Journal of Antimicrobial Chemotherapy最新文献

{"title":"Surveying genetic markers of antibiotic resistance and genomic background in Chlamydia trachomatis: insights from a multiplex NGS-based approach in clinical strains from Portugal.","authors":"Zohra Lodhia, Jorge Costa Da Silva, Cristina Correia, Dora Cordeiro, Inês João, Teresa Carreira, Sandra Schäfer, Elzara Aliyeva, Clara Portugal, Isabel Monge, Elsa Gonçalves, Susana Matos, Ana Paula Dias, Rita Côrte-Real, Dina Carpinteiro, Sílvia Duarte, Luís Vieira, João Paulo Gomes, Vítor Borges, Maria José Borrego","doi":"10.1093/jac/dkaf036","DOIUrl":"https://doi.org/10.1093/jac/dkaf036","url":null,"abstract":"<p><strong>Objectives: </strong>To survey genetic markers of potential antimicrobial resistance (AMR) to macrolides and fluoroquinolones among Chlamydia trachomatis-positive samples from the collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections (STIs), and explore a multiplex PCR approach coupled with NGS to provide complementary information regarding a strain's genomic backbone.</p><p><strong>Methods: </strong>A total of 502 C. trachomatis-positive samples, mostly anorectal exudates, were subjected to PCR and sequencing of five targets, including loci potentially driving AMR (23S rRNA, gyrA and parC) and loci potentially informative about a strain's genomic backbone with emphasis on differentiation of lymphogranuloma venereum (LGV)/non-LGV and L2/L2b (a 9 bp insertion in pmpH, a 74 bp insertion upstream from CT105 and the polymorphic CT442).</p><p><strong>Results: </strong>No samples evidenced 23S rRNA mutations recognizably linked to macrolide resistance. Three samples harboured the Ser83Ile mutation in GyrA putatively driving fluoroquinolone resistance: two recombinant L2-L2b/D-Da (0.4%) and one L2 (0.2%). The screened regions in pmpH, upstream CT105 and CT442 were fully concordant with LGV/non-LGV differentiation. As expected, the pmpH L2b-specific genetic trait locus was detected in all L2b and recombinant L2-L2b/D-Da ompA genotypes, but also in 96.0% of L2 specimens, which also likely possess an L2b genomic backbone. The insertion upstream from CT105 exhibited full LGV specificity, constituting a promising target for the development of rapid LGV diagnostic assays.</p><p><strong>Conclusions: </strong>This study contributes to enhancing the knowledge of C. trachomatis molecular epidemiology, suggesting that the known genetic determinants of AMR are not disseminated in clinical C. trachomatis strains, and presents an exploratory approach that can be suitable for LGV/non-LGV and L2/L2b genomic background differentiation.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early clinical experience using tecovirimat during the 2022 mpox epidemic in Toronto underscores ongoing clinical equipoise and the need for randomized trials.","authors":"Shreya S Khera, Sharmistha Mishra, Oscar Javier Pico Espinosa, Kevin Gough, Charlie Tan, Sharon Walmsley, Alice Zhabokritsky, Malika Sharma, Adrienne K Chan, Jerome A Leis, Myo Minn Oo, Darrell H S Tan","doi":"10.1093/jac/dkaf010","DOIUrl":"https://doi.org/10.1093/jac/dkaf010","url":null,"abstract":"<p><strong>Background: </strong>Tecovirimat is an antiviral drug that was used compassionately for treating mpox in high-income settings during the 2022 global outbreak. Randomized controlled trials of its efficacy have not yet been completed.</p><p><strong>Objectives: </strong>To describe medication adherence, tolerability and clinical outcomes of adults receiving open-label tecovirimat for mpox infection.</p><p><strong>Methods: </strong>We conducted a prospective observational study and a retrospective case series of adults with mpox cared for at three academic hospitals in Toronto, Canada, between May and August 2022. We present a descriptive analysis of those prescribed oral tecovirimat 600 mg twice daily for 14 days for the management of severe manifestations.