Antimicrobial Agents and Chemotherapy最新文献

{"title":"Use of baloxavir as adjunctive antiviral therapy to neuraminidase inhibitors in severely immunocompromised individuals infected with influenza.","authors":"Pauline Vetter, Ana Rita Goncalves Cabecinhas, Manuel Schibler, Laurent Kaiser, Karen Cruz-Fauquex, Yves Chalandon, Stavroula Masouridi-Levrat, Dionysios Neofytos","doi":"10.1128/aac.01659-25","DOIUrl":"10.1128/aac.01659-25","url":null,"abstract":"<p><p>Immunocompromised patients are at risk of developing severe influenza, with protracted viral shedding and development of resistance-associated mutations under antiviral treatment. We report a case series of severely immunocompromised hematology patients, including allogeneic hematopoietic cell transplantation (HCT) recipients, treated with both baloxavir and oseltamivir and describe clinical and virological outcomes and the safety profile of prolonged combination therapy. Allogeneic HCT recipients with influenza infection treated with baloxavir were retrieved via institutional databases. All hospitalized allogeneic HCT patients treated with a combination therapy of baloxavir and oseltamivir over five influenza seasons between October 2019 and May 2025 were included. Six influenza-infected hematology patients (5/6 allogeneic HCT recipients) were treated with combination therapy of oseltamivir and baloxavir. All patients presented with lower respiratory tract infections. Oseltamivir treatment duration ranged from 5 to 31 days, and the number of administered baloxavir doses ranged between one and five. Baloxavir administration was well tolerated, and no adverse events could be attributed to the administered antiviral treatment. All-cause mortality at 3 months post-infection was 66% (4/6), mainly driven by underlying disease. In two patients with protracted shedding, combination therapy did not prevent the development of resistance mutation(s). Combination treatment with prolonged courses of oseltamivir and repeated doses of baloxavir was well tolerated. No definitive conclusions on the efficacy of this approach could be drawn from this study. More data are required on the best treatment of hematology patients infected with influenza.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0165925"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525611","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":"RNA Polymerase 1 inhibitors against African trypanosomes <i>in vitro</i> and in mice.","authors":"Alexander V Cumming, Nathaniel P Nenortas, Elizabeth Nenortas, Rahul P Bakshi, Emily R Caton, Estefany Rios-Guzman, Mary E Barry, James C Barrow, Marikki Laiho, Theresa A Shapiro","doi":"10.1128/aac.01492-25","DOIUrl":"10.1128/aac.01492-25","url":null,"abstract":"<p><p>Therapy of human African trypanosomiasis, fatal if not treated, has been greatly improved by orally available and safer fexinidazole, but reliable cure of late-stage central nervous system (CNS) infection remains a challenge. African trypanosomes are unique among eukaryotes in having an RNA Polymerase 1 that transcribes not only rRNA but also mRNA that encodes the abundant variable surface glycoprotein (VSG) that coats the cell membrane of bloodstream-form parasites and allows them to evade host immune defenses. RNA Pol 1 inhibitor BMH-21, an intercalator not associated with DNA damage and a lead for new cancer therapy, has reported activity against the synthesis of rRNA and VSG mRNA in <i>Trypanosoma brucei brucei</i>. We evaluated a library of BMH-21 analogs against bloodstream-form <i>T. b. brucei in vitro</i> and found limited tolerance for structural modification. Striking and time-dependent bimodal dose-response curves indicate these compounds have a complex mechanism of action. Most potent against <i>T. b. brucei</i> was benzopyridoquinazoline Compound <b>2</b>, with an EC₅₀ of 84 nM. Analysis of <i>in vitro</i> pharmacokinetic-pharmacodynamic (PK-PD) relationships by a hollow fiber model system revealed that in <i>T. b. brucei</i>, the kinetic driver of Compound <b>2</b> is drug concentration, a finding that was confirmed by dose fractionation in infected mice and that highlights the utility of the <i>in vitro</i> system for assessing antitrypanosomal PK-PD. Although Compound <b>2</b> accumulates 20-fold in mouse brain tissue vs plasma, efficacy against CNS <i>T. b. brucei</i> in mice was limited. RNA Pol 1 remains an attractive target for developing new and more selectively toxic antitrypanosomal agents.