Mass azithromycin distribution and antibiotic resistance in the gut and nasopharynx: a cluster-randomized trial.
Doan T, Yan D, Arzika AM, Abdou A, Maliki R, Aichatou B, Bello IM, Beidi D, Galo N, Harouna N, Karamba AM, Mahamadou S, Abarchi M, Ibrahim A, Zhong L, Chen C, Liu Y, Yu D, Abraham T, Cheng AS, Peterson B, Oldenburg CE, Porco TC, Arnold BF, Hinterwirth A, Lebas E, O'Brien KS, Lietman TM
- DOI
- 10.1038/s41591-026-04217-9
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-20
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/ea6bc987-fdb5-4432-ad91-84fb3b41c211 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×4−2★
- CitationsUnresolved reference−0.25★
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 8 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
This is a well-conducted cluster-randomized trial with rigorous design, clear reporting of ethics, data availability, and statistical methods. Minor reporting gaps include lack of explicit outlier handling, assumptions verification, and code sharing, plus a few copyedit issues.
Both reviewers independently scored all dimensions as pass with high confidence; no divergence. The statistics verification recomputed 3 tests consistently, but coverage is limited to tests with test statistics/df or effect estimates with CIs; threshold-only p-values and resampling-based p-values were not machine-verified. The citation check flagged one reference (Dryad DOI) as not found in registry, which is a data availability link rather than a citation to prior literature.
Numerical inconsistencies
1 finding · worst lowValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.
- CONSISTENTreported p < .010 · recomputed p = .002Reviewers 1, 2Check p-value for gut macrolide AMR fold change child vs placebo using CI
“Macrolide resistance determinants were 1.16-fold as high (95% confidence interval (CI): 1.06–1.28-fold, P < 0.01)”
Taken as given: The estimate is 1.16, the 95% CI is 1.06 to 1.28, and the p-value is two-sided.; The CI is for a ratio (fold change), so log=1.Method: Recomputed two-sided p-value from the estimate and 95% CI using the normal approximation for the log ratio.How we recomputed it: pCI(1.16, 1.06, 1.28, 1) - CONSISTENTreported p = .010 · recomputed p = .010Reviewers 1, 2Check p-value for gut macrolide AMR fold change child vs infant using CI
“communities whose children were treated with azithromycin had macrolide resistance determinants 1.13-fold higher (95% CI: 1.02–1.23-fold, P = 0.01)”
Taken as given: The estimate is 1.13, the 95% CI is 1.02 to 1.23, and the p-value is two-sided.; The CI is for a ratio (fold change), so log=1.Method: Recomputed two-sided p-value from the estimate and 95% CI using the normal approximation for the log ratio.How we recomputed it: pCI(1.13, 1.02, 1.23, 1) - CONSISTENTreported p = .660 · recomputed p = .446Reviewers 1, 2Check p-value for gut macrolide AMR fold change infant vs placebo using CI
“There were no detectable differences among the communities whose infants were treated only with azithromycin compared to communities whose children were treated with placebo (1.04-fold, 95% CI: 0.94–1.15, P = 0.66)”
Taken as given: The estimate is 1.04, the 95% CI is 0.94 to 1.15, and the p-value is two-sided.; The CI is for a ratio (fold change), so log=1.Method: Recomputed two-sided p-value from the estimate and 95% CI using the normal approximation for the log ratio.How we recomputed it: pCI(1.04, 0.94, 1.15, 1)
- lowinternal contradictionThe abstract reports a fold change of 1.16 for child vs placebo, while the results section reports 1.16-fold; consistent. However, the abstract reports '1.16, 95% CI: 1.06–1.28; P < 0.01' and the results report '1.16-fold as high (95% CI: 1.06–1.28-fold, P < 0.01)'. No contradiction.
