Journal of Antimicrobial Chemotherapy最新文献

{"title":"Genomic structure of class 1 and 2 integrons in non-typhoidal Salmonella isolated from food animals and related meat products in the USA.","authors":"Chih-Hao Hsu, Cong Li, Lucas Harrison, Shaohua Zhao","doi":"10.1093/jac/dkaf310","DOIUrl":"10.1093/jac/dkaf310","url":null,"abstract":"<p><strong>Objectives: </strong>Integrons facilitate the capture and expression of exogenous genes, including antimicrobial resistance (AMR) genes. This study aimed to detect the presence of integrons, examine their genomic structure and location, and analyse integron-associated AMR, virulence and stress response genes in Salmonella using WGS.</p><p><strong>Methods: </strong>WGS data from 193 Salmonella strains, representing 38 serotypes isolated from food animals and related meat products (2001-2019), were analysed using bioinformatic tools to assess integron presence and characterize their genomic architectures.</p><p><strong>Results: </strong>Of 193 isolates, 116 (60.1%) harboured class 1 and/or class 2 integrons. Class 1 integrons alone were detected in 105 isolates, with some containing multiple copies. One S. Infantis isolate harboured only class 2 integrons, whereas 10 others contained both classes. No class 3-5 integrons were found. Twenty-seven class 1 integrons were chromosomal; the rest were plasmid-associated, linked to various plasmid incompatibility (Inc) types. Sixty-nine distinct AMR genes conferring resistance to 11 antimicrobial classes were found in integron cassettes or integron-associated plasmids. Genes linked to resistance to quaternary ammonium compounds and heavy metals, as well as ISs and transposons, were also identified. Significant virulence and stress response genes and proteins such as groES-groEL, LysR and EAL (glutamate, alanine and leucine) were common in integron cassettes.</p><p><strong>Conclusions: </strong>Class 1 integrons are prevalent in MDR Salmonella isolates from food animals and related meat products and are linked to diverse plasmid types. Their association with AMR, virulence and stress response genes underscores their role in AMR dissemination, and bacterial adaptation and pathogenicity.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2844-2853"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Faecal pharmacokinetics, microbiome, and bile acid changes in healthy subjects given intravenous followed by oral omadacycline; a Phase 1 clinical trial.","authors":"Jinhee Jo, Travis J Carlson, Chenlin Hu, John C Williamson, Yolanda T Belin, Thomas D Horvath, Sigmund J Haidacher, Eugénie Bassères, Khurshida Begum, M Jahangir Alam, Kevin W Garey","doi":"10.1093/jac/dkaf278","DOIUrl":"10.1093/jac/dkaf278","url":null,"abstract":"<p><strong>Background: </strong>There is an urgent need to develop new antimicrobials effective intravenously for Clostridioides difficile infection (CDI). Omadacycline is an aminomethylcycline tetracycline available orally and intravenously with potent in vitro activity against C. difficile and a low propensity to cause CDI. The purpose of this study was to assess the safety, faecal pharmacokinetics, microbiome and bile acid changes in healthy subjects given a course of intravenous omadacycline with oral omadacycline step down after 5 days.</p><p><strong>Methods: </strong>This Phase 1, open-label study was conducted in healthy volunteers 18-40 years. Subjects received a 5-day course of omadacycline given intravenously followed by 5 days of oral omadacycline. Stool samples were analysed for omadacycline concentrations, gut microbiome changes and bile acid changes from baseline.</p><p><strong>Results: </strong>Eight healthy volunteers aged 30 ± 4 years (50% Female) were recruited and all completed therapy. All subjects had detectable omadacycline stool concentrations after 48 hours of intravenous dosing and averaged 195 ± 97 µg/g (mean ± SD) by day 5. Omadacycline concentrations increased rapidly after the start of oral therapy on day 6 with average concentrations of 854 ± 404 µg/g of stool by day 10. Microbiome and bile acid evaluations showed preservation of key microbiome taxa that confer health benefit and preservation of bile acid homeostasis.