Journal of Antimicrobial Chemotherapy最新文献

{"title":"Population pharmacokinetic analysis of teicoplanin in paediatric patients, including those receiving continuous kidney replacement therapy: a prospective cohort study.","authors":"Laura Butragueño-Laiseca, Gastón García-Orueta, Natalia Riva, Iñaki F Trocóniz, Sarah N Fernández, Verónica Camacho Vicente, Belén Padilla, María Slöcker, María José Santiago","doi":"10.1093/jac/dkaf012","DOIUrl":"https://doi.org/10.1093/jac/dkaf012","url":null,"abstract":"<p><strong>Objectives: </strong>Teicoplanin is a commonly used antibiotic in critically ill children. However, teicoplanin dosing is often inaccurate, especially in children undergoing continuous kidney replacement therapy (CKRT). This study aims to develop a population pharmacokinetic (PK) model to optimize teicoplanin dosing in critically ill children, including those on CKRT.</p><p><strong>Methods: </strong>Data from 26 critically ill children (12 with CKRT) receiving the standard dosing regimen were analysed. In total, 172 teicoplanin concentration measurements from plasma, pre- and post-filter ports were modelled simultaneously using NONMEM 7.4. Simulations were conducted to assess the target attainment (Cmin = 10 mg/L and AUC24/MIC > 800 h) of the current standard dosing regimen and of different alternative dosing regimens.</p><p><strong>Results: </strong>A two-compartment model was selected. Weight significantly affected renal clearance and volume of distribution of the central compartment, while filter surface area affected haemofilter clearance. Only 16 patients (59%) achieved a Cmin of >10 mg/L with the standard dosing regimen, and only 1 achieved the target AUC/MIC. Based on simulation results, 3 × 15 mg/kg q12h + 10 mg/kg q24h (CKRT) and 3 × 15 mg/kg q12h + 15 mg/kg q24h (no CKRT) could be better alternative regimens.</p><p><strong>Conclusions: </strong>This population model is a good proof of concept to develop modelling approaches that could help in an individualized dosing approach that needs to be adopted in critically ill paediatric patients. The standard paediatric dosage for teicoplanin could be insufficient for optimal exposure, and higher doses may benefit both CKRT and non-CKRT patients.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023570","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":"Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023.","authors":"Alioune Wade, Seynabou D Sene, Emanuelle Caspar, Fatoumata Diallo, Lucien Platon, Lucas Thiebaut, Mariama N Pouye, Aboubacar Ba, Laty Gaye Thiam, Magal Fall, Bacary Djilocalisse Sadio, Ife Desamours, Noemi Guerra, Kelly Hagadorn, Alfred Amambua-Ngwa, Amy K Bei, Ines Vigan-Womas, Didier Ménard, Alassane Mbengue","doi":"10.1093/jac/dkaf006","DOIUrl":"https://doi.org/10.1093/jac/dkaf006","url":null,"abstract":"<p><strong>Background: </strong>Since 2006, artemisinin-based combination therapies (ACTs) have been introduced in Senegal in response to chloroquine resistance (CQ-R) and have shown high efficacy against Plasmodium falciparum. However, the detection of the PfKelch13R515K mutation in Kaolack, which confers artemisinin resistance in vitro, highlights the urgency of strengthening antimalarial drug surveillance to achieve malaria elimination by 2030.</p><p><strong>Objective: </strong>To assess the proportion of P. falciparum parasites carrying molecular signatures associated with antimalarial resistance (PfKelch13, Pfmdr1, Pfcrt, dhfr and dhps) in isolates collected at Kédougou using multiplex amplicon deep sequencing.</p><p><strong>Methods: </strong>Venous blood samples were collected from patients diagnosed with P. falciparum infection over a 3-year period (2021, 2022 and 2023). Parasite DNA was extracted, and multiplex amplicon sequencing was used to investigate gene polymorphisms.</p><p><strong>Results: </strong>Analysis of PfKelch13 did not reveal any non-synonymous mutations. Pfcrt mutations were present in 45% of the samples, mainly K76T (44%) and I356T (36%). The dominant Pfmdr-1 allele was Y184F (62%). The sextuple mutant 51I/59R/108N + 436A/437G/613S dhfr/dhps was observed in 10% of the samples.</p><p><strong>Conclusion: </strong>The absence of PfKelch13 mutants suggests that ACT efficacy remains uncompromised, although clinical outcome studies are required to confirm this. Analysis of Pfcrt and Pfmdr-1 shows that CQ-R alleles, probably from previous CQ use, are slowly decreasing. Likewise, the detection of the dhfr/dhps sextuple mutant highlights the need to monitor sulfadoxine-pyrimethamine resistance and the emergence of 581G. There is therefore a need for continued antimalarial resistance surveillance in Senegal.