Maaike C Swets, Zsuzsa Bakk, Annette C Westgeest, Karla Berry, George Cooper, Wynne Sim, Rui Shian Lee, Tze Yi Gan, William Donlon, Antonia Besu, Emily Heppenstall, Luke Tysall, Simon Dewar, Mark de Boer, Vance G Fowler, David H Dockrell, Guy E Thwaites, Miquel Pujol, Natàlia Pallarès, Cristian Tebé, Jordi Carratalà, Alexander Szubert, Geert H Groeneveld, Clark D Russell
Background: Staphylococcus aureus bacteremia (SAB) is a clinically heterogeneous disease. The ability to identify subgroups of patients with shared traits (subphenotypes) is an unmet need to allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically relevant subphenotypes can be reproducibly identified among patients with SAB.
Methods: We studied 3 cohorts of adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n = 458), the UK ARREST trial (n = 758), and the Spanish SAFO trial (n = 214). Latent class analysis was used to identify subphenotypes using routinely collected clinical data without considering outcomes. Mortality and microbiologic outcomes were then compared between subphenotypes.
Results: Included patients had predominantly methicillin-susceptible SAB (1366 of 1430, 95.5%). We identified 5 distinct, reproducible clinical subphenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the subphenotypes. Mortality was highest in subphenotype A and lowest in subphenotypes B and E. Microbiologic outcomes were worse in subphenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased mortality in subphenotype B and improved microbiologic outcomes in subphenotype C.
Conclusions: We have identified reproducible and clinically relevant subphenotypes within SAB and provide proof of principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these subphenotypes could contribute to a personalized medicine approach to SAB.
背景:金黄色葡萄球菌菌血症(SAB)是一种临床异质性疾病。识别具有共同特征(亚表型)的患者亚群的能力是一项尚未满足的需求,这种能力可对患者进行分层,以便于临床管理和研究。我们的目的是验证一个假设,即可以在 SAB 患者中重复识别出与临床相关的亚表型:我们研究了三组住院成人单微生物SAB患者:英国回顾性观察研究(爱丁堡队列,n=458)、英国ARREST随机试验(n=758)和西班牙SAFO随机试验(n=214)。在不考虑结果的情况下,使用常规收集的临床数据进行潜类分析以确定亚型。然后对不同亚型的死亡率和微生物学结果进行比较:纳入的患者主要患有对甲氧西林敏感的 SAB(1366/1430,95.5%)。我们发现了五种不同的、可重复的临床亚型:(A) 与高龄和合并症相关的 SAB,(B) 在无合并症的年轻人中发生的与鼻腔静脉导管相关的 SAB,(C) 社区获得的转移性 SAB,(D) 与慢性肾病相关的 SAB,以及 (E) 与注射吸毒相关的 SAB。不同亚型的存活率和微生物学结果各不相同。亚型 A 的 84 天死亡率最高,亚型 B 和亚型 E 最低。亚型 C 的微生物学结果较差。在 ARREST 试验的二次分析中,辅助利福平与亚型 B 的 84 天死亡率增加和亚型 C 的微生物学结果改善有关:我们在 SAB 中发现了可重复的临床相关亚型,并提供了不同治疗效果的原理证明。通过丰富临床试验和对患者进行分层,这些亚型可为 SAB 的个性化医疗方法做出贡献。
{"title":"Clinical Subphenotypes of Staphylococcus aureus Bacteremia.","authors":"Maaike C Swets, Zsuzsa Bakk, Annette C Westgeest, Karla Berry, George Cooper, Wynne Sim, Rui Shian Lee, Tze Yi Gan, William Donlon, Antonia Besu, Emily Heppenstall, Luke Tysall, Simon Dewar, Mark de Boer, Vance G Fowler, David H Dockrell, Guy E Thwaites, Miquel Pujol, Natàlia Pallarès, Cristian Tebé, Jordi Carratalà, Alexander Szubert, Geert H Groeneveld, Clark D Russell","doi":"10.1093/cid/ciae338","DOIUrl":"10.1093/cid/ciae338","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus bacteremia (SAB) is a clinically heterogeneous disease. The ability to identify subgroups of patients with shared traits (subphenotypes) is an unmet need to allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically relevant subphenotypes can be reproducibly identified among patients with SAB.