Journal of Antimicrobial Chemotherapy最新文献

{"title":"Cefiderocol AST in a real-life Klebsiella pneumoniae collection: challenges in the ATU range.","authors":"Juan Antonio Castillo-Polo, Marta Hernández-García, Ainhize Maruri-Aransolo, María-Isabel Morosini, Patricia Ruiz-Garbajosa, Rafael Cantón","doi":"10.1093/jac/dkae477","DOIUrl":"https://doi.org/10.1093/jac/dkae477","url":null,"abstract":"<p><strong>Objectives: </strong>FDC susceptibility testing is challenging as none of the commercial tests have been proven to accurately determine the susceptibility in the area of technical uncertainty (ATU). Here, we evaluated the performance of different FDC testing methods on Klebsiella pneumoniae isolates around this range.</p><p><strong>Methods: </strong>A challenging collection of 104 K. pneumoniae isolates with different FDC susceptibility was designed, including high representation (70%) of the 2024-ATU (21-23 mm) ± 1 mm. MICs were determined by broth-microdilution (BMD) reference method, commercial BMD (ComASP®, EUMDROXF®), MIC-gradient strips (Liofilchem) and disk-diffusion (DD) (Liofilchem, ThermoFisher). MIC devices evaluation was performed following ISO 20776-2:2021, calculating essential agreement (EA) and bias. DD results were evaluated following 2023 and 2024-EUCAST-guidelines, calculating major errors (ME) and very major errors. Categorical agreement (CA) was determined for all the methods.</p><p><strong>Results: </strong>Overall, EUMDROXF® and ComASP® showed 81.7% (95% CI = 72.9-88.6) and 88.5% (95% CI = 80.8-93.9) EA, +2.6% and +27.9% bias and 99.0% (95% CI = 94.7-99.9) and 98.1% (95% CI = 93.3-99.8) CA, respectively. Liofilchem MIC-gradient strips exhibited 47.1% (95% CI = 37.2-57.1) EA, +2.9% bias and 93.3% (95% CI = 86.7-97.3) CA. In DD, variability between manufacturers was elevated. CA lowered and ME increased more than 10% with 2024-EUCAST-breakpoints modification.</p><p><strong>Conclusions: </strong>DD performance was insufficient to assess FDC resistance in K. pneumoniae and modification of EUCAST-breakpoints did not solve the problem. ComASP® panel fulfilled ISO criteria and could be used as MIC-confirmatory method, at least in K. pneumoniae. However, EUMDROXF®, even close, did not fulfil the EA criterion. MIC-gradient strips exhibited major limitations.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983677","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":"Reply: prolonged sitafloxacin and doxycycline combination regimen for treating infections by highly resistant Mycoplasma genitalium.","authors":"Naokatsu Ando, Daisuke Mizushima, Hiroyuki Gatanaga","doi":"10.1093/jac/dkaf001","DOIUrl":"https://doi.org/10.1093/jac/dkaf001","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983681","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":"No virological failure in patients living with HIV with past NNRTI resistance-associated mutations switched to doravirine-containing regimens.","authors":"B Abdi, S Saliba, M Wirden, A Faycal, T Cocherie, R Palich, L Schneider, S Seang, M A Valantin, V Pourcher, V Calvez, A Marcelin, C Katlama","doi":"10.1093/jac/dkae481","DOIUrl":"https://doi.org/10.1093/jac/dkae481","url":null,"abstract":"<p><strong>Background: </strong>Doravirine is licensed in patients living with HIV (PWH) harbouring no prior resistance to any NNRTIs. We aimed to evaluate in real life the efficacy of doravirine with prior NNRTI virological failure and NNRTI resistance-associated mutations (RAMs).</p><p><strong>Methods: </strong>This observational study included PWH switched to a doravirine-containing regimen between 30 September 2019 and 1 May 2022, with an HIV-1 RNA of ≤50 copies/mL and past NNRTI-RAMs. The main outcome was the proportion of participants with virological failure at Week 48 and Week 96. Secondary outcomes evaluated the rate of viral suppression and transient virological blip, RAMs in the case of virological failure and side effects.</p><p><strong>Results: </strong>A total of 102 patients were analysed, mostly men (63%), with a median age of 59 years (IQR 51-63). The median time since HIV-1 diagnosis was 26 years (IQR 16-31), on ART for 22 years (IQR 14-26) and virally suppressed for 7 years (IQR 1-11).Of the patients analysed, 25/102 (25%) had documented historical RAMs to doravirine, 9/25 (36%) showing possible resistance and 16/25 (64%) showing major resistance. The resistance profile primarily (21/23) consisted of the K103N, Y181C and/or G190A/E reverse transcriptase substitutions. Median time since the last detection of NNRTI-RAMs was 12 years (5-17). Over 2 years follow-up, no virological failure occurred, neither at Week 48 (0/87; 0%) nor Week 96 (0/86; 0%).