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023569","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":"Prevalence of drug resistance mutations in low-level viremia patients under antiretroviral therapy in Southwestern China: a cross-sectional study.","authors":"Yuanlu Shu, Jiafa Liu, Cuixian Yang, Jianjian Li, Mi Zhang, Yuan Li, Xuemei Deng, Xingqi Dong","doi":"10.1093/jac/dkaf017","DOIUrl":"https://doi.org/10.1093/jac/dkaf017","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the prevalence and characteristics of drug resistance mutations (DRMs) in patients with low-level viremia (LLV) in Southwestern China, as it has become a growing challenge in AIDS clinical practice.</p><p><strong>Methods: </strong>This cross-sectional study was performed in Yunnan Province, Southwestern China. LLV was defined as 50-999 copies/mL of plasma viral load with antiretroviral therapy (ART) for at least 6 months. HIV-1 DRM detection used validated in-house protocol.</p><p><strong>Results: </strong>A total of 470 sequences were obtained, and 13 HIV-1 genotypes were identified, among which CRF08_BC (47.5%), CRF07_BC (22.3%) and CRF01_AE (10.0%) subtypes were the most prevalent. The overall prevalence of DRMs was 45.7% (215/470), and the prevalence of DRMs to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) was 39.4% (185/470), 20.6% (97/470) and 5.3% (25/470), respectively. The most common NNRTI-associated mutations were K103N (16.0%), E138A (6.6%), V179D (6.6%) and P225H (4.9%), and those in NRTIs were M184V (17.0%), D67N (3.4%) and K65R (3.0%). PI-associated mutations were infrequent, occurring in less than 1.8% of cases. The prevalence of NNRTI-associated mutations (K101E and Y188C) was found to be statistically significant among various LLV groups. Additionally, significant variations were observed in the prevalence of NNRTI-associated mutations (V106I, V106M, E138A and P225H), NRTI-associated mutation (K65R) and PI-associated mutations (L33F and Q58E) across different subtypes.</p><p><strong>Conclusions: </strong>The prevalence of DRMs in ART-experienced patients with LLV was high, and HIV-1 genotypes exhibited diversity in Yunnan Province. These findings indicate that regular DRM monitoring during LLV episodes was essential for effective clinical treatment and management in this region.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005907","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":"Sofosbuvir as post-exposure prophylaxis for yellow fever-associated viscerotropic disease (YEL-AVD).","authors":"Jessica Barrett, Ernest Muntengesa, Clare Warrell, Tommy Rampling, Jodie Owen, Dipti Patel, Sanjay Bhagani, Rachel Moores, Antonia Scobie","doi":"10.1093/jac/dkae484","DOIUrl":"https://doi.org/10.1093/jac/dkae484","url":null,"abstract":"<p><strong>Objectives: </strong>Yellow fever-associated viscerotropic disease (YEL-AVD) is a rare but serious complication arising from administration of live-attenuated yellow fever vaccine to individuals with risk factors such as thymectomy. At present there is no evidence-based treatment, and case fatality rates are high. Sofosbuvir, an NS5B nucleotide inhibitor, has activity against yellow fever virus in vitro and in vivo.</p><p><strong>Patient and methods: </strong>Here we describe clinical and virological response to use of off-licence sofosbuvir as post-exposure prophylaxis for a patient inadvertently given yellow fever vaccine despite previous thymectomy.</p><p><strong>Results: </strong>A 14-day course of oral sofosbuvir was administered in an outpatient setting with regular clinical and biochemical monitoring. The patient remained well without developing clinical features of YEL-AVD and did not experience adverse effects from the treatment.</p><p><strong>Conclusions: </strong>This supports the use of sofosbuvir as post-exposure prophylaxis in patients at high risk of developing YEL-AVD. Ongoing trials of efficacy of sofosbuvir in yellow fever infection may result in stronger support for this approach in the future.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005910","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: Major role of dolutegravir in the emergence of the S147G integrase resistance mutation.","authors":"","doi":"10.1093/jac/dkaf014","DOIUrl":"https://doi.org/10.1093/jac/dkaf014","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005898","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":"Surveillance of Clostridioides difficile on hospital admission and outpatient antibiotic use in Germany-a 9 year ecological analysis.","authors":"Selin Saydan, Frank Schwab, Jakob Holstiege, Jörg Bätzing, Michael Behnke, Sandra Schneider, Jörg Clausmeyer, Petra Gastmeier, Christine Geffers, Friederike Maechler","doi":"10.1093/jac/dkae483","DOIUrl":"https://doi.org/10.1093/jac/dkae483","url":null,"abstract":"<p><strong>Background: </strong>Antibiotic consumption is considered an important risk factor for Clostridioides difficile infection (CDI). This ecological analysis investigates the influence of outpatient antibiotic prescriptions in statutory health insurance (SHI) on the admission prevalence of CDI in German hospitals participating in voluntary CDI surveillance through the hospital infection surveillance system (Krankenhaus-Infektions-Surveillance-System; KISS).