Journal of Antimicrobial Chemotherapy最新文献

{"title":"Correction to: Pharmacokinetics of anti-TB drugs in children and adolescents with drug-resistant TB: a multicentre observational study from India.","authors":"","doi":"10.1093/jac/dkae421","DOIUrl":"https://doi.org/10.1093/jac/dkae421","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620713","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":"Clinical outcomes following acute sore throat assessment at community pharmacy versus general practice: a retrospective, longitudinal, data linkage study.","authors":"Efi Mantzourani, Haroon Ahmed, Jackie Bethel, Samantha Turner, Ashley Akbari, Andrew Evans, Matthew Prettyjohns, Gareth John, Ronny Gunnarsson, Rebecca Cannings-John","doi":"10.1093/jac/dkae400","DOIUrl":"https://doi.org/10.1093/jac/dkae400","url":null,"abstract":"<p><strong>Background: </strong>To date, no research has compared longer-term outcomes (antibiotic provision; re-consultations; hospital admissions for quinsy; cost-effectiveness) following presentation with acute sore throat at general practice (GP) versus newer, pharmacy-led services.</p><p><strong>Methods: </strong>A retrospective, longitudinal cohort study of sore throat consultations between 1 November 2018 and 28 February 2020 either with the Wales pharmacy-led sore throat test and treat (STTT) service or with a healthcare professional at GP. Individual-level pharmacy consultation data from the national Choose Pharmacy IT application were securely uploaded to the Secure Anonymised Information Linkage Databank and linked to routinely collected, anonymized, population-scale, individual-level, anonymized health and administrative data.</p><p><strong>Results: </strong>Of 72 736 index consultations, 6495 (8.9%) were with STTT and 66 241 (91.1%) with GP. Antibiotic provision at the index consultation was 1382 (21%) with STTT and 25 506 (39%) with GP [adjusted odds ratio (AOR), 0.30; 95% CI, 0.27 to 0.32]. Antibiotic provision within 28 days of index occurred in 1820 (28%) STTT and 26 369 (40%) GP consultations (AOR, 0.44; 95% CI, 0.41 to 0.47). GP re-consultation rate within 28 days of index date was 21% (n = 1389) with STTT compared with 7.4% (n = 4916) with GP (AOR, 3.8; 95% CI, 3.5 to 4.1). Coding limitations may lead to overestimates of GP re-consultations rates in the STTT group. Hospital admissions for quinsy were rare in both STTT (n = 20, 0.31%) and GP (n = 274, 0.41%) (AOR, 0.68; 95% CI, 0.43 to 1.1). STTT was less costly than consultation with GP.</p><p><strong>Conclusions: </strong>The pharmacy-led STTT service is safe, cost-effective, and contributes to antimicrobial stewardship.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620633","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":"Safety, tolerability and pharmacokinetics of subcutaneous meropenem as an alternative to intravenous administration.","authors":"Fionnuala Murray, Okhee Yoo, Samuel Brophy-Williams, Matthew Rawlins, Steven C Wallis, Jason A Roberts, Edward Raby, Sam Salman, Laurens Manning","doi":"10.1093/jac/dkae398","DOIUrl":"https://doi.org/10.1093/jac/dkae398","url":null,"abstract":"<p><strong>Background: </strong>Subcutaneous delivery of antibiotics is a practical alternative to IV administration. Meropenem is commonly used to treat infections caused by resistant Gram-negative organisms.</p><p><strong>Methods: </strong>This was a prospective, crossover self-controlled study in 11 stable inpatients established on meropenem. Participants received a single dose of subcutaneous meropenem, in 50 mL normal saline via gravity feed. Venous blood sampling was performed at baseline, 0.5, 1, 2, 4 and 8 h following the subcutaneous and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were assessed.</p><p><strong>Results: </strong>Subcutaneous meropenem was well tolerated. The bioavailability of subcutaneous administration was 81.5% (95% CI 71.6%-93.2%). Increasing BMI was associated with slower absorption from subcutaneous tissue. Compared with IV, subcutaneous administration resulted in lower peak and higher trough concentrations. Despite the lower bioavailability observed, the PTA for free drug concentrations greater than the MIC for more than 40% of the time between doses was higher for subcutaneous than IV administration at MIC values between 0.03 and 8 mg/L. Simulated subcutaneous doses of 1.5 g twice daily, or 3 g continuous 24 h infusion had improved PTA relative to standard IV dosing of 1 g three times daily.