JAC-Antimicrobial Resistance最新文献

{"title":"Impact of a multifaceted intervention programme on antibiotic prescribing in out-of-hours primary care in five European countries: secondary analyses of the HAPPY PATIENT project.","authors":"Ingrid Keilegavlen Rebnord, Carl Llor, Fabiana Raynal Floriano, Malene Plejdrup Hansen, Jesper Lykkegaard, Jonas Olsen, Pia Touboul-Lundgren, Pascale Bruno, Anna Kowalczyk, Christos Lionis, Ruta Radzeviciene, Lina Jaruseviciene, Lars Bjerrum, Ana Garcia-Sangenis, Bent Håkan Lindberg","doi":"10.1093/jacamr/dlag219","DOIUrl":"10.1093/jacamr/dlag219","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance is a major global health threat, driven mainly by excessive and inappropriate antibiotic use. As most antibiotics are prescribed outside hospitals, primary care measures are crucial for reducing use. The study aimed to investigate diagnostic coding and antibiotic prescribing for respiratory tract (RTI) and urinary tract (UTI) infections treated in out-of-hours clinics before and after a multifaceted intervention.</p><p><strong>Methods: </strong>Audit and feedback with analyses of prescription data from five out-of-hours clinics in Europe before and after a multifaceted intervention. The intervention consisted of an audit with reports and feedback to the prescriber, participation in workshops, communication and e-learning courses, and distribution of information materials to patients.</p><p><strong>Results: </strong>A total of 67 physicians recorded 1786 cases in the first period and 1820 in the second. Common cold/influenza was the most frequent diagnosis, increasing from 19.4% (95% CI 18-21) in the first to 28.7% (95% CI 27-31) in the second period. COVID-19 declined by 65.7% (<i>P</i> < 0.001), while pharyngotonsillitis increased by 31.7% (<i>P</i> = 0.001). The intervention did not alter the overall antibiotic prescribing rate for RTIs (49.3% versus 48.7%, <i>P</i> = 0.748), and more than three-quarters of RTI prescriptions were judged unnecessary or inappropriate. For UTIs, the use of first-line antibiotics increased significantly from 70.0% to 79.5% (<i>P</i> = 0.027).</p><p><strong>Conclusions: </strong>The study provided important insights into which RTIs are potentially inappropriately treated with antibiotics, although the intervention did not produce a statistically significant reduction in antibiotic prescribing. Positively, the use of first-line antibiotics for UTIs increased significantly.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag219"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of combination therapy with minocycline for treating <i>Stenotrophomonas maltophilia</i> infections.","authors":"Tuvanont Pongdumbun, Yong Rongrungruang, Adhiratha Boonyasiri","doi":"10.1093/jacamr/dlag224","DOIUrl":"10.1093/jacamr/dlag224","url":null,"abstract":"<p><strong>Background: </strong><i>Stenotrophomonas maltophilia</i> is a multidrug-resistant opportunistic pathogen associated with substantial in-hospital mortality. However, data supporting the efficacy of treating <i>S. maltophilia</i> infections using a combination of antimicrobials remain inconclusive.</p><p><strong>Objectives: </strong>To assess whether adjunctive minocycline improves clinical outcomes of <i>S. maltophilia</i> infections compared with standard monotherapy.</p><p><strong>Methods: </strong>This randomized, double-blind, placebo-controlled trial was conducted at Siriraj Hospital, Thailand. Adults with confirmed <i>S. maltophilia</i> infections were randomized to receive minocycline or a matching placebo in addition to monotherapy with either levofloxacin or trimethoprim/sulfamethoxazole.</p><p><strong>Results: </strong>This trial enrolled 112 patients (71.4% [<i>n</i> = 80/112] of patients requiring an intensive care unit [ICU] and 66.1% [<i>n</i> = 74/112] of patients were diagnosed with ventilator-associated pneumonia [VAP]). Baseline demographic and clinical characteristics were balanced between intervention and control groups. Adjunctive minocycline did not significantly reduce 28-day-mortality (<i>n</i> = 24/55[43.6%] vs <i>n</i> = 22/57[38.6%], <i>P</i> = 0.590) but did achieve significantly higher microbiological response rates at early assessment (<i>n</i> = 25/55[45.5%] vs <i>n</i> = 8/57[14.0%], <i>P</i> < 0.001) and the end of treatment (<i>n</i> = 44/55[80.0%] vs <i>n</i> = 32/57[56.1%], <i>P</i> = 0.023). In contrast, clinical response rates did not differ between groups at either 72 h after the start of study treatment or the end of study treatment. In multivariable analysis, two factors were independently associated with 28-day mortality: history of antibiotic use before admission (adjusted odds ratio [aOR]: 7.65, 95% confidence interval [CI]: 2.04-28.76; <i>P</i> = 0.030) and septic shock (aOR: 7.24, 95% CI: 2.75-19.23; <i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>Although adding minocycline to either levofloxacin or trimethoprim/sulfamethoxazole therapy enhanced microbiological eradication, it did not confer a measurable survival or clinical advantage. Combination therapy was well tolerated. This study is potentially of interest to those treating ICU patients, as the majority of infections were VAP.