Journal of Antimicrobial Chemotherapy最新文献

{"title":"Placental transfer of medications to treat COVID-19, molnupiravir, favipiravir and nirmatrelvir/ritonavir, in the ex vivo human cotyledon model.","authors":"Solene Labaye, Fatima Djellali, Gilles Peytavin, Laurent Mandelbrot","doi":"10.1093/jac/dkaf302","DOIUrl":"10.1093/jac/dkaf302","url":null,"abstract":"<p><strong>Objectives: </strong>There have been few studies in pregnant women of medications that are used to reduce severe complications from COVID-19 infection. Currently, nirmatrelvir/ritonavir (Paxlovid) is recommended by the National Institutes for Health to treat non-hospitalized pregnant patients with mild-to-moderate COVID-19 illness. The aim of this study was to determine the transplacental passage of molnupiravir, nirmatrelvir/ritonavir and favipiravir utilizing an ex vivo placental perfusion model.</p><p><strong>Methods: </strong>Human placental cotyledons were continuously perfused in a double open circuit. The study molecules and antipyrine, a marker of placental viability, were dissolved in the maternal solution. The experiment was conducted over 90 minutes, and every 5 minutes, samples of the maternal solution and fetal exchange solutions were collected for analysis. We calculated the concentrations of study molecules, fetal transfer ratios and the clearance indexes to determine placental transfer.</p><p><strong>Results: </strong>Of 18 placentas analysed, 14 were validated by antipyrine transfer. Nirmatrelvir alone had low placental transfer, with a fetal transfer ratio of 0.025. Its placenta transfer increased in the presence of ritonavir, with a fetal transfer ratio of 0.06. The molnupiravir metabolite, β-D-N-4-hydroxycytidine (EIDD 1931), showed low placental transfer, with an average fetal transfer ratio of 0.04. By contrast, favipiravir crossed the placenta with an average fetal transfer ratio of 0.425.</p><p><strong>Conclusions: </strong>Placental transfer was high for the nucleoside analogue favipiravir, while it was low for molnupiravir and low for the protease inhibitor nirmatrelvir but increased by ritonavir. Clinical data are required to confirm the placental transfer and determine the safety of COVID antivirals in pregnancy.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2807-2813"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955136","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":"Rifampicin concentrations throughout the entire treatment duration of active tuberculosis; impact of sex and body mass index.","authors":"Teres Samuelsson, Elisabet Lönnermark, Jesper Sundell, Aylin Yilmaz","doi":"10.1093/jac/dkaf300","DOIUrl":"10.1093/jac/dkaf300","url":null,"abstract":"<p><strong>Objectives: </strong>Rifampicin is a crucial part of an effective tuberculosis (TB) treatment. It has complicated pharmacokinetics (PK) with auto-induction and nonlinearity. Our objectives were to examine rifampicin concentrations throughout the entire treatment duration in individuals with active TB and to determine correlations between rifampicin concentrations, sex at birth, and body mass index (BMI).</p><p><strong>Methods: </strong>We measured concentrations at 2-3 h post-dose (C2h) in an attempt to capture peak concentrations of rifampicin at treatment weeks 2, 4, 8, and subsequently every fourth week throughout the treatment period in patients with active TB. Linear mixed modelling was performed to analyse correlations between rifampicin concentration, week of treatment, sex at birth, and BMI.</p><p><strong>Results: </strong>Forty-two participants were included, resulting in a total of 230 rifampicin concentration measurements. The intra-individual concentrations varied substantially throughout treatment but there was no correlation between week of treatment and rifampicin concentration. The concentration levels were significantly lower in men than in women, median difference -4.3 µg/mL (P < 0.001), median dose 13 mg/kg. Over time, women had a trend of decreasing concentrations and men an increasing trend. Underweight patients had significantly lower concentrations than normal weight individuals, median difference -4.1 µg/mL (P = 0.002). Rifampicin concentrations were below the recommended level of 8 µg/mL in 35/206 measurements (17%). No relapses occurred during 6 months of follow-up.</p><p><strong>Conclusions: </strong>We found no significant changes in rifampicin concentrations during TB treatment. Both sex and BMI were associated with rifampicin concentrations.