Fariba M Donovan, Omar Marín Fernández, Gurjinder Bains, Lisa DiPompo
{"title":"Coccidioidomycosis: a growing global concern.","authors":"Fariba M Donovan, Omar Marín Fernández, Gurjinder Bains, Lisa DiPompo","doi":"10.1093/jac/dkaf002","DOIUrl":"10.1093/jac/dkaf002","url":null,"abstract":"<p><p>Coccidioidomycosis (CM) has been a recognized disease for about 130 years. The organisms (Coccidioides spp. fungi) inhabit desert soil in the southwestern USA, Mexico, and parts of Central and South America. Natural events such as dust storms, wildfires or outdoor activities including construction and gardening can disrupt the fungal arthroconidia, which easily become airborne and inhaled by the host. Approximately 60% of those exposed to arthroconidia are asymptomatic and do not require medical attention, but 30% show signs of pulmonary infection with symptoms ranging from a flu-like illness to pneumonia. In 5%-10% of cases serious or disseminated disease develops, which requires prompt diagnosis and management. About 1%-3% of infections disseminate to the CNS and if not appropriately treated are often fatal. There is an urgent need for improved diagnostics and treatments.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"80 Supplement_1","pages":"i40-i49"},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630455","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}
Nidhi Singh, Bikash Dangi, Jeremy J Johnson, Arnold Louie, Arunkumar Karunanidhi, Brooke N Curry, Satoshi Mitarai, Charles L Daley, Sven N Hobbie, Zackery P Bulman
{"title":"Pharmacodynamic assessment of apramycin against Mycobacterium abscessus in a hollow fibre infection model.","authors":"Nidhi Singh, Bikash Dangi, Jeremy J Johnson, Arnold Louie, Arunkumar Karunanidhi, Brooke N Curry, Satoshi Mitarai, Charles L Daley, Sven N Hobbie, Zackery P Bulman","doi":"10.1093/jac/dkaf073","DOIUrl":"https://doi.org/10.1093/jac/dkaf073","url":null,"abstract":"<p><strong>Background: </strong>Mycobacterium abscessus is an important cause of pulmonary infections, particularly among people with cystic fibrosis. Current treatment options for M. abscessus are suboptimal. Apramycin is a promising alternative aminoglycoside for M. abscessus, in part due to its ability to avoid intrinsic aminoglycoside-modifying enzymes in this pathogen.</p><p><strong>Objectives: </strong>Define the pharmacodynamic activity of apramycin doses against M. abscessus.</p><p><strong>Methods: </strong>Apramycin and amikacin pharmacodynamics were assessed against two amikacin-susceptible M. abscessus subsp. abscessus isolates (ATCC 19977 and NR-44261) using a 14-day hollow fibre infection model (HFIM). Viable bacterial counts were determined during exposure to amikacin (15-20 mg/kg q24h) and 3 fractionated doses of apramycin (15 mg/kg q12h, 30 mg/kg q24h, 60 mg/kg q48h) using pharmacokinetic profiles predicted in epithelial lining fluid.</p><p><strong>Results: </strong>Against ATCC 19977, apramycin activity exceeded that of amikacin, with maximum bacterial reductions between 1.51 and 2.18 log10 cfu/mL for the different doses. Apramycin 15 mg/kg q12h displayed slightly better killing compared with the other apramycin dosing regimens between 96 and 144h before regrowth occurred. NR-44261 was not inhibited by amikacin and the activity of apramycin against this isolate was similar between the three doses (∼0.5 log10 cfu/mL reductions). After 14 days of exposure to apramycin monotherapy, ATCC 19977 and NR-44261 became apramycin resistant with MICs of >32 mg/L.</p><p><strong>Conclusions: </strong>Apramycin exhibited greater pharmacodynamic activity than amikacin against amikacin-susceptible M. abscessus isolates and may be a promising therapy for this pathogen. However, antibiotic combination strategies to minimize apramycin resistance from emerging may be necessary.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624585","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}
Oanh Ngoc Nguyen, Doaa Amin, James Bennett, Øystein Hetlevik, Sara Malik, Andrew Tout, Heike Vornhagen, Akke Vellinga
{"title":"GP or ChatGPT? Ability of large language models (LLMs) to support general practitioners when prescribing antibiotics.","authors":"Oanh Ngoc Nguyen, Doaa Amin, James Bennett, Øystein Hetlevik, Sara Malik, Andrew Tout, Heike Vornhagen, Akke Vellinga","doi":"10.1093/jac/dkaf077","DOIUrl":"https://doi.org/10.1093/jac/dkaf077","url":null,"abstract":"<p><strong>Introduction: </strong>Large language models (LLMs) are becoming ubiquitous and widely implemented. LLMs could also be used for diagnosis and treatment. National antibiotic prescribing guidelines are customized and informed by local laboratory data on antimicrobial resistance.</p><p><strong>Methods: </strong>Based on 24 vignettes with information on type of infection, gender, age group and comorbidities, GPs and LLMs were prompted to provide a treatment. Four countries (Ireland, UK, USA and Norway) were included and a GP from each country and six LLMs (ChatGPT, Gemini, Copilot, Mistral AI, Claude and Llama 3.1) were provided with the vignettes, including their location (country). Responses were compared with the country's national prescribing guidelines. In addition, limitations of LLMs such as hallucination, toxicity and data leakage were assessed.