</p><p><strong>Methods: </strong>We studied 3 cohorts of adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n = 458), the UK ARREST trial (n = 758), and the Spanish SAFO trial (n = 214). Latent class analysis was used to identify subphenotypes using routinely collected clinical data without considering outcomes. Mortality and microbiologic outcomes were then compared between subphenotypes.</p><p><strong>Results: </strong>Included patients had predominantly methicillin-susceptible SAB (1366 of 1430, 95.5%). We identified 5 distinct, reproducible clinical subphenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the subphenotypes. Mortality was highest in subphenotype A and lowest in subphenotypes B and E. Microbiologic outcomes were worse in subphenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased mortality in subphenotype B and improved microbiologic outcomes in subphenotype C.</p><p><strong>Conclusions: </strong>We have identified reproducible and clinically relevant subphenotypes within SAB and provide proof of principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these subphenotypes could contribute to a personalized medicine approach to SAB.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":"1153-1161"},"PeriodicalIF":8.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander M Tatara, Anna Apostolopoulou, Anna A Agan, Laura DelloStritto, Chanu Rhee, Michael Klompas
Background: Crude and adjusted mortality rates for patients with non-ventilator hospital-acquired pneumonia (NV-HAP) are among the highest of all healthcare-associated infections, leading to calls for greater prevention. Patients prone to NV-HAP, however, tend to be severely ill at baseline, making it unclear whether their high mortality rates are due to NV-HAP, their underlying conditions, or both.
Methods: Two infectious disease physicians conducted detailed medical record reviews on 150 randomly selected adults from 4 hospitals who died in-hospital following an NV-HAP event between April 2016 and May 2021. Reviewers abstracted risk factors, estimated the preventability of NV-HAP, identified causes of death, and adjudicated the preventability of death.
Results: The patients' median age was 69.3 (IQR, 60.7-77.4) years and 43.3% were female. Comorbidities were common: 57% had cancer, 30% chronic kidney disease, 29% chronic lung disease, and 27% had heart failure. At least 1 hospice-eligible condition was present before NV-HAP in 54% and "Do Not Resuscitate" orders in 24%. Most (99%) had difficult-to-modify NV-HAP risk factors: 76% altered mental status, 35% dysphagia, and 27% nasogastric/orogastric tubes. NV-HAP was deemed possibly or probably preventable in 21% and hospital death likely or very likely preventable in 8.6%.
Conclusions: Most patients who die following NV-HAP have multiple, severe underlying comorbidities and difficult-to-modify risk factors for NV-HAP. Only 1 in 5 NV-HAPs that culminated in death and 1 in 12 deaths following NV-HAP were judged potentially preventable. This does not diminish the importance of NV-HAP prevention programs but informs expectations about the potential magnitude of their impact on hospital deaths.
