Excess mortality during periods of respiratory virus circulation is very high compared with the number of reported deaths because of these infections. We aimed to estimate the prevalence of infection by influenza and other respiratory viruses in deceased persons during four influenza seasons.
Methods
Deceased persons, regardless the cause, were swabbed postmortem and tested by PCR for respiratory viruses in the 2016/2017 to 2019/2020 seasons in Navarre, Spain. Postmortem results were compared with the diagnoses from clinical PCR testing.
Results
Of 857 deceased persons with a valid test result, 312 (36.4%) were positive for respiratory viruses: 98 rhinovirus (11.4%), 94 influenza (11.0%), 61 human coronavirus (7.1%), 59 respiratory syncytial virus (6.9%), 14 parainfluenza (1.6%), eight adenovirus (0.9%), six metapneumovirus (0.7%), four bocavirus (0.5%), one enterovirus (0.1%), and one SARS-CoV-2 (0.1%). The prevalence of any respiratory virus remained high throughout the seasons (78/263, 29.7% to 27/57, 47.4%). Among people who tested positive for influenza postmortem, only 41.5% (39/94) had been hospitalized and 17.0% (16/94) had a positive test result for influenza within 30 days before death. The prevalence of influenza postmortem (94/857, 11.0%) contrasted with the prevalence of premortem diagnosis of influenza (23/857, 2.7%) and only 1.4% (12/857) of deaths recorded with influenza as the cause of death.
Conclusions
Respiratory viral infections were frequently detected in winter deaths, but most of them were not laboratory confirmed before death. The impact of influenza infection on mortality could be higher than the number of persons who are reported as dying from influenza or who die with a confirmed diagnosis of this infection.
{"title":"Prevalence of influenza and other respiratory viral infections in deceased persons: a population-based observational study over four influenza seasons","authors":"Camino Trobajo-Sanmartín , Ana Navascués , Maddi Olazábal-Arruiz , Lucía Argente-Colas , Irene Iniesta , Itziar Casado , Marcela Guevara , Jesús Castilla , Iván Martínez-Baz","doi":"10.1016/j.cmi.2025.11.019","DOIUrl":"10.1016/j.cmi.2025.11.019","url":null,"abstract":"<div><h3>Objective</h3><div>Excess mortality during periods of respiratory virus circulation is very high compared with the number of reported deaths because of these infections. We aimed to estimate the prevalence of infection by influenza and other respiratory viruses in deceased persons during four influenza seasons.</div></div><div><h3>Methods</h3><div>Deceased persons, regardless the cause, were swabbed postmortem and tested by PCR for respiratory viruses in the 2016/2017 to 2019/2020 seasons in Navarre, Spain. Postmortem results were compared with the diagnoses from clinical PCR testing.</div></div><div><h3>Results</h3><div>Of 857 deceased persons with a valid test result, 312 (36.4%) were positive for respiratory viruses: 98 rhinovirus (11.4%), 94 influenza (11.0%), 61 human coronavirus (7.1%), 59 respiratory syncytial virus (6.9%), 14 parainfluenza (1.6%), eight adenovirus (0.9%), six metapneumovirus (0.7%), four bocavirus (0.5%), one enterovirus (0.1%), and one SARS-CoV-2 (0.1%). The prevalence of any respiratory virus remained high throughout the seasons (78/263, 29.7% to 27/57, 47.4%). Among people who tested positive for influenza postmortem, only 41.5% (39/94) had been hospitalized and 17.0% (16/94) had a positive test result for influenza within 30 days before death. The prevalence of influenza postmortem (94/857, 11.0%) contrasted with the prevalence of premortem diagnosis of influenza (23/857, 2.7%) and only 1.4% (12/857) of deaths recorded with influenza as the cause of death.</div></div><div><h3>Conclusions</h3><div>Respiratory viral infections were frequently detected in winter deaths, but most of them were not laboratory confirmed before death. The impact of influenza infection on mortality could be higher than the number of persons who are reported as dying from influenza or who die with a confirmed diagnosis of this infection.</div></div>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 474-481"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630766","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}
Pub Date : 2026-03-01Epub Date: 2025-11-28DOI: 10.1016/j.cmi.2025.11.025
Annette C. Westgeest , Merel M.C. Lambregts , Felicity Edwards , Adam G. Stewart , Joshua T. Thaden , Kevin B. Laupland , European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES)
{"title":"Is female sex a risk factor for acquisition and mortality in Enterobacterales bloodstream infection? A population-based cohort study","authors":"Annette C. Westgeest , Merel M.C. Lambregts , Felicity Edwards , Adam G. Stewart , Joshua T. Thaden , Kevin B. Laupland , European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES)","doi":"10.1016/j.cmi.2025.11.025","DOIUrl":"10.1016/j.cmi.2025.11.025","url":null,"abstract":"","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 501-503"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647629","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}
Pub Date : 2026-03-01Epub Date: 2025-12-02DOI: 10.1016/j.cmi.2025.11.031
Song Song , David Shu Cheong Hui , Samuel Yeung Shan Wong , Chak Sing Lau , Ivan Fan Ngai Hung , Francisco Tsz Tsun Lai
{"title":"Two-year prognosis of mRNA vaccine-related myocarditis compared with historical conventional myocarditis: a population-based cohort study","authors":"Song Song , David Shu Cheong Hui , Samuel Yeung Shan Wong , Chak Sing Lau , Ivan Fan Ngai Hung , Francisco Tsz Tsun Lai","doi":"10.1016/j.cmi.2025.11.031","DOIUrl":"10.1016/j.cmi.2025.11.031","url":null,"abstract":"","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 504-506"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676508","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}
Pub Date : 2026-03-01Epub Date: 2025-11-28DOI: 10.1016/j.cmi.2025.11.027
Sean W.X. Ong , Ruxandra Pinto , Robert K. Mahar , Neta Petersiel , Robert A. Fowler , Joshua S. Davis , Nick Daneman , Steven Y.C. Tong
Objectives
Hierarchical composite endpoints (HCEs) are increasingly being used in infectious disease research. In this paper, we illustrate different methods for analysing HCEs in post hoc analyses of the Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) and Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA2) clinical trials.
