Journal of Infection最新文献

{"title":"Epidemiological and genomic characterisation of an outbreak of Streptococcus pyogenes emm5.23","authors":"Davide Pagnossin ,&nbsp;Andrew Smith ,&nbsp;William Weir ,&nbsp;Eisin McDonald ,&nbsp;Juliana Coelho ,&nbsp;Roisin Ure ,&nbsp;Katarína Oravcová","doi":"10.1016/j.jinf.2025.106498","DOIUrl":"10.1016/j.jinf.2025.106498","url":null,"abstract":"<div><h3>Objectives</h3><div>This retrospective cross-sectional study examined the epidemiology, clinical presentations, and genomics of <em>Streptococcus pyogenes</em> genotype <em>emm</em>5.23, linked to severe outcomes in Scotland.</div></div><div><h3>Methods</h3><div>Between 2014 and 2022, 58 cases of invasive Group A <em>Streptococcus</em> (iGAS) disease associated with <em>emm</em>5.23 were reported in Scotland. Surveillance data from 45 cases were analysed for clinical characteristics and risk factors. Whole-genome sequencing (WGS) included all available <em>emm</em>5.23 strains from Scotland (n=58), a subset from England (n=29), and <em>emm</em>5 strains of non-5.23 subtypes from Scotland (n=10), England (n=2), and Canada (n=1).</div></div><div><h3>Results</h3><div>Nearly all cases (96%, 43/45) were hospitalised, of whom 33% (15/45) required intensive care and 20% (9/45) died with iGAS. The most common presentations were bacteraemia (51%, 23/45) and pneumonia (24%, 11/45). WGS identified an emerging <em>emm</em>5.23 clade in Scotland, encompassing most isolates, which shared highly similar genomes and three non-synonymous polymorphisms.</div></div><div><h3>Conclusions</h3><div>Although genomic traits known to increase GAS virulence potential were not found, polymorphisms that may affect the <em>emm</em>5.23 phenotype were detected. This suggests this <em>emm</em>5.23 genotype was transiently successful rather than hypervirulent, with low population-level immunity contributing to its spread. This study emphasises the need for integration of real-time genomic data in public health surveillance to enhance source attribution and guide interventions.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 6","pages":"Article 106498"},"PeriodicalIF":14.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discordance between measures of Mycobacterium tuberculosis sensitization and type 2 diabetes mellitus in the United States (NHANES): A population-based cohort study","authors":"Itai M. Magodoro ,&nbsp;Katalin A. Wilkinson ,&nbsp;Brian L. Claggett ,&nbsp;Ntobeko A.B. Ntusi ,&nbsp;Mark J. Siedner M ,&nbsp;Robert J. Wilkinson","doi":"10.1016/j.jinf.2025.106496","DOIUrl":"10.1016/j.jinf.2025.106496","url":null,"abstract":"<div><h3>Objective</h3><div>We examined how latent TB infection (LTBI), evaluated by cell-mediated immune responses to <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) antigens, impacts glucose metabolism in US adults.</div></div><div><h3>Methods</h3><div><em>Mtb</em> sensitization was evaluated by interferon-γ (IFN-γ) release assay (IGRA+: assay reactivity) and tuberculin skin testing (TST+: skin induration ≥10 mm), and categorized as: IGRA-/TST- (TB uninfected controls); IGRA-/TST+; IGRA+/TST-; or IGRA+/TST+. Diabetes was ascertained by fasting plasma glucose (FPG) ≥7.0 mmol/L, HbA1c ≥6.5% and/or antidiabetic medication. Adjusted generalized additive models examined nonlinear effects of skin induration and IFN-γ reactivity on FPG and HbA1c; and LTBI on diabetes prevalence.</div></div><div><h3>Results</h3><div>Among 1787 (IGRA-/TST-), 101 (IGRA-/TST+), 92 (IGRA+/TST-), and 99 (IGRA+/TST+) adults, skin induration linearly associated with FPG [effective degrees of freedom (EDF) =1.01; p&lt;0.001] and non-linearly with HbA1c [EDF=1.76; p=0.003]. IFN-γ reactivity correlated with neither FPG [p=0.58] nor HbA1c [p=0.94]. Relatedly, adjusted diabetes prevalence was greater in IGRA-/TST+ [24.9%; p=0.048] and IGRA+/TST+ [27.3%; p=0.004] but not IGRA+/TST- [15.9%; p=0.69] individuals than among controls [15.3%].