{"title":"Preventability of Hospital Deaths in Patients With Non-Ventilator Hospital-Acquired Pneumonia.","authors":"Alexander M Tatara, Anna Apostolopoulou, Anna A Agan, Laura DelloStritto, Chanu Rhee, Michael Klompas","doi":"10.1093/cid/ciae418","DOIUrl":"10.1093/cid/ciae418","url":null,"abstract":"<p><strong>Background: </strong>Crude and adjusted mortality rates for patients with non-ventilator hospital-acquired pneumonia (NV-HAP) are among the highest of all healthcare-associated infections, leading to calls for greater prevention. Patients prone to NV-HAP, however, tend to be severely ill at baseline, making it unclear whether their high mortality rates are due to NV-HAP, their underlying conditions, or both.</p><p><strong>Methods: </strong>Two infectious disease physicians conducted detailed medical record reviews on 150 randomly selected adults from 4 hospitals who died in-hospital following an NV-HAP event between April 2016 and May 2021. Reviewers abstracted risk factors, estimated the preventability of NV-HAP, identified causes of death, and adjudicated the preventability of death.</p><p><strong>Results: </strong>The patients' median age was 69.3 (IQR, 60.7-77.4) years and 43.3% were female. Comorbidities were common: 57% had cancer, 30% chronic kidney disease, 29% chronic lung disease, and 27% had heart failure. At least 1 hospice-eligible condition was present before NV-HAP in 54% and \"Do Not Resuscitate\" orders in 24%. Most (99%) had difficult-to-modify NV-HAP risk factors: 76% altered mental status, 35% dysphagia, and 27% nasogastric/orogastric tubes. NV-HAP was deemed possibly or probably preventable in 21% and hospital death likely or very likely preventable in 8.6%.</p><p><strong>Conclusions: </strong>Most patients who die following NV-HAP have multiple, severe underlying comorbidities and difficult-to-modify risk factors for NV-HAP. Only 1 in 5 NV-HAPs that culminated in death and 1 in 12 deaths following NV-HAP were judged potentially preventable. This does not diminish the importance of NV-HAP prevention programs but informs expectations about the potential magnitude of their impact on hospital deaths.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":"1269-1276"},"PeriodicalIF":8.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: The Growing Threat of NDM-Producing Escherichia coli With Penicillin-Binding Protein 3 Mutations in the United States-Is There a Potential Role for Durlobactam?","authors":"","doi":"10.1093/cid/ciae414","DOIUrl":"10.1093/cid/ciae414","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":"1326"},"PeriodicalIF":8.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281452","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}
Miriam B Barshak, Marlene L Durand, Akash Gupta, Amir M Mohareb, Thomas H Dohlman, George N Papaliodis
{"title":"State-of-the-Art Review: Ocular Infections.","authors":"Miriam B Barshak, Marlene L Durand, Akash Gupta, Amir M Mohareb, Thomas H Dohlman, George N Papaliodis","doi":"10.1093/cid/ciae433","DOIUrl":"https://doi.org/10.1093/cid/ciae433","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"79 5","pages":"e48-e64"},"PeriodicalIF":8.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686276","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":"An Unusual Case of Forehead Swelling in a Geriatric Patient.","authors":"Samuel Baumgart, Genevieve McKew","doi":"10.1093/cid/ciae299","DOIUrl":"https://doi.org/10.1093/cid/ciae299","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"79 5","pages":"1303-1304"},"PeriodicalIF":8.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686274","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}
Raphael J Landovitz, Li Tao, Juan Yang, Melanie de Boer, Christoph Carter, Moupali Das, Jared M Baeten, Albert Liu, Karen W Hoover, Connie Celum, Beatriz Grinsztejn, Sheldon Morris, Darrell P Wheeler, Kenneth H Mayer, Sarit A Golub, Linda-Gail Bekker, Souleymane Diabaté, Elske Hoornenborg, Janet Myers, Ashley A Leech, Sheena McCormack, Philip A Chan, Michael Sweat, Lynn T Matthews, Robert Grant
Background: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings.
Methods: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies.
Results: Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63-.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9-5.3), .24 (.060-.95), .27 (.12-.60), and .054 (.008-.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports.
Conclusions: Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.
{"title":"Type 1 Human Immunodeficiency Virus (HIV-1) Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis: Pooled Analysis From 72 Global Studies.","authors":"Raphael J Landovitz, Li Tao, Juan Yang, Melanie de Boer, Christoph Carter, Moupali Das, Jared M Baeten, Albert Liu, Karen W Hoover, Connie Celum, Beatriz Grinsztejn, Sheldon Morris, Darrell P Wheeler, Kenneth H Mayer, Sarit A Golub, Linda-Gail Bekker, Souleymane Diabaté, Elske Hoornenborg, Janet Myers, Ashley A Leech, Sheena McCormack, Philip A Chan, Michael Sweat, Lynn T Matthews, Robert Grant","doi":"10.1093/cid/ciae143","DOIUrl":"10.1093/cid/ciae143","url":null,"abstract":"<p><strong>Background: </strong>Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings.</p><p><strong>Methods: </strong>HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies.</p><p><strong>Results: </strong>Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63-.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9-5.3), .24 (.060-.95), .27 (.12-.60), and .054 (.008-.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports.</p><p><strong>Conclusions: </strong>Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":"1197-1207"},"PeriodicalIF":8.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Giacomelli, Spinello Antinori, Andrea Gori, Alessandro Cozzi-Lepri
{"title":"COVID-19: Find the Right Questions to be Answered.","authors":"Andrea Giacomelli, Spinello Antinori, Andrea Gori, Alessandro Cozzi-Lepri","doi":"10.1093/cid/ciae078","DOIUrl":"10.1093/cid/ciae078","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":"1322-1323"},"PeriodicalIF":8.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139897937","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}
Connor Prosty, Mark Sorin, Khaled Katergi, Roy Khalaf, Clare Fogarty, Malick Turenne, Todd C Lee, Emily G McDonald
Background: Guidelines recommend adjunctive gentamicin for the treatment of Enterococcus faecalis infective endocarditis (EFIE) despite a risk of toxicity. We sought to revisit the evidence for adjunctive therapy in EFIE and to synthesize the comparative safety and effectiveness of aminoglycosides versus ceftriaxone by systematic review and meta-analysis.