Methods
We constructed post hoc HCEs for each trial by combining clinical efficacy and safety outcomes: (a) mortality, relapse of bacteraemia, and antibiotic adverse events for BALANCE, and (b) mortality, primary treatment failure, infectious complications, and antibiotic adverse events for CAMERA2. For both trials, we additionally included length of stay or duration of antibiotic treatment as tiebreakers after the primary HCE in separate analyses. We applied these analytic methods: (a) logistic regression using a binary composite outcome, (b) generalized pairwise comparisons using different outcome permutations, (c) Wilcoxon rank sum approach for an ordinal outcome, (d) proportional odds model, and (e) probabilistic index model. We estimated the probabilistic index, win ratio, win odds, net treatment benefit, or odds ratio where possible using each method.
Results
For the BALANCE trial, all analyses of the primary HCE resulted in the same conclusion of no evidence of differences between treatment groups. Inclusion of length of stay as a tiebreaker resulted in 7 of 11 analyses finding the 7-day treatment arm superior to the 14-day arm, whereas inclusion of antibiotic duration resulted in all analyses concluding superiority of the 7-day treatment arm. For the CAMERA2 trial, all analyses found no evidence of differences between the two treatment groups. For all analyses, there were only minor differences in estimates across different analytic methods.
Conclusions
In these post hoc analyses, different methods for analysing HCEs resulted in similar effect estimates and conclusions consistent with the primary analyses of the BALANCE and CAMERA2 trials. These analyses illustrate how different HCEs can be constructed and analysed, and may be useful to other researchers in designing future studies that use HCEs.
{"title":"Comparing different methods for analysing hierarchical composite endpoints: two illustrative case studies with post hoc analyses of the BALANCE (Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness) and CAMERA2 (Combination Antibiotics for methicillin-resistant Staphylococcus aureus) randomized clinical trials","authors":"Sean W.X. Ong , Ruxandra Pinto , Robert K. Mahar , Neta Petersiel , Robert A. Fowler , Joshua S. Davis , Nick Daneman , Steven Y.C. Tong","doi":"10.1016/j.cmi.2025.11.027","DOIUrl":"10.1016/j.cmi.2025.11.027","url":null,"abstract":"<div><h3>Objectives</h3><div>Hierarchical composite endpoints (HCEs) are increasingly being used in infectious disease research. In this paper, we illustrate different methods for analysing HCEs in post hoc analyses of the Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) and Combination Antibiotics for MEthicillin Resistant <em>Staphylococcus aureus</em> (CAMERA2) clinical trials.</div></div><div><h3>Methods</h3><div>We constructed post hoc HCEs for each trial by combining clinical efficacy and safety outcomes: (a) mortality, relapse of bacteraemia, and antibiotic adverse events for BALANCE, and (b) mortality, primary treatment failure, infectious complications, and antibiotic adverse events for CAMERA2. For both trials, we additionally included length of stay or duration of antibiotic treatment as tiebreakers after the primary HCE in separate analyses. We applied these analytic methods: (a) logistic regression using a binary composite outcome, (b) generalized pairwise comparisons using different outcome permutations, (c) Wilcoxon rank sum approach for an ordinal outcome, (d) proportional odds model, and (e) probabilistic index model. We estimated the probabilistic index, win ratio, win odds, net treatment benefit, or odds ratio where possible using each method.</div></div><div><h3>Results</h3><div>For the BALANCE trial, all analyses of the primary HCE resulted in the same conclusion of no evidence of differences between treatment groups. Inclusion of length of stay as a tiebreaker resulted in 7 of 11 analyses finding the 7-day treatment arm superior to the 14-day arm, whereas inclusion of antibiotic duration resulted in all analyses concluding superiority of the 7-day treatment arm. For the CAMERA2 trial, all analyses found no evidence of differences between the two treatment groups. For all analyses, there were only minor differences in estimates across different analytic methods.</div></div><div><h3>Conclusions</h3><div>In these post hoc analyses, different methods for analysing HCEs resulted in similar effect estimates and conclusions consistent with the primary analyses of the BALANCE and CAMERA2 trials. These analyses illustrate how different HCEs can be constructed and analysed, and may be useful to other researchers in designing future studies that use HCEs.</div></div>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 482-489"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647710","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}