</div></div><div><h3>Conclusions</h3><div>LTBI associated with glycemic measures and diabetes when assessed by skin induration, but not IFN-γ release. This suggests an association with innate immune activation rather than acquired T-cell response, as determined by <em>ex vivo</em> IFN-γ release assay.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 6","pages":"Article 106496"},"PeriodicalIF":14.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 test sensitivity and duration of positivity in the UK during the 2023/2024 Winter: A prospective cohort study based on self-reported data","authors":"Christopher E. Overton ,&nbsp;Martyn Fyles ,&nbsp;Jonathon Mellor ,&nbsp;Robert S. Paton ,&nbsp;Alexander M. Phillips ,&nbsp;Alex Glaser ,&nbsp;Andre Charlett ,&nbsp;Thomas Ward","doi":"10.1016/j.jinf.2025.106485","DOIUrl":"10.1016/j.jinf.2025.106485","url":null,"abstract":"<div><div>Estimating epidemiological parameters is essential for informing an effective public health response during waves of infectious disease transmission. However, many parameters are challenging to estimate from real-world data and rely on human challenge studies or mass community testing. During Winter 2023/2024, a community cohort study of SARS-CoV-2 was conducted across households in England and Scotland. From this survey, questionnaire data and follow-up testing protocols provided valuable data on the duration of positivity and test sensitivity for lateral flow device (LFD) tests. Here, Bayesian statistical modelling methods are developed and applied to estimate the underlying parameters. The duration of LFD positivity is found to increase with increasing age, with a mean of 9.1 days (95% CrI: 8.4 days, 9.9 days) in the 18 to 34 years age group compared to 10.8 days (95% CrI: 10.3 days, 11.3 days) in the 75 years and over age group. Sex is found to have no impact on the duration of positivity. LFD test sensitivity at the time of symptom onset is very high, with an estimated sensitivity of 95% (95% CrI: 92%, 98%) across all age groups. As a function of time since symptom onset, LFD test sensitivity decays fastest in the youngest age group, reaching a minimum sensitivity of 0.26 (95% CrI: 0.16, 0.37) compared to 0.53 (95% CrI: 0.46, 0.6). Such patterns are expected since younger individuals experience less severe symptoms of COVID-19 and are likely to clear the virus faster. Females are found to have a slightly faster rate at which sensitivity decreases, but the same minimum sensitivity as Males. Combining the duration of positivity and test sensitivity distributions, we estimate the probability of returning a positive LFD test. Close to the symptom onset date, this probability is approximately 95%. However, this rapidly drops off, dropping below 5% after 13.8 days (95% CrI: 11.0 days, 17.3 days) for the youngest age group (3 to 17 years) and 17.8 days (95% CrI: 16.6 days, 19.2 days) for the 75 years and over age group. Although the probability of returning a positive LFD test rapidly drops off, it remains very high close to the time of symptom onset, which is when individuals are expected to be the most infectious.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 6","pages":"Article 106485"},"PeriodicalIF":14.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The successful implementation of comprehensive control paradigm for eliminating leprosy in Yunnan Province, China","authors":"Tian Ma ,&nbsp;Qing Zhen ,&nbsp;Fuying Guo,&nbsp;Shun Zha,&nbsp;Shuo Kou,&nbsp;Xiaojun Yu,&nbsp;Xiangyu Yan,&nbsp;Tiejun Shui","doi":"10.1016/j.jinf.2025.106492","DOIUrl":"10.1016/j.jinf.2025.106492","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 6","pages":"Article 106492"},"PeriodicalIF":14.