Paul Loubet,Sébastien Czernichow,Caroline Giboin,Ariane Sultan,Thomas Guimard,Emmanuel Disse,Marie-Pierre Tavolacci,Ines Ben Ghezala,Séverine Ledoux,Cécile Janssen,Helena Mosbah,Maeva Lefebvre,Arnaud De Luca,Liem Binh Luong Nguyen,Véronique Taillard,Julien Couster,Christian Duale,Claire Carette,Claire Rives-Lange,Sofia Zemouri,Corinne Desaint,Florence Tubach,Odile Launay
INTRODUCTIONIndividuals living with severe obesity are at increased risk of severe influenza and may have impaired immune responses to vaccination. Recombinant influenza vaccine (RIV) may provide enhanced protection compared with egg-based standard-dose influenza vaccine (SD), but data in this high-risk population are limited.METHODSThe AP-HP FLUO trial (NCT05409612) was an open-label, randomized clinical trial conducted in 15 centers in France (November 2022-March 2023) with 6 months of follow-up. Adults with BMI ≥35 kg/m² were randomized 1:1 to receive RIV or SD, using minimization by center, age (<50 vs ≥50 years), and BMI (<40 vs ≥40 kg/m²). The primary outcome was the ratio (RIV/SD) of geometric mean hemagglutinin-inhibition (HAI) titers (GMTs) for four influenza strains 28 days after vaccination. Safety and reactogenicity were also assessed.RESULTSA total of 206 participants were included (104 RIV, 102 SD). Median age was 50 years, 60.2% were women, and median BMI was 41.0 kg/m². At Day 28, GMT ratios favored RIV for A/H1N1 (1.6; 95% CI, 1.1-2.3), A/H3N2 (2.0; 95% CI, 1.3-3.2), and B/Yamagata (1.3; 95% CI, 1.0-1.8), but not for B/Victoria (0.9; 95% CI, 0.6-1.3). The effect did not vary significantly across the different age and BMI groups. By Day 180, titers did not differ significantly. Reactogenicity and safety profiles were similar between groups.CONCLUSIONIn adults living with severe obesity, RIV elicited stronger short-term humoral immune responses than an egg-based standard-dose vaccine, suggesting potential additional benefit for influenza prevention in this vulnerable population.
{"title":"Recombinant vs Standard Influenza Vaccine in Adults With Severe Obesity: A Randomized Clinical Trial.","authors":"Paul Loubet,Sébastien Czernichow,Caroline Giboin,Ariane Sultan,Thomas Guimard,Emmanuel Disse,Marie-Pierre Tavolacci,Ines Ben Ghezala,Séverine Ledoux,Cécile Janssen,Helena Mosbah,Maeva Lefebvre,Arnaud De Luca,Liem Binh Luong Nguyen,Véronique Taillard,Julien Couster,Christian Duale,Claire Carette,Claire Rives-Lange,Sofia Zemouri,Corinne Desaint,Florence Tubach,Odile Launay","doi":"10.1093/cid/ciag200","DOIUrl":"https://doi.org/10.1093/cid/ciag200","url":null,"abstract":"INTRODUCTIONIndividuals living with severe obesity are at increased risk of severe influenza and may have impaired immune responses to vaccination. Recombinant influenza vaccine (RIV) may provide enhanced protection compared with egg-based standard-dose influenza vaccine (SD), but data in this high-risk population are limited.METHODSThe AP-HP FLUO trial (NCT05409612) was an open-label, randomized clinical trial conducted in 15 centers in France (November 2022-March 2023) with 6 months of follow-up. Adults with BMI ≥35 kg/m² were randomized 1:1 to receive RIV or SD, using minimization by center, age (<50 vs ≥50 years), and BMI (<40 vs ≥40 kg/m²). The primary outcome was the ratio (RIV/SD) of geometric mean hemagglutinin-inhibition (HAI) titers (GMTs) for four influenza strains 28 days after vaccination. Safety and reactogenicity were also assessed.RESULTSA total of 206 participants were included (104 RIV, 102 SD). Median age was 50 years, 60.2% were women, and median BMI was 41.0 kg/m². At Day 28, GMT ratios favored RIV for A/H1N1 (1.6; 95% CI, 1.1-2.3), A/H3N2 (2.0; 95% CI, 1.3-3.2), and B/Yamagata (1.3; 95% CI, 1.0-1.8), but not for B/Victoria (0.9; 95% CI, 0.6-1.3). The effect did not vary significantly across the different age and BMI groups. By Day 180, titers did not differ significantly. Reactogenicity and safety profiles were similar between groups.CONCLUSIONIn adults living with severe obesity, RIV elicited stronger short-term humoral immune responses than an egg-based standard-dose vaccine, suggesting potential additional benefit for influenza prevention in this vulnerable population.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"16 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483458","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}