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0149225"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525629","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":"Case Commentary: When one target is not enough-PBP3 insertions and target redundancy in <i>Escherichia coli</i>.","authors":"Madison E Stellfox, Yohei Doi","doi":"10.1128/aac.00053-26","DOIUrl":"10.1128/aac.00053-26","url":null,"abstract":"<p><p>This challenging clinical case highlights the impact of PBP3 insertions in <i>Escherichia coli</i>, which reduce susceptibility to key β-lactam agents and complicate treatment, particularly in the setting of NDM production (C. Fabrizio, F. Valzano, S. Giuliano, E. Morelli, et al., Antimicrob Agents Chemother 70:e00887-25, 2026, https://doi.org/10.1128/aac.00887-25). Clinical improvement was achieved with imipenem-relebactam plus aztreonam, supporting the idea that targeting multiple penicillin-binding proteins can overcome functional redundancy. These findings emphasize the clinical relevance of PBP3-mediated resistance and the need for treatment strategies that address complex β-lactam resistance in Gram-negative pathogens.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0005326"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621619","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":"Single point mutations in global regulatory genes restore cephalosporin resistance in a low-MIC <i>Enterococcus faecium</i> natural isolate.","authors":"Miquel Sánchez-Osuna, Paula Bierge, Inmaculada Gómez-Sánchez, Judith Guitart-Matas, Víctor Monsálvez, Patricia Rabanal, Ana P Pereira, Ana R Freitas, Luisa Peixe, Mateu Espasa, Oriol Gasch, Carla Novais, Oscar Q Pich","doi":"10.1128/aac.01948-25","DOIUrl":"10.1128/aac.01948-25","url":null,"abstract":"<p><p><i>Enterococcus faecium</i> exhibits intrinsic resistance to cephalosporins (CPHs), yet the genetic determinants of this phenotype remain incompletely understood. To date, <i>E. faecium</i> strains with low minimum inhibitory concentrations (MICs) of CPH have only been described following genetic manipulation. At Parc Taulí University Hospital, we identified a clinical isolate of ampicillin-susceptible <i>E. faecium</i> (Efm5) that exhibited unusually low MICs to cefotaxime (1 mg/L), ceftriaxone (3 mg/L), and ceftaroline (0.19 mg/L). Upon single exposure to ceftriaxone (100 mg/L), Efm5 rapidly yielded variants with markedly increased MICs of ceftriaxone (>256 mg/L) and cefotaxime (>32 mg/L), while MICs of ampicillin and ceftaroline were unaffected. Whole-genome sequencing revealed that the high-MIC variants carried single-nucleotide polymorphisms leading to non-synonymous mutations in <i>croS</i>, <i>nusG</i>, or <i>rpoB</i> genes. Phenotypic assays confirmed that these mutations were associated with ceftriaxone resistance, and immunoblots revealed increased expression of penicillin-binding protein 5 (PBP5) in all the high-MIC variants. Transcriptional profiling showed upregulation of the <i>pbp5</i> operon, which includes <i>ftsW</i>, <i>psr</i>, and <i>pbp5</i>, in the <i>croS</i> variants. This study provides evidence that <i>E. faecium</i> isolates with low MICs to CPH can arise in clinical settings without laboratory manipulation, enabling further investigation of resistance pathways.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0194825"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497524","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":"Pharmacokinetic profiling of limnetrelvir in non-Japanese and Japanese populations: results of two phase 1 single- and multiple-dose studies.","authors":"Ekram A Chowdhury, Christine M Lee, Janki M Desai, Izna Ali, Amelia Orejudos, Shelly V Gupta, Christopher J Ocampo, Michael G Miller, Jayanthy Jayanth, Jeffrey M Schmidt, Ahmed Hamed Salem, Nael M Mostafa","doi":"10.1128/aac.01443-25","DOIUrl":"10.1128/aac.01443-25","url":null,"abstract":"<p><p>COVID-19's main protease (Mpro) unique structure and function, which are conserved among coronaviruses, make it an attractive target for viral inhibition. Limnetrelvir is a novel Mpro inhibitor intended for once-daily administration. The pharmacokinetics, safety, and tolerability results of two phase 1 studies of limnetrelvir are reported herein. These studies consisted of a first-in-human, single-, and multiple-ascending dose study in healthy non-Japanese participants and a single- and multiple-dose study in healthy Japanese participants. Across both studies, a total of 104 participants received limnetrelvir single doses ranging from 200 to 800 mg and multiple doses from 200 to 800 mg QD for 10 days. The harmonic mean half-life of limnetrelvir ranged from 6 to 21 h following a single dose. No clinically significant differences in exposures were observed between Japanese and non-Japanese participants. Limnetrelvir was generally well tolerated in both studies in healthy participants with up to 10 days of dosing, with only mild or moderate adverse events observed.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05691699 and NCT06009237.