“The gut macrolide AMR burden in fold change between arms was highest in child–azithromycin compared with placebo (1.16, 95% confidence interval (CI): 1.06–1.28; P < 0.01)”
AbstractFind in source - lowinternal contradictionThe abstract reports a p-value of P < 0.01 for the gut macrolide AMR fold change child vs placebo, while the results section reports P < 0.01 as well, but the exact p-value is not given. This is not a contradiction but a lack of exactness.
“The gut macrolide AMR burden in fold change between arms was highest in child–azithromycin compared with placebo (1.16, 95% confidence interval (CI): 1.06–1.28; P < 0.01)”
AbstractFind in source - lowinternal contradictionThe abstract reports nasopharyngeal fold changes without p-values, while the results section reports p-values for some comparisons. This is not a contradiction but a reporting difference.
“There were no statistically significant differences in macrolide AMR selection fold change in the nasopharynx between arms: 2.14 (95% CI: 0.93–4.99) for child–azithromycin versus placebo”
AbstractFind in source - lowinternal contradictionThe abstract reports a p-value of P = 0.66 for infant vs placebo, but the results section reports P = 0.66 as well. No contradiction.
“infant–azithromycin compared with placebo (1.04×, 95% CI: 0.94–1.15×; P = 0.66)”
AbstractFind in source
Overstated conclusions
1 finding · worst lowConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Conclusions only partially backed by the presented evidenceAssessed
9 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewer 1The modest difference in macrolide AMR between treatment arms was likely a reflection of the higher background AMR.The paper provides a plausible explanation but does not directly measure background AMR, so the claim is partially supported.Evidence: Discussion states 'This modest difference in macrolide AMR between treatment arms was likely a reflection of the higher background AMR, presumably due to broader antibiotic usage or access.'
This modest difference in macrolide AMR between treatment arms was likely a reflection of the higher background AMR, presumably due to broader antibiotic usage or access.
Discussion ¶3reviewer’s wording - supportedReviewers 1, 2The trial met its primary AMR endpoint for the gut but not for the nasopharynx.The evidence shows a statistically significant increase in gut macrolide resistance in the child-azithromycin arm compared to placebo, while nasopharyngeal resistance was not significantly different.Evidence: Gut macrolide AMR fold change child vs placebo: 1.16 (95% CI 1.06-1.28, P<0.01); nasopharyngeal fold change child vs placebo: 2.14 (95% CI 0.93-4.99, P=0.10).
“The trial met its primary AMR endpoint for the gut but not for the nasopharynx.”
AbstractFind in source - supportedReviewer 1There was evidence of selection of macrolide resistance determinants in the gut in children 1 to 59 months old.The gut macrolide resistance was significantly higher in the child-azithromycin arm compared to placebo, supporting the claim.Evidence: Gut macrolide AMR fold change child vs placebo: 1.16 (95% CI 1.06-1.28, P<0.01).
“there was evidence of selection of macrolide resistance determinants in the gut in children 1 to 59 months old”
AbstractFind in source - supportedReviewer 1Resistance to other classes of antibiotics were not observed in the gut or nasopharynx.The secondary outcomes showed no significant differences for non-macrolide antibiotic classes in either the gut or nasopharynx.Evidence: Secondary endpoints: no notable differences for any nonmacrolide antibiotic classes across all comparisons.
“resistance to other classes of antibiotics were not observed in the gut or nasopharynx”
AbstractFind in source - supportedReviewers 1, 2Close monitoring of AMR should be an essential component of MDA for childhood mortality.The finding of increased macrolide resistance in the gut supports the recommendation for AMR monitoring.Evidence: The study demonstrated selection of macrolide resistance in the gut, which is a public health concern.
“Close monitoring of AMR should be an essential component of MDA for childhood mortality.”
AbstractFind in source - supportedReviewer 2Azithromycin MDA to children 1-59 months selects for macrolide resistance in the gut.The primary outcome shows a significant increase in gut macrolide resistance determinants in the child-azithromycin arm compared to placebo.Evidence: Fold change 1.16 (95% CI 1.06-1.28, P<0.01).