Pub Date : 2026-03-01Epub Date: 2025-06-07DOI: 10.1016/j.cmi.2025.05.035
Ronen Ben-Ami , Matteo Bassetti , Emilio Bouza , Alex Kosman , Antonio Vena , ESCMID Fungal Infection Study Group (EFISG)
Background
Candida infective endocarditis (CIE) is a rare but potentially devastating condition. Although it accounts for only 1–1.5% of infective endocarditis cases, CIE carries a high mortality rate (36–49%) and a substantial risk of relapse. Despite advances in diagnostic and therapeutic strategies, significant uncertainties persist regarding the role and selection of imaging modalities and the most effective medical and surgical management. Furthermore, the best follow-up strategy to promptly detect recurrences in patients with a confirmed diagnosis remains inadequately defined.
Objectives
This review explores the diagnosis and management of CIE with a particular focus on: (a) optimal use of cardiac imaging studies; (b) challenges associated with antifungal therapy; (c) the limitations and real-world impact of surgical intervention; and (d) strategies for long-term follow-up.
Sources
A comprehensive literature search was conducted in PubMed using the terms Candida endocarditis, fungal biomarkers, echocardiography, antifungal therapy, and surgical management. Additional studies were identified through reference screening. Only clinically relevant articles, as judged by the authors, were included.
Content
Diagnosis remains difficult due to intermittently negative blood cultures and limitations of standard endocarditis criteria. Echocardiography is the primary diagnostic modality for patients with candidaemia, and risk stratification to guide its use remains exploratory. Novel diagnostic methods, including fungal biomarkers (1,3-β-D-glucan), molecular assays, and positron emission tomography/computed tomography, may improve detection, but robust clinical data are lacking. Management requires a multimodal approach, combining prolonged antifungal therapy and, when feasible, surgical intervention. Echinocandins or liposomal amphotericin B plus flucytosine are first-line treatments, with fluconazole as a step-down option. Prosthetic valve infections often require lifelong suppressive therapy due to high relapse rates.
Implications
Given the high mortality and recurrence rates, early multidisciplinary involvement is crucial. With emerging antifungal resistance, antibiofilm strategies and next-generation antifungals are needed to improve outcomes.
背景：念珠菌感染性心内膜炎（CIE）是一种罕见但具有潜在破坏性的疾病。虽然仅占感染性心内膜炎病例的1-1.5%，但CIE具有很高的死亡率（36-49%）和很大的复发风险。尽管在诊断和治疗策略方面取得了进展，但在成像方式的作用和选择以及最有效的医疗和外科治疗方面，仍然存在重大的不确定性。此外，在确诊的患者中及时发现复发的最佳随访策略仍然没有充分的定义。目的：本综述探讨了CIE的诊断和管理，特别关注：i)心脏成像研究的最佳应用；Ii)与抗真菌治疗相关的挑战；iii)手术干预的局限性和现实世界的影响；iv)长期随访的策略。资料来源：在PubMed上进行了全面的文献检索，使用术语念珠菌心内膜炎，真菌生物标志物，超声心动图，抗真菌治疗和外科治疗。通过参考筛选确定了其他研究。仅纳入作者判断的临床相关文章。内容：由于间歇性阴性血培养和标准心内膜炎标准的局限性，诊断仍然困难。超声心动图是念珠菌病患者的主要诊断方式，指导其使用的风险分层仍然是探索性的。新的诊断方法，包括真菌生物标志物（1,3-β- d -葡聚糖），分子测定和PET/CT，可能会提高检测，但缺乏可靠的临床数据。治疗需要多模式的方法，结合长期抗真菌治疗和可行时的手术干预。棘白菌素或脂质体两性霉素B加氟胞嘧啶是一线治疗，氟康唑作为降压选择。由于复发率高，人工瓣膜感染通常需要终生抑制治疗。意义：考虑到高死亡率和复发率，早期多学科介入至关重要。随着抗真菌耐药性的出现，需要抗生物膜策略和下一代抗真菌药物来改善结果。
{"title":"Candida endocarditis: current perspectives on diagnosis and therapy","authors":"Ronen Ben-Ami , Matteo Bassetti , Emilio Bouza , Alex Kosman , Antonio Vena , ESCMID Fungal Infection Study Group (EFISG)","doi":"10.1016/j.cmi.2025.05.035","DOIUrl":"10.1016/j.cmi.2025.05.035","url":null,"abstract":"<div><h3>Background</h3><div><em>Candida</em><span><span> infective endocarditis<span> (CIE) is a rare but potentially devastating condition. Although it accounts for only 1–1.5% of infective endocarditis cases, CIE carries a high </span></span>mortality rate (36–49%) and a substantial risk of relapse. Despite advances in diagnostic and therapeutic strategies, significant uncertainties persist regarding the role and selection of imaging modalities and the most effective medical and surgical management. Furthermore, the best follow-up strategy to promptly detect recurrences in patients with a confirmed diagnosis remains inadequately defined.