</p><p><strong>Methods: </strong>The annual CDI admission prevalence of a hospital at the federal state level was associated with the outpatient antibiotic consumption of the corresponding federal state. The quantification of outpatient antibiotic prescriptions was determined as the average DDD per 1000 insured persons per day. The risk factors for CDI on hospital admission included the annual consumption of the eight substance groups aminopenicillin combinations/staphylococcal penicillins, basic penicillins, cephalosporins, quinolones, lincosamides/macrolides, nitrofurantoin/fosfomycin/nitroxoline, sulphonamides/trimethoprim and tetracyclines, the type of care provided by the hospital, and the calendar year, and were examined using multivariable regression analyses (generalized estimating equations models).</p><p><strong>Results: </strong>Between 2011 and 2019, the number of outpatient antibiotic prescriptions decreased from 13.9 to 10.4 DDD per 1000 insured persons per day (-25%), and the CDI admission prevalence decreased from 0.22 to 0.12 per 100 patients (-45%). Basic penicillins and cephalosporins were identified as risk factors for increased CDI admission prevalence, while nitrofurantoin/fosfomycin/nitroxoline and sulphonamides/trimethoprim were associated with decreased CDI admission prevalence.</p><p><strong>Conclusions: </strong>A decrease in outpatient antibiotic prescriptions with known risk of developing CDI was associated with a decrease in hospital CDI admission prevalence. Our ecological analysis indicates that rational and restrained antibiotic use in the outpatient setting may reduce the incidence of CDI in the population requiring inpatient treatment.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005096","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":"Individualization of piperacillin dosage based on therapeutic drug monitoring with or without model-informed precision dosing: a scenario analysis.","authors":"David Haefliger, Lynn Mina, Monia Guidi, Catia Marzolini, Paul Thoueille, Laura E Rothuizen, Yann Thoma, Laurent A Decosterd, Benoit Guery, François R Girardin, Thierry Buclin","doi":"10.1093/jac/dkaf007","DOIUrl":"https://doi.org/10.1093/jac/dkaf007","url":null,"abstract":"<p><strong>Background: </strong>Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics.</p><p><strong>Objectives: </strong>To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure.</p><p><strong>Methods: </strong>Measurements from 80 courses of intermittent piperacillin infusions, each with two TDM samples, were retrospectively submitted to our MIPD software TUCUXI. We considered six dosage adjustment strategies: identical dosage for all (4000 mg q8h), actual initial dosage (chart-based), actual empirical adjustment following first TDM, a priori MIPD-based dosage, a posteriori MIPD-based adjustment after first TDM and MIPD including both TDM measurements. Dosing strategies were compared regarding daily dosage, trough levels distribution and PTA (with target trough 8-32 mg/L).</p><p><strong>Results: </strong>Median trough concentration fell within 8-32 mg/L for all strategies except a priori MIPD-based dosage (42 mg/L). Distributions of trough concentrations predicted with the six dosage adjustment strategies showed significant differences, with both a posteriori MIPD-based strategies best reducing their standard deviation (P < 0.001). PTA of 32%, 32%, 55%, 29%, 83% and 94% were estimated, respectively for the six strategies (P < 0.001). Poor performance of a priori MIPD-based dosage did not hinder a posteriori MIPD-based strategies from significantly improving target attainment.</p><p><strong>Conclusions: </strong>Whilst empirical TDM improves exposure standardization and target attainment compared with no TDM, MIPD can still bring further improvement. Prospective trials remain warranted to confirm MIPD benefits not only on target attainment but also on clinical endpoints.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005904","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: Synergistic effects of colistin-rifampin-based triple antimicrobial combination therapy against Carbapenem-resistant Pseudomonas aeruginosa: a time-kill assay.","authors":"","doi":"10.1093/jac/dkaf021","DOIUrl":"https://doi.org/10.1093/jac/dkaf021","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005901","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":"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}