</p><p><strong>Conclusions: </strong>Subcutaneous meropenem appears to be well tolerated and has a favourable pharmacokinetic profile. Either 1.5 g twice daily or 3 g as a 24 h subcutaneous infusion could be considered for future evaluation.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620733","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 monitoring of drug resistance emergence during stepwise induction of bedaquiline and clofazimine, alone and in combination: a phenotypic and genotypic analysis.","authors":"Suting Chen, Yuanyuan Shang, Jifang Zheng, Fengmin Huo, Yi Xue, Liping Zhao, Guanglu Jiang, Naihui Chu, Hairong Huang","doi":"10.1093/jac/dkae405","DOIUrl":"https://doi.org/10.1093/jac/dkae405","url":null,"abstract":"<p><strong>Objectives: </strong>The co-resistance between bedaquiline and clofazimine raises significant concerns, as they are commonly co-administered as core drugs in drug-resistant TB regimens. The present study aimed to monitor drug resistance-associated gene mutations and the phenotypic change in Mycobacterium tuberculosis (Mtb) under a stepwise drug resistance induction in vitro using bedaquiline, clofazimine or combined drugs.</p><p><strong>Methods: </strong>Drug-resistant Mtb strains were gradually induced in vitro on a drug-containing solid medium with a 2-fold increasing concentration of bedaquiline, clofazimine and their combination. The MIC of the induced drug-resistant Mtb strains was determined. The drug resistance-associated genes, including Rv0678, Rv1979c, atpE and pepQ, were sequenced and analysed.</p><p><strong>Results: </strong>Unlike exposure to bedaquiline alone or the combination of these two drugs, clofazimine alone resulted in drug resistance gene mutations occurring later, specifically in the fourth round of induction as opposed to the second round of induction. Besides, nucleotide deletion or insertion in Rv0678 was the main mutation type for induction under the two-drug combination, while single-nucleotide polymorphisms (SNPs) in Rv0678 were the major mutation types when induced by bedaquiline or clofazimine alone. Rv0678 mutation happened at a relatively lower bedaquiline concentration exposure alone, while atpE mutation occurred at a higher bedaquiline concentration. Regardless of the drug exposure manner, a strong correlation between bedaquiline MICs and clofazimine MICs was observed in all drug resistance strains.</p><p><strong>Conclusions: </strong>Combined exposure to bedaquiline and clofazimine developed Rv0678 mutation as early as exposure to bedaquiline alone. However, rather than SNPs, deletion and insertion were the dominant mutation types in dual-drug exposure strain.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620715","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":"One Health bottom-up analysis of the dissemination pathways concerning critical priority carbapenemase- and ESBL-producing Enterobacterales from storks and beyond.","authors":"Sandra Martínez-Álvarez, Ursula Höfle, Pierre Châtre, Carla Andrea Alonso, María Ángeles Asencio-Egea, Pauline François, Teresa Cardona-Cabrera, Myriam Zarazaga, Jean-Yves Madec, Marisa Haenni, Carmen Torres","doi":"10.1093/jac/dkae371","DOIUrl":"https://doi.org/10.1093/jac/dkae371","url":null,"abstract":"<p><strong>Background: </strong>'One Health' initiatives to tackle the rising risk of antimicrobial resistance (AMR) have flourished due to increasing detection of Enterobacterales producing extended-spectrum beta-lactamases (ESBLs) and carbapenemases (CPs).</p><p><strong>Objectives: </strong>This study aimed to conduct an in-depth holistic analysis of Escherichia coli (Ec) and Klebsiella pneumoniae (Kp) isolates recovered from landfill-foraging white stork faecal samples and clinical isolates from a nearby hospital.