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2790-2798"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955249","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":"The catA1 chloramphenicol resistance gene originated in Atlantibacter hermannii.","authors":"Robert A Moran, Ruth M Hall","doi":"10.1093/jac/dkaf227","DOIUrl":"10.1093/jac/dkaf227","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2874-2876"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608409","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":"In vitro activity of thiamphenicol against drug-susceptible and drug-resistant strains of Mycoplasma genitalium.","authors":"Sofie Skovmand, Christina Nørgaard, Kirsten Salado-Rasmussen, Jørgen Skov Jensen","doi":"10.1093/jac/dkaf272","DOIUrl":"10.1093/jac/dkaf272","url":null,"abstract":"<p><strong>Objectives: </strong>Mycoplasma genitalium causes a range of urogenital infections. It is inherently resistant to beta-lactam antibiotics, and the first and second-line treatments recommended are azithromycin and moxifloxacin, respectively. However, resistance towards these drugs is rising, and third-line treatment options exhibit cure rates between 40% and 80%. Thiamphenicol, a chloramphenicol analogue, is excreted unchanged in the urine in high concentrations and has previously successfully treated uncomplicated gonorrhoea. This study aimed to test the in vitro activity of thiamphenicol in a collection of M. genitalium strains with various resistance patterns and to exclude antagonism between thiamphenicol and doxycycline.</p><p><strong>Methods: </strong>Fifty-three strains of M. genitalium were tested for macrolide resistance mutations in the 23S rRNA gene and quinolone resistance-associated mutations in the parC gene. MICs of thiamphenicol, doxycycline, azithromycin, and moxifloxacin were determined using Vero cell cultures followed by quantitative PCR. A chequerboard analysis was performed to exclude antagonism between thiamphenicol and doxycycline in four isolates of M. genitalium.</p><p><strong>Results: </strong>The thiamphenicol MICs ranged from 1 to 64 mg/L with a median of 8 mg/L, and 94% (n = 50) of the strains had a thiamphenicol MIC ≤ 16 mg/L. Resistance to macrolides, quinolones, and dual-class resistance did not affect the MIC levels of thiamphenicol. The chequerboard analysis excluded antagonism in all four isolates and indicated a synergistic effect in one isolate.</p><p><strong>Conclusions: </strong>Our study offered encouraging results on the therapeutic potential of thiamphenicol for M. genitalium infections. The possible synergistic relationship between thiamphenicol and doxycycline encourages further studies.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2676-2681"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835188","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":"Risk-benefit balance of blood cultures among patients with stage IV cancer in unplanned admission: a nationwide propensity score-weighted study in Japan.","authors":"Yuki Hashimoto, Norihiko Inoue, Takuaki Tani, Shinobu Imai","doi":"10.1093/jac/dkaf368","DOIUrl":"https://doi.org/10.1093/jac/dkaf368","url":null,"abstract":"<p><strong>Objectives: </strong>Infection commonly causes unplanned admission in patients with stage IV cancer; however, the risk-benefit balance of blood cultures remains unclear. We evaluated clinical outcomes of blood culture among patients with stage IV cancer in unplanned admission.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study across Japan (April 2016 to March 2023). Patients with stage IV solid cancer receiving IV antimicrobials in unplanned admission were divided into blood culture (BC) and no blood culture (NC) groups. After overlap propensity score weighting, we compared mortality, functional disability, length of stay from antimicrobial initiation to discharge (LOS), and total hospitalization costs. Mortality risk was assessed using modified Poisson regression. Interaction tests were used to evaluate subgroup differences. Composite outcomes (mortality and functional disability) were assessed using a win-ratio approach (a hierarchical comparison of outcomes, prioritizing mortality over functional status).</p><p><strong>Results: </strong>Among 10 915 patients (BC: 4029, NC: 6886), mortality was lower in the BC than the NC group (23.9% versus 29.2%; risk ratio: 0.81; 95% CI, 0.75-0.88). Mortality reduction was significantly greater in patients with prior chemotherapy or immunosuppressive agents. Composite outcomes were more favourable in the BC than the NC group (win ratio: 1.22; 95% CI, 1.13-1.32). However, BCs were associated with longer LOS (1.0 days; 95% CI, 0.0-1.9) and higher hospitalization costs (345.0 USD; 95% CI, 72.5-628.1).</p><p><strong>Conclusions: </strong>BCs were associated with reduced mortality in patients with stage IV cancer, particularly those with immunosuppression. These findings may support personalized decision-making and resource allocation.