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0144325"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497457","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":"Safety and efficacy of echinocandin antifungal agents in <i>Candida albicans</i> endophthalmitis.","authors":"Yue Zhang, Yi Tang, Yanjie Zhou, Hong Wu","doi":"10.1128/aac.01670-25","DOIUrl":"10.1128/aac.01670-25","url":null,"abstract":"<p><p>To evaluate the safety and efficacy of echinocandins (rezafungin, RZF; anidulafungin, AFG) in <i>Candida albicans (C. albicans</i>) endophthalmitis, with a particular focus on the novel drug RZF. In vitro safety was assessed by CCK-8 and live/dead staining on ARPE-19, Müller, and RAW 264.7. For <i>in vivo</i> safety, we administered therapeutic doses via intravitreal injection in rabbit eyes and performed fundus photography and histopathological analysis on day 3. Antifungal effect evaluation included minimum inhibitory concentration (MIC) determination, biofilm inhibition, and structural damage observation (confocal laser scanning microscopy, CLSM; scanning/transmission electron microscopy, SEM/TEM). We measured inflammatory responses via TNF-α/IL-1β qRT-PCR in RAW 264.7 cells. A rabbit <i>C. albicans</i> endophthalmitis model was established. At 48 h post-infection, rabbits received intravitreal injections of liposomal amphotericin B (L-AmB, 10 μg), voriconazole (VCZ, 50 μg), RZF (35 μg), AFG (35 μg), or saline (control). Clinical scores, ocular fungal burden, aqueous humor TNF-α, and histopathological scores were assessed. Echinocandins showed lower IC50 values <i>in vitro</i>, yet maintained acceptable safety at clinically relevant low concentrations compared with traditional drugs, with no significant tissue toxicity <i>in vivo</i>. RZF and AFG exhibited lower MICs (0.016-0.03125 μg/mL) than L-AmB (4 μg/mL) and VCZ (0.125-0.25 μg/mL). All four drugs inhibited biofilm formation, disrupted fungal structures, and downregulated inflammatory responses. <i>In vivo</i>, RZF/AFG reduced clinical and histopathological scores, fungal burden, and TNF-α levels, performing similarly to traditional drugs. RZF and AFG demonstrate potent antifungal activity against <i>C. albicans</i> comparable to conventional drugs, along with significant anti-inflammatory effects and acceptable safety profiles.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0167025"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497489","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":"Emergence of KPC-producing <i>Pseudomonas aeruginosa</i> in Spain: insights into an outbreak and resistance to the novel carbapenem/β-lactamase inhibitor combinations imipenem/relebactam and meropenem/vaborbactam.","authors":"Gloria Pérez-Rodríguez, Pablo Aja-Macaya, Lucía González-Pinto, Biel Taltavull, María Tarriño-León, María Del Mar Gallardo-García, Tania Blanco-Martín, Salud Rodríguez-Pallares, Lucía Sánchez-Peña, Miriam Moscoso, Alejandro Beceiro, Antonio Oliver, Germán Bou, Jorge Arca-Suárez","doi":"10.1128/aac.01657-25","DOIUrl":"10.1128/aac.01657-25","url":null,"abstract":"<p><p>We report an outbreak of KPC-producing <i>Pseudomonas aeruginosa</i> in Spain, involving four patients and an environmental isolate recovered from a hospital sink. All isolates belonged to clone ST253 and exhibited difficult-to-treat resistance, including resistance to imipenem/relebactam and meropenem/vaborbactam. Genomic analysis confirmed a plasmid-encoded <i>bla</i>_KPC-2 and OprD deficiency. Functional assays demonstrated synergy between KPC-2 production and porin loss on resistance to carbapenem/β-lactamase inhibitors. The findings highlight the clinical threat posed by KPC-producing <i>P. aeruginosa</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0165725"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525627","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":"Adjunctive povidone-iodine for <i>Acanthamoeba</i> keratitis: a randomized trial.","authors":"Revathi Rajaraman, Isabell Kassaye, Sankalp S Sharma, N Venkatesh Prajna, Prajna Lalitha, Arunkumar Panigrahi, Ram Rammohan, Krisianne M Aromin, Catherine Cook, Travis C Porco, Thomas M Lietman, Gerami D Seitzman, Jeremy D Keenan","doi":"10.1128/aac.01512-25","DOIUrl":"10.1128/aac.01512-25","url":null,"abstract":"<p><p>The aim of this study was to determine the antiamoebic efficacy of povidone-iodine when used as an adjunct to topical biguanide therapy for <i>Acanthamoeba</i> keratitis. Patients with smear- or culture-positive <i>Acanthamoeba</i> keratitis received topical chlorhexidine 0.04%, half-hourly for 2 days, then hourly for days 3-6, then eight times per day for days 7-28. Participants were randomized in a 1:1 ratio to receive either adjunctive topical povidone-iodine at the same frequency as chlorhexidine or no additional therapy (i.e., control group). Povidone-iodine was initially administered as a 2.5% solution but was reduced to a 1% solution after several reports of intolerance. The primary outcome was <i>Acanthamoeba</i> growth from the culture of corneal scrapings at 1, 2, and 4 weeks after randomization, as assessed by laboratory staff masked to treatment allocation. Of 49 patients enrolled, 25 were randomized to adjunctive povidone-iodine (mean age 48 [SD 16] years; 32% female) and 24 to control (mean age 43 [15] years; 33% female). Four (16%) participants discontinued 2.5% povidone-iodine prematurely due to intolerance. The proportion of participants with a positive culture during the initial 4 weeks of antiamoebic treatment was not significantly different in the povidone-iodine group (6/18 [33%] at 4 weeks) and control group (5/16 [31%] at 4 weeks) (RR 0.90, 95%CI: 0.35-2.29; <i>P</i> = 0.82). When used as an adjunctive to standard biguanide therapy, povidone-iodine did not markedly accelerate the clearance of <i>Acanthamoeba</i> organisms from the corneal surface over the initial month of therapy.This study is registered with ClinicalTrials.gov as NCT03484507.