</p><p><strong>Methods: </strong>Faecal samples (n = 211) were collected from storks foraging at two landfills in Spain. Ec/Kp stork isolates were recovered on selective media and whole-genome sequencing (WGS), together with isolates obtained from the nearby hospital. These genomic data were compared with public genomes from different contexts (clinical, environmental, or animal hubs) to understand global transmission dynamics.</p><p><strong>Results: </strong>A wide range of blaESBL/blapAmpC (blaCTX-M/blaSHV-12/blaDHA) were detected in 71 stork samples (33.6%), while blaCP (blaKPC/blaNDM/blaOXA-48/blaVIM) were identified in 28 (13.3%) samples. Clonal and plasmid transmissions were evidenced inside and between both landfills. Mapping against 10 624 public Ec/Kp genomes and from those of nearby hospital revealed that identical strains (<10 allelic differences with Ec-ST38/ST131 and Kp-ST512 lineages) and epidemic plasmids (full identity/coverage with IncN/blaKPC-2, IncF/blaKPC-3, IncX3/blaNDM-7, IncL/blaOXA-48) were found from clinical isolates in countries located along the storks' migration routes.</p><p><strong>Conclusions: </strong>Storks may be contaminated by bacterial isolates from a likely human origin and become non-human reservoirs of critical genes, which can be dispersed over long distances. Identifying strains/plasmids along the stork's routes that are identical or closely related to those described here opens new perspectives for large-scale research to understand the AMR transmission dynamics.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620728","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":"Serum concentration threshold and risk factors of tigecycline-induced hypofibrinogenaemia in critically ill patients.","authors":"Mengxue Li, Jie He, Gaoqiu Dong, Linlin Hu, Hua Shao","doi":"10.1093/jac/dkae396","DOIUrl":"https://doi.org/10.1093/jac/dkae396","url":null,"abstract":"<p><strong>Objectives: </strong>Hypofibrinogenaemia is a serious adverse reaction associated with tigecycline (TGC) therapy and may lead to the discontinuation of the treatment. This study aimed to explore the relevant factors of TGC-induced hypofibrinogenaemia and determine the thresholds of serum concentration as a predictive indicator of TGC-induced hypofibrinogenaemia.</p><p><strong>Methods: </strong>A retrospective single-centre study was conducted on patients with severe infection who were treated with TGC. Clinical data and serum concentration parameters were extracted from the electronic medical records of these patients. Patients were divided into the hypofibrinogenaemia group (< 2.0 g/L) and the normal fibrinogen group (≥ 2.0 g/L) in order to evaluate risk factors associated with TGC-induced hypofibrinogenaemia. Logistic regression analysis and receiver operating characteristic curves were utilized to identify the risk factors associated with TGC-induced hypofibrinogenaemia and to establish plasma concentration thresholds as predictive indicators.</p><p><strong>Results: </strong>A total of 114 patients were enrolled in this study, with 59.6% experiencing hypofibrinogenaemia. The multivariate regression analysis indicated that baseline fibrinogen level, trough concentration (Cmin), peak concentration (Cmax), the concentration at 6 h after the dosing (C6h) and the area under the concentration-time curve over a 24-h period (AUC0-24) were significantly associated with hypofibrinogenaemia (P < 0.05). Furthermore, it was found that AUC0-24 is the optimal predictor of TGC-induced hypofibrinogenaemia. The optimal cut-off for the AUC0-24 of TGC in ICU patients was determined to be 17.03 mg h/L.</p><p><strong>Conclusions: </strong>TGC exposure is highly predictive of TGC-induced hypofibrinogenaemia. We recommend closely monitoring plasma concentrations of TGC in patients to ensure patient efficacy and safety.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603283","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":"Saliva-based point-of-care assay to measure the concentration of pyrazinamide using a mobile UV spectrophotometer.","authors":"Ricky Hao Chen, Thi Anh Nguyen, Hannah Yejin Kim, Sophie L Stocker, Jan-Willem C Alffenaar","doi":"10.1093/jac/dkae404","DOIUrl":"https://doi.org/10.1093/jac/dkae404","url":null,"abstract":"<p><strong>Introduction: </strong>Pyrazinamide, one of the first-line antituberculosis drugs, displays variability in drug exposure that is associated with treatment response. A simple, low-cost assay may be helpful to optimize treatment. This study aimed to develop and validate a point-of-care assay to quantify the concentration of pyrazinamide in saliva.