Antimicrobial Agents and Chemotherapy最新文献

{"title":"Colonization with resistant bacteria in hospital employees: an epidemiological surveillance and typing study.","authors":"Tina Badinski, Salome N Seiffert, Fabian Grässli, Baharak Babouee Flury, Ulrike Besold, Elsbeth Betschon, Michael Biggel, Angela Brucher, Alexia Cusini, Tamara Dörr, Adrian Egli, Stephan Goppel, Sabine Güsewell, Joelle Keller, Matthias von Kietzell, J Carsten Möller, Oliver Nolte, Manuela Ortner, Tim Roloff, Markus Ruetti, Matthias Schlegel, Helena M B Seth-Smith, Roger Stephan, Reto Stocker, Danielle Vuichard-Gysin, Barbara Willi, Stefan P Kuster, Christian R Kahlert, Philipp Kohler","doi":"10.1128/aac.00985-24","DOIUrl":"https://doi.org/10.1128/aac.00985-24","url":null,"abstract":"<p><p>The objective of this study was to determine the prevalence, molecular epidemiology, and risk factors for gut colonization with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenemase-producing Enterobacterales (CPE), and vancomycin-resistant enterococci (VRE) in healthcare workers (HCWs). In September/October 2022, we performed a cross-sectional study among HCW from 14 institutions in Northeastern Switzerland. HCWs reported risk factors for antimicrobial resistance (covering the last 12-24 months) and provided rectal swabs. Swabs were screened for ESBL-E, CPE, and VRE; whole-genome sequencing (WGS) was performed to assess the genetic relatedness. Logistic regression was used to identify occupational and non-occupational risk factors. Among approximately 22,500 employees, 1,209 participated (median age 46 years, 82% female). Prevalences of ESBL-E (<i>n</i> = 65) and CPE (<i>n</i> = 1) were 5.4% [95% confidence interval (CI) 4.2-6.8] and 0.1% (95% CI 0.0-0.5), respectively; no VREs were detected. In the multivariable analysis, non-European ethnicity [adjusted odds ratio (aOR) 7.0, 95% CI 1.4-27.3], travel to high-risk countries (aOR 4.9, 95% CI 2.5-9.3), systemic antibiotics (aOR 2.1, 95% CI 1.1-3.7), antibiotic eye drops (aOR 4.7, 95% CI 1.7-11.9), and monthly sushi consumption (aOR 2.4, 95% CI 1.4-4.3) were positively associated with ESBL-E colonization, whereas alcohol consumption (aOR 0.5 per glass/week, 95% CI 0.3-0.9) was negatively associated with ESBL-E colonization. Occupational factors showed no association. Among ESBL-<i>Escherichia coli</i>, ST131 (15 of 61, 25%) and <i>bla</i>_CTX-M-15 (37/61; 61%) were most common; one isolate co-harbored <i>bla</i>_OXA-244. WGS data did not show relevant clustering. Occupational exposure is not associated with ESBL-E colonization in HCW. Given the potential public health and antibiotic stewardship implications, the role of sushi consumption and antibiotic eye drops as risk factors should be further elucidated.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339924","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":"Parametric and nonparametric population pharmacokinetic analysis of fluconazole in critically ill patients and dosing simulations for <i>Candida</i> infections.","authors":"Elodie Matusik, Olivia Vassal, Anne Conrad, Tristan Ferry, Aurélien Millet, Damien Dupont, Lola Grandjean, Jérôme Guitton, Sandrine Roux, Anne-Lise Bienvenu, Julien Bohé, Arnaud Friggeri, Sylvain Goutelle","doi":"10.1128/aac.00991-24","DOIUrl":"https://doi.org/10.1128/aac.00991-24","url":null,"abstract":"<p><p>Large pharmacokinetic (PK) variability of fluconazole has been reported in critically ill patients, but the implications for fluconazole dosing remain unclear. The objectives of this study were to evaluate the population PK of fluconazole and identify appropriate dosage regimens by simulations. This was a retrospective analysis of fluconazole PK data from patients hospitalized in critical care and infectious disease departments. Both parametric and nonparametric population approaches were used. Various loading and maintenance fluconazole doses were evaluated by simulations, with computation of the probabilities of PK/pharmacodynamic (PD) target attainment (PTA) and cumulative fractions of response (CFR) based on international and local minimum inhibitory concentration (MIC) distributions of <i>Candida</i> sp. Data from 36 critically ill patients and 16 non-critically ill patients were available for model building (<i>n</i> = 202 concentrations). The final model adequately described the data, including the external data set (13 patients). After 24 h of therapy, 65% and 74% of patients had trough and area under the concentration-time curve values below the usual targets. Standard dosages were associated with low PTA for MIC >1 mg/L at 24 h. Higher loading doses administered two times daily improved PTA. CFR were >90% for <i>C. albicans</i> with standard dosages, while they were very low for <i>C. glabrata</i>, even with high dosages. <i>Candida</i> species and associated MIC distributions strongly influence fluconazole dosage requirements. Higher loading doses may be necessary for the achievement of PK/PD targets up to MIC breakpoints. The use of fluconazole for invasive <i>C. glabrata</i> infection should be discouraged because of poor PK/PD target attainment.