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent invasive pneumococcal disease in children: A retrospective cohort study, England, 2006/07-2017/18","authors":"Marta Bertran ,&nbsp;Fariyo Abdullahi ,&nbsp;Joshua C. D’Aeth ,&nbsp;Zahin Amin-Chowdhury ,&nbsp;Nick J. Andrews ,&nbsp;Seyi Eletu ,&nbsp;David Litt ,&nbsp;Mary E. Ramsay ,&nbsp;Godwin Oligbu ,&nbsp;Shamez N. Ladhani","doi":"10.1016/j.jinf.2025.106490","DOIUrl":"10.1016/j.jinf.2025.106490","url":null,"abstract":"<div><h3>Background</h3><div>Recurrent invasive pneumococcal disease (IPD) is rare in children and usually associated with underlying comorbidities. We aimed to assess the risk and describe the characteristics of children with recurrent IPD over a 12-year period covering the introduction of the 7-valent (PCV7), followed by the 13-valent (PCV13) pneumococcal conjugate vaccine (PCV) in the national childhood immunisation programme in England.</div></div><div><h3>Methods</h3><div>We used enhanced national surveillance data for England and included all laboratory-confirmed IPD cases in children (&lt;15 years) during 2006/07–2017/18. We assessed the risk and rate of recurrent IPD, the serotypes responsible and the demographics, comorbidity status and prevalence, vaccination status, clinical presentation and outcomes in children with recurrent IPD compared to those with a single IPD episode.</div></div><div><h3>Findings</h3><div>There were 5158 IPD episodes reported in 5033 children over 12 years and 2.2% (105/4814) of those surviving their first IPD had at least one recurrence. Recurrence risk decreased with increasing age and over time. During 2015/16–2017/18, five years after PCV13 replaced PCV7, IPD recurrence rate was 229.0 (95% CI 154.8–339.0) per 100,000 person-years, with all recurrent cases caused by non-PCV13 serotypes. Where serotype information was available, recurrence was due to the same serotype in 25 cases, with a shorter median (IQR) interval of 88 (57–177) days between recurrent episodes, and in 60 cases due to different serotypes, with a median (IQR) interval of 223 (125–574) days (p=0.001). Compared to healthy children (103.0; 95%CI 63.1–168.1), recurrence rate per 100,000 person-years was 10 times higher in children with any comorbidity (1061.0; 95% CI 827.2–1360.9; 62/78 [79.5%] with available information had comorbidities), and almost 30 times higher in immunosuppressed children (2788.5; 95%CI 2029.0–3832.2; 38/78 [48.7%] were immunosuppressed). The 30-day case-fatality rate after recurrent IPD was 2.9% (3/105) compared to 4.4% (219/4928; p=0.63) after single-episode IPD.</div></div><div><h3>Interpretation</h3><div>Recurrent IPD is rare in children and occurs mainly in children with comorbidities, especially immunosuppression. Higher-valent PCVs have the potential to further reduce the risk of recurrent IPD in children.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 6","pages":"Article 106490"},"PeriodicalIF":14.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic global variation in resistance and hypervirulence of carbapenem-resistant Klebsiella pneumoniae between 2010 and 2023","authors":"Zhang Feilong,&nbsp;Yang Wenting,&nbsp;Lu Binghuai,&nbsp;Cao Bin","doi":"10.1016/j.jinf.2025.106493","DOIUrl":"10.1016/j.jinf.2025.106493","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 6","pages":"Article 106493"},"PeriodicalIF":14.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imidazole propionate is increased in severe COVID-19 and correlates with cardiac involvement","authors":"Tuva B. Dahl,&nbsp;Friha Aftab,&nbsp;Christian Prebensen,&nbsp;Jan-Erik Berdal,&nbsp;Thor Ueland,&nbsp;Andreas Barratt-Due,&nbsp;Anne Ma Dyrhol Riise,&nbsp;Per Magne Ueland,&nbsp;Johannes R. Hov,&nbsp;Marius Trøseid,&nbsp;Pål Aukrust,&nbsp;Ida Gregersen,&nbsp;Peder L. Myhre,&nbsp;Torbjørn Omland,&nbsp;Bente Halvorsen","doi":"10.1016/j.jinf.2025.106494","DOIUrl":"10.1016/j.jinf.2025.106494","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 6","pages":"Article 106494"},"PeriodicalIF":14.