</p><p><strong>Results: </strong>GPs' answers to the vignettes showed high accuracy in relation to diagnosis (96%-100%) and yes/no antibiotic prescribing (83%-92%). GPs referenced (100%) and prescribed (58%-92%) according to national guidelines, but dose/duration of treatment was less accurate (50%-75%). Overall, the GPs' accuracy had a mean of 74%. LLMs scored high in relation to diagnosis (92%-100%), antibiotic prescribing (88%-100%) and the choice of antibiotic (59%-100%) but correct referencing often failed (38%-96%), in particular for the Norwegian guidelines (0%-13%). Data leakage was shown to be an issue as personal information was repeated in the models' responses to the vignettes.</p><p><strong>Conclusions: </strong>LLMs may be safe to guide antibiotic prescribing in general practice. However, to interpret vignettes, apply national guidelines and prescribe the right dose and duration, GPs remain best placed.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624583","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 and in vivo antibacterial activity, resistance analysis and molecular docking study of pleuromutilin derivatives against Streptococcus suis.","authors":"Sujuan Wu, Lu Zhang, Xinyue Luo, Changcheng Lin, Peng Wan, Honghao Huang, Yixing Lu, Youzhi Tang, Zhenling Zeng","doi":"10.1093/jac/dkaf064","DOIUrl":"https://doi.org/10.1093/jac/dkaf064","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the in vitro and in vivo antimicrobial activity of pleuromutilin derivatives modified with C14 side-chain against Streptococcus suis.</p><p><strong>Methods: </strong>To determine the minimum inhibitory concentrations (MICs) of 268 pleuromutilin derivatives with C14 side-chain modifications against S. suis ATCC 43 765 using the broth dilution method. Derivative B43, B49, B52, B53 and B54, which exhibited better antimicrobial activity, were selected for further investigation of their in vitro antibacterial effect, cytotoxicity, and in vivo antibacterial effect.</p><p><strong>Results: </strong>Determination activity of five derivatives against clinical strains (n = 37), as well as growth and time-killing curves. Those experiments showed that all the five derivatives had good activity against S. suis in vitro. Resistance-inducing assays demonstrated that, except for B43, the derivatives had similar abilities to induce resistance to tiamulin. In addition, the five derivatives did not have erythrocyte haemolytic toxicity (0.25-16 mg/L) and cytotoxicity (1.25-80 mg/L). In the mouse thigh infection model, the derivative of B49 exhibited superior antibacterial efficacy. About 40 mg/kg B49 had good activity and improved the survival rate of mice by 33.3% in the S. suis mouse peritonitis model. Molecular docking study and scanning electron microscopy revealed that B49 can effectively bind to the active site of the 50S ribosome and disrupt cell membranes.</p><p><strong>Conclusions: </strong>A total of 68.66% of the 268 C14 side-chain modified pleuromutilin derivatives showed potent activity against S. suis. Among them, B49 showed good in vitro and in vivo antimicrobial effects against S. suis, indicating that B49 can be intensively studied as an antimicrobial candidate compound.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624584","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}
Ayodeji Matuluko, Efi Mantzourani, Haroon Ahmed, Rebecca Cannings-John, Andrew Evans, Mirza Lalani, Nicholas Mays, Rebecca E Glover
{"title":"Comparison of antibiotic provision associated with acute sore throat symptom management in community pharmacies in Wales and England: a natural policy experiment.","authors":"Ayodeji Matuluko, Efi Mantzourani, Haroon Ahmed, Rebecca Cannings-John, Andrew Evans, Mirza Lalani, Nicholas Mays, Rebecca E Glover","doi":"10.1093/jac/dkaf057","DOIUrl":"https://doi.org/10.1093/jac/dkaf057","url":null,"abstract":"<p><strong>Background: </strong>Acute sore throat is managed in community pharmacies in England and Wales under different clinical pathways: Acute Sore Throat Pharmacy First (ASTPF) and Sore Throat Test and Treat (STTT), respectively. ASTPF launched in 2024 and allows antibiotic supply with FeverPAIN scores 4 and 5. STTT launched in 2018 and allows antibiotic supply with FeverPAIN ≥2 or Centor ≥3, if point-of-care testing confirms presence of group A Streptococcus (GAS).</p><p><strong>Objectives: </strong>To compare antibiotic supply rates of ASTPF and STTT, between 1 February 2024 and 30 July 2024, covering the first 6 months of ASTPF.</p><p><strong>Methods: </strong>A descriptive study using anonymized individual-level data from electronic pharmacy records of STTT and anonymized population-level aggregate data from electronic records of ASTPF consultations meeting the gateway criteria for reimbursement.