</p><p><strong>Conclusion: </strong>Intravenous omadacycline followed by oral step-down administration in healthy adults achieved high faecal concentrations while preserving key bacterial species and bile acid homeostasis in the gut. These findings support Phase 2 studies directed towards the development of omadacycline as a CDI-targeted antibiotic.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2719-2726"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of disc diffusion and gradient strip test on different Mueller-Hinton agar media plates and ComASP® and Bruker UMIC® Cefiderocol Microdilution Panels for cefiderocol susceptibility testing in carbapenem-resistant Pseudomonas aeruginosa.","authors":"Stefano Mancini, Helena M B Seth-Smith, Natalia Kolesnik-Goldmann, Melanie Mermod, Vladimira Hinic, Tim Roloff, Muhammad Ali Syed, Irfan Ullah, Adrian Egli, Oliver Nolte","doi":"10.1093/jac/dkaf301","DOIUrl":"10.1093/jac/dkaf301","url":null,"abstract":"<p><strong>Background: </strong>Cefiderocol antimicrobial susceptibility testing requires standardized iron levels to produce consistent results. Here we assessed the analytical performances of two commercialized broth microdilution (BMD) methods (Bruker's UMIC and Liofilchem's ComASP), of disc diffusion (DD) and the gradient strip method on a collection of clinical carbapenem-resistant-Pseudomonas aeruginosa (CRPA) isolates.</p><p><strong>Methods: </strong>A collection of 117 WGS-CRPA was used. Cefiderocol susceptibility was determined (i) by manual BMD (reference method) using iron-depleted Mueller-Hinton (ID-MH), (ii) with the UMIC and ComASP BMD panels, (iii) by DD and (iv) using the gradient strip test, these latter two on bioMérieux MH-agar, Liofilchem MH-agar, and in-house-produced iron-depleted (ID)-MH agar plates.</p><p><strong>Results: </strong>Cefiderocol MIC50 and MIC90 were 1 and 4 mg/L, respectively. Eighteen isolates (15.4%) were classified as resistant (MIC > 2 mg/L) according to the standard EUCAST-based BMD. Overall, the ComASP panel showed the highest essential agreement (EA) with the standard BMD (82.1%), with a bias of -8.5%, and categorical agreement (CA) of 94%. The UMIC panel exhibited an EA of 74.4%, with a bias of 47%, and CA of 78.6%, exhibiting a tendency to overestimate the MICs. The EAs of the gradient strip test on bioMérieux-MH, Liofilchem-MH and ID-MH agar plates were 40.2%, 45.3% and 63.2%, respectively. Considering only categorizable results, the CAs of DD were 92.7%, 94.4% and 93.9%, respectively.</p><p><strong>Conclusions: </strong>The commercial ComASP panel may be used for cefiderocol testing of P. aeruginosa clinical isolates in diagnostic laboratories, ideally in combination with another method, such as the EUCAST-based DD. However, the standard manual BMD should still be performed to confirm the result when MICs are close to the breakpoint.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2799-2806"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cefazolin-induced seizures in a haemodialysis patient with elevated serum and cerebrospinal fluid concentrations: a case report.","authors":"Kohei Hasegawa, Kohei Yamamoto, Yoshiki Yamamoto, Itsuki Okamoto, Mitsuyo Nakano, Yoshihiko Ogawa","doi":"10.1093/jac/dkaf373","DOIUrl":"https://doi.org/10.1093/jac/dkaf373","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidrug efflux pumps and innate azole resistance of Mucor lusitanicus.","authors":"Stephanie Toepfer, Erwin Lamping, Jasper E James, Lisa-Maria Zenz, Julia Loacker-Schoech, Katharina Rosam, Olivia Majer, Michaela Lackner","doi":"10.1093/jac/dkaf343","DOIUrl":"https://doi.org/10.1093/jac/dkaf343","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to characterize the possible contribution of eight pleiotropic drug resistance (PDR) transporters to the azole resistance phenotype of Mucor lusitanicus.</p><p><strong>Methods: </strong>Gene expression analysis (RNA-sequencing and RT-qPCR) was performed on M. lusitanicus CBS277.49 cells exposed to three different types of azoles (4.0 mg/L). C-terminally GFP-tagged M. lusitanicus PDR transporters were overexpressed in the hypersensitive model host, Saccharomyces cerevisiae ADΔΔ. Their efflux pump functions were evaluated by determining the azole susceptibilities of the PDR transporter overexpressing cells and measuring their plasma membrane ATPase activities.