</p><p><strong>Methods: </strong>All measurements were conducted using the nano-volume drop function on the mobile ultraviolet (UV) spectrophotometer (NP80, Implen, Germany). Assay development involved applying second derivative spectroscopy in combination with the Savitzky-Golay filter between wavelengths of 200-300 nm to increase spectral resolution. Assay validation included assessing selectivity, linearity, accuracy, precision, carry-over and matrix effects. Specificity was also analysed by evaluating the impact of co-administered medications on pyrazinamide results. Sample stability was measured at various temperatures up to 40°C.</p><p><strong>Results: </strong>The calibration curve (7.5-200 mg/L) was linear (R2 = 0.9991). The overall accuracy (bias%) and precision (CV%) ranged from -0.66% to 5.15%, and 0.56% to 4.95%, respectively. Carry-over and matrix effects were both acceptable with a bias% of <±4% and CV% of <7.5%. Commonly co-administered medications displayed negligible interferences. Levofloxacin displayed analytical interference (bias% = -10.21%) at pyrazinamide concentrations < 25 mg/L, but this will have little clinical implications. Pyrazinamide was considered stable in saliva after 7 days in all storage conditions with a CV% of <6.5% and bias% of <±10.5% for both low- and high-quality control concentrations.</p><p><strong>Conclusions: </strong>A saliva-based assay for pyrazinamide has been successfully developed and validated using the mobile UV spectrophotometer.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602071","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":"Diagnostic uncertainties in patients with bacteraemia: impact on antibiotic prescriptions and outcome.","authors":"Pierre-Marie Roger, Anne-Claire Strzelecki, Véronique Dautezac, Marc-Antoine Hennet, Gaëlle Borredon, Patrick Brisou, Delphine Girard, Assi Assi","doi":"10.1093/jac/dkae401","DOIUrl":"https://doi.org/10.1093/jac/dkae401","url":null,"abstract":"<p><strong>Objectives: </strong>To establish a formal diagnosis in infectious disease is not an easy task. Our aim was to characterize diagnostic uncertainty (DU) in patients for whom blood cultures were positive (PBC) and to determine its impact on both the antibiotic therapy and the outcome.</p><p><strong>Methods: </strong>This was a prospective multicentre study including PBC for 6 months. The laboratory gave the PBC result to the infectious disease (ID) specialists in real time (24/7). The latter analysed all data from electronic patient charts and gave therapeutic advice to the physicians in charge of the patient to either initiate an antibiotic therapy, or to modify or to pursue continuing antimicrobial treatment. A DU was defined as no diagnosis of ID after thorough reading of the patient's chart, or more than two diagnoses despite two medical opinions obtained before PBC. An unfavourable outcome was defined by the occurrence of death during hospitalization.</p><p><strong>Results: </strong>One hundred and nighty-nine PBCs were communicated to ID specialists, including 93 DUs (47%). In multivariate analysis, DU was associated with hospitalization in medical wards: [adjusted odds ratio (AOR) (95% CI): 6.94 (3.41-14.28)], the advice to initiate an antibiotic treatment: [3.89 (1.56-9.70)] and piperacillin-tazobactam use [3.75 (1.56-9.00)]; ICU requirement at initiation of care was a protective factor [0.38 (0.17-0.84)]. An unfavourable outcome was observed in 22 cases, and in a second logistic regression showed that DU was associated with the latter [AOR (95% CI): 5.07 (1.60-16.12)].