Methods: For historical context, we reviewed seminal case series and in vitro studies on the evolution from penicillin monotherapy to modern-day regimens for EFIE. Next, we searched MEDLINE and Embase from inception to 16 January 2024 for studies of EFIE that compared adjunctive aminoglycosides versus ceftriaxone or adjunctive versus monotherapy. Where possible, clinical outcomes were compared between regimens using random effects meta-analysis. Otherwise, data were narratively summarized.
Results: The meta-analysis was limited to 10 observational studies at high risk of bias (911 patients). Relative to adjunctive ceftriaxone, gentamicin had similar all-cause mortality (risk difference [RD], -0.8%; 95% confidence interval [CI], -5.0 to 3.5), relapse (RD, -0.1%; 95% CI, -2.4 to 2.3), and treatment failure (RD, 1.1%; 95% CI, -1.6 to 3.7) but higher discontinuation due to toxicity (RD, 26.3%; 95% CI, 19.8 to 32.7). The 3 studies that compared adjunctive therapy to monotherapy included only 30 monotherapy patients, and heterogeneity precluded meta-analysis.
Conclusions: Adjunctive ceftriaxone appeared to be equally effective and less toxic than gentamicin for the treatment of EFIE. The existing evidence does not clearly establish the superiority of either adjunctive therapy or monotherapy. Pending randomized evidence, if adjunctive therapy is to be used, ceftriaxone appears to be a reasonable option.
{"title":"Revisiting the Evidence Base That Informs the Use of Adjunctive Therapy for Enterococcus faecalis Endocarditis: A Systematic Review and Meta-Analysis.","authors":"Connor Prosty, Mark Sorin, Khaled Katergi, Roy Khalaf, Clare Fogarty, Malick Turenne, Todd C Lee, Emily G McDonald","doi":"10.1093/cid/ciae379","DOIUrl":"10.1093/cid/ciae379","url":null,"abstract":"<p><strong>Background: </strong>Guidelines recommend adjunctive gentamicin for the treatment of Enterococcus faecalis infective endocarditis (EFIE) despite a risk of toxicity. We sought to revisit the evidence for adjunctive therapy in EFIE and to synthesize the comparative safety and effectiveness of aminoglycosides versus ceftriaxone by systematic review and meta-analysis.</p><p><strong>Methods: </strong>For historical context, we reviewed seminal case series and in vitro studies on the evolution from penicillin monotherapy to modern-day regimens for EFIE. Next, we searched MEDLINE and Embase from inception to 16 January 2024 for studies of EFIE that compared adjunctive aminoglycosides versus ceftriaxone or adjunctive versus monotherapy. Where possible, clinical outcomes were compared between regimens using random effects meta-analysis. Otherwise, data were narratively summarized.</p><p><strong>Results: </strong>The meta-analysis was limited to 10 observational studies at high risk of bias (911 patients). Relative to adjunctive ceftriaxone, gentamicin had similar all-cause mortality (risk difference [RD], -0.8%; 95% confidence interval [CI], -5.0 to 3.5), relapse (RD, -0.1%; 95% CI, -2.4 to 2.3), and treatment failure (RD, 1.1%; 95% CI, -1.6 to 3.7) but higher discontinuation due to toxicity (RD, 26.3%; 95% CI, 19.8 to 32.7). The 3 studies that compared adjunctive therapy to monotherapy included only 30 monotherapy patients, and heterogeneity precluded meta-analysis.</p><p><strong>Conclusions: </strong>Adjunctive ceftriaxone appeared to be equally effective and less toxic than gentamicin for the treatment of EFIE. The existing evidence does not clearly establish the superiority of either adjunctive therapy or monotherapy. Pending randomized evidence, if adjunctive therapy is to be used, ceftriaxone appears to be a reasonable option.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":"1162-1171"},"PeriodicalIF":8.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747637","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}