</p><p><strong>Results: </strong>Of 69 consenting participants, all were cisgender men, of whom 60 (87%) identified as gay, and 6 (9%) as bisexual. Nearly half (46%) were living with HIV, with a median (IQR) CD4 count of 468 (328-678) cells/mm3, among whom plasma HIV RNA was <20 copies/mL in 29 (91%) participants. One-third (33%) of participants received tecovirimat during the course of their illness. All participants experienced a decline in number of symptoms over time, but three treated participants initially experienced worsening symptoms despite therapy. Self-reported adherence to tecovirimat was excellent and tolerability was good.</p><p><strong>Conclusions: </strong>Our experience prescribing tecovirimat for mpox suggests it is safe and well tolerated, but the evolution of symptoms in some tecovirimat-treated patients underscores the ongoing uncertainty regarding its efficacy. In the context of considerable community demand for the drug, efforts should be made to connect mpox patients to rigorous randomized controlled trials, given this ongoing clinical equipoise.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of antifungal allergies in the general population.","authors":"Meron W Shiferaw, Monica A Donnelley, George R Thompson","doi":"10.1093/jac/dkaf037","DOIUrl":"https://doi.org/10.1093/jac/dkaf037","url":null,"abstract":"<p><strong>Objectives: </strong>Invasive fungal infections are increasing in frequency and are associated with high patient morbidity and mortality. The use of antifungal therapy is thus also increasing, and patients reporting hypersensitivity or allergic reactions to the limited antifungal agents currently available complicates management. There are no prior studies defining the incidence of antifungal allergies reported by patients.</p><p><strong>Methods: </strong>A multicentre retrospective cohort review of all patient encounters at five large academic centres during 2023 was conducted. The primary outcome of this study was to find the prevalence of reported antifungal allergy across the University of California Health System, and secondarily determine the incidence of antifungal allergies among patients with documented administration of antifungal agent.</p><p><strong>Results: </strong>A total of 1 704 176 patients were included and 2602 patients exhibited a documented antifungal allergy. Prevalences of antifungal allergies were: fluconazole 1591 (0.093%), general antifungal allergy 395 (0.023%), triazole 361 (0.021%), itraconazole 145 (0.008%), amphotericin 110 (0.006%) and flucytosine <10 (0.001%). In the secondary outcome (incidence), 9829 patients received an antifungal agent and 298 reported an antifungal allergy (2.98%).</p><p><strong>Conclusions: </strong>Increasing age and use of antifungal therapy are associated with antifungal allergy prevalence. Antifungal allergy rates (prevalence and incidence) are also comparable to the rates reported for antibacterial agents and are highest with fluconazole.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased susceptibility to cefepime/zidebactam among carbapenemase-producing Escherichia coli from Stockholm, Sweden with alterations in PBP2.","authors":"Chaitanya Tellapragada, Chantel Dunleavy, Patrik Jonsson, Christian G Giske","doi":"10.1093/jac/dkaf045","DOIUrl":"https://doi.org/10.1093/jac/dkaf045","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to investigate the in vitro activity and genetic determinants of decreased susceptibility (DS; MIC > 4 mg/L) to cefepime/zidebactam of carbapenemase-producing Escherichia coli.</p><p><strong>Methods: </strong>Clinical isolates (N = 150) of carbapenemase-producing E. coli (CP-EC) belonging to seven distinct STs, isolated at a university clinical microbiology laboratory during 2019-2023 in Stockholm, Sweden were included. MICs for cefepime/zidebactam were determined using the broth microdilution method and interpreted using the tentative EUCAST clinical breakpoints (Susceptible; MIC < 4 mg/L; based on cefepime breakpoint). Whole genome sequences of the isolates were analysed with an emphasis on identifying alterations in PBPs 2 and 3.