Milo Gatti,Riccardo De Paola,Beatrice Giorgi,Federico Pea
BACKGROUNDCeftolozane-tazobactam and ceftazidime-avibactam are considered first-line treatment of multidrug-resistant (MDR) and/or difficult-to-treat (DTR) Pseudomonas aeruginosa (PA) infections. Conflicting results in terms of clinical outcome and resistance development emerged from real-world comparative studies. We perform a systematic review with meta-analysis for comparing ceftolozane-tazobactam and ceftazidime-avibactam in the treatment of MDR/DTR PA infections.METHODSTwo authors independently searched PubMed-MEDLINE and Scopus database from inception to 18th November 2025 for retrieving studies comparing ceftolozane-tazobactam vs. ceftazidime-avibactam in the management of MDR/DTR-PA infections. Clinical cure was set as the primary outcome, whereas 90-day resistance development, microbiological failure, and 30-day mortality rate were set as the secondary outcomes. Meta-analysis was performed by pooling the odds ratios (ORs) retrieved from studies providing adjustment for confounders by means of a random-effects model with the inverse variance method. Risk of bias of the included studies was independently assessed according to the RoB 2.0 and the ROBINS-I tools.RESULTSAmong a total of 1,193 articles screened, six observational studies were retrieved and included (N=1,161, 644 receiving ceftolozane-tazobactam vs. 517 receiving ceftazidime-avibactam). Ceftolozane-tazobactam showed higher clinical cure rate compared to ceftazidime-avibactam (N=4; OR 1.82; 95%CI 1.10-2.99; I2=25.3%). No difference emerged in terms of microbiological failure (N=2; OR 0.66; 95%CI 0.36-1.19; I2=21.9%), 90-day resistance development (N=3; OR 1.11; 95%CI 0.51-2.42; I2=50.0%) and 30-day mortality rate (N=4; OR 1.00; 95%CI 0.89-1.12; I2=0.0%).CONCLUSIONSOur meta-analysis showed that, after adjusting appropriately for confounders, ceftolozane-tazobactam could grant higher clinical cure rate in the treatment of MDR/DTR PA infections compared to ceftazidime-avibactam.
背景：头孢噻嗪-他唑巴坦和头孢噻啶-阿维巴坦被认为是耐多药（MDR）和/或难治性（DTR）铜绿假单胞菌（PA）感染的一线治疗药物。在临床结果和耐药性发展方面的矛盾结果出现在现实世界的比较研究中。我们进行了一项系统综述，采用荟萃分析比较了头孢唑嗪-他唑巴坦和头孢他啶-阿维巴坦治疗MDR/DTR PA感染的效果。方法两位作者独立检索PubMed-MEDLINE和Scopus数据库，检索从成立到2025年11月18日头孢他唑巴坦与头孢他啶-阿维巴坦治疗MDR/ ddr - pa感染的比较研究。临床治愈被设定为主要结局，而90天耐药发展、微生物学失败和30天死亡率被设定为次要结局。荟萃分析采用随机效应模型和逆方差法，汇集从提供混杂因素校正的研究中检索到的比值比（or）。根据rob2.0和ROBINS-I工具独立评估纳入研究的偏倚风险。结果在筛选的1193篇文章中，检索并纳入了6项观察性研究（N= 1161，接受头孢噻嗪-他唑巴坦治疗的644对接受头孢噻嗪-阿维巴坦治疗的517）。头孢噻嗪-他唑巴坦临床治愈率高于头孢噻啶-阿维巴坦（N=4; OR 1.82; 95%CI 1.10-2.99; I2=25.3%）。在微生物学失败（N=2; OR 0.66; 95%CI 0.36-1.19; I2=21.9%）、90天耐药发展（N=3; OR 1.11; 95%CI 0.51-2.42; I2=50.0%）和30天死亡率（N=4; OR 1.00; 95%CI 0.89-1.12; I2=0.0%）方面没有差异。结论荟萃分析显示，在适当调整混杂因素后，头孢他嗪-他唑巴坦治疗MDR/DTR - PA感染的临床治愈率高于头孢他啶-阿维巴坦。
{"title":"Comparison of ceftolozane-tazobactam and ceftazidime-avibactam in the treatment of MDR/DTR Pseudomonas aeruginosa infections: a systematic review and meta-analysis.","authors":"Milo Gatti,Riccardo De Paola,Beatrice Giorgi,Federico Pea","doi":"10.1093/cid/ciag194","DOIUrl":"https://doi.org/10.1093/cid/ciag194","url":null,"abstract":"BACKGROUNDCeftolozane-tazobactam and ceftazidime-avibactam are considered first-line treatment of multidrug-resistant (MDR) and/or difficult-to-treat (DTR) Pseudomonas aeruginosa (PA) infections. Conflicting results in terms of clinical outcome and resistance development