</p><p><strong>Results: </strong>During the study period, 317 864 ASTPF and 27 684 STTT consultations were recorded across participating pharmacies, representing 551.0 and 874.9 consultations per 100 000 population in England (57 690 300) and Wales (3 164 400), respectively. The antibiotic supply rate was 72.7% (95% CI: 72.5% to 72.8%) for ASTPF and 29.9% (95% CI: 29.4% to 30.5%) for STTT.</p><p><strong>Conclusions: </strong>In this natural experiment in two similar healthcare systems with pharmacy-led sore throat services, we found different rates of antibiotic supply. Differences could be attributable to service implementation, pharmacists' initial training, engagement with GPs, pathway differences (e.g. gateway criteria and use of point-of-care tests), symptom severity, or most likely a combination of multiple factors. This early analysis suggests adapting the ASTPF pathway, to include point-of-care testing, could lead to reductions in unnecessary antibiotic supply.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605057","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":"Resistance profiles of carbapenemase-producing Enterobacterales in a large centre in England: are we already losing cefiderocol?-authors' response.","authors":"Ioannis Baltas, Trupti Patel, Ana Lima Soares","doi":"10.1093/jac/dkaf075","DOIUrl":"https://doi.org/10.1093/jac/dkaf075","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604783","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}
Christopher M Longshaw, Boudewijn L M Dejonge, Yoshinori Yamano
{"title":"Comment on: Resistance profiles of carbapenemase-producing Enterobacterales in a large centre in England: are we already losing cefiderocol?","authors":"Christopher M Longshaw, Boudewijn L M Dejonge, Yoshinori Yamano","doi":"10.1093/jac/dkaf074","DOIUrl":"https://doi.org/10.1093/jac/dkaf074","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605055","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}
Timothy M Rawson, Maxwell Al-Hassan, Ilona Brzeska-Trafny, Anna Morkowska, Elita Jauneikaite, Razan Saman, Hugo Donaldson, Frances Davies
{"title":"Comment on: Resistance profiles of carbapenemase-producing Enterobacterales in a large centre in England: are we already losing cefiderocol?","authors":"Timothy M Rawson, Maxwell Al-Hassan, Ilona Brzeska-Trafny, Anna Morkowska, Elita Jauneikaite, Razan Saman, Hugo Donaldson, Frances Davies","doi":"10.1093/jac/dkaf060","DOIUrl":"https://doi.org/10.1093/jac/dkaf060","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605053","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}
Qihui Liu, Xian Zhou, Zhuoying Du, Xuan Wang, Ning Li
{"title":"Intraventricular injection of eravacycline in the treatment of carbapenem-resistant Acinetobacter baumannii meningitis: a case report.","authors":"Qihui Liu, Xian Zhou, Zhuoying Du, Xuan Wang, Ning Li","doi":"10.1093/jac/dkaf069","DOIUrl":"https://doi.org/10.1093/jac/dkaf069","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604817","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}
Chanté Brand, Mae Newton-Foot, Melanie Grobbelaar, Andrew Whitelaw
{"title":"Antibiotic-induced stress responses in Gram-negative bacteria and their role in antibiotic resistance.","authors":"Chanté Brand, Mae Newton-Foot, Melanie Grobbelaar, Andrew Whitelaw","doi":"10.1093/jac/dkaf068","DOIUrl":"https://doi.org/10.1093/jac/dkaf068","url":null,"abstract":"<p><p>Bacteria adapt to changes in their natural environment through a network of stress responses that enable them to alter their gene expression to survive in the presence of stressors, including antibiotics. These stress responses can be specific to the type of stress and the general stress response can be induced in parallel as a backup mechanism. In Gram-negative bacteria, various envelope stress responses are induced upon exposure to antibiotics that cause damage to the cell envelope or result in accumulation of toxic metabolic by-products, while the heat shock response is induced by antibiotics that cause misfolding or accumulation of protein aggregates. Antibiotics that result in the production of reactive oxygen species (ROS) induce the oxidative stress response and those that cause DNA damage, directly and through ROS production, induce the SOS response. These responses regulate the expression of various proteins that work to repair the damage that has been caused by antibiotic exposure. They can contribute to antibiotic resistance by refolding, degrading or removing misfolded proteins and other toxic metabolic by-products, including removal of the antibiotics themselves, or by mutagenic DNA repair. This review summarizes the stress responses induced by exposure to various antibiotics, highlighting their interconnected nature, as well the roles they play in antibiotic resistance, most commonly through the upregulation of efflux pumps. This can be useful for future investigations targeting these responses to combat antibiotic-resistant Gram-negative bacterial infections.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575853","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}