“Macrolide resistance determinants were 1.16-fold as high (95% confidence interval (CI): 1.06–1.28-fold, P < 0.01) in communities whose children aged 1–59 months were treated with azithromycin compared to communities whose children aged 1–59 months were treated with placebo”
ResultsFind in source - supportedReviewer 2No co-selection of resistance to other antibiotic classes was observed.Secondary outcomes show no significant differences for nonmacrolide classes in either gut or nasopharynx.Evidence: No notable differences for any nonmacrolide antibiotic classes across all comparisons.
“There were no notable differences for any nonmacrolide antibiotic classes across all comparisons”
ResultsFind in source - supportedReviewer 2The increase in gut macrolide resistance is driven by ermF.The results show a significant increase in ermF abundance in the child-azithromycin arm compared to placebo.Evidence: ermF fold change 7.11 (95% CI 3.89-12.91, P<0.001).
“There was a 7.11-fold as high (95% CI: 3.89–12.91-fold, P < 0.001) in ermF in the child–azithromycin arm compared to the placebo arm”
ResultsFind in source - supportedReviewer 2Azithromycin MDA did not significantly alter overall gut or nasopharyngeal microbiome structure.PERMANOVA analyses show no significant differences in beta diversity between arms.Evidence: Bray-Curtis PERMANOVA P=0.62 for gut, P=0.21 for nasopharynx.
“beta diversity using Bray–Curtis dissimilarity showed no differences in microbial composition at the species level between treatment arms for the gut (PERMANOVA, P = 0.62) and for the nasopharynx (PERMANOVA, P = 0.21)”
ResultsFind in source
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
None foundRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
Checked — nothing surfaced.
The introduction cites prior trials (MORDOR, AVENIR) and WHO guidelines, establishing the context and the need to balance mortality benefits with AMR risk. The rationale for the study is logical, linking the premise to the objective of evaluating AMR selection. Limitations of prior research are addressed in the discussion, such as the lack of placebo arms in some prior studies and the potential for AMR spillover.
“Mass drug distribution (MDA) of broad-spectrum antibiotics to preschool children prevents mortality of those under 5 years old in some regions in sub-Saharan Africa – .”
“A fundamental challenge for local stakeholders and policymakers has been how to best balance the mortality benefits of azithromycin MDA with the risk of AMR selection , .”
“That study, however, lacked a placebo arm for all 5 years, and AMR spillover among communities may have been a confounder and cannot be ruled out.”
“That study, however, lacked a placebo arm for all 5 years, and AMR spillover among communities may have been a confounder and cannot be ruled out.”
Randomization method is described (response-adaptive, generated by a biostatistician using R), and the unit is the community (grappe). Blinding is described for all personnel except the biostatistician. Power analysis is provided for both rectal and nasopharyngeal outcomes. Inclusion/exclusion criteria are detailed for communities and individuals. Outlier handling is not explicitly described, but the analysis population is defined. Controls are the placebo arm. Independent replication is not applicable for a single trial, but the study is part of a larger program.
“The randomization sequence was generated by a biostatistician who was aware of the group assignments, using the R software (R Foundation for Statistical Computing).”
“Aside from the UCSF biostatistician and data analyst responsible for the randomization, all other study personnel, participants, laboratory personnel and all field workers responsible for administering and sample collection were masked to treatment allocation.”
“For load of genetic resistance determinants in nasopharyngeal swabs, we estimated that 50 communities per group would provide 80% power to detect an approximately 2-fold difference in any pairwise comparison, assuming an alpha of 0.05 and a s.d. of the log base 2 read count of 1.88.”
“The randomization sequence was generated by a biostatistician who was aware of the group assignments, using the R software (R Foundation for Statistical Computing).”
“Aside from the UCSF biostatistician and data analyst responsible for the randomization, all other study personnel, participants, laboratory personnel and all field workers responsible for administering and sample collection were masked to treatment allocation.”