</p><p><strong>Conclusions: </strong>This is the first real-world study to provide new insight about the use of doravirine-containing regimens as a treatment in long-term suppressed patients whose viruses harboured specific NNRTI-RAMs in their history.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983679","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":"Quantification of maternal and fetal valaciclovir exposure in a pharmacokinetic study of cytomegalovirus-infected pregnant women treated to prevent vertical transmission.","authors":"Valentine Faure-Bardon, Naïm Bouazza, Sihem Benaboud, Frantz Foissac, Steeve Rouillon, Léo Froelicher-Bournaud, Marianne Leruez-Ville, Tiffany Guilleminot, Gabrielle Lui, Jean-Marc Tréluyer, Yves Ville","doi":"10.1093/jac/dkae470","DOIUrl":"https://doi.org/10.1093/jac/dkae470","url":null,"abstract":"<p><strong>Background: </strong>In cases of maternal primary infection with cytomegalovirus (CMV-MPI) maternal treatment with oral valaciclovir 8 g/day has been shown to reduce the risk of fetal infection. The pharmacological profile of this high dosage during pregnancy is not yet known.</p><p><strong>Objectives: </strong>To quantify maternal-fetal exposure to valaciclovir 8 g/day in a population pharmacokinetic (popPK) study.</p><p><strong>Methods: </strong>Between October 2019 and April 2023, pregnant women referred for CMV-MPI were offered to participate following: (i) CMV-MPI <14 weeks of gestation; (ii) acceptance of valaciclovir 8 g/day; and (iii) consent for amniocentesis. Amniotic fluid was tested for (i) CMV PCR for prenatal diagnosis; and (ii) dosage of aciclovir concentration (the active form of valaciclovir). Maternal serum levels of aciclovir were also measured. Aciclovir assays in both compartments were used for popPK analysis. Pharmacokinetics were described using non-linear mixed-effect modelling.</p><p><strong>Results: </strong>We prospectively included 119 women with their 122 fetuses. CMV-MPI occurred at a median of 3.0 (range: -12; + 14) weeks of gestation. CMV-infected pregnant women were treated at a median of 12.3 (range: 4.6-21.4) weeks of gestation for a median duration of 35 days (range: 7-90 days). Median pharmacokinetic parameters (Cmin, Cmax and AUC0-24) were all successfully defined in both maternal blood and amniotic fluid compartments. No differences in aciclovir exposure were observed between infected (n = 12, 9.8%) and non-infected fetuses. Simulations showed that after a last maternal dose, aciclovir concentration would be undetectable in the amniotic fluid after 43-47 h.</p><p><strong>Conclusions: </strong>In this popPK study, maternal and fetal pharmacokinetics were established using in vivo data. The results provide a better understanding of how this fetal therapy works.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983680","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 scoring system to predict resistance to ceftolozane/tazobactam in respiratory isolates of Pseudomonas aeruginosa.","authors":"Eda Karadogan, Ahmet Sertcelik, Gulcin Telli Dizman, Hanife Uzar, Gulsen Hazirolan, Banu Cakir, Gokhan Metan","doi":"10.1093/jac/dkae476","DOIUrl":"https://doi.org/10.1093/jac/dkae476","url":null,"abstract":"<p><strong>Objectives: </strong>To develop a scoring system to predict resistance to ceftolozane/tazobactam in Pseudomonas aeruginosa strains isolated from respiratory specimens.</p><p><strong>Methods: </strong>A case-control study was conducted to evaluate the risk factors associated with resistance to ceftolozane/tazobactam. Patients with P. aeruginosa were defined as cases if they had ceftolozane/tazobactam-resistant strains, whereas those with ceftolozane/tazobactam-susceptible strains were defined as test-negative controls. A predictive scoring system based on binary logistic regression coefficients was formulated to predict resistance to ceftolozane/tazobactam. The score's performance was assessed using ROC curves and AUC. The sensitivity, specificity and predictive values of the score were determined on the basis of a cut-off point, using the Youden index.