</span></div></div><div><h3>Objectives</h3><div><span>This review explores the diagnosis and management of CIE with a particular focus on: (a) optimal use of cardiac imaging studies; (b) challenges associated with </span>antifungal therapy; (c) the limitations and real-world impact of surgical intervention; and (d) strategies for long-term follow-up.</div></div><div><h3>Sources</h3><div>A comprehensive literature search was conducted in PubMed using the terms <em>Candida</em><span><span> endocarditis, fungal biomarkers, </span>echocardiography<span>, antifungal therapy, and surgical management. Additional studies were identified through reference screening. Only clinically relevant articles, as judged by the authors, were included.</span></span></div></div><div><h3>Content</h3><div><span>Diagnosis remains difficult due to intermittently negative blood cultures and limitations of standard endocarditis criteria. Echocardiography is the primary diagnostic modality for patients with candidaemia<span><span>, and risk stratification to guide its use remains exploratory. Novel diagnostic methods, including fungal biomarkers (1,3-β-D-glucan), molecular assays, and positron emission tomography/computed tomography, may improve detection, but robust clinical data are lacking. Management requires a multimodal approach, combining prolonged antifungal therapy and, when feasible, surgical intervention. </span>Echinocandins or liposomal </span></span>amphotericin B<span> plus flucytosine<span> are first-line treatments, with fluconazole<span> as a step-down option. Prosthetic valve infections often require lifelong suppressive therapy due to high relapse rates.</span></span></span></div></div><div><h3>Implications</h3><div>Given the high mortality and recurrence rates, early multidisciplinary involvement is crucial. With emerging antifungal resistance<span>, antibiofilm strategies and next-generation antifungals are needed to improve outcomes.</span></div></div>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 382-388"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257420","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}
Pub Date : 2026-03-01Epub Date: 2025-11-21DOI: 10.1016/j.cmi.2025.11.013
Michal Chowers , Dor Atias , Batsheva Gottesman , Marcelo Low , Uri Obolski
Objectives
Understanding the impact of antibiotic use on future resistant infections is essential for appropriate antibiotic therapy. Our objective was to assess the effect of exposure to commonly used antibiotics in community settings on resistance of future urine culture isolates.
Methods
A retrospective study including adult Health Maintenance Organization members who purchased cefazolin, cefuroxime, amoxicillin-clavulanate (AMC), or fluoroquinolones (FQ) between 1 January 2017 and 31 December 2019. The outcome was the antibiotic susceptibility profile of the first urine culture within 6 months from antibiotic purchase. We emulated the two following target trials: (1) patients treated with first-generation cephalosporins (1st CEP) would instead receive second-generation cephalosporins (2nd CEP), AMC, or FQ. (2) Patients treated with AMC or FQ would instead receive 2nd CEP. We used matching, standardisation, postmatching covariate adjustments and inverse probability of censoring weighting to correct for confounding and selection bias and estimate the risk difference (RD) for resistance.
Results
Included were 23 297 patients. In the first target trial, exposure to any of the non-1st CEP antibiotics led to the highest increase in resistance of the same antibiotic class, greatest when treatment and outcome were FQ (RD, 22.1%; 95% CI, 20.0–24.2) and AMC (RD, 8.2%; 95% CI, 6.1–10.3). In the second trial, the 2nd CEP led to higher increases in resistance to all cephalosporins compared with AMC. The 2nd CEP was also associated with higher 3rd CEP resistance compared with FQ (RD, −2.1%, 95% CI, −3.9, −0.4).
Conclusions
Our study provides novel estimates of the impact of exposure to oral antibiotics on the resistance of future urinary pathogens. These estimates are relevant for both antibiotic treatment guidelines and clinical decision-making.