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding post-mortem infection dynamics of SARS-CoV-2, IAV and RSV: New insights for public health and emerging infectious diseases management","authors":"Run Chen ,&nbsp;Zeyi Hao ,&nbsp;Jian Ye ,&nbsp;Xingchun Zhao ,&nbsp;Sheng Hu ,&nbsp;Jianliang Luo ,&nbsp;Junhua Li ,&nbsp;Hao Wu ,&nbsp;XingGong Liang ,&nbsp;Chen Shen ,&nbsp;Mingyan Deng ,&nbsp;Wanqing Zhang ,&nbsp;Zhengyang Zhu ,&nbsp;Yudong Qin ,&nbsp;Gengwang Hu ,&nbsp;Letong Zhang ,&nbsp;Fan Cao ,&nbsp;Yuzhao Liu ,&nbsp;Ruina Liu ,&nbsp;Qinru Sun ,&nbsp;Zhenyuan Wang","doi":"10.1016/j.jinf.2025.106489","DOIUrl":"10.1016/j.jinf.2025.106489","url":null,"abstract":"<div><h3>Objectives</h3><div>The persistence and infectivity of respiratory viruses in cadavers remain poorly characterized, posing significant biosafety risks for forensic and healthcare professionals. This study systematically evaluates the post-mortem stability and transmission potential of SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV) under varying environmental conditions, providing critical insights into viral kinetics.</div></div><div><h3>Methods</h3><div>To assess the post-mortem stability of SARS-CoV-2, tissue samples were collected from infected cadavers at 4 ℃, room temperature (RT, 20–22 ℃), and 37 ℃ over a predetermined timeframe. Viral kinetics were analyzed using quantitative assays, while histopathology and immunohistochemistry characterized tissue-specific distribution. Additionally, comparative analyses were conducted both in vitro and in cadaveric tissues to characterize the survival dynamics of IAV and RSV under identical conditions.</div></div><div><h3>Results</h3><div>SARS-CoV-2 exhibited prolonged post-mortem infectivity, persisting for up to 5 days at RT and 37 ℃ and over 7 days at 4 ℃, with the highest risk of transmission occurring within the first 72 h at RT and 24 h at 37 ℃. In contrast, RSV remained viable for 1–2 days, while IAV persisted for only a few hours post-mortem. Viral decay rates were temperature-dependent and varied across tissues, demonstrating distinct post-mortem survival kinetics.</div></div><div><h3>Conclusions</h3><div>This study presents the first comprehensive analysis of viral persistence in cadavers, revealing prolonged SARS-CoV-2 stability compared to IAV and RSV. These findings underscore the need for enhanced post-mortem biosafety protocols to mitigate occupational exposure risks in forensic and clinical settings. By elucidating viral decay dynamics across environmental conditions, this research establishes a critical foundation for infection control strategies, informing biosafety policies for emerging respiratory pathogens.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 6","pages":"Article 106489"},"PeriodicalIF":14.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous versus intermittent bolus dosing of beta-lactam antibiotics in a South African multi-disciplinary intensive care unit: A randomized controlled trial","authors":"Ayesha Bibi Khan ,&nbsp;Mohd Hafiz Abdul-Aziz ,&nbsp;Lucy Hindle ,&nbsp;Jeffrey Lipman ,&nbsp;Fetolang Simelela ,&nbsp;Shahed Omar","doi":"10.1016/j.jinf.2025.106487","DOIUrl":"10.1016/j.jinf.2025.106487","url":null,"abstract":"<div><h3>Background</h3><div>Beta-lactams exhibit time-dependent bactericidal effects with continuous infusion (CI) suggested to provide superior antibiotic concentrations compared to intermittent bolus (IB).</div></div><div><h3>Objective</h3><div>To determine whether beta-lactam CI improves day 14 clinical cure compared to IB in a South African, multi-disciplinary intensive care unit (ICU).