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339941","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":"Naamidine A reveals a promising zinc-binding strategy for topical antifungal therapy.","authors":"Emily Puumala, Sunna Nabeela, Christopher C Thornburg, Tanja Grkovic, Priya Uppuluri, Luke Whitesell, Barry R O'Keefe, Nicole Robbins, Leah E Cowen","doi":"10.1128/aac.01194-24","DOIUrl":"https://doi.org/10.1128/aac.01194-24","url":null,"abstract":"<p><p>Fungal disease affects over a billion people worldwide. Naamidine A inhibits the growth of diverse fungal pathogens through an unknown mechanism. Here, we show that the supplementation of medium with excess zinc abolishes the antifungal activity of naamidine A. Furthermore, we highlight that naamidine A has <i>in vitro</i> activity against terbinafine-resistant <i>Trichophyton spp</i>. and <i>in vivo</i> efficacy in a mouse model of dermatomycosis caused by <i>T. mentagrophytes,</i> highlighting its therapeutic potential as a topical treatment.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339940","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":"Impact of obesity on clinical outcomes of methicillin-susceptible <i>Staphylococcus aureus</i> bloodstream infections.","authors":"Anthony S Wasielewski, Anthony M Casapao, Christopher A Jankowski, Carmen L Isache, Malleswari Ravi, Ashlan J Kunz Coyne","doi":"10.1128/aac.00752-24","DOIUrl":"https://doi.org/10.1128/aac.00752-24","url":null,"abstract":"<p><p>Obesity affects over one-third of U.S. adults and complicates the treatment of methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA) bloodstream infections (BSI). A study at the University of Florida Health Centers compared clinical outcomes between 233 obese and non-obese patients receiving cefazolin for MSSA BSI. No significant differences were found in clinical success (81.9% vs 82.7%), mortality (7.2% vs 5.3%), or adverse events (3.6% vs 3.3%). However, obese patients took longer to clear blood cultures (4.62 vs 4.01 days, <i>P</i> = 0.017).</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339926","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":"An arylsulfonamide that targets cell wall biosynthesis in <i>Mycobacterium tuberculosis</i>.","authors":"Renee Allen, Lauren Ames, Vanessa Pietrowski Baldin, Arielle Butts, Kenneth J Henry, Greg Durst, Diana Quach, Joseph Sugie, Joe Pogliano, Tanya Parish","doi":"10.1128/aac.01037-24","DOIUrl":"https://doi.org/10.1128/aac.01037-24","url":null,"abstract":"<p><p>We investigated the mechanism of action of an arylsulfonamide with whole-cell activity against <i>Mycobacterium tuberculosis</i>. We newly synthesized the molecule and confirmed it had activity against both extracellular and intracellular bacilli. The molecule had some activity against HepG2 cells but maintained some selectivity. Bacterial cytological profiling suggested that the mechanism of action was via disruption of cell wall synthesis, with similarities to an inhibitor of the mycolic acid exporter MmpL3. The compound induced expression from the IniB promoter and caused a boost in ATP production but did not induce reactive oxygen species. A mutation in MmpL3 (S591I) led to low-level resistance. Taken together, these data confirm the molecule targets cell wall biosynthesis with MmpL3 as the most probable target.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339923","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":"Molecular insights into the evolutionary trajectory of a <i>Klebsiella aerogenes</i> clinical isolate with a complex trade-off between resistance and virulence.","authors":"Youssouf Sereme, Hélène Faury, Victor Gravrand, Elisabeth Ageron, Claire Poyart, David Skurnik, Hedi Mammeri","doi":"10.1128/aac.01036-24","DOIUrl":"10.1128/aac.01036-24","url":null,"abstract":"<p><p>The fitness cost associated with antimicrobial resistance has an important influence on evolutionary dynamics. We compared the genomes of three <i>Klebsiella aerogenes</i> isolates recovered from blood samples or deep abscess cultures from the same patient: the wild-type strain (CT_WT), a piperacillin-tazobactam-resistant strain (CT_PENI), and an extended-spectrum-cephalosporin (ESC)-resistant strain (CT_R). Whole-genome sequencing revealed that CT_PENI had acquired a TEM-1 β-lactamase with a mutated promoter, accounting for overproduction. CT_PENI then acquired an E240G substitution in the TEM-1 β-lactamase (resulting in TEM-207) and lost the porin-encoding <i>ompK36</i> gene to give CT_R. All three strains showed the same virulence in a mouse model of intraperitoneal infection. The