</p><p><strong>Results: </strong>Of the 150 isolates, 145 (96.6%) isolates had MICs <4 mg/L indicating susceptibility and 5 (3.3%) had MICs >4 mg/L. MICs for zidebactam alone among the five isolates with DS to cefepime/zidebactam were ≥8 mg/L. WGS analysis revealed that these five isolates were NDM-5 producers and belonged to ST405 (n = 1), ST410 (n = 2) and ST648 (n = 2). Presence of four-amino-acid inserts (YRIK/YRIN) in PBP3 was observed in 80/150 (53.3%) isolates, and mutations leading to alterations in PBP2 were observed in 41/150 (27.3%) isolates. Presence of other β-lactamases (CTX-M group) and/or cephalosporinases (blaCMY) did not have an impact on the susceptibility to cefepime/zidebactam. Three of the five isolates with DS had a V522I substitution in PBP2.</p><p><strong>Conclusions: </strong>Our results indicate that DS to cefepime/zidebactam among clinical isolates of E. coli could arise due to targeted mutations in PBP2.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly adsorptive removal of cefiderocol during continuous venovenous hemodiafiltration equipped with oXiris filter in an orthotopic liver transplant recipient having septic shock caused by VIM-producing Klebsiella pneumoniae.","authors":"Milo Gatti, Matteo Rinaldi, Cristiana Laici, Antonio Siniscalchi, Simone Ambretti, Maddalena Giannella, Pierluigi Viale, Federico Pea","doi":"10.1093/jac/dkaf040","DOIUrl":"https://doi.org/10.1093/jac/dkaf040","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and safety of rifapentine in children: dosing for latent tuberculosis infection.","authors":"Weijian Liu, Nuo Xu, Wei Li, Wen Yao Mak, Tian He, Hongjuan Qin, Shuihua Lu, Hongzhou Lu, Xiaoqiang Xiang, Xiao Zhu, Peize Zhang","doi":"10.1093/jac/dkaf029","DOIUrl":"https://doi.org/10.1093/jac/dkaf029","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the safety of 4-week daily rifapentine-isoniazid regimen in latent tuberculosis for Chinese children, and to provide paediatric-specific evidence for extrapolating adult dosing strategies to children.</p><p><strong>Methods: </strong>An open-label, prospective, single-arm clinical trial was conducted among eligible patients (aged <10 years old). Rifapentine concentrations and laboratory safety biomarker (total bilirubin) were analysed and used for population pharmacokinetic-toxicity model development. Simulations were performed to compare efficacy and safety of weight-based and flat-dosing strategy.</p><p><strong>Results: </strong>Once-daily rifapentine treatment was well tolerated: 310 samples (rifapentine n = 139; total bilirubin n = 171) from 36 children (age range 0.89-10 years) were captured well by a joint one-compartment pharmacokinetic with time-varying clearance and an indirect response model. The model adequately described rifapentine autoinduction, reaching a plateau after 21 days and increasing clearance by 70.4%. Simulation suggested that weight-based dosing may cause underexposure in children under 14.5 kg. A flat-dosing strategy could ensure plasma levels within the therapeutic windows. Rifapentine's impact on total bilirubin was within a 2-fold range, and the effect subsided within 5 days after discontinuation.</p><p><strong>Conclusions: </strong>Our study suggested that a flat-dosing strategy of rifapentine was potentially safe and effective for latent tuberculosis infection treatment in Chinese children aged 1 to 10 years old.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the appropriateness of antifungal prescribing: key results from the implementation of a novel audit tool in Australian hospitals.","authors":"A Khanina, N Singh, R James, D C M Kong, M A Slavin, K A Thursky","doi":"10.1093/jac/dkaf044","DOIUrl":"https://doi.org/10.1093/jac/dkaf044","url":null,"abstract":"<p><strong>Objectives: </strong>To utilize the Antifungal National Antimicrobial Prescribing Survey (Antifungal NAPS), a novel tool utilizing international consensus metrics for antifungal stewardship, to assess the quality of systemic antifungal prescribing in Australian hospitals, in order to identify quality improvement targets.</p><p><strong>Methods: </strong>Participating hospitals were directed to audit all systemic antifungals or focus on a specific antifungal drug or class. Data entry into the Antifungal NAPS online portal occurred between October 2022 and June 2023. The data collection tool comprised patient details, reasons precluding use of antifungals, prescription details (guideline compliance, appropriateness, and reasons for inappropriate prescribing) and patient outcomes. Descriptive statistics were used to analyse the data.