目的：了解抗生素使用对未来耐药感染的影响对于适当的抗生素治疗至关重要。我们的目的是评估在社区环境中暴露于常用抗生素对未来尿培养分离株耐药性的影响。方法：对2017年1月1日至2019年12月31日期间购买头孢唑林、头孢呋辛、阿莫西林-克拉维酸酯（AMC）或氟喹诺酮类药物的成人健康维护组织会员进行回顾性研究。结果是抗生素购买后6个月内首次尿液培养的抗生素敏感性。我们模拟了以下两项目标试验：(1)用第一代头孢菌素（1st CEP）治疗的患者会转而使用第二代头孢菌素（2nd CEP）、AMC或FQ。（II）接受AMC或FQ治疗的患者将接受第二次CEP治疗。我们使用匹配、标准化、匹配后协变量调整和审查权重的逆概率来纠正混杂和选择偏差，并估计耐药性的风险差异（RD）。结果：纳入23297例患者。在第一个目标试验中，暴露于任何非第一CEP抗生素导致同一抗生素类别的耐药性增加最高，当治疗和结果为FQ （RD 22.1%, 95% CI 20.0-24.2）和AMC （RD 8.2%, 95% CI 6.1-10.3）时最大。在第二项试验中，与AMC相比，第2次CEP导致对所有头孢菌素的耐药性增加更高。与FQ相比，第2次CEP也与较高的第3次CEP耐药相关（RD -2.1%, 95%CI -3.9, -0.4）。结论：我们的研究为口服抗生素暴露对未来泌尿系统病原体耐药性的影响提供了新的估计。这些估计对抗生素治疗指南和临床决策都有意义。
{"title":"Estimating antibiotic resistance following antibiotic treatment in outpatients: a retrospective study","authors":"Michal Chowers , Dor Atias , Batsheva Gottesman , Marcelo Low , Uri Obolski","doi":"10.1016/j.cmi.2025.11.013","DOIUrl":"10.1016/j.cmi.2025.11.013","url":null,"abstract":"<div><h3>Objectives</h3><div>Understanding the impact of antibiotic use on future resistant infections is essential for appropriate antibiotic therapy. Our objective was to assess the effect of exposure to commonly used antibiotics in community settings on resistance of future urine culture isolates.</div></div><div><h3>Methods</h3><div>A retrospective study including adult Health Maintenance Organization members who purchased cefazolin, cefuroxime, amoxicillin-clavulanate (AMC), or fluoroquinolones (FQ) between 1 January 2017 and 31 December 2019. The outcome was the antibiotic susceptibility profile of the first urine culture within 6 months from antibiotic purchase. We emulated the two following target trials: (1) patients treated with first-generation cephalosporins (1st CEP) would instead receive second-generation cephalosporins (2nd CEP), AMC, or FQ. (2) Patients treated with AMC or FQ would instead receive 2nd CEP. We used matching, standardisation, postmatching covariate adjustments and inverse probability of censoring weighting to correct for confounding and selection bias and estimate the risk difference (RD) for resistance.</div></div><div><h3>Results</h3><div>Included were 23 297 patients. In the first target trial, exposure to any of the non-1st CEP antibiotics led to the highest increase in resistance of the same antibiotic class, greatest when treatment and outcome were FQ (RD, 22.1%; 95% CI, 20.0–24.2) and AMC (RD, 8.2%; 95% CI, 6.1–10.3). In the second trial, the 2nd CEP led to higher increases in resistance to all cephalosporins compared with AMC. The 2nd CEP was also associated with higher 3rd CEP resistance compared with FQ (RD, −2.1%, 95% CI, −3.9, −0.4).</div></div><div><h3>Conclusions</h3><div>Our study provides novel estimates of the impact of exposure to oral antibiotics on the resistance of future urinary pathogens. These estimates are relevant for both antibiotic treatment guidelines and clinical decision-making.</div></div>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 446-452"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585936","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}
Pub Date : 2026-03-01Epub Date: 2025-10-29DOI: 10.1016/j.cmi.2025.10.014
Rosanne Sprute , Oliver A. Cornely
{"title":"Optimising the management of invasive candidiasis","authors":"Rosanne Sprute , Oliver A. Cornely","doi":"10.1016/j.cmi.2025.10.014","DOIUrl":"10.1016/j.cmi.2025.10.014","url":null,"abstract":"","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 362-364"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421327","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}
Pub Date : 2026-03-01Epub Date: 2025-11-22DOI: 10.1016/j.cmi.2025.11.016
Asa Auta , Emmanuel O. Adewuyi , Erick Wesley Hedima , Emmanuel Agada David , Lomikga Balachandran , Aaron Akpu Philip , Davies Adeloye , Barry Strickland-Hodge
Background
Antibiotic resistance threatens effective infection treatment and medical procedures. Global initiatives, such as World Antimicrobial Resistance Awareness Week, aim to improve public understanding and promote rational antibiotic use to combat this growing crisis.
Objective
This systematic review synthesized and analysed existing evidence on the public's knowledge of antibiotic use and resistance to provide pooled global, regional and national estimates.
