococcal B vaccines might reduce N. gonorrhoeae transmission in the future. Doxycycline postexposure prophylaxis may further reduce gonococcal incidence in the short term; however, its long-term impact on the human resistome/microbiome remains unknown.

1 Jan 2026

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