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag224"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence and dissemination of an IncC plasmid co-harbouring <i>bla</i> _KPC-2, <i>bla</i> _NDM-1 and <i>bla</i> _VIM-24 carbapenemase genes across multiple Gram-negative species in Colombia.","authors":"Roberto Sierra, Betsy Castro, Elsa De La Cadena, Laura J Rojas, Juan Carlos García-Betancur, Mélanie Roch, Steven M Marshall, Nalleth Bolaño-Ardila, Susan D Rudin, Janneth J Escobar-Arcos, Clara J Salazar-Montes, Belkis Palacio-Villalba, Elizabeth Paz, Robert A Bonomo, María Virginia Villegas, Diego O Andrey","doi":"10.1093/jacamr/dlag222","DOIUrl":"10.1093/jacamr/dlag222","url":null,"abstract":"<p><strong>Objectives: </strong>Carbapenem-resistant Gram-negative bacilli (CRGNB) pose a public health threat, increasingly driven by plasmid-mediated dissemination of carbapenemase genes. As part of a Colombian genomic monitoring programme, we aimed to characterize CRGNB co-harbouring multiple carbapenemase genes and determine their genetic context.</p><p><strong>Methods: </strong>We screened 832 carbapenem-resistant isolates collected during 2011-2023 using carbapenemase-targeted qPCR. Ten isolates co-harbouring <i>bla</i> _KPC, <i>bla</i> _NDM and <i>bla</i> _VIM underwent antimicrobial susceptibility testing, long-read whole-genome sequencing, comparative genomics and conjugation assays.</p><p><strong>Results: </strong>Nine Enterobacterales isolates and one <i>Aeromonas caviae</i> isolate from unrelated patients in geographically distant Colombian hospitals carried closely related IncC plasmids ranging from 160 to 317 kb. These plasmids co-harboured <i>bla</i> _KPC-2, <i>bla</i> _NDM-1 and <i>bla</i> _VIM-24 within three conserved multidrug resistance regions, including a Tn<i>21</i>-associated region carrying <i>bla</i> _NDM-1 and <i>bla</i> _VIM-24 and a Tn<i>6454</i>-associated <i>bla</i> _KPC-2 platform, alongside class 1 integrons, insertion sequences and multiple additional antimicrobial resistance determinants. The ten isolates were resistant to multiple β-lactam/β-lactamase inhibitor combinations, and five were cefiderocol resistant. Aztreonam/avibactam remained active against all isolates; colistin resistance was confined to intrinsically resistant <i>Providencia rettgeri</i> and <i>Serratia sarumanii</i>. Conjugation assays demonstrated plasmid transfer to <i>Escherichia coli</i> J53, and sequencing confirmed transfer of a 179 kb IncC plasmid with functional conjugation machinery. Comparative genomic analysis showed a highly conserved IncC plasmid backbone across multiple species, supporting broad dissemination of this resistance platform.</p><p><strong>Conclusions: </strong>This first report of a single plasmid co-harbouring three carbapenemase genes. This finding highlights a concerning mechanism for interspecies dissemination of MDR Gram-negative pathogens and underscores the importance of long-read genomic surveillance focused on high-risk plasmids.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag222"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of household size and living with children in antibiotic use and antibiotic-related behaviours and beliefs: results from a general population survey in Poland.","authors":"Iga Palacz-Poborczyk, Julia Kuzminska, Aleksandra Luszczynska, Aleksandra J Borek","doi":"10.1093/jacamr/dlag223","DOIUrl":"10.1093/jacamr/dlag223","url":null,"abstract":"<p><strong>Background: </strong>The threat of antimicrobial resistance (AMR) is driven by both infection transmission and the overuse of antibiotics. These factors may interact with sociodemographic contexts, as larger households or those with children could increase opportunities for pathogen transmission and informal antibiotic sharing.</p><p><strong>Objectives: </strong>We aimed to determine if antibiotic use, or related beliefs and behaviours, were associated with household status (with/without children) or size (single, two persons, 3-4 persons, more than four persons).</p><p><strong>Methods: </strong>This was a pre-registered, cross-sectional survey of 1000 adults representative of the general population in Poland. The questions addressed (1) antibiotic use/behaviours; (2) opinions on antibiotics and (3) opinions on AMR.</p><p><strong>Results: </strong>Household size or the presence of children were unrelated to the antibiotic use. However, the presence of children in the household was associated with a tendency to acquire antibiotics from informal sources (family/friends), interrupt the antibiotic course when symptoms improved and self-test for infections. Living with children was linked to better knowledge of antibiotic effectiveness but limited concern about the effects of AMR. Middle-sized and big households were less likely than smaller households to acquire antibiotics informally but more likely to believe antibiotics accelerate recovery from respiratory tract infections.