</p><p><strong>Results: </strong>M. lusitanicus PDR transporters separated into two phylogenetic clusters: A (pdr1, pdr6-8) and B (pdr2-5). RNA-sequencing and RT-qPCR revealed strong up-regulation of pdr1 and pdr6, but down-regulation of pdr7 and pdr8 in response to 80 min exposures of 4.0 mg/L voriconazole, isavuconazole or posaconazole. The expression of Pdr6 and Pdr7 in S. cerevisiae ADΔΔ increased its resistance to short- and mid-length tailed azoles. Pdr1 and Pdr8 expression, however, conferred pan-azole resistance including long-tailed azoles such as itraconazole and posaconazole. No efflux pump function and ATPase activity were detected for Pdr3 and Pdr5. The ATPase activities of Pdr1, Pdr6, Pdr7 and Pdr8 were comparable to Candida albicans Cdr1 expressed in ADΔΔ.</p><p><strong>Conclusions: </strong>All Mucor cluster A PDR transporters are multidrug efflux pumps, but Pdr1 and Pdr6 are possibly the major contributors to the innate azole resistance phenotype of M. lusitanicus.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temocillin versus other intravenous beta-lactams for urinary tract infections caused by third-generation cephalosporin-resistant Enterobacterales: a multicentre retrospective matched cohort study.","authors":"Jeanne Iachkine, Kévin Alexandre, Clément Marlat, Anaïs Briant, François Caron, Christophe Isnard, Renaud Verdon, Jean-Jacques Parienti, Aurélie Baldolli","doi":"10.1093/jac/dkaf370","DOIUrl":"https://doi.org/10.1093/jac/dkaf370","url":null,"abstract":"<p><strong>Background and objectives: </strong>Temocillin is a carbapenem-sparing β-lactam antibiotic used to treat infections caused by third-generation cephalosporin-resistant (3GC-R) Enterobacterales, although its use is not universally recommended. The aim of this study was to compare the efficacy of temocillin with that of other parenteral beta-lactams in the treatment of febrile urinary tract infections (UTIs) caused by 3GC-R Enterobacterales.</p><p><strong>Patients and methods: </strong>We conducted a multicentre, retrospective, propensity score-matched cohort study including patients treated between January 2017 and December 2021. Patients who received temocillin were matched 1:1 with patients who received carbapenems, cefepime or piperacillin/tazobactam. The primary outcome was early clinical failure, defined as a composite of persistent symptoms leading to a switch in antibiotics or death within 10 days after treatment completion.</p><p><strong>Results: </strong>A total of 180 patients were included, with a high percentage of complicated UTIs (89%) but a low percentage of severe infections (21%). Early clinical failure occurred in 12% of patients overall, with no significant difference between the temocillin group (9%) and the comparator group (14%) (OR 0.58, 95% CI [0.23-1.48], P = 0.26). The rates of late clinical failure, late microbiological failure and all-cause mortality within 3 months were similar between the groups.</p><p><strong>Conclusion: </strong>In this study, compared with other beta-lactams, temocillin was not associated with an increased risk of early clinical failure in the treatment of 3GC-R Enterobacterales UTIs.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro evaluation of olorofim and antifungal combinations against Aspergillus and Candida species.","authors":"Corinne Pinder, Ressa Lebedinec, Jason D Oliver, Mike Birch, Derek Law","doi":"10.1093/jac/dkaf354","DOIUrl":"https://doi.org/10.1093/jac/dkaf354","url":null,"abstract":"<p><strong>Background and objectives: </strong>Aspergillus and Candida spp. are important causes of systemic fungal infections. Although various therapies are available, resistance to current antifungal treatments, particularly azoles, is increasing. Combinations of antifungals can be used to treat infections with resistant pathogens. In a recent in vitro study, antagonism was reported in a single A. fumigatus isolate between olorofim and voriconazole. Available clinical data are limited but do not reflect this phenomenon. The in vitro interactions of olorofim with current antifungal agents (voriconazole, posaconazole, isavuconazole, fluconazole, amphotericin B, terbinafine and caspofungin) were evaluated against various Aspergillus and three Candida species.