Journal of Antimicrobial Chemotherapy最新文献

{"title":"A retrospective observational cohort study of oral azithromycin treatment for Legionnaires' disease.","authors":"Lorna Pairman, Yong Tai Beh, Hannah Maher, Sharon J Gardiner, Paul Chin, Jonathan Williman, Stephen T Chambers","doi":"10.1093/jac/dkaf081","DOIUrl":"https://doi.org/10.1093/jac/dkaf081","url":null,"abstract":"<p><strong>Background: </strong>Legionnaires' disease (LD) is typically treated with macrolides, including the azalide azithromycin, or quinolones. In 2013, guidelines for empirical treatment of community-acquired pneumonia at Christchurch Hospital, New Zealand were changed to prioritize oral azithromycin over IV clarithromycin.</p><p><strong>Objectives: </strong>To determine whether the change in antimicrobial guidelines led to altered outcomes for patients subsequently confirmed to have LD.</p><p><strong>Methods: </strong>Patients with confirmed LD between 2010 and 2020 were identified from clinical and laboratory data. Hospital records were used to identify mortality, ICU admission, length of hospital stay, time to clinical stability, and time to first anti-Legionella treatment. Mean differences, risk ratios (RRs) and an interrupted time series with propensity adjustment were used to compare patient outcomes before and after the guideline change.</p><p><strong>Results: </strong>There were 323 patients included: 128 before and 195 after the change. Patient outcomes generally improved after the change including: mortality within 30 days (RR 0.4, 95% CI 0.2-0.8); ICU admission (RR 0.6, 95% CI 0.5-0.9); length of stay (difference -2.3 days, 95% CI -4.3 to -0.4); and time to clinical stability (difference -2.4 days, 95% CI -4.3 to -0.5). The interrupted time series analysis suggested improvements in patient outcomes may have occurred regardless of the guideline change.</p><p><strong>Conclusions: </strong>Outcomes for patients with LD were not worsened by the change in antimicrobial guidelines and may have improved. Overall rates of mortality were low. This result was reassuring given the harm that may result from unnecessary use of IV compared with oral antimicrobial agents.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673930","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 tear production of tecovirimat in a single hospitalized mpox patient: a pharmacokinetic analysis.","authors":"Stephen D Woolley, Iheukwumere Duru, Luca Pagano, Rebecca Lester, Karen Devine, Shazaad Ahmad, Raqib Huq, Suzanne Marshall, Danielle McLaughlan, Mark Lavery, Elizabeth Challenger, Laura J Else, Malcolm G Semple, Stephen Kaye, Saye H Khoo, Michael B J Beadsworth","doi":"10.1093/jac/dkaf071","DOIUrl":"https://doi.org/10.1093/jac/dkaf071","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669926","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":"Utilizing dried blood spot micro-sampling and population pharmacokinetic modelling and simulation to inform ampicillin dosing in Chinese neonates.","authors":"Jianmei Lv, Rao Li, Quanyao Chen, Yao Chen, Zhi Zheng, Xiaoyan Zhao, Huayan Chen, Feifan Xie","doi":"10.1093/jac/dkaf091","DOIUrl":"https://doi.org/10.1093/jac/dkaf091","url":null,"abstract":"<p><strong>Objectives: </strong>Ampicillin, a β-lactam antibiotic frequently prescribed for bacterial infections, is used off-label in neonates. Blood sampling limitations in neonatal pharmacokinetic (PK) studies make dried blood spots (DBS) a promising matrix for micro-sampling. This study aims to develop a population PK (PopPK) model using a DBS-based approach to optimize ampicillin dosing in Chinese neonatal patients.</p><p><strong>Methods: </strong>DBS samples were collected at predefined intervals from neonatal patients after ampicillin dosing. A PopPK model was developed using NONMEM 7.5, followed by model-based simulations to provide dosing recommendations in virtual population. During the simulations, the predicted blood concentrations were converted to unbound plasma concentrations using a blood-to-plasma ratio of 0.56 and an unbound fraction of 0.8. The PK/pharmacodynamic (PD) target was 100% of the time with the unbound drug plasma concentration above the MIC (%fT > MIC), and the risk of toxicity threshold was defined as a steady-state peak plasma concentration exceeding 140 mg/L.