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212338","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":"Comment on: Outcomes of ceftriaxone 2 g versus 1 g daily in hospitalized patients with pneumonia: a nationwide retrospective cohort study.","authors":"Giancarlo Ceccarelli, Gabriella d'Ettorre, Alberto Enrico Maraolo","doi":"10.1093/jac/dkaf326","DOIUrl":"https://doi.org/10.1093/jac/dkaf326","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"80 10","pages":"2884-2885"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225430","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 priori optimization of levofloxacin dose regimen based on a population pharmacokinetics model.","authors":"Emmanuel Enard, Matthieu Grégoire, Éric Dailly, Ronan Le Floch, Karim Lakhal, Antoine Roquilly, Emmanuel Canet, David Boutoille, Louise Ruffier d'Epenoux, Stéphane Corvec, Raphaël Lecomte, Ronan Bellouard","doi":"10.1093/jac/dkaf273","DOIUrl":"10.1093/jac/dkaf273","url":null,"abstract":"<p><strong>Background: </strong>Levofloxacin is a broad-spectrum fluoroquinolone with pharmacokinetic characteristics that facilitate its use in many types of infections.</p><p><strong>Objectives: </strong>To develop a population pharmacokinetics (PK) model of levofloxacin and to identify covariates influencing its PK, to determine the best dose regimens for pharmacodynamic target achievement.</p><p><strong>Patients and methods: </strong>Patients treated with levofloxacin were retrospectively included from December 2014 to February 2021. The population PK analysis was performed using Pmetrics. Multiple covariates were tested: age, height, weight, ideal weight, BMI, body surface area (BSA), plasma protein and creatinine levels, and absolute glomerular filtration rate (aGFR) calculated from the chronic kidney disease-epidemiology formula and BSA. Dosing simulations were performed for all combinations of covariates and MIC values. The AUC0-24/MIC ratio targets were 50 for Streptococcus pneumoniae and 125 for other bacterial species.</p><p><strong>Results: </strong>A total of 39 patients were included, of which 23 patients were hospitalized in ICUs. The population PK analysis was performed on 175 plasma concentrations of levofloxacin. A two-compartment model best described levofloxacin PK with three covariates: aGFR for the elimination rate constant and both plasma protein level and BSA for the central compartment volume. Tables with proposed dose regimens according to patient covariates and pharmacodynamic targets values are provided.</p><p><strong>Conclusions: </strong>This study provided a priori dose regimen adaptation based on a population PK model for levofloxacin. For patients with increased renal function or infection by high MIC bacteria, the pharmacodynamic target could not be reliably achieved with standard dosages.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2682-2692"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835182","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":"Cefixime versus benzathine penicillin G for the treatment of early syphilis-a randomized, controlled open label trial.","authors":"Tamara Klementová, Hana Zákoucká, Beatrice Bížová, Magnus Unemo, Filip Rob","doi":"10.1093/jac/dkaf268","DOIUrl":"10.1093/jac/dkaf268","url":null,"abstract":"<p><strong>Objectives: </strong>Cefixime is a promising oral treatment alternative for early syphilis but only very limited efficacy data exist. We evaluated the efficacy and safety of cefixime for the treatment of early syphilis.</p><p><strong>Methods: </strong>A randomized controlled, open label trial in patients with confirmed early syphilis who were randomized to treatment with cefixime 400 mg orally twice a day for 14 consecutive days or to a single dose of benzathine penicillin G (BPG) 2.4 MIU intramuscular. The outcome was a 4-fold or more (≥2 dilution steps) decrease in Venereal Disease Research Laboratory test (VDRL) titre from baseline to 3 months (primary outcome) or 12 months (secondary outcome) after the treatment.</p><p><strong>Results: </strong>Of 61 randomized patients, 58 (95.1%) completed the study (28 patients in the cefixime arm and 30 in the BPG arm). In the intention to treat analysis, the primary endpoint was achieved after 3 months in 22 of 30 (73.3%) of patients in the cefixime arm and 27 of 31 (87.1%) in the BPG arm, and after 12 months in 28 of 30 (93.3%) of patients in the cefixime arm and 30 of 31 (96.8%) of patients in the BPG arm. Both treatments were well tolerated and no serious adverse events or adverse events with severe intensity were reported.</p><p><strong>Conclusions: </strong>The results from our study are consistent with current limited knowledge and suggest that oral cefixime can be an effective and safe therapy for the treatment of early syphilis. However, additional efficacy data from larger treatment studies are imperative.