“For load of genetic resistance determinants in nasopharyngeal swabs, we estimated that 50 communities per group would provide 80% power to detect an approximately 2-fold difference in any pairwise comparison, assuming an alpha of 0.05 and a s.d. of the log base 2 read count of 1.88.”
Sex is reported for both rectal and nasopharyngeal samples, with percentages. Age is reported as median and IQR, and age categories are provided. Demographics are detailed in Table 1. Since both sexes are included, sex_justified is not applicable. Species/strain and housing conditions are not applicable for human subjects.
“Baseline characteristics of samples analyzed.”
“Inclusion criteria for individual participants were: age 1–59 months and weighing at least 3,000 g”
The paper states ethical approval from the University of California, San Francisco Committee for Human Research and the Comité National Éthique pour la Recherche en Santé in Niger. Informed consent is described: verbal consent from community leaders and written informed consent from guardians. Regulatory compliance is stated with adherence to Good Clinical Practice and the Declaration of Helsinki.
“We obtained ethical approval for the study from the University of California, San Francisco Committee for Human Research and the Comité National Éthique pour la Recherche en Santé in Niger.”
“Additional verbal consent was obtained from community leaders, and written informed consent was obtained from the guardians for sample collection, which was documented electronically.”
“This trial was conducted according to Good Clinical Practice guidelines and adhered to the principles of the Declaration of Helsinki.”
“We obtained ethical approval for the study from the University of California, San Francisco Committee for Human Research and the Comité National Éthique pour la Recherche en Santé in Niger.”
“written informed consent was obtained from the guardians for sample collection, which was documented electronically.”
“This trial was conducted according to Good Clinical Practice guidelines and adhered to the principles of the Declaration of Helsinki.”
Azithromycin is identified as the investigational product, with dose (20 mg/kg) and regimen (semiannual). The placebo is also described. Software tools are identified: R version 4.3.1, Kraken2 version 2.1.2, Bracken version 2.5, DESeq2, Topconfects. Antibodies, cell lines, mycoplasma, and organisms are not applicable as this is a human trial without wet-lab assays.
“Interventions involved a single 20 mg kg − 1 dose of oral azithromycin or placebo suspension offered to children aged 1–59 months at study months 0, 6, 12 and 18.”
“All statistical analyses were conducted in R (R Foundation for Statistical Computing, version 4.3.1).”
“Kraken2 (version 2.1.2) was used for taxonomic classification for microbiome assessment for both rectal and nasopharyngeal samples, and Bracken (version 2.5) was used for estimation of genus and species abundances – .”
“Interventions involved a single 20 mg kg − 1 dose of oral azithromycin or placebo suspension offered to children aged 1–59 months at study months 0, 6, 12 and 18.”
“Sequencing libraries were performed using the NEBNext Ultra II DNA Library Prep Kit (New England Biolabs) per manufacturer’s recommendations.”
Tests are named: Wilcoxon rank-sum, t-test, PERMANOVA, ANOVA, DESeq2. Effect sizes with 95% CIs are reported for primary and secondary outcomes. Software is identified. Data presentation includes per-group n and CIs. Exact p-values are reported for primary outcomes (e.g., P < 0.01, P = 0.01). Assumptions are not explicitly verified, but the use of non-parametric tests and the large sample size mitigate this. Mathematical plausibility is not applicable due to continuous outcomes and large N.
“For macrolide resistance determinants at the class level, pairwise Wilcoxon rank-sum tests were performed between each treatment arm.”
“pairwise Wilcoxon rank-sum tests were performed between each treatment arm.”
“Macrolide resistance determinants were 1.16-fold as high (95% confidence interval (CI): 1.06–1.28-fold, P < 0.01)”
“1.16-fold as high (95% confidence interval (CI): 1.06–1.28-fold, P < 0.01)”
The data availability statement provides a concrete route: nonhost sequencing reads are available at BioProject ID PRJNA1337442, and limited deidentified individual information is available via Dryad at 10.5061/dryad.p8cz8wb48. Requests for more information are subject to approval by the AVENIR Study Group with a stated timeframe (120 days). Code sharing is not explicitly mentioned, but the analysis software is identified.