Background To address antibiotic overuse, the Japanese government implemented a novel financial incentive policy in 2018. The policy enables eligible healthcare facilities to claim 800 JPY (≈5.7 USD) per case wherein a rationale to not prescribe antibiotics is offered to children aged <3 years with acute upper respiratory tract infections or gastroenteritis. Although the short-term effect of this policy was observed in our previous study, its long-term effects have not been evaluated nationwide. Methods We conducted a quasi-experimental study using a staggered difference-in-differences design with propensity score matching. Data from 165,113 children born between April 2017 and March 2019 were extracted from two nationwide administrative databases. The study tracked these children until May 2022, comparing those exposed to the policy with those who were not. Results The introduction of financial incentives led to a 44.9% reduction (95%CI, 41.1% to 47.7%) in total antibiotic prescriptions within the first month and 19.5% reduction (95%CI, 8.7% to 29.1%) over 48 months. Broad-spectrum antibiotic use also decreased by 24.4% (95%CI, 14.0% to 33.6%) over the same period. The policy did not result in increased hospitalizations, after-hours visits, or healthcare costs, but was associated with a slight increase in the number of office visits. A dose-response relationship was observed, with reductions in antibiotic use leveling off after approximately five incentives. Conclusions Financial incentives effectively reduced antibiotic prescriptions in children without adverse health outcomes, demonstrating sustained benefits over four years. This antimicrobial stewardship intervention offers a scalable model for other countries aiming to curb antibiotic overuse and combat antimicrobial resistance.
{"title":"Long-term Effectiveness of Financial Incentives for Not Prescribing Unnecessary Antibiotics to Children with Acute Respiratory and Gastrointestinal Infections: A Japan’s Nationwide Quasi-Experimental Study","authors":"Yusuke Okubo, Kazuhiro Uda, Isao Miyairi","doi":"10.1093/cid/ciae577","DOIUrl":"https://doi.org/10.1093/cid/ciae577","url":null,"abstract":"Background To address antibiotic overuse, the Japanese government implemented a novel financial incentive policy in 2018. The policy enables eligible healthcare facilities to claim 800 JPY (≈5.7 USD) per case wherein a rationale to not prescribe antibiotics is offered to children aged &lt;3 years with acute upper respiratory tract infections or gastroenteritis. Although the short-term effect of this policy was observed in our previous study, its long-term effects have not been evaluated nationwide. Methods We conducted a quasi-experimental study using a staggered difference-in-differences design with propensity score matching. Data from 165,113 children born between April 2017 and March 2019 were extracted from two nationwide administrative databases. The study tracked these children until May 2022, comparing those exposed to the policy with those who were not. Results The introduction of financial incentives led to a 44.9% reduction (95%CI, 41.1% to 47.7%) in total antibiotic prescriptions within the first month and 19.5% reduction (95%CI, 8.7% to 29.1%) over 48 months. Broad-spectrum antibiotic use also decreased by 24.4% (95%CI, 14.0% to 33.6%) over the same period. The policy did not result in increased hospitalizations, after-hours visits, or healthcare costs, but was associated with a slight increase in the number of office visits. A dose-response relationship was observed, with reductions in antibiotic use leveling off after approximately five incentives. Conclusions Financial incentives effectively reduced antibiotic prescriptions in children without adverse health outcomes, demonstrating sustained benefits over four years. This antimicrobial stewardship intervention offers a scalable model for other countries aiming to curb antibiotic overuse and combat antimicrobial resistance.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"78 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694213","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}