</p><p><strong>Conclusions: </strong>Cohabitation with children and household size are associated with specific, often contrary, antibiotic-related beliefs and behaviours, but not with antibiotic use. Further qualitative research is required to investigate the underlying reasons for these links. Interventions targeting families with children should capitalize on their self-management skills and knowledge, while addressing their low concern regarding AMR.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag223"},"PeriodicalIF":3.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.","authors":"Erin K McCreary, Emily L Heil, Samuel L Aitken, Maria F Mojica, Jason M Pogue, Alejandro J Vila, Ryan K Shields","doi":"10.1093/jacamr/dlag221","DOIUrl":"10.1093/jacamr/dlag221","url":null,"abstract":"<p><p>Infections caused by metallo-β-lactamase (MBL)-producing gram-negative pathogens represent a formidable and emerging threat to public health. MBLs compromise the activity of carbapenems and many newly developed β-lactam/β-lactamase inhibitor agents, leaving few treatment options. Remarkably, these enzymes have disseminated globally at an unprecedented rate. Therapeutic management of MBL-producing pathogens remains a major challenge because the enzymes are not inhibited by currently available β-lactamase inhibitors, and most pathogens that harbour MBLs are equipped with mechanisms of resistance to all available antibiotic classes. Recent advances have elucidated the biochemical and structural function of diverse MBLs thereby improving the development of future antibiotics. In this review, we summarize the contemporary global epidemiology of clinically relevant MBLs, describe the molecular mechanisms driving their dissemination and evaluate current and emerging therapeutic strategies for infections caused by MBL-producing gram-negative pathogens including Enterobacterales, <i>Pseudomonas aeruginosa, Acinetobacter baumannii</i> and <i>Stenotrophomonas maltophilia</i>.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag221"},"PeriodicalIF":3.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal resistance patterns of <i>Candida</i> species isolated from a private laboratory in Zambia: implications for antifungal stewardship programs.","authors":"Misheck Chileshe, Thresa Mulenga, Mwape Kunda, Steward Mudenda, Victor Daka, Vernon Julius","doi":"10.1093/jacamr/dlag228","DOIUrl":"10.1093/jacamr/dlag228","url":null,"abstract":"<p><strong>Background: </strong>Fungal infections pose a significant but often underestimated public health threat. These infections range from superficial conditions, such as skin and nail infections, to invasive diseases like candidemia, which can be life-threatening. <i>Candida</i> species, in particular, have shown increasing resistance, contributing to higher morbidity and mortality among affected patients. This study investigated the resistance patterns of <i>Candida</i> species isolated from Mary Begg facilities.</p><p><strong>Methods: </strong>This cross-sectional study utilized microbiology reports containing <i>Candida</i> species and the antifungal susceptibility results from October 2024 to October 2025.</p><p><strong>Results: </strong>Of the 57 <i>Candida</i> species isolated between October 2024 and October 2025, the majority were <i>Candida albicans</i> (75.4%; 43/57) and were mainly from high vaginal swab samples (84.2%; 48/57). Among isolated <i>C. albicans</i>, resistance to fluconazole was 7.5% and to micafungin 7.1%. <i>Candida krusei</i> showed varied resistance to available drugs, with 25% of isolated species resistant to micafungin, caspofungin, and voriconazole.</p><p><strong>Conclusion: </strong><i>Candida albicans</i> remains most prevalent and largely susceptible to first-line agents; emerging non-albicans species present a severe therapeutic challenge. Therefore, the country needs to strengthen surveillance and diagnostic capacity to address the growing problem of fungal infections and antifungal resistance.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag228"},"PeriodicalIF":3.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Point-of-care testing in community pharmacies to improve antimicrobial stewardship in respiratory infections: a scoping review of effectiveness, implementation and cost-effectiveness.","authors":"Abdulrasheed Ibrahim","doi":"10.1093/jacamr/dlag220","DOIUrl":"https://doi.org/10.1093/jacamr/dlag220","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag220"},"PeriodicalIF":3.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INVICTUS II: comparison of disc diffusion and broth microdilution methods for susceptibility testing of ceftolozane/tazobactam and five comparator agents against a subset of INVICTUS I <i>Pseudomonas aeruginosa</i> clinical isolates.","authors":"Kate Baldwin, Adela Alvarez-Buylla, Michael Allen, Ricky Henry-Grant, Edita Custic Weguelin, Mandy Wootton","doi":"10.1093/jacamr/dlag212","DOIUrl":"10.1093/jacamr/dlag212","url":null,"abstract":"<p><strong>Objectives: </strong>A subset of clinical <i>Pseudomonas aeruginosa</i> isolates from the INVICTUS I study was selected to compare antimicrobial susceptibility performance for disc diffusion and broth microdilution of ceftolozane/tazobactam and five comparator antipseudomonal agents.