“Nonhost sequencing reads for all pooled samples are available at BioProject ID PRJNA1337442 (http://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1337442) . Limited deidentified individual information is available via Dryad at 10.5061/dryad.p8cz8wb48 (ref. ).”
“Nonhost sequencing reads for all pooled samples are available at BioProject ID PRJNA1337442”
“Requests for more information, beyond the scope of the reported results in this article, are subject to approval by the AVENIR Study Group and must comply with legal and regulatory requirements. Requests can be made to the PIs, Tom.Lietman@ucsf.edu and/or Kieran.Obrien@ucsf.edu, and will be addressed within 120 days.”
“Nonhost sequencing reads for all pooled samples are available at BioProject ID PRJNA1337442 (http://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1337442) . Limited deidentified individual information is available via Dryad at 10.5061/dryad.p8cz8wb48”
“BioProject ID PRJNA1337442”
Methods are detailed enough for replication. Trial registration is provided (NCT04224987). Reporting guideline is not explicitly mentioned, but the paper follows a structured format. All outcomes are reported, including negative results. Limitations are extensively discussed. Conclusions are proportional to the evidence. Funding sources and COI are stated.
“ClinicalTrials.gov registration: NCT04224987 (http://clinicaltrials.gov/ct2/show/NCT04224987)”
“This study has multiple limitations inherent to simple, large, randomized controlled trials.”
“This work was funded by the Bill and Melinda Gates Foundation (INV-002454: T.M.L.), the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01AI175250: T.M.L. and K.S.O’B.) and an unrestricted grant from Research to Prevent Blindness.”
“ClinicalTrials.gov registration: NCT04224987”
“This study has multiple limitations inherent to simple, large, randomized controlled trials.”
“This work was funded by the Bill and Melinda Gates Foundation (INV-002454: T.M.L.), the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01AI175250: T.M.L. and K.S.O’B.) and an unrestricted grant from Research to Prevent Blindness.”
Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
1 finding · worst lowReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
- References not resolvable to a published paperRecomputed
Checked 66 references by DOI: 1 verified — 1 DOI unresolved, 64 no DOI (shown, not verified).
- UNRESOLVED10.5061/dryad.p8cz8wb48Supplementary data for “Effect of mass azithromycin distribution on antibiotic resistance in the gut and nasopharynx: a cluster-randomized trial”Cited DOI does not resolve to any Crossref record.
- NO DOIAzithromycin to reduce childhood mortality in sub-Saharan AfricaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: verbal autopsy results from a cluster-randomised controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILonger-term assessment of azithromycin for reducing childhood mortality in AfricaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMass azithromycin distribution to prevent child mortality in Burkina Faso: the CHAT randomized clinical trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAzithromycin to reduce mortality—an adaptive cluster-randomized trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWHO Guideline on Mass Drug Administration of Azithromycin to Children Under Five Years of Age to Promote Child SurvivalNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMass drug administration of azithromycin: an analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEthical challenges in mass drug administration for reducing childhood mortality: a qualitative studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWHO Policy Recommendation: Seasonal Malaria Chemoprevention (SMC) for Plasmodium falciparum Malaria Control in Highly Seasonal Transmission Areas of the Sahel Sub-region in AfricaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIModulation of fecal microbiota and reductions in fecal antibiotic resistance genes (ARGs) driven by Weissella -fermented feed in growing pigsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDetection of tetQ and ermF antibiotic resistance genes in Prevotella and Porphyromonas isolates from clinical specimens and resident microbiota of humansNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPrevalence of antimicrobial resistance genes in Bacteroides spp. and Prevotella spp. Dutch clinical isolatesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIInsights from Bacteroides species in children with type 1 diabetesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMass azithromycin distribution and community microbiome: a cluster-randomized trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMacrolide resistance in MORDOR I—a cluster-randomized trial in NigerNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distributionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMacrolide and nonmacrolide resistance with mass azithromycin distributionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGut resistome of preschool children after prolonged mass azithromycin distribution: a cluster-randomized trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIProlonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: a sub-study of a cluster-randomized trial (MORDOR)No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe role of ‘spillover’ in antibiotic resistanceNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIHost range of the ermF rRNA methylase gene in bacteria of human and animal originNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIComplete nucleotide sequence and transcription of ermF, a macrolide-lincosamide-streptogramin B resistance determinant from Bacteroides fragilisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAzithromycin and erythromycin susceptibility and macrolide resistance genes in Prevotella from patients with periodontal diseaseNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDiversity of antimicrobial resistance genes in Bacteroides and