Methods
A systematic review and meta-analysis.
Data sources
We searched PubMed, Embase, CINAHL, grey literature and reference lists of primary studies.
Study eligibility criteria
Observational studies published between January 2015 and October 2025 that reported the knowledge of antibiotic use and resistance among the public.
Assessment of risk of bias
The Joanna Briggs Institute's critical appraisal framework for prevalence studies was used.
Methods of data synthesis
Pooled estimates of correct knowledge were determined using random-effects meta-analysis.
Results
Of the 13 960 articles identified, 227 studies from 98 countries were included. The majority of the public correctly understood that antibiotics are effective against bacterial infections, with a pooled estimate of 73.2% (95% CI, 70.2–76.0). However, only 42.1% (95% CI, 39.2–44.9) recognized that antibiotics are ineffective against viral infections. Notable national variations were observed regarding the ineffectiveness of antibiotics against viral infections, with estimates ranging from 7.2% (95% CI, 5.3–9.7) in Lao People's Democratic Republic (Lao DPR) to 77.0% (95% CI, 74.4–79.4) in Sweden. Our findings indicate that a substantial proportion of the public is aware that unnecessary antibiotic use reduces their effectiveness, with a pooled estimate of 72.5% (95% CI, 69.9–75.0). However, significantly fewer individuals (39.1%; 95% CI, 33.7–44.6) were aware that antibiotic-resistant bacteria can spread from person to person.
Conclusions
Although antibiotic awareness campaigns have expanded globally, public understanding remains insufficient, particularly concerning the ineffectiveness of antibiotics against viral infections and the transmission of antibiotic-resistant bacteria. These findings underscore the need for multifaceted strategies to promote public awareness and advance sustainable antibiotic stewardship worldwide.
{"title":"Global and regional knowledge of antibiotic use and resistance among the general public: a systematic review and meta-analysis","authors":"Asa Auta , Emmanuel O. Adewuyi , Erick Wesley Hedima , Emmanuel Agada David , Lomikga Balachandran , Aaron Akpu Philip , Davies Adeloye , Barry Strickland-Hodge","doi":"10.1016/j.cmi.2025.11.016","DOIUrl":"10.1016/j.cmi.2025.11.016","url":null,"abstract":"<div><h3>Background</h3><div>Antibiotic resistance threatens effective infection treatment and medical procedures. Global initiatives, such as World Antimicrobial Resistance Awareness Week, aim to improve public understanding and promote rational antibiotic use to combat this growing crisis.</div></div><div><h3>Objective</h3><div>This systematic review synthesized and analysed existing evidence on the public's knowledge of antibiotic use and resistance to provide pooled global, regional and national estimates.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis.</div></div><div><h3>Data sources</h3><div>We searched PubMed, Embase, CINAHL, grey literature and reference lists of primary studies.</div></div><div><h3>Study eligibility criteria</h3><div>Observational studies published between January 2015 and October 2025 that reported the knowledge of antibiotic use and resistance among the public.</div></div><div><h3>Assessment of risk of bias</h3><div>The Joanna Briggs Institute's critical appraisal framework for prevalence studies was used.</div></div><div><h3>Methods of data synthesis</h3><div>Pooled estimates of correct knowledge were determined using random-effects meta-analysis.</div></div><div><h3>Results</h3><div>Of the 13 960 articles identified, 227 studies from 98 countries were included. The majority of the public correctly understood that antibiotics are effective against bacterial infections, with a pooled estimate of 73.2% (95% CI, 70.2–76.0). However, only 42.1% (95% CI, 39.2–44.9) recognized that antibiotics are ineffective against viral infections. Notable national variations were observed regarding the ineffectiveness of antibiotics against viral infections, with estimates ranging from 7.2% (95% CI, 5.3–9.7) in Lao People's Democratic Republic (Lao DPR) to 77.0% (95% CI, 74.4–79.4) in Sweden. Our findings indicate that a substantial proportion of the public is aware that unnecessary antibiotic use reduces their effectiveness, with a pooled estimate of 72.5% (95% CI, 69.9–75.0). However, significantly fewer individuals (39.1%; 95% CI, 33.7–44.6) were aware that antibiotic-resistant bacteria can spread from person to person.</div></div><div><h3>Conclusions</h3><div>Although antibiotic awareness campaigns have expanded globally, public understanding remains insufficient, particularly concerning the ineffectiveness of antibiotics against viral infections and the transmission of antibiotic-resistant bacteria. These findings underscore the need for multifaceted strategies to promote public awareness and advance sustainable antibiotic stewardship worldwide.</div></div>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 399-407"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596109","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}
Pub Date : 2026-03-01Epub Date: 2025-12-02DOI: 10.1016/j.cmi.2025.11.035
Sebastian T. Tandar , Arnaud De Clercq , Linda B.S. Aulin , Wim Van Biesen , Sigurd Delanghe , Floris Vanommeslaeghe , Peter De Paepe , J.G. Coen van Hasselt , Pieter A. De Cock , Sunny Eloot
Objectives
Patients on haemodialysis (HD) are commonly treated with teicoplanin for Gram-positive infections. Kidney replacement therapy is known to alter drug pharmacokinetics (PK), which impacts treatment success. This study aimed to characterize teicoplanin PK, explore potential covariate predictors for interindividual variability, and derive an evidence-based dosing strategy for patients undergoing maintenance HD.