</p><p><strong>Results: </strong>Eleven hospitals contributed data for 516 prescriptions for 438 patients. Of these, 77.1% of prescriptions were appropriate, with the highest appropriateness for prophylactic (189/222; 85.1%), followed by directed (105/130; 80.8%) and empirical therapy (104/164; 63.4%). Fluconazole was the most commonly prescribed agent, which had the lowest rate of appropriateness (132/209; 63.2%). The most common reasons for inappropriate prescribing were no antifungal required (35/105; 33.3%), incorrect dose or frequency (30/105; 28.6%) and incorrect duration (19/105; 18.1%). Compliance with guidelines was 73.6%.</p><p><strong>Conclusions: </strong>This study outlines the successful implementation of the Antifungal NAPS, a standardized electronic audit tool for the assessment of antifungal prescribing quality. Key areas for quality improvement identified were the overuse of empirical fluconazole for urinary tract and intra-abdominal infections, the importance of invasive fungal infection risk assessment to guide prophylaxis prescribing and greater infectious diseases and antifungal stewardship oversight of antifungal prescribing to guide optimal prescribing.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulated exposures of oritavancin in in vitro pharmacodynamic models select for methicillin-resistant Staphylococcus aureus with reduced susceptibility to oritavancin but minimal cross-resistance or seesaw effect with other antimicrobials.","authors":"Brian J Werth, Rutan Zhang, Ismael A Barreras Beltran, Kelsi Penewit, Adam Waalkes, Elizabeth A Holmes, Stephen J Salipante, Libin Xu","doi":"10.1093/jac/dkaf042","DOIUrl":"https://doi.org/10.1093/jac/dkaf042","url":null,"abstract":"<p><strong>Background: </strong>Dalbavancin exposures select for VAN and daptomycin cross-resistance in Staphylococcus aureus often by walK-related mutations. Oritavancin is another long-acting lipoglycopeptide, but its proclivity to select for cross-resistance is unknown. The objective of this study was to determine if post-distributional pharmacokinetic oritavancin exposures select for meaningful susceptibility changes in S. aureus.</p><p><strong>Methods: </strong>We simulated average post-distributional, free-drug exposures of oritavancin 1200 mg IV once (fCmax 11.2 µg/mL; β-elimination t1/2 13.4 h; γ-elimination t1/2 245 h) in an in vitro pharmacodynamic model for 28 days against five S. aureus including four MRSA. Samples were taken daily for colony enumeration and resistance screening. Susceptibility testing was repeated on isolates from resistance screening plates against oritavancin, vancomycin, daptomycin, dalbavancin and 6 beta-lactams with varying penicillin-binding protein affinities.</p><p><strong>Results: </strong>Tested oritavancin exposures were bactericidal against 5/5 strains for 2-17 days before regrowth of less-susceptible subpopulations occurred. Isolates with reduced susceptibility to oritavancin were detected as early as 5 days, but the MIC increased above the susceptibility breakpoint (>0.125 mg/L) in 4/5 strains eventually. Vancomycin and daptomycin MICs increased by 2- to 8-fold but did not exceed the susceptibility breakpoints in most isolates. β-lactam MICs were largely unchanged among the recovered isolates with reduced oritavancin susceptibility. Mutations were diverse but often involved purR with 13 unique variants identified among 4/5 strains.</p><p><strong>Conclusions: </strong>Oritavancin-selected resistance was primarily associated with purR mutation and less frequently associated with cross-resistance and walK mutation than dalbavancin-selected resistance in similar strains and conditions. The reason for this is unclear but may stem from differences in the mechanism(s) and divergent mutational pathways.