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0151225"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580240","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":"Nitroxoline exerts potent anti-<i>Aspergillus fumigatus</i> activity by disrupting copper homeostasis and inducing oxidative stress.","authors":"Yiru Zhang, Yuxin Han, Dan Cao, Xin Yuan, Pusheng Xu, Yanghui Xiang, Yi Li, Ying Zhang","doi":"10.1128/aac.01831-25","DOIUrl":"10.1128/aac.01831-25","url":null,"abstract":"<p><p>Invasive pulmonary aspergillosis (IPA) caused by <i>Aspergillus fumigatus</i> remains a clinical challenge due to limited therapies and rising antifungal resistance. Here, we evaluated nitroxoline (NTX), an FDA-approved 8-hydroxyquinoline derivative, for its antifungal potential and mechanism of action. NTX exhibited potent <i>in vitro</i> activity against 64 clinical isolates and the AF293 reference strain, delaying conidial maturation and significantly improving survival, reducing pulmonary fungal burden, and alleviating lung inflammation and hyphal invasion in an IPA mouse model. Transcriptomic analysis revealed marked downregulation of the high-affinity Cu transporter <i>ctrC</i> and superoxide dismutase <i>sodB</i>, disrupting the copper homeostasis-oxidative stress axis. Copper supplementation restored hyphal growth and intracellular ROS levels, supporting a mechanism of copper deprivation-induced oxidative stress. These findings demonstrate that NTX exerts strong anti-<i>A</i>. <i>fumigatus</i> effects <i>in vitro</i> and <i>in vivo</i> by perturbing copper homeostasis and inducing oxidative stress, highlighting its unique antifungal potential and providing a conceptual basis for metal-targeted therapeutic strategies against IPA and drug-resistant fungal infections.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0183125"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580292","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":"Antibiotic dose-response curves can measure antibiotic activity against <i>Mycobacterium abscessus</i> and <i>Mycobacterium peregrinum</i>.","authors":"Husain Poonawala, Kathleen Davis, Myles E Kenny, Ares Alivisatos, Nhi Van, Tracy Washington, Vinicius Calado Nogueira de Moura, Charles L Daley, Bree B Aldridge","doi":"10.1128/aac.01876-25","DOIUrl":"10.1128/aac.01876-25","url":null,"abstract":"<p><p><i>Mycobacterium abscessus</i> is a drug-resistant pathogen associated with poor clinical outcomes despite prolonged treatment with multidrug antibiotic regimens. Apart from clarithromycin, antimicrobial susceptibility testing (AST) results for <i>Mycobacterium abscessus</i> cannot guide antibiotic selection. AST involves measuring the minimum inhibitory concentration (MIC), which is allowed to span a fourfold range in concentration. This accepted variability of the MIC limits the clinical utility of AST. Antimicrobial dose-response curves, obtained by measuring the growth inhibition of a given organism to increasing concentrations of an antibiotic, can yield metrics of antibiotic activity that are less variable than the MIC. We used Clinical and Laboratory Standards Institute growth conditions for rapidly growing nontuberculous mycobacteria AST to generate 990 dose-response curves across three time points (72 h, 96 h, and 120 h) for six guideline-recommended (clarithromycin, amikacin, cefoxitin, linezolid, tigecycline, and clofazimine) and five new (omadacycline, tedizolid, SPR719, SQ109, and bedaquiline) antibiotics against <i>Mycobacterium abscessus</i> subspecies <i>abscessus</i> ATCC 19977 and <i>Mycobacterium peregrinum</i> ATCC 700686. We established the fit of the dose-response curve (<i>R</i>²) as a quality control metric. Using the geometric standard deviation and median coefficient of variation, we demonstrated that the IC₅₀ and IC₇₅ (antibiotic concentrations corresponding to 50% and 75% growth inhibition, respectively) are less variable than the MIC. We identified time-dependent changes in dose-response curve metrics that allow the detection of inducible clarithromycin resistance with only 5 days of incubation. This study demonstrates the potential of dose-response curves in measuring antibiotic activity against <i>Mycobacterium abscessus</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0187625"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621630","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}