Parabacteroides strains isolated in GermanyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe prevalence of antibiotic resistance genes in Bacteroides fragilis group strains isolated in different European countriesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIBacteroides : the good, the bad, and the nitty-grittyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMechanisms of reduced susceptibility and genotypic prediction of antibiotic resistance in Prevotella isolated from cystic fibrosis (CF) and non-CF patientsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDistribution, trends, and antimicrobial susceptibility of Bacteroides , Clostridium , Fusobacterium , and Prevotella species causing bacteremia in Japan during 2011–2020: a retrospective observational study based on national surveillance dataNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICommensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel diseaseNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDefining dysbiosis for a cluster of chronic diseasesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMobile elements carrying ermF and tetQ genes in gram-positive and gram-negative bacteriaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEscherichia coli as reservoir for macrolide resistance genesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMobile genetic elements in the genus Bacteroides , and their mechanism(s) of disseminationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICultivation of anaerobic bacteria: foundations and principlesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITemporal trends in phenotypic macrolide and nonmacrolide resistance for Streptococcus pneumoniae nasopharyngeal samples up to 36 months after mass azithromycin administration in a cluster-randomized trial in NigerNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe antimicrobial susceptibility of Porphyromonas gingivalis: genetic repertoire, global phenotype, and review of the literatureNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAntibiotic susceptibility and resistance genes in oral clinical isolates of Prevotella intermedia , Prevotella nigrescens , and Prevotella melaninogenicaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEmergence of antibiotic-resistant Porphyromonas gingivalis in United States periodontitis patientsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPresence and antibiotic resistance of Porphyromonas gingivalis , Prevotella intermedia , and Prevotella nigrescens in childrenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMacrolide resistance mechanisms in Gram-positive cocciNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAntimicrobial resistance following azithromycin mass drug administration: potential surveillance strategies to assess public health impactNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILimitations of current techniques in clinical antimicrobial resistance diagnosis: examples and future prospectsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOINeonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonizationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAltering the intestinal microbiota during a critical developmental window has lasting metabolic consequencesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAntibiotic use in children is associated with increased risk of asthmaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIntestinal microbiome is related to lifetime antibiotic use in Finnish pre-school childrenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIHow colonization by microbiota in early life shapes the immune systemNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMetabolic and metagenomic outcomes from early-life pulsed antibiotic treatmentNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe invisible extinctionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIHigh-throughput sequencing of pooled samples to determine community-level microbiome diversityNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIUnveiling microbial diversity: harnessing long-read sequencing technologyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDeep longitudinal lower respiratory tract microbiome profiling reveals genome-resolved functional and evolutionary dynamics in critical illnessNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILongitudinal analyses of infants’ microbiome and metabolome reveal microbes and metabolites with seemingly coordinated dynamicsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance databaseNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIdentification of acquired antimicrobial resistance genesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIFLASH: a next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequencesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMEGARes: an antimicrobial resistance database for high throughput sequencingNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMEGARes and AMR++, v3.0: an updated comprehensive database of antimicrobial resistance determinants and an improved software pipeline for classification using high-throughput sequencingNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImpact of database choice and confidence score on the performance of taxonomic classification using Kraken 2No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImproved metagenomic analysis with Kraken 2No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIBracken: estimating species abundance in metagenomics dataNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIvegan: Community ecology packageNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIModerated estimation of fold change and dispersion for RNA-seq data with DESeq2No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITopconfects: a package for confident effect sizes in differential expression analysis provides a more biologically useful ranked gene listNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
1 data/code link checked; 1 live.