</p><p><strong>Results: </strong>Ceftolozane/tazobactam resistance was detected in 18.4% of P. aeruginosa isolates from 473 patients. In multivariate analysis, a history of bronchoscopy [OR (95% CI) = 2.1 (1.1-4.3), P = 0.035], invasive mechanical ventilation [OR (95% CI) = 2.4 (1.2-4.5), P = 0.009], colistin/polymyxin B use [OR (95% CI) = 3.2 (1.8-5.7), P < 0.001] and fluoroquinolone use [OR (95% CI) = 2.3 (1.1-4.8), P = 0.024] in the preceding month prior to P. aeruginosa isolation were significantly associated with ceftolozane/tazobactam resistance. The AUC (95% CI) of the score was 0.734 (0.675-0.794), with a sensitivity of 69%, specificity of 71.8%, positive predictive value of 35.5% and negative predictive value of 91.1% at the cut-off point of 2, out of a range of 0-5.</p><p><strong>Conclusions: </strong>In respiratory tract infections caused by P. aeruginosa, use of the proposed scoring system may reduce inappropriate use of ceftolozane/tazobactam in empirical treatment.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983676","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":"Navigating the complexities of azole antifungal therapy through pharmacokinetic concepts: a case of prolonged isavuconazole toxicity.","authors":"Manon Launay, Florian Saunier, Sarah Baklouti, Marlène Damin-Pernik, Aurélien Millet, Peggy Gandia, Elisabeth Botelho-Nevers","doi":"10.1093/jac/dkae439","DOIUrl":"https://doi.org/10.1093/jac/dkae439","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983678","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":"Pharmacodynamics of NOSO-502 studied in vitro and in vivo: determination of the dominant pharmacodynamic index driver.","authors":"Sanne van den Berg, Marie G L Attwood, Pippa Griffin, Sebastiaan D T Sassen, Anouk E Muller, Merel N Raaphorst, Maxime Gualtieri, Emilie Racine, Shampa Das, Alan R Noel, Joseph Meletiadis, Alasdair P MacGowan","doi":"10.1093/jac/dkae469","DOIUrl":"https://doi.org/10.1093/jac/dkae469","url":null,"abstract":"<p><strong>Background: </strong>NOSO-5O2 is the first clinical candidate of a new antimicrobial class-the odilorhabdins. The pharmacodynamics of NOSO-502 were studied in vitro and in vivo to establish the pharmacodynamic index (PDI) driver.</p><p><strong>Methods: </strong>A dilutional pharmacokinetic system was used for in vitro experiments. In vivo experiments were conducted in the neutropenic murine thigh infection model. Three Escherichia coli and two Klebsiella pneumoniae strains were used. NOSO-502 pharmacokinetics (PK) in mice were described in a population PK model. Dose fractionation and escalation exposures were performed and bacteriostatic and 1 log10 and 2 log10 kill effects were determined using an Emax model. The coefficient of determination (R2) was used to estimate the variance that might be due to regression with various PDIs (fAUC/MIC, fCmax/MIC, %fT>MIC and fAUC/MIC per length of dosing interval fAUC/MIC·1/tau).</p><p><strong>Results: </strong>Exposure fractionation in both in vitro and in vivo studies indicated that 6-hourly dosing resulted in a greater reduction in K. pneumoniae bacterial burden compared with either 12- or 24-hourly dosing. Similar observations were made with three E. coli strains in vitro and a single strain of E. coli in vivo. For K. pneumoniae, R2 for fAUC/MIC·1/tau was 0.8376 in vitro and 0.6001 in vivo, which was greater than R2 with other PDIs. Analysis of pooled in vitro data from three strains of E. coli produced an R2 of 0.7073 for fAUC/MIC and 0.6100 for fAUC/MIC·1/tau.</p><p><strong>Conclusions: </strong>NOSO-502 exhibits both dose- and time-dependent in vitro and in vivo activity against both E. coli and K. pneumoniae.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970905","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":"Efficacy and safety of antiviral therapies for the treatment of persistent COVID-19 in immunocompromised patients since the Omicron surge: a systematic review.","authors":"Caroline Hirsch, Nina Kreuzberger, Nicole Skoetz, Ina Monsef, Stefan Kluge, Christoph D Spinner, Jakob J Malin","doi":"10.1093/jac/dkae482","DOIUrl":"https://doi.org/10.1093/jac/dkae482","url":null,"abstract":"<p><strong>Background: </strong>Persistent COVID-19 (pCOVID-19) in immunocompromised patients is characterized by unspecific symptoms and pulmonary infiltrates due to ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication. Treatment options remain unclear, leading to different approaches, including combination therapy and extended durations. The purpose of this study was to assess the efficacy and safety of antiviral therapies for pCOVID-19 in immunocompromised patients since the Omicron surge.