</p><p><strong>Conclusion: </strong>DUs were frequent during infections proved by PBC, and were associated with admission in medical wards, broad-spectrum antibiotic use and a high rate of unfavourable outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605006","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":"Liver cyst penetration of antibiotics at the target site of infection: a randomized pharmacokinetic trial.","authors":"Lucas H P Bernts, Roger J M Brüggemann, Anouk M E Jansen, Nynke G L Jager, Heiman F L Wertheim, Joost P H Drenth, Marten A Lantinga","doi":"10.1093/jac/dkae394","DOIUrl":"https://doi.org/10.1093/jac/dkae394","url":null,"abstract":"<p><strong>Background: </strong>The EASL cystic liver disease guideline states that drug penetration at the site of infection (liver cyst) is essential for successful treatment, but pharmacokinetic (PK) data on cyst penetration are limited.</p><p><strong>Objectives: </strong>This study aims to investigate tissue penetration of four antibiotics in non-infected liver cysts and explores influencing factors.</p><p><strong>Methods: </strong>We performed a prospective, randomized single-dose PK-study. Before percutaneous drainage of a non-infected liver cyst, an intravenous (IV) dose of either ciprofloxacin and piperacillin/tazobactam (group 1); or co-trimoxazole (trimethoprim/sulfamethoxazole) and doxycycline (group 2) was given. Cyst fluid was collected during drainage. Blood samples were obtained before, during and after drainage (within 12 h). Drug concentrations were measured with a validated LC-MS/MS. Primary outcome was liver cyst penetration, defined as the cyst-fluid-to-plasma concentration ratio (%) expressed as median (IQR).</p><p><strong>Results: </strong>We included 20 patients, and 21 liver cysts were drained (group 1: n = 11, group 2: n = 10). Median drained cyst volume was 700 mL. Median time between infusion and drainage was 139 min (IQR 120-188 min). Median cyst-fluid-to-plasma concentration ratio was 4.2% (IQR 1.6%-8.9%) for ciprofloxacin, 0.3% (IQR 0.0%-1.3%) for piperacillin, 0.2% (IQR 0.0%-1.3%) for tazobactam, 12.2% (IQR 6.3%-16.1%) for trimethoprim, 0.4% (IQR 0.2%-3.8%) for sulfamethoxazole and 1.6% (IQR 0.9%-2.3%) for doxycycline. Time between trimethoprim infusion and cyst drainage was correlated with increased cyst-fluid-to-plasma concentration ratio (P < 0.01).</p><p><strong>Conclusions: </strong>Trimethoprim and ciprofloxacin have the highest penetration ratios amongst antibiotics tested. We found that liver cyst penetration varies widely between drugs after a single IV dose.</p><p><strong>Clinical trial number: </strong>NTR8499The trial was originally registered in the Netherlands Trial Register (ID: NL7290), which was converted to the International Clinical Trials Registry Platform in 2022.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605007","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":"Rapid viral suppression using integrase inhibitors during acute HIV-1 infection.","authors":"Mehri S McKellar, Jessica R Keys, Lindsey M Filiatreau, Kara S McGee, Joann D Kuruc, Guido Ferrari, David M Margolis, Joseph J Eron, Charles B Hicks, Cynthia L Gay","doi":"10.1093/jac/dkae391","DOIUrl":"https://doi.org/10.1093/jac/dkae391","url":null,"abstract":"<p><strong>Background: </strong>Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited.</p><p><strong>Methods: </strong>This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA <200 copies/mL and <50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).</p><p><strong>Results: </strong>Thirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22-42). Demographics were similar between the two AHI cohorts. By Week 24, 100% in the INSTI and 99% in the NNRTI cohort were <200 copies/mL; by Week 48, 100% in both cohorts were <50 copies/mL. Time to viral suppression was shorter in the INSTI cohort (median 54 versus 99 days). Mean weight change was similar with a 3.6 kg increase in the INSTI cohort and 2.4 kg in the NNRTI cohort at 96 weeks.</p><p><strong>Conclusions: </strong>INSTI-based ART during AHI resulted in rapid and sustained viral suppression. Over 96 weeks, weight increased in the INSTI-based cohort but was similar to weight increase in a historical NNRTI-based AHI cohort.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590663","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}