- dataBioProjectLIVEHTTP 200http://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1337442Resolves to BioProject (data repository).
Copyediting
5 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 5 minor suggestions below.
5 copyedit issues flagged: mostly consistency, typo, clarity.
- MINORtypoResults, Secondary endpoints“micriobiome”→ microbiomeTypographical error in 'micriobiome'.
- MINORconsistencyAbstract“1.16, 95% confidence interval (CI): 1.06–1.28; P < 0.01”→ 1.16-fold, 95% CI: 1.06–1.28; P < 0.01Inconsistent use of 'fold' in the abstract; later text uses '1.16-fold'.
- MINORconsistencyResults, Primary endpoints“1.04-fold, 95% CI: 0.94–1.15, P = 0.66”→ 1.04-fold, 95% CI: 0.94–1.15-fold, P = 0.66Inconsistent use of 'fold' in the CI.
- MINORconsistencyAbstract“1.16, 95% confidence interval (CI): 1.06–1.28; P < 0.01”→ Ensure consistent use of 'fold' or '×' in reporting fold changes.Inconsistent notation for fold change (e.g., '1.16' vs '1.04×').
- MINORclarityMethods, Statistical methods“log 2 ( x + 1/nonhost reads)”→ Clarify the transformation formula; it may be ambiguous.The transformation formula could be misinterpreted; consider adding parentheses.
The published work is robust and well-reported; an informed reader should weigh the minor reporting gaps (outlier handling, assumptions verification, code sharing) and the unresolved Dryad DOI as points to verify. No erratum appears warranted based on the checks performed, but the authors should consider clarifying the Dryad DOI and adding code availability if applicable.
- 1.HIGHdata codeVerify and correct the Dryad DOI (10.5061/dryad.p8cz8wb48) in the Data availability section, as it was not found in the registry.A non-resolvable DOI undermines the data availability statement and may indicate a fabrication or typo.
- 2.HIGHreportingAdd a statement on code availability in the Data availability section, even if code is available upon request.Transparency about analysis code enhances reproducibility and is expected for a data-driven paper.
- 3.MEDIUMstatisticsIn the Methods/Statistical methods, explicitly state how outliers were defined and handled, or justify that no outliers were excluded.Outlier handling is a key methodological detail that is currently not described.
- 4.MEDIUMstatisticsIn the Methods/Statistical methods, state that assumptions for statistical tests were verified (e.g., normality, equal variance) or justify the use of non-parametric tests.Assumption verification is part of sound statistical reporting.
- 5.MEDIUMreportingAdd a reporting guideline checklist (e.g., CONSORT) to the supplementary materials.A reporting checklist improves transparency and completeness of trial reporting.
- 6.MEDIUMreportingClarify the handling of missing data or samples not analyzed (e.g., samples excluded due to quality) in the Methods.Missing data handling is important for interpreting results.
- 7.MEDIUMreportingConsider reporting the results of the phenotypic resistance analysis when available, as it is a prespecified outcome.Reporting all prespecified outcomes, including phenotypic data, is important for completeness.
- 8.LOWcopyeditFix the typo 'micriobiome' to 'microbiome' in Results, Secondary endpoints.Typographical errors reduce professionalism.
- 9.LOWcopyeditStandardize the use of 'fold' in reporting fold changes (e.g., '1.16-fold' vs '1.16') in the Abstract and Results.Consistent notation improves clarity.
- 10.LOWcopyeditClarify the transformation formula 'log 2 ( x + 1/nonhost reads)' in Methods, Statistical methods by adding parentheses.The formula is ambiguous and could be misinterpreted.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.