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world efficacy and tolerability of CAB+RPV LA in women: addressing the gender gap in HIV treatment research.","authors":"Marta Rosas Cancio-Suárez, Ana Moreno, Santos Del Campo Terrón, María Jesús Vivancos, Alejandro G García-Ruiz De Morales, Javier Martínez-Sanz, Raquel Ron, Sofía Sánchez-Izquierdo, Manuel Vélez-Díaz-Pallarés, Santiago Moreno, María Jesús Pérez-Elías","doi":"10.1093/jac/dkaf038","DOIUrl":"https://doi.org/10.1093/jac/dkaf038","url":null,"abstract":"<p><strong>Background: </strong>Women, particularly those of advanced age with comorbidities and polypharmacy, are often underrepresented in clinical trials evaluating long-acting (LA) antiretroviral therapy (ART) regimens like cabotegravir and rilpivirine (CAB + RPV LA). This single-center study aims to address this gap by assessing the effectiveness, tolerability, and adherence to CAB + RPV LA, focusing on women who often have complex health profiles.</p><p><strong>Methods: </strong>In this single-center, retrospective study, we analyzed virologic suppression rates, adherence and tolerability in our cohort of women living with HIV comparing their outcomes to men on the same regimen.</p><p><strong>Results: </strong>A total of 270 individuals (42 women and 228 men) were included. Women had a higher prevalence of comorbidities (86% versus 49%, P = 0.0001), and were more likely to have used ≥5 ART lines (69% versus 29%, P < 0.0001), and 31% were aged ≥60 years compared to 13% of men (P = 0.003). Despite higher rates of comorbidities and polypharmacy, women achieved virologic suppression and adherence levels comparable to men. CAB + RPV LA was well-tolerated in both groups, with no significant gender-based differences in treatment outcomes.</p><p><strong>Conclusion: </strong>CAB + RPV LA is effective and well-tolerated in women with complex ART histories, providing a viable long-acting alternative for populations traditionally underrepresented in clinical trials. These findings underscore the importance of including women in studies of novel ART regimens to ensure equitable access and outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating the herd effects of antimicrobial prevention interventions on ventilator-associated pneumonia within ICU populations: a cluster randomized trial emulation using data from Cochrane reviews.","authors":"James C Hurley","doi":"10.1093/jac/dkaf033","DOIUrl":"https://doi.org/10.1093/jac/dkaf033","url":null,"abstract":"<p><strong>Background: </strong>The herd effects of antimicrobial interventions used to prevent ICU-acquired infections are unknown. The objective here was to estimate these herd effects within a single three-tiered cluster randomized trial (CRT) emulated using ventilator-associated pneumonia (VAP) data from randomized concurrent control trials (RCCTs) abstracted within Cochrane reviews.</p><p><strong>Methods: </strong>Control and intervention group data derived from 13 Cochrane reviews of 72 RCCTs of antibiotic (Tier 3) and antiseptic (Tier 2) decontamination versus 109 RCCTs of various non-decontamination (Tier 1, serving as benchmark) VAP prevention interventions were arranged as a three-tiered CRT. The direct and indirect (herd) effects of Tiers 2 and 3 each versus Tier 1 interventions were obtained using estimators derived in meta-regression models.</p><p><strong>Results: </strong>Benchmark (Tier 1) VAP incidences derived for control and intervention groups from non-decontamination RCCTs were 23.3 (95% CI: 20.6-26.1; n = 111) and 19.2 (95% CI: 16.8-21.8; n = 112), respectively. The mean VAP incidences for antibiotic and antiseptic decontamination control groups were 5% to 15% higher than the control group benchmark. The direct effects of antibiotic and antiseptic interventions versus Tier 1 benchmarks (ORs) were 0.77 (95% CI: 0.55-1.09) and 0.97 (95% CI: 0.71-1.33) whereas the indirect effects were 2.17 (95% CI: 1.56-3.03) and 1.38 (95% CI: 1.0-1.91), respectively.</p><p><strong>Conclusions: </strong>Indirect (herd) effects from antimicrobial interventions, although inapparent within individual RCCTs, are strong. These effects on control group VAP incidences, which spuriously conflate the appearance of benefit, constitute herd peril.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}