emerged from real-world comparative studies. We perform a systematic review with meta-analysis for comparing ceftolozane-tazobactam and ceftazidime-avibactam in the treatment of MDR/DTR PA infections.METHODSTwo authors independently searched PubMed-MEDLINE and Scopus database from inception to 18th November 2025 for retrieving studies comparing ceftolozane-tazobactam vs. ceftazidime-avibactam in the management of MDR/DTR-PA infections. Clinical cure was set as the primary outcome, whereas 90-day resistance development, microbiological failure, and 30-day mortality rate were set as the secondary outcomes. Meta-analysis was performed by pooling the odds ratios (ORs) retrieved from studies providing adjustment for confounders by means of a random-effects model with the inverse variance method. Risk of bias of the included studies was independently assessed according to the RoB 2.0 and the ROBINS-I tools.RESULTSAmong a total of 1,193 articles screened, six observational studies were retrieved and included (N=1,161, 644 receiving ceftolozane-tazobactam vs. 517 receiving ceftazidime-avibactam). Ceftolozane-tazobactam showed higher clinical cure rate compared to ceftazidime-avibactam (N=4; OR 1.82; 95%CI 1.10-2.99; I2=25.3%). No difference emerged in terms of microbiological failure (N=2; OR 0.66; 95%CI 0.36-1.19; I2=21.9%), 90-day resistance development (N=3; OR 1.11; 95%CI 0.51-2.42; I2=50.0%) and 30-day mortality rate (N=4; OR 1.00; 95%CI 0.89-1.12; I2=0.0%).CONCLUSIONSOur meta-analysis showed that, after adjusting appropriately for confounders, ceftolozane-tazobactam could grant higher clinical cure rate in the treatment of MDR/DTR PA infections compared to ceftazidime-avibactam.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"146 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471692","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}
John R Koethe,Jordan E Lake,Amy Kantor,Laura Smeaton,Kristine Erlandson,Laura Moran,Pablo Belaunzaran-Zamudio,Alan Landay,Rafael E Campo,Paula Debroy,Jaclyn Ann Bennet,Jane O'Halloran,Win Min Han,Oladapo Alli,Michael Leonard,Roy M Gulick
BACKGROUNDIntegrase inhibitors (INSTI) and tenofovir alafenamide (TAF) have been associated with greater weight gain compared to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and tenofovir disoproxil fumarate (TDF), but the effects of an antiretroviral regimen switch on weight are unclear.METHODSThis 48-week, 3 parallel group, open-label, multicenter, randomized controlled trial (NCT04636437) in people with HIV and obesity on an INSTI (bictegravir, dolutegravir, or raltegravir) with TAF/emtricitabine (FTC) assessed whether switching to the NNRTI doravirine (DOR) with TAF/FTC or TDF/FTC results in weight loss or stabilization. Treatment effects were estimated using linear regression adjusted for sex, race, and entry weight.RESULTSOf 147 participants randomized, 145 initiated their assigned treatment. At entry, median age was 49 years; BMI was 34.9 kg/m2, and time on INSTI+TAF/FTC was 3.4 years; 49% were female and 53% Black. After 48 weeks, estimated mean change in weight was -0.47% (95% confidence interval [CI]: -2.09,1.14) for the DOR+TAF/FTC arm, -2.73% (-4.22, -1.23) for DOR+TDF/FTC, and -1.84% (-3.37, -0.30) for INSTI+TAF/FTC. Estimated mean difference in weight change at 48 weeks for DOR vs. INSTI (both with TAF/FTC) was 1.36 percentage points (97.5% CI: -1.20,3.92), and -0.89 percentage points (-3.34,1.57) for DOR+TDF/FTC vs. INSTI+TAF/FTC. There was no evidence of variation by sex or race, nor of treatment differences for changes in fasting lipids, insulin resistance, fat mass, or bone mineral density.CONCLUSIONSIn people with HIV and obesity, switching from an INSTI+TAF/FTC regimen to DOR/FTC with either TAF or TDF did not produce clinically meaningful differences in weight change or metabolic health after 48 weeks.