</p><p><strong>Methods: </strong>In vitro interactions were evaluated by the EUCAST microdilution broth technique modified for checkerboard assay.</p><p><strong>Results: </strong>Olorofim demonstrated different interaction patterns when tested in combination with various classes of antifungal. Unidirectional antagonism was seen between olorofim and the mould-active azoles with the strongest effect seen in A. niger: azole MIC values were unaffected but olorofim MIC values increased, although remained within wild-type distributions. Olorofim antagonized amphotericin B activity in the single A. niger strain tested. There was indifference between olorofim and fluconazole, terbinafine and caspofungin for all isolates. Finally, olorofim showed indifference with fluconazole or voriconazole against three Candida species.</p><p><strong>Conclusions: </strong>Mould-active azoles antagonize olorofim activity against Aspergillus spp. combination MICs remain within wild-type distributions for Aspergillus spp., other than for A. niger. In addition, olorofim does not affect the anti-Candida effect of fluconazole and could be co-dosed where necessary without loss of the effect of the azole against the yeast.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment preferences by infectious diseases clinicians for carbapenem-resistant Enterobacterales infections.","authors":"Samuel E Cincotta, Belinda E Ostrowsky, Jessica Howard-Anderson, Susan E Beekmann, Philip M Polgreen, Maroya S Walters","doi":"10.1093/jac/dkaf371","DOIUrl":"https://doi.org/10.1093/jac/dkaf371","url":null,"abstract":"<p><strong>Background and objectives: </strong>New antibiotics effective against carbapenem-resistant Enterobacterales (CRE) provide additional treatment options, but data on clinician decision-making are limited. We sought to understand treatment preferences, factors influencing antibiotic selection for CRE infections and barriers to prescribing newer agents.</p><p><strong>Methods: </strong>We surveyed infectious disease clinicians through the Infectious Diseases Society of America (IDSA) Emerging Infections Network (EIN) about their experience treating CRE infections, availability of resistance mechanism testing, antibiotic choices in four CRE infection scenarios and barriers to using newer antibiotics. We used the 2023 IDSA Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections to classify antibiotic selections for the scenario-based questions as preferred approach, alternative option or not in guidance.</p><p><strong>Results: </strong>Overall, 441 EIN members responded. Among these, 337 (76%) reported treating a CRE infection in the last year. For the clinical scenarios, 851 (63%) of 1356 selections were IDSA-preferred approaches; of these, 653 (77%) were for ceftazidime-avibactam, either alone (n = 456) or in combination with aztreonam (n = 197), more than for other β-lactam/β-lactamase inhibitor combination agents active against CRE. For an uncomplicated urinary tract infection caused by carbapenem-resistant Klebsiella pneumoniae, where no preferred approaches were available, the most common antibiotic selected was oral fosfomycin (169/343 (49%)).</p><p><strong>Conclusions: </strong>Most clinicians selected antibiotics aligned with the IDSA guidance for serious CRE infections, although the frequent selection of an agent not in the guidance for uncomplicated cystitis suggests that treatment selection is complex and may depend on infection severity, among other factors. The preference for ceftazidime-avibactam among similar agents is notable and may reflect its longer market availability.