results of recombination and transformation assays indicated that when present separately, the TEM-207 overproduction and the <i>ompK36</i> gene deletion had only small effects on susceptibility to ESCs. However, the combination of the two changes led to a much lower susceptibility to ESCs. Moreover, the levels of fitness <i>in vitro</i> and <i>in vivo</i> in a murine model of gut colonization were significantly lower after TEM-1 β-lactamase overproduction and lower still after E240G substitution and OmpK36 loss. We hypothesize that the chosen courses of antibiotics led to the stepwise emergence of a clone with resistance to penicillins and ESCs and no loss of virulence. However, acquired resistance may have a fitness cost that limits evolutionary success. Our results might explain why the overproduction of extended-spectrum β-lactamases (which should confer a high level of piperacillin-tazobactam resistance) is not observed in clinical practice and why TEM-207 has rarely been detected in clinical isolates.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307018","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":"Pharmacologic evaluation of delayed long-acting cabotegravir administration among cisgender women in HPTN 084.","authors":"Mark A Marzinke, Kelong Han, Brett Hanscom, Xu Guo, Estelle Piwowar-Manning, Craig W Hendrix, Scott Rose, Elizabeth Spooner, Carrie Mathew, Steven Innes, Rogers Sekabira, Mercy Mutambanengwe, James F Rooney, Alex R Rinehart, Adeola Adeyeye, Myron S Cohen, Mina Hosseinipour, Susan L Ford, Sinead Delany-Moretlwe","doi":"10.1128/aac.00994-24","DOIUrl":"10.1128/aac.00994-24","url":null,"abstract":"<p><p>HPTN 084 demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with daily oral tenofovir disoproxil fumarate-emtricitabine (F/TDF) for HIV prevention in women. CAB-LA (600 mg) or placebo injections were administered 4 weeks after an initial dose (loading dose) and every 2 months (Q2M) thereafter; this is the approved regimen. Participants experienced both loading dose and Q2M delays during the trial. CAB concentrations were evaluated before a delay, at the visit associated with the delay, and the visit after a delayed injection was administered. During the blinded phase of the trial, 194 participants randomized to CAB-LA experienced at least one injection delay. Plasma CAB concentrations were maintained above the 4× protein adjusted 90% inhibitory concentration (4× PA-IC₉₀; protocol-specific threshold) for all loading dose and 98% of Q2M delays when injections were administered up to 6 weeks late. The feasibility of shifting to an every 3-month (Q3M) regimen in females was interrogated via simulation studies using a population pharmacokinetic model. Q3M injections in both CAB-naïve (with a loading dose) and previously CAB-exposed females were predicted to yield higher steady-state exposures than in males on the approved Q2M regimen. Although there is observed forgiveness following an isolated delayed CAB-LA injection and simulations suggest acceptable CAB-LA exposures in women with a 600 mg CAB-LA Q3M regimen, empirical efficacy of this regimen has not been established, and transitioning to this dosing schema is not recommended. Future pharmacokinetic bridging studies are aimed at evaluating higher dose CAB-LA formulations administered less frequently.</p><p><strong>Clinical trials: </strong>This study is registered with ClinicalTrials.gov as NCT03164564.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279698","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":"Detection of cefiderocol and aztreonam/avibactam resistance in epidemic <i>Escherichia coli</i> ST-361 carrying <i>bla</i>_NDM-5 and <i>bla</i>_KPC-3 from foreign fighters evacuated from Ukraine.","authors":"Melissa J Martin, Ting L Luo, Valentyn Kovalchuk, Viacheslav Kondratiuk, Henry D Dao, Iryna Kovalenko, Brandon J Plaza, Joanna M Kettlewell, Cole P Anderson, Jason R Smedberg, Ana C Ong, Yoon I Kwak, Joshua S Hawley-Molloy, Jason W Bennett, Patrick T McGann, Francois Lebreton","doi":"10.1128/aac.01090-24","DOIUrl":"https://doi.org/10.1128/aac.01090-24","url":null,"abstract":"<p><p>Genomic surveillance detected clonal <i>Escherichia coli</i> sequence type-361 isolates carrying <i>bla</i>_NDM-5, <i>bla</i>_KPC-3, <i>bla</i>_CTX-M-15, and <i>rmtB1</i> from a patient in Ukraine and four wounded foreign soldiers evacuated to Germany. Isolates were non-susceptible to carbapenems, aminoglycosides, and cefiderocol and aztreonam/avibactam due to a PBP3 YRIN insertion and the <i>bla</i>_CMY-145 AmpC β-lactamase. Coordinated surveillance efforts across civilian, military, and veteran healthcare systems are essential to prevent further spread as international volunteers return home after medical evacuation from Ukraine.