{"title":"A 48-week, Randomized Controlled Trial of Doravirine for Individuals with HIV and Obesity on Integrase Inhibitors and Tenofovir Alafenamide: The Do IT Study (ACTG A5391).","authors":"John R Koethe,Jordan E Lake,Amy Kantor,Laura Smeaton,Kristine Erlandson,Laura Moran,Pablo Belaunzaran-Zamudio,Alan Landay,Rafael E Campo,Paula Debroy,Jaclyn Ann Bennet,Jane O'Halloran,Win Min Han,Oladapo Alli,Michael Leonard,Roy M Gulick","doi":"10.1093/cid/ciag196","DOIUrl":"https://doi.org/10.1093/cid/ciag196","url":null,"abstract":"BACKGROUNDIntegrase inhibitors (INSTI) and tenofovir alafenamide (TAF) have been associated with greater weight gain compared to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and tenofovir disoproxil fumarate (TDF), but the effects of an antiretroviral regimen switch on weight are unclear.METHODSThis 48-week, 3 parallel group, open-label, multicenter, randomized controlled trial (NCT04636437) in people with HIV and obesity on an INSTI (bictegravir, dolutegravir, or raltegravir) with TAF/emtricitabine (FTC) assessed whether switching to the NNRTI doravirine (DOR) with TAF/FTC or TDF/FTC results in weight loss or stabilization. Treatment effects were estimated using linear regression adjusted for sex, race, and entry weight.RESULTSOf 147 participants randomized, 145 initiated their assigned treatment. At entry, median age was 49 years; BMI was 34.9 kg/m2, and time on INSTI+TAF/FTC was 3.4 years; 49% were female and 53% Black. After 48 weeks, estimated mean change in weight was -0.47% (95% confidence interval [CI]: -2.09,1.14) for the DOR+TAF/FTC arm, -2.73% (-4.22, -1.23) for DOR+TDF/FTC, and -1.84% (-3.37, -0.30) for INSTI+TAF/FTC. Estimated mean difference in weight change at 48 weeks for DOR vs. INSTI (both with TAF/FTC) was 1.36 percentage points (97.5% CI: -1.20,3.92), and -0.89 percentage points (-3.34,1.57) for DOR+TDF/FTC vs. INSTI+TAF/FTC. There was no evidence of variation by sex or race, nor of treatment differences for changes in fasting lipids, insulin resistance, fat mass, or bone mineral density.CONCLUSIONSIn people with HIV and obesity, switching from an INSTI+TAF/FTC regimen to DOR/FTC with either TAF or TDF did not produce clinically meaningful differences in weight change or metabolic health after 48 weeks.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"213 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471689","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}
The report on Plasmodium ovale recurrences among patients in Tanzania by Carey-Ewend et al. in CID highlights the importance of plasmodial infections that defy conventional diagnostics. The findings add to the growing body of evidence of malaria transmission despite seemingly inadequate presence in peripheral blood.
{"title":"Invisible Malarias","authors":"J Kevin Baird","doi":"10.1093/cid/ciag201","DOIUrl":"https://doi.org/10.1093/cid/ciag201","url":null,"abstract":"The report on Plasmodium ovale recurrences among patients in Tanzania by Carey-Ewend et al. in CID highlights the importance of plasmodial infections that defy conventional diagnostics. The findings add to the growing body of evidence of malaria transmission despite seemingly inadequate presence in peripheral blood.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"77 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147489784","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}
Joy Yang,Kasereka Masumbuko Claude,Emily Kimani,Michael T Hawkes
We assessed impact and durability of an infection prevention and control (IPC) bundle intervention during the Kivu/Ituri Ebolavirus outbreak (2018-2020). IPC scores increased initially, then declined 6 months post-intervention (median 19/36, 30/36, and 28/36, p<0.0001). Without sustained IPC practices, health facilities remain vulnerable to nosocomial transmission in future Ebolavirus outbreaks.
{"title":"Limited durability of improvements in infection prevention and control practices following reactive interventions leaves healthcare facilities vulnerable to Ebola virus transmission.","authors":"Joy Yang,Kasereka Masumbuko Claude,Emily Kimani,Michael T Hawkes","doi":"10.1093/cid/ciag192","DOIUrl":"https://doi.org/10.1093/cid/ciag192","url":null,"abstract":"We assessed impact and durability of an infection prevention and control (IPC) bundle intervention during the Kivu/Ituri Ebolavirus outbreak (2018-2020). IPC scores increased initially, then declined 6 months post-intervention (median 19/36, 30/36, and 28/36, p<0.0001). Without sustained IPC practices, health facilities remain vulnerable to nosocomial transmission in future Ebolavirus outbreaks.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"37 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471690","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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