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2654-2658"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835183","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":"Uptake of drug-reduced antiretroviral strategies and impact on costs over 2015-22: experience from an HIV clinic in Paris, France.","authors":"L Sagaon-Teyssier, A Eremin, M A Valantin, A Fauchois, R Tubiana, S Seang, L Schneider, A Fayçal, S Saliba, M Wirden, C Soulié, G Peytavin, V Pourcher, R Agher, R Palich, C Katlama","doi":"10.1093/jac/dkaf307","DOIUrl":"10.1093/jac/dkaf307","url":null,"abstract":"<p><strong>Background: </strong>While current HIV care includes drug-reduced antiretroviral strategies, intermittent therapy, recently recommended in France, could benefit from further evaluation in real-life clinical practice.</p><p><strong>Objectives: </strong>To evaluate the uptake, efficacy and cost impact of drug-reduced antiretroviral strategies (DRS) in a large HIV clinic in Paris.</p><p><strong>Methods: </strong>This retrospective study included all virally suppressed adult individuals living with HIV treated at our clinic from 2015 to 2022, on three-drug (3-DR) or two-drug (2-DR) daily regimens, with ≥1 clinical and viral load assessment recorded per year. We defined DRS as either 2-DR or intermittent oral regimen (4 or 5 days weekly). Main outcomes included DRS uptake, factors associated with DRS prescription, virological failure (VF) by ART strategy and costs.</p><p><strong>Findings: </strong>We analysed 2170 individuals (median age: 50.6, viral suppression: 6.0 years) on daily 3-DR (77.5%) and 2-DR (22.5%). Over 8 years, 1048 participants (48.3%) switched to a DRS that consisted of intermittent ART (ART-I) in 580 participants and a 2-DR in 442 participants. The VF rate was 11.2% for 3-DR, 5.3% for 2-DR and 1.8% for intermittent ART. Overall, in 2022, 1184 participants (54.6%) were receiving a DRS. Average yearly cost of HIV care per participant dropped from €15 687 in 2015 to €7437 in 2022, with per-participant costs of €7643 for 3-DR, €8869 for 2-DR and €3388 for ART-I.</p><p><strong>Conclusions: </strong>Drug-reduced ART regimens were prescribed to over half of the study population. Intermittent regimens, widely used in our setting, are highly effective and cost-saving, and deserve to be evaluated for implementation, particularly in resource-constrained contexts.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2825-2833"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955227","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":"Effectiveness of piperacillin/tazobactam loading dose for extended infusion dosing among patients with Gram-negative bacteraemia.","authors":"Savan Patel, Sana Mohayya, Arsheena Yassin, Judy Dao, Emily Aboujaoude, Pinki J Bhatt, Ahmed Abdul Azim, Keith S Kaye, Nathaniel J Rhodes, Marc H Scheetz, Navaneeth Narayanan","doi":"10.1093/jac/dkaf259","DOIUrl":"10.1093/jac/dkaf259","url":null,"abstract":"<p><strong>Objective: </strong>To examine the effect of a loading dose (LD) for extended infusion piperacillin/tazobactam on clinical outcomes.</p><p><strong>Methods: </strong>This single-centre, retrospective cohort study evaluated adult patients with Gram-negative bacteraemia who received extended infusion piperacillin/tazobactam for ≥48 hours between 2015 and 2022. In December 2019, the study institution developed a policy that automatically ordered a piperacillin/tazobactam LD whenever piperacillin/tazobactam was prescribed. The study compared patients who received piperacillin/tazobactam LD to those who did not. The primary endpoint was 30-day all-cause mortality. Key secondary endpoints included clinical cure, 14-day all-cause mortality, in-hospital all-cause mortality and microbiologic cure. Logistic regression modelling was performed to control for confounding variables.</p><p><strong>Results: </strong>A total of 151 patients were included in the analysis, with 84 patients in the LD group and 67 patients in the no LD group. Baseline characteristics were similar in both treatment groups, except for immunocompromised status, severity of illness and serum creatinine, with most mortality prognosticators in the LD group. In the bivariate analysis, 30-day mortality was 10.7% (9/84) in the LD group compared to 9.0% (6/67) in the no LD group (P = 0.72). This was consistent with the multivariable logistic regression model (adjusted OR, 0.71; 95% CI, 0.21-2.41).</p><p><strong>Conclusions: </strong>Overall, we observed no significant association between LD for extended infusion piperacillin/tazobactam and mortality, and no signal that use of LD was associated with more adverse events. We hypothesize a potential benefit of LD administration for severely ill patients, but larger adequately powered prospective cohorts or randomized trials are needed to examine this.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2635-2643"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775433","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}