</p><p><strong>Methods: </strong>Overall, 159 non-cystic fibrosis isolates were chosen from INVICTUS I that had the smallest zone diameters from disc testing to ceftolozane/tazobactam, including isolates that were close to the breakpoints. The isolates were tested across 14 centres in the UK. Susceptibility results were interpreted using EUCAST 2026 criteria.</p><p><strong>Results: </strong>Discrepancy analysis showed combined error rates (very major and major errors) highest for ceftolozane/tazobactam, ceftazidime and piperacillin/tazobactam (15.7%, 14.5% and 12.6%, respectively); when adjusted to remove isolates close to the breakpoint for ceftolozane/tazobactam and piperacillin/tazobactam there were still remarkably high error rates (10.6% and 7.2%, respectively). Essential agreement and bias analysis were not performed as MICs were being compared with zone diameters.</p><p><strong>Discussion: </strong>Our findings highlight substantial challenges in performing and interpreting susceptibility testing for these two important antipseudomonal β-lactam/β-lactamase inhibitors, which are commonly employed as either first-line empirical therapy (piperacillin/tazobactam) or for serious and MDR infection (ceftolozane/tazobactam). A review of disc testing for these agents may be warranted, and diagnostic laboratories may wish to review the technical limitations and put in place mitigating measures.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag212"},"PeriodicalIF":3.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point-of-care testing in community pharmacies to improve antimicrobial stewardship in respiratory infections: a scoping review of effectiveness, implementation and cost-effectiveness-right-to-reply.","authors":"Sajal K Saha, Shukla Promite, Carly L Botheras, Elizabeth Manias, Nomvuyo Mothobi, Suzanne Robinson, Eugene Athan","doi":"10.1093/jacamr/dlag217","DOIUrl":"10.1093/jacamr/dlag217","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag217"},"PeriodicalIF":3.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promethazine use and QT prolongation risk during treatment with a shortened all-oral regimen for MDR/RR-TB.","authors":"Edmund Q L Shen, Letizia Trevisi, Stephane Mpinda, Allison Lahood, Llang Maama, Meseret Tamirat, Sebakeng Phate, Lawrence Oyewusi, Matthew Romo, Elna Osso, Michael L Rich, Carole D Mitnick, Kwonjune Justin Seung, Molly F Franke, Kunda Kwabisha Mikanda","doi":"10.1093/jacamr/dlag215","DOIUrl":"10.1093/jacamr/dlag215","url":null,"abstract":"<p><strong>Background: </strong>Shortened all-oral regimens for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) combine multiple QTc prolonging agents, including bedaquiline and delamanid, which act partly through hERG potassium channel binding. Promethazine, a first-generation antihistamine used for nausea during TB therapy, shares this mechanism. Whether adjunctive promethazine further raises the risk of clinically relevant QTc prolongation in this setting is unclear.</p><p><strong>Methods: </strong>We conducted secondary analyses from a prospective observational cohort study of patients ≥15 years in Lesotho who received a 9- to 12-month all-oral regimen (bedaquiline, linezolid, levofloxacin, clofazimine, delamanid) for pulmonary MDR/RR-TB. We modelled time-varying promethazine exposure using the Andersen-Gill formulation of Cox regression, with time-to-first grade ≥3 (>500 ms) QTc event as the outcome of interest. We conducted comparator analyses with time-varying exposure to metoclopramide, ondansetron, and episodes of nausea, dizziness, and vomiting.</p><p><strong>Results: </strong>Among 247 participants (median age 41, 63.2% living with HIV), 62 (25.1%) received promethazine. Grade ≥3 QTc prolongation occurred in 10 (4.0%). Incident clinically significant QTc prolongation was higher during promethazine-exposed than unexposed periods (7.4 versus 1.3 per 10 000 person-days; HR 7.0, 95% CI: 1.4-35.3). No comparable elevation was seen in analyses of exposure to metoclopramide (HR 1.0, 95% CI: 0.3-3.6), ondansetron, or episodes of nausea, dizziness, or vomiting (HR 1.5, 95% CI: 0.3-6.9).</p><p><strong>Conclusions: </strong>Promethazine use was associated with increased risk of clinically relevant QTc prolongation within a QTc-burdened all-oral MDR/RR-TB regimen. These findings provide preliminary evidence that clinicians may consider when selecting anti-emetics as part of MDR/RR-TB therapy with a shortened all-oral regimen and highlight the importance of evaluating adjunctive medications in DR-TB care.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"8 5","pages":"dlag215"},"PeriodicalIF":3.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}