</p><p><strong>Results: </strong>Data from 53 patients with 102 DBS samples were collected, and the ranges of body weight and postmenstrual age (PMA) were 1.91-4.25 kg and 34.3-41.4 weeks, respectively. Ampicillin PK were characterized using a one-compartment model with first-order elimination. An allometric scaling and renal maturation model were integrated into the model to describe the developmental PK in hospitalized neonates. Simulations suggest that the optimal dosing regimen is 25 mg/kg administered intravenously every 6 h across PMA of 32-42 weeks.</p><p><strong>Conclusions: </strong>We successfully developed a PopPK model of ampicillin using DBS sampling for Chinese neonates and proposed evidence-based dosing recommendations.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669936","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":"Screening for carbapenemase-producing Enterobacterales (CPE)-considering the practical implications of molecular results, the value of culture and deciding criteria for resistance.","authors":"Mairead Skally, Jacqueline Cafferkey, Miriam Russell, Lynn Mcbrierty, Rincy Bijoy, Karen Burns, Kathleen Bennett, Hilary Humphreys, Fidelma Fitzpatrick","doi":"10.1093/jac/dkaf088","DOIUrl":"https://doi.org/10.1093/jac/dkaf088","url":null,"abstract":"<p><strong>Background: </strong>Carbapenemase-producing Enterobacterales (CPE) are of international concern. Screening for CPE can encompass single- or two-step approaches, using culture, PCR or a combination. Each approach has benefits, but none are without disadvantage.</p><p><strong>Objectives: </strong>To reflect on the challenges and implications of PCR-positive/culture-negative CPE screening results and assess if PCR cycle threshold (Ct) value can be helpful in predicting positive culture results.</p><p><strong>Patients and methods: </strong>Risk factor-based CPE screening swabs were tested using a two-step algorithm: PCR followed by culture of PCR-positive specimens. Data on all PCR-positive specimens between 1 August 2022 and 31 May 2024 were extracted. ORs were estimated using receiver operating characteristic (ROC) curves to compare Ct values and culture. Youden's index was calculated to establish the optimal Ct cut-off value. Compliance with the CPE screening pathway for newly identified CPE PCR-positive patients was assessed.</p><p><strong>Results: </strong>Of 61 268 CPE screens, 292 were PCR positive (0.5%), with 298 genes identified. Of these, 81.5% were culture confirmed. ROC analysis showed an AUC of 0.82 and Youden's index yielding a Ct cut-off value of 33.7. Repeat CPE screens were obtained from 33 new PCR-positive, culture-negative inpatients. Further investigation was not possible for 17 new PCR-positive, culture-negative patients (11%).</p><p><strong>Conclusions: </strong>Molecular platforms alone cannot detect species or antimicrobial resistance. A molecular-followed-by-culture algorithm can reduce workloads associated with culture, resulting in comprehensive data, including antimicrobial susceptibility results, to support informed clinical, policy and epidemiological decision-making.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656964","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":"Prophylaxis against Pneumocystis jirovecii pneumonia and toxoplasmosis with low-dose Trimethoprim-sulfamethoxazole (cotrimoxazole 20/100 mg) in heart transplant patients. The PAPTO-LOCO observational comparative study.","authors":"Dahlia Aggoun, Constance Verdonk, Alexandre Bleibtreu, Arnaud Fekkar, Sandrine Houze, Lara Zafrani, Eva Desire, Shaida Varnous, Pascal Leprince, Guillaume Coutance, Mickael Lescroart","doi":"10.1093/jac/dkaf087","DOIUrl":"https://doi.org/10.1093/jac/dkaf087","url":null,"abstract":"<p><strong>Objectives: </strong>Practice concerning post-transplant Pneumocystis prophylaxis remains heterogeneous. SXT benefits must be balanced with frequent toxicity. We aimed to assess whether a low-dose SXT strategy might limit toxicities while maintaining an undisrupted prophylaxis compared with a standard dose in a retrospective cohort of heart transplant population.