</p><p><strong>Methods: </strong>We searched MEDLINE and Scopus from 1 January 2022 to 6 August 2024 for cohort studies and case series on nirmatrelvir/ritonavir, remdesivir, ensitrelvir and molnupiravir. Evidence certainty was rated using Grading of Recommendations Assessment, Development, and Evaluation for outcomes including viral clearance, recurrence/relapse, mortality, adverse events (AEs) and symptom resolution.</p><p><strong>Results: </strong>Thirteen studies involving 127 cases were included. Evidence certainty was very low. In combination therapy with at least two direct antiviral agents, viral clearance was 79%, with a 16% recurrence rate. All-cause mortality was 9%, and mortality was 6% while SARS-CoV-2 positive. In 47 cases, AEs were reported in 11%. Symptom resolution ranged from 3 to 6 days in two studies. In combination therapy with one direct antiviral agent and passive immunization, viral clearance was 89%, with an 11% recurrence rate and no deaths. In four documented cases, no AEs were observed. In monotherapy, viral clearance was 100%, with a 15% recurrence rate. One death, unrelated to SARS-CoV-2, occurred. In 12 documented cases, no AEs were observed.</p><p><strong>Conclusions: </strong>Based on very low certainty evidence, combining one direct antiviral with passive immunization resulted in high rates of viral clearance and few recurrences. AEs occurred in cases treated with at least two direct antivirals. Controlled studies are needed.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970895","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":"Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-omicron or omicron variants: a modelling analysis of the randomized DisCoVeRy trial-authors' response.","authors":"Maxime Beaulieu, Jérémie Guedj","doi":"10.1093/jac/dkae447","DOIUrl":"https://doi.org/10.1093/jac/dkae447","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970886","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":"Comparison of the immunological and virological responses to cART between HIV-1/O and HIV-1/M patients followed up in France.","authors":"Guillemette Unal, Rémonie Seng, Elodie Alessandri-Gradt, Lorraine Plessis, Mathilde Ghislain, Cécile Goujard, Marie Leoz, Jean-Christophe Plantier, Laurence Meyer","doi":"10.1093/jac/dkae475","DOIUrl":"https://doi.org/10.1093/jac/dkae475","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic outcomes for patients infected by genetically divergent HIV-1/O are not well-known due to scarce data and the lack of an appropriate comparison with patients infected by pandemic HIV-1/M. We aimed to compare the immunological and virological response to cART between HIV-1/O and HIV-1/M patients followed in France.</p><p><strong>Methods: </strong>All naïve HIV-1/O subjects initiating cART in France in ANRS-ORIVAO study were compared to naïve HIV-1/M subjects initiating cART in ANRS-COPANA cohort. Piecewise linear mixed-effect models and Kaplan-Meier survival curves were used to analyse immunological and virological response to cART overall (65 HIV-1/O versus 279 HIV-1/M), then only in patients initiating 2INTI + 1PI/r.</p><p><strong>Results: </strong>Plasma viral load (pVL) at treatment initiation was 0.6 log10 copies/mL lower in HIV-1/O than in HIV-1/M patients (P = 0.004) in the overall population, but there was no difference in the time to pVL < 200 cp/mL after cART initiation (log rank test, P = 0.57). Meanwhile, baseline CD4 counts were lower in HIV-1/O (median 180/mm3) than HIV-1/M (248/mm3) patients (P = 0.001). At 4 months, the increase in CD4 counts did not differ (P = 0.96) between groups but remained lower in HIV-1/O patients beyond 4 months of treatment (P = 0.04).In PI/r population, baseline pVL was 1 log10 copies/mL lower for HIV-1/O than HIV-1/M patients, leading to significantly faster attainment of pVL < 200 cp/mL (log rank test: P < 0.001); immunological response to cART was similar.</p><p><strong>Conclusions: </strong>HIV-1/O and HIV-1/M immunological and virological responses to cART did not differ when epidemiological characteristics of the patients were taken into account. In France, treating HIV-1/O following HIV-1/M guidelines leads to similar therapeutic outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970889","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}