Methods
A monocentric prospective observational PK study in patients undergoing maintenance HD was conducted at the Ghent University Hospital and its low care at the General Hospital Aalst. Total and unbound teicoplanin concentrations were used to inform the development of a teicoplanin population PK model. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for predialysis teicoplanin concentrations (Cpredialysis) of 20–50 mg/L across dosing regimens. The impact of administration of a predialysis dose and therapeutic drug monitoring (TDM) on target attainment was evaluated.
Results
This study included 31 patients on teicoplanin therapy undergoing maintenance HD or haemodiafiltration (HDF). The final model consists of a two-compartment population PK model with a semimechanistic dialyser flow. High clearance variability was observed across the cohort. The standard 12 mg/kg thrice-weekly regimen achieved PTA of 13.6% (HD) and 6.8% (HDF) after the first dose, which increased to approximately 50% with subsequent doses. A fixed-dose regimen was proposed with a single 1600 mg loading dose, followed by an 800 mg maintenance dose (1200 mg for 3-day interdialytic periods). The proposed dosing regimen increased PTA to 71.7% (HD) and 66.9% (HDF) after the first loading dose, with week 1 averages of 61.1% and 59.9%, respectively. Cpredialysis-based TDM further improved PTA to >70% in both groups.
Conclusions
This study proposed an optimized dosing strategy to maximize PTA in patients undergoing maintenance HD, although prospective validation is recommended before clinical implementation. Furthermore, the estimated high clearance variability underscores the need for TDM in teicoplanin dosing for this population.
{"title":"Model-based optimisation for teicoplanin dosing in patients undergoing maintenance haemodialysis","authors":"Sebastian T. Tandar , Arnaud De Clercq , Linda B.S. Aulin , Wim Van Biesen , Sigurd Delanghe , Floris Vanommeslaeghe , Peter De Paepe , J.G. Coen van Hasselt , Pieter A. De Cock , Sunny Eloot","doi":"10.1016/j.cmi.2025.11.035","DOIUrl":"10.1016/j.cmi.2025.11.035","url":null,"abstract":"<div><h3>Objectives</h3><div>Patients on haemodialysis (HD) are commonly treated with teicoplanin for Gram-positive infections. Kidney replacement therapy is known to alter drug pharmacokinetics (PK), which impacts treatment success. This study aimed to characterize teicoplanin PK, explore potential covariate predictors for interindividual variability, and derive an evidence-based dosing strategy for patients undergoing maintenance HD.</div></div><div><h3>Methods</h3><div>A monocentric prospective observational PK study in patients undergoing maintenance HD was conducted at the Ghent University Hospital and its low care at the General Hospital Aalst. Total and unbound teicoplanin concentrations were used to inform the development of a teicoplanin population PK model. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for predialysis teicoplanin concentrations (<em>C</em><sub><em>predialysis</em></sub>) of 20–50 mg/L across dosing regimens. The impact of administration of a predialysis dose and therapeutic drug monitoring (TDM) on target attainment was evaluated.</div></div><div><h3>Results</h3><div>This study included 31 patients on teicoplanin therapy undergoing maintenance HD or haemodiafiltration (HDF). The final model consists of a two-compartment population PK model with a semimechanistic dialyser flow. High clearance variability was observed across the cohort. The standard 12 mg/kg thrice-weekly regimen achieved PTA of 13.6% (HD) and 6.8% (HDF) after the first dose, which increased to approximately 50% with subsequent doses. A fixed-dose regimen was proposed with a single 1600 mg loading dose, followed by an 800 mg maintenance dose (1200 mg for 3-day interdialytic periods). The proposed dosing regimen increased PTA to 71.7% (HD) and 66.9% (HDF) after the first loading dose, with week 1 averages of 61.1% and 59.9%, respectively. <em>C</em><sub><em>predialysis</em></sub>-based TDM further improved PTA to >70% in both groups.</div></div><div><h3>Conclusions</h3><div>This study proposed an optimized dosing strategy to maximize PTA in patients undergoing maintenance HD, although prospective validation is recommended before clinical implementation. Furthermore, the estimated high clearance variability underscores the need for TDM in teicoplanin dosing for this population.</div></div>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 466-473"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676526","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}
Pub Date : 2026-03-01Epub Date: 2025-12-29DOI: 10.1016/j.cmi.2025.12.016
George R. Thompson III , Anke H.W. Bruns , Jannik Helweg-Larsen , Philipp Koehler , Jeffrey D. Jenks , Bennett Penn , Martin Hoenigl , Johan Maertens , Andrej Spec , Thomas J. Walsh , Mark Bresnik , John H. Rex
Objectives
Paradoxical reactions to appropriate antimicrobial therapy are seldom reported in systemic fungal diseases. Olorofim (formerly F901318) is an orally available first-in-class antifungal and exhibits in vitro killing. Recently, an open-label, single-arm phase IIb study (NCT03583164) enrolling patients with invasive fungal diseases for which there were limited or no other treatment options was completed. During the conduct of this trial, several investigators noted a transient worsening of disease in a subset of treated patients despite subsequent improvement, and we aimed to describe these patients in detail to assist clinicians prescribing olorofim treatment.