</p><p><strong>Methods: </strong>Patients undergoing heart transplant from two distinct centres, receiving daily SXT 20/100 mg versus daily SXT 80/400 mg between 2018 and 2020, were retrospectively included in the study. Demographic, immunosuppression and survival characteristics were collected to ensure group comparability. The occurrence of adverse effects and the rate of SXT discontinuation were compared between the two groups.</p><p><strong>Results: </strong>Overall, 359 patients were recruited in the study, 108 patients for the standard-dose group and 251 patients for the low-dose group. The leading cause of prophylaxis discontinuation was cytopenia. We observed significantly more discontinuation in the standard-dose compared with the low-dose group (24.1% and 6.4%, respectively, P < 0.001). No patient with ongoing prophylaxis presented Pneumocystis pneumonia or toxoplasmosis during the 2-year follow-up. Two Pneumocystis infections in the low-dose group occurred during prophylaxis breaks. The rate of toxoplasmosis seroconversion was similar in both groups.</p><p><strong>Conclusions: </strong>This retrospective study suggests that a low-dose SXT Pneumocystis prophylaxis strategy might offer a more favourable safety/efficacy profile than standard-dose prophylaxis after heart transplantation. These results should be confirmed in an interventional trial. Caution remains for toxoplasmosis serology D+/R- profiles.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656963","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":"Correction to: Linezolid brain penetration in neurointensive care patients.","authors":"","doi":"10.1093/jac/dkaf099","DOIUrl":"https://doi.org/10.1093/jac/dkaf099","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657025","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":"First report of SME-carbapenemase-producing Serratia marcescens in France.","authors":"Manon Robert, Marion Leterrier-Plong, Leslie Bouard, Chloé Chantereau-Jansen, Laurent Dortet, Cécile Emeraud, Eve-Marie Takoudju","doi":"10.1093/jac/dkaf072","DOIUrl":"https://doi.org/10.1093/jac/dkaf072","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663617","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":"Ceftazidime-avibactam plus aztreonam cocktail for the treatment of VIM-producing Pseudomonas aeruginosa infections: good enough to have another?","authors":"Manuel Pina-Sánchez, Marta Rua, Carla López-Causapé, Idoia Bilbao, Miquel Àngel Sastre-Femenia, Antonio Oliver, José Luis Del Pozo","doi":"10.1093/jac/dkaf083","DOIUrl":"https://doi.org/10.1093/jac/dkaf083","url":null,"abstract":"<p><strong>Background: </strong>Few active antibiotic options are available to treat MBL-producing Pseudomonas aeruginosa infections, and some of these options are either poorly tolerated or have pharmacokinetic limitations. The use of aztreonam monotherapy for treating MBL-producing P. aeruginosa remains controversial due to the risk of selecting resistant mutants during treatment.</p><p><strong>Objectives: </strong>To describe the clinical outcomes of patients treated with ceftazidime-avibactam plus aztreonam for VIM-producing P. aeruginosa infections. The assessed outcomes include clinical success, clinical cure, all-cause mortality at day 28, combination therapy-associated adverse events, infection relapse and microbiological recurrence.</p><p><strong>Methods: </strong>This retrospective observational single-centre study was conducted at Clínica Universidad de Navarra, Pamplona, Spain. Eight patients with VIM-producing P. aeruginosa infections were included. Whole-genome sequencing of isolates was performed at Hospital Universitario Son Espases, Palma, Spain.