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279669","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":"What makes <i>Candida auris</i> pan-drug resistant? Integrative insights from genomic, transcriptomic, and phenomic analysis of clinical strains resistant to all four major classes of antifungal drugs.","authors":"Johanna Rhodes, Jonathan Jacobs, Emily K Dennis, Swati R Manjari, Nilesh K Banavali, Robert Marlow, Mohammed Anower Rokebul, Sudha Chaturvedi, Vishnu Chaturvedi","doi":"10.1128/aac.00911-24","DOIUrl":"10.1128/aac.00911-24","url":null,"abstract":"<p><p>The global epidemic of drug-resistant <i>Candida auris</i> continues unabated. The initial report on pan-drug resistant (PDR) <i>C. auris</i> strains in a hospitalized patient in New York was unprecedented. PDR <i>C. auris</i> showed both known and unique mutations in the prominent gene targets of azoles, amphotericin B, echinocandins, and flucytosine. However, the factors that allow <i>C. auris</i> to acquire pan-drug resistance are not known. Therefore, we conducted a genomic, transcriptomic, and phenomic analysis to better understand PDR <i>C. auris</i>. Among 1,570 genetic variants in drug-resistant <i>C. auris</i>, 299 were unique to PDR strains. The whole-genome sequencing results suggested perturbations in genes associated with nucleotide biosynthesis, mRNA processing, and nuclear export of mRNA. Whole transcriptome sequencing of PDR <i>C. auris</i> revealed two genes to be significantly differentially expressed-a DNA repair protein and DNA replication-dependent chromatin assembly factor 1. Of 59 novel transcripts, 12 transcripts had no known homology. We observed no fitness defects among multi-drug resistant (MDR) and PDR <i>C. auris</i> strains grown in nutrient-deficient or -enriched media at different temperatures. Phenotypic profiling revealed wider adaptability to nitrogenous nutrients and increased utilization of substrates critical in upper glycolysis and tricarboxylic acid cycle. Structural modeling of a 33-amino acid deletion in the gene for uracil phosphoribosyl transferase suggested an alternate route in <i>C. auris</i> to generate uracil monophosphate that does not accommodate 5-fluorouracil as a substrate. Overall, we find evidence of metabolic adaptations in MDR and PDR <i>C. auris</i> in response to antifungal drug lethality without deleterious fitness costs.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279699","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":"Oxazolidinone antibiotics impair <i>ex vivo</i> megakaryocyte differentiation from hematopoietic progenitor cells and their maturation into platelets.","authors":"Tamara V Milosevic, Gaëlle Vertenoeil, William Vainchenker, Paul M Tulkens, Stefan N Constantinescu, Françoise Van Bambeke","doi":"10.1128/aac.00533-24","DOIUrl":"https://doi.org/10.1128/aac.00533-24","url":null,"abstract":"<p><p>Oxazolidinones (linezolid and tedizolid) adverse reactions include thrombocytopenia, the mechanism of which is still largely unknown. In cultured cells, oxazolidinones impair mitochondrial protein synthesis and oxidative metabolism. As mitochondrial activity is essential for megakaryocyte differentiation and maturation into platelets, we examined whether oxazolidinones impair these processes <i>ex vivo</i> and alter, in parallel, the activity of mitochondrial cytochrome <i>c</i>-oxidase (CYTOX; enzyme partly encoded by the mitochondrial genome) and cell morphology. Human CD34+ cells were isolated, incubated with cytokines (up to 14 days) and clinically relevant oxazolidinone concentrations or in control conditions, and used for (i) clonogenic assays [counting of megakaryocyte (CFU-Mk), granulocyte-monocyte (CFU-GM), burst-forming unit-erythroid (BFU-E) colonies]; (ii) the measure of the expression of megakaryocyte surface antigens (CD34 to CD41 and CD42); (iii) counting of proplatelets; (iv) the measurement of CYTOX activity; and (v) cell morphology (optic and electron microscopy). Oxazolidinones caused a significant decrease in BFU-E but not CFU-Mk or CFU-GM colonies. Yet, the megakaryocytic lineage was markedly affected, with a decreased differentiation of CD34+ into CD41+/CD42+ cells, an abolition of proplatelet formation and striking decrease in the numbers of large polylobulated nucleus megakaryocytes, with a complete loss of intracellular demarcation membrane system, disappearance of mitochondria, and suppression of CYTOX activity. These alterations were more marked in cells incubated with tedizolid than linezolid. These data suggest that oxazolidinones may induce thrombocytopenia by impairing megakaryocytic differentiation through mitochondrial dysfunction. Pharmacological interventions to prevent this toxicity might therefore be difficult as mitochondrial toxicity is most probably inherently linked to their antibacterial activity.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279697","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}