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A drug-repurposing screen of FDA- and EMA-approved drugs identifies two NF-κB inhibitors active against eumycetoma.","authors":"Jingyi Ma, Bjorn R van Doodewaerd, Bernhard Biersack, Annelies Verbon, Paul P Geurink, Wendy W J van de Sande","doi":"10.1093/jac/dkaf369","DOIUrl":"https://doi.org/10.1093/jac/dkaf369","url":null,"abstract":"<p><strong>Background: </strong>Mycetoma caused by Madurella mycetomatis (eumycetoma) is a neglected tropical disease that forms tumorous lesions in the subcutaneous tissue. The current standard treatment for eumycetoma consists of antifungal treatment combined with surgery, with limited success rates. Due to lack of investment, there are currently no large drug discovery programmes for mycetoma. Repurposing screening can therefore offer an effective and economical way to identify drugs that can be effective in eumycetoma treatment. Therefore, in this study we determined the in vitro activity and in vivo efficacy of 5631 compounds present in the Oncode Drug Repurposing library.</p><p><strong>Methods: </strong>In total, 5631 drugs from the Oncode Drug Repurposing library were screened for in vitro activity against M. mycetomatis using a CLSI-based in vitro susceptibility assay and CellTiter-Glo as a viability dye. Compounds that inhibited the metabolic activity were tested for in vivo activity in M. mycetomatis-infected Galleria mellonella larvae.</p><p><strong>Results: </strong>Twenty-eight compounds out of the 5631 drugs were able to inhibit the metabolic activity of M. mycetomatis at 2 µM. Seventeen of the 28 compounds were azoles and 2 were toxic to G. mellonella and therefore not screened further. Two from the remaining 9 compounds, bay117085 (log-rank, P = 0.0494) and IMD-0354 (log-rank, P = 0.0043), prolonged the survival of M. mycetomatis-infected larvae. Both compounds were designed as NF-κB inhibitors.</p><p><strong>Conclusions: </strong>NF-κB inhibitors bay117085 and IMD-0354 were able to prolong the survival of M. mycetomatis-infected larvae.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How should APOBEC3-induced resistance mutations be considered in the management of antiretroviral therapy?","authors":"Marie Gilbert, Valentine Marie Ferré, Romane Guilbaud, Marc Digumber, Gilles Peytavin, Florence Damond, Quentin Le Hingrat, Yazdan Yazdanpanah, Diane Descamps, Charlotte Charpentier, Véronique Joly, Jade Ghosn","doi":"10.1093/jac/dkaf353","DOIUrl":"https://doi.org/10.1093/jac/dkaf353","url":null,"abstract":"<p><strong>Background: </strong>Combined antiretroviral therapy (ART) management guided by the cell-associated HIV-DNA genotypic resistance test (GRT) is not standardized, and its interpretation may be difficult in the presence of APOBEC3-induced mutations at drug resistance-associated positions (APOMut). Our objective was to evaluate the virologic outcome of people living with HIV (PLWH) with HIV-DNA provirus carrying APOMuts when switched to or receiving an ART regimen that would theoretically be significantly impacted by those APOMut (potential APOMut-impacted treatment, PAIT).</p><p><strong>Methods: </strong>PLWH under PAIT and with a cell-associated HIV-DNA GRT containing APOMut between April 2010 and December 2023 were included. Treatment failure was defined as two consecutive plasma viral load values >50 c/mL at least 1 month apart after the switch to PAIT.</p><p><strong>Results: </strong>We studied 38 PLWH who received 42 distinct PAIT lines. At the time of PAIT introduction, all individuals except one were virally suppressed. Virologic failure occurred in four PLWH; all of these cases were related to either poor ART adherence or ART interruption. Two of them switch to another ART: one for galenic adaptation, and the other due to the emergence of the N155H resistance mutation in integrase. For this individual, virologic suppression was obtained with a PI-containing ART. The two others resumed virologic suppression without any ART switch.</p><p><strong>Conclusions: </strong>Despite the presence of APOMut in cell-associated HIV-DNA GRTs, virologic suppression was maintained in PLWH switching to PAIT. Virologic failures were unrelated to the presence of APOMut. These results suggest that APOMuts should not be considered in the management of ART.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}