</p><p><strong>Results: </strong>All isolates were susceptible to aztreonam and aztreonam-avibactam. No resistance mechanisms against these antibiotics were identified through whole-genome sequencing, except in one isolate that overexpressed the MexAB-OprM efflux pump. Clinical success and clinical cure were achieved in seven of eight patients, while all-cause mortality at day 28 was two of eight. Clinical cure was documented for five different infections and three distinct P. aeruginosa clones. No adverse events related to antibiotic therapy were reported, and no infection relapses occurred after treatment. Microbiological recurrence was observed in two cases.</p><p><strong>Conclusions: </strong>In our experience, patients with VIM-producing P. aeruginosa infections treated with ceftazidime-avibactam plus aztreonam mostly achieved clinical success. However, given the limited sample size, further research is required to validate these findings.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro susceptibility testing of vancomycin-resistant Enterococcus faecium to fosfomycin.","authors":"Stefano Mancini, Michael Greiner, Adrian Egli, Oliver Nolte","doi":"10.1093/jac/dkaf084","DOIUrl":"https://doi.org/10.1093/jac/dkaf084","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656961","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":"Exceedingly high levels of tetracycline resistance in Neisseria gonorrhoeae in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme countries in three WHO regions, 2021-2024-doxycycline post-exposure prophylaxis will unlikely impact gonorrhoea burdens.","authors":"Daniel Schröder, Thitima Cherdtrakulkiat, Le Huu Doanh, Daniel Golparian, Lon Say Heng, Irving Hoffman, Susanne Jacobsson, Manuel C Jamoralin, Francis Kakooza, Rossaphorn Kittiyaowamarn, Peter Kyambadde, Venessa Maseko, Mitch Matoga, Etienne Müller, Thuy Thi Phan Nguyen, Vichea Ouk, Vivi Setiawaty, Sonia B Sia, Verawati Sulaiman, Mot Virak, Nguyen Thi Thuy Van, Teodora Wi, Ismael Maatouk, Magnus Unemo","doi":"10.1093/jac/dkaf066","DOIUrl":"https://doi.org/10.1093/jac/dkaf066","url":null,"abstract":"<p><strong>Objectives: </strong>Doxycycline post-exposure prophylaxis (doxycycline-PEP) can reduce incident cases of syphilis, chlamydia and possibly gonorrhoea especially among men who have sex with men with recent bacterial sexually transmitted infections (STIs). Owing to potential implementation of doxycycline-PEP internationally, global tetracycline/doxycycline resistance data for contemporary Neisseria gonorrhoeae isolates has become imperative. We report tetracycline resistance data for gonococcal isolates (n = 2993) from eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) countries in three WHO regions in 2021-2024, i.e. to estimate potential impact of doxycycline-PEP on the incident gonorrhoea cases in these WHO EGASP countries.</p><p><strong>Methods: </strong>WHO EGASP isolates cultured from men with urethral discharge in Cambodia (n = 482), Indonesia (n = 101), Malawi (n = 121), The Philippines (n = 843), South Africa (n = 597), Thailand (n = 250), Uganda (n = 350) and Vietnam (n = 249) in 2021-2024 were examined. MICs (mg/L) of tetracycline were determined using Etest.</p><p><strong>Results: </strong>The tetracycline resistance (range) using the current EUCAST (MIC > 0.5 mg/L) and CLSI (MIC > 1 mg/L) clinical resistance breakpoints in the eight WHO EGASP countries was 92.2% (83.5%-99.6%) and 80.6% (66.3%-98.6%), respectively. Using a previous minocycline-PEP resistance breakpoint (MIC > 2 mg/L) and breakpoint for high-level plasmid (tetM)-mediated tetracycline resistance (MIC > 8 mg/L), the tetracycline resistance (range) was 77.3% (47.4%-98.6%) and 74.3% (31.3%-98.6%), respectively.</p><p><strong>Conclusions: </strong>The exceedingly high levels of gonococcal tetracycline resistance (independent of resistance breakpoint used) in the eight WHO EGASP countries elucidate that doxycycline-PEP will unlikely significantly reduce the gonorrhoea cases in these countries. Furthermore, doxycycline-PEP might rapidly select for additional gonococcal strains with tetracycline resistance (low- and high-level) and MDR/XDR strains, i.e. because these strains are mostly resistant to tetracycline.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657026","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}