Methods
Detailed methods and results of the phase 2b trial have been previously described, and a subsequent managed access programme used the same rules as the phase 2b study for enrolment (combined N = 470). Briefly, patients with hyaline moulds, thermally dimorphic fungi, or other fungi requiring sponsor approval were enrolled and given olorofim therapy. A paradoxical reaction was defined as worsening clinical or radiological findings following initiation of treatment (olorofim) in the absence of evidence for underlying disease worsening/relapse or the presence of an alternative diagnosis after initiation of treatment.
Results
Case review identified six patients meeting criteria, and 4/6 were immunocompetent. The timing of paradoxical responses was variable and ranged from days to months following initiation of olorofim. All patients were maintained on olorofim and paradoxical reactions resolved without specific intervention, and all patients exhibited a subsequent successful response to therapy.
Conclusions
Paradoxical reactions to appropriate antimicrobial therapy are infrequently observed in systemic fungal diseases. Similar responses are seen in the treatment of both tuberculosis (worsening of lymphadenitis) and leprosy (reversal reactions), suggesting a similar pathophysiologic mechanism may be responsible given the overlapping immune response between mycobacterial and fungal pathogens. Awareness of this potential syndrome is essential during the treatment of patients with olorofim therapy.
{"title":"Paradoxical worsening on olorofim in patients undergoing treatment for invasive fungal diseases","authors":"George R. Thompson III , Anke H.W. Bruns , Jannik Helweg-Larsen , Philipp Koehler , Jeffrey D. Jenks , Bennett Penn , Martin Hoenigl , Johan Maertens , Andrej Spec , Thomas J. Walsh , Mark Bresnik , John H. Rex","doi":"10.1016/j.cmi.2025.12.016","DOIUrl":"10.1016/j.cmi.2025.12.016","url":null,"abstract":"<div><h3>Objectives</h3><div>Paradoxical reactions to appropriate antimicrobial therapy are seldom reported in systemic fungal diseases. Olorofim (formerly F901318) is an orally available first-in-class antifungal and exhibits <em>in vitro</em> killing. Recently, an open-label, single-arm phase IIb study (NCT03583164) enrolling patients with invasive fungal diseases for which there were limited or no other treatment options was completed. During the conduct of this trial, several investigators noted a transient worsening of disease in a subset of treated patients despite subsequent improvement, and we aimed to describe these patients in detail to assist clinicians prescribing olorofim treatment.</div></div><div><h3>Methods</h3><div>Detailed methods and results of the phase 2b trial have been previously described, and a subsequent managed access programme used the same rules as the phase 2b study for enrolment (combined <em>N</em> = 470). Briefly, patients with hyaline moulds, thermally dimorphic fungi, or other fungi requiring sponsor approval were enrolled and given olorofim therapy. A paradoxical reaction was defined as worsening clinical or radiological findings following initiation of treatment (olorofim) in the absence of evidence for underlying disease worsening/relapse or the presence of an alternative diagnosis after initiation of treatment.</div></div><div><h3>Results</h3><div>Case review identified six patients meeting criteria, and 4/6 were immunocompetent. The timing of paradoxical responses was variable and ranged from days to months following initiation of olorofim. All patients were maintained on olorofim and paradoxical reactions resolved without specific intervention, and all patients exhibited a subsequent successful response to therapy.</div></div><div><h3>Conclusions</h3><div>Paradoxical reactions to appropriate antimicrobial therapy are infrequently observed in systemic fungal diseases. Similar responses are seen in the treatment of both tuberculosis (worsening of lymphadenitis) and leprosy (reversal reactions), suggesting a similar pathophysiologic mechanism may be responsible given the overlapping immune response between mycobacterial and fungal pathogens. Awareness of this potential syndrome is essential during the treatment of patients with olorofim therapy.</div></div>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":"32 3","pages":"Pages 490-495"},"PeriodicalIF":8.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877874","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}
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