</div></div><div><h3>Methods</h3><div>Adult patients with sepsis receiving amoxicillin-clavulanate, piperacillin-tazobactam, imipenem-cilastatin and meropenem were randomized to 24-hour CI or IB. On screening, patients who received study antibiotics for more than 24 h, pregnant patients or patients on renal replacement therapy were excluded. The primary outcome, clinical cure, was defined as completion of antibiotics by day 14 without recommencement within 48 h. Secondary outcomes included ICU length of stay (LOS), ICU, day 28 and day 90 mortality.</div></div><div><h3>Results</h3><div>We enrolled 122 patients. The groups were balanced for baseline age, weight, sex, severity of illness, organ support, HIV status, diagnostic category and site of infection. Median antibiotic duration, CI group, 7 days (IQR 5–8.5) vs. IB group, 6 days (IQR 4–8), p=0.191, and median ICU LOS, CI, 9.5 days (IQR 6–15.5) vs. IB, 9 days (IQR 5–16), p= 0.575, were similar. Clinical cure in the CI group was 81% (52/64) vs. 74.1% (43/58) in the IB group), p=0.345. Day 90 relative risk of death was 0,57, 95% Confidence Interval 0.32 – 1.01) for the CI group compared to IB.</div></div><div><h3>Conclusion</h3><div>Among critically ill patients meeting the sepsis-3 definition, this study could not demonstrate the superiority of continuous infusion of beta-lactam antibiotics compared to intermittent bolus in achieving a clinical cure.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 5","pages":"Article 106487"},"PeriodicalIF":14.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton pump inhibitors and the risk of Clostridioides difficile infection: A systematic review and dose-response meta-analysis","authors":"Matilda Finke ,&nbsp;Annelies Boven ,&nbsp;Erika Vlieghe ,&nbsp;Lars Engstrand ,&nbsp;Nicola Orsini ,&nbsp;Nele Brusselaers","doi":"10.1016/j.jinf.2025.106488","DOIUrl":"10.1016/j.jinf.2025.106488","url":null,"abstract":"<div><h3>Background</h3><div><em>Clostridioides difficile</em> is a leading cause of healthcare-associated infections globally with proton pump inhibitor (PPI) use as important modifiable risk factor. This study aimed to systematically synthesise global evidence on the dose-response relationship of PPI usage and the <em>Clostridioides difficile</em> infection (CDI) risk and to identify potential safe thresholds of PPI usage regarding CDI.</div></div><div><h3>Methods</h3><div>PubMed, Embase, Web of Science, and Cochrane Library were searched for longitudinal studies regarding PPIs and CDI. Aggregated data were included in two separate two-stage random-effects dose-response meta-analyses regarding Defined Daily Dose (DDD) and PPI therapy duration. Pooled adjusted relative risks (RRs) with 95% confidence intervals compared to non-users of PPIs were estimated.</div></div><div><h3>Findings</h3><div>Overall, 15 observational cohort and case-control studies were included with 7 studies (n=483,821) in the meta-analysis per DDD and 7 studies (n=516,441) per PPI therapy duration. The risk of bias was modest. Pooled dose-response estimates suggest linear trends with a RR of 1^.05 (95% CI 0^.89,1^.23) per 10 mg DDD and of 1^.02 (95% CI 1^.00,1^.05) per day of PPI therapy. Substantial residual heterogeneity was detected in both analyses (I2=91^.4% per DDD and I2=99^.4% per therapy duration), but inferring potential sources was limited.</div></div><div><h3>Interpretation</h3><div>Our results indicate a possible increase in the risk of CDI with increasing dose and duration of PPI therapy. Underlying mechanisms and dosage thresholds for a clinically relevant risk increase remain unclear.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 5","pages":"Article 106488"},"PeriodicalIF":14.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}