Journal of Antimicrobial Chemotherapy最新文献

{"title":"Intrapulmonary concentrations of ceftobiprole high doses administered by continuous infusion in critically ill patients with community-acquired pneumonia.","authors":"Claire Roger, Bernard Allaouchiche, Daniel Quintão De Moraes, Olivier Ulrich Feudjio, Bob-Valéry Occean, Arnaud Friggeri, Jean-Yves Lefrant, Laurent Muller, Dominique Breilh","doi":"10.1093/jac/dkaf267","DOIUrl":"10.1093/jac/dkaf267","url":null,"abstract":"<p><strong>Background: </strong>Optimal antimicrobial drug exposure in the lung is required for ensuring successful treatment of community-acquired pneumonia (CAP). Little is known about the intrapulmonary pharmacokinetics (PK) of ceftobiprole when administered by continuous infusion (CI).</p><p><strong>Objective: </strong>To determine the PK of high doses (3 g/day) CI of ceftobiprole in the plasma and epithelial lining fluid (ELF) in mechanically ventilated patients with CAP.</p><p><strong>Methods: </strong>Patients receiving a CI of ceftobiprole (2.5 g daily after a 0.5 g bolus loading dose) for the treatment of severe CAP were eligible. Plasma and ELF samples were collected over 3 days of therapy. Concentrations were analysed by HPLC-UV, and population PK modelling was conducted using Monolix™. Monte Carlo simulations were performed to estimate the probability of target attaining a free ELF concentration of 100% of time above MIC.</p><p><strong>Results: </strong>Twelve patients, 2 female, median (IQR) age 67 (58-71), were enrolled with 108 plasma and 12 ELF concentrations included in the population analysis. The median (min-max) lung penetration ratio was 30 (15-45) % after 3 doses of ceftobiprole. In the Monte Carlo simulations, higher doses given as CI (3 g/day) may be necessary for MICs up to 2 mg/L in patients with normal renal function. The final PK model using a 4 × MIC plasma target may help to approximate ELF target attainment.</p><p><strong>Conclusions: </strong>The use of high doses of ceftobiprole given by CI may be necessary to achieve PK/pharmacodynamic targets in ELF in critically ill patients with CAP and normal renal function, especially when less susceptible pathogen is suspected or identified.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2644-2653"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775434","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":"Assessment of the risk of developing cefepime-induced abnormal liver enzyme levels using the albumin-bilirubin score and fibrosis-4 index: a single-centre retrospective case-control study.","authors":"Hiroki Katsu, Yuki Asai, Takuya Iwamoto, Ryuji Hirano","doi":"10.1093/jac/dkaf291","DOIUrl":"10.1093/jac/dkaf291","url":null,"abstract":"<p><strong>Background: </strong>Although the albumin-bilirubin (ALBI) score and fibrosis-4 (FIB-4) index may help predict cefepime-induced liver enzyme abnormalities, the relationship between these measures and liver enzyme abnormalities has not been elucidated.</p><p><strong>Objectives: </strong>This study investigated the relevance and predictive accuracy of the ALBI score and FIB-4 index for cefepime-induced liver enzyme abnormalities.</p><p><strong>Patients and methods: </strong>This single-centre retrospective case-control study included 473 patients. The primary outcomes were cefepime-induced abnormal liver enzyme levels. Cox regression analysis was performed with male sex, cumulative dose (≥36 g), concomitant use of acetaminophen or voriconazole, alkaline phosphatase (≥238 IU/L), ALBI score (≥-1.45) and FIB-4 index (≥4.69) as explanatory variables. The predictive accuracies of the ALBI score and FIB-4 index were evaluated based on the AUC using the receiver operating characteristic curve. We performed 1:1 propensity score matching between FIB-4 index ≥4.69 and FIB-4 index < 4.69 groups.</p><p><strong>Results: </strong>The incidence of abnormal liver enzyme levels was 15.6% (74/473). Cox regression analysis revealed that the ALBI score (adjusted hazard ratio, 2.10; 95% CI, 1.268-3.491; P = 0.004) and FIB-4 index (adjusted hazard ratio, 2.33; 95% CI, 1.425-3.796; P = 0.001) were independent risk factors for liver enzyme abnormalities. For all patients, the FIB-4 index (AUC: 0.629) exceeded the ALBI score (AUC: 0.530). Similar results were observed even after propensity score matching.</p><p><strong>Conclusions: </strong>The progression of liver fibrosis before cefepime administration, as assessed using the FIB-4 index, could be more useful than the ALBI score in predicting the risk of developing abnormal liver enzyme levels.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2742-2751"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775429","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":"Therapeutic efficacy monitoring of pyronaridine-artesunate (Pyramax®) in treating uncomplicated Plasmodium falciparum malaria in Gia Lai province, Vietnam from 2022 to 2023.","authors":"Nguyen Van Thanh, Huynh Hong Quang, Nguyen Ngoc San, Nguyen Kien Cuong, Nguyen Thi Minh Trinh, Chau Van Khanh, Kimberly A Edgel, Huy C Nguyen, Andrew G Letizia, Geoffrey W Birrell, Nicholas J Martin, Michael D Edstein, Marina Chavchich","doi":"10.1093/jac/dkaf234","DOIUrl":"10.1093/jac/dkaf234","url":null,"abstract":"<p><strong>Objectives: </strong>We assessed the therapeutic efficacy of pyronaridine-artesunate (Pyramax®) for the treatment of uncomplicated Plasmodium falciparum malaria in Gia Lai province, Central Vietnam where parasites are partially resistant to artemisinins.</p><p><strong>Methods: </strong>In an open-label, single-arm trial, Pyramax® was administered to 120 patients (adults and children) infected with P. falciparum residing in Gia Lai province from March 2022 to December 2023. Patients received Pyramax® once daily for 3 days and single-dose primaquine under direct observation therapy. Patients' Day 7 blood pyronaridine concentrations were measured by liquid chromatography-mass spectrometry to determine drug exposure.</p><p><strong>Results: </strong>After Pyramax® treatment, the proportion of patients with PCR-adjusted adequate clinical and parasitological response at Day 42 was 92.5% (95% CI: 85.5-96.2; 98/106). The median parasite and fever clearance times were 84 h (range: 24-132) and 36 h (range: 12-108), respectively. The median (IQR) parasite clearance half-life was 7.4 h (6.3-8.4), with 50.4% (60/119) of patients had parasites detected by microscopy at 72 h after commencing treatment, suggestive of partial artemisinin resistance. The eight patients who experienced malaria recrudescence had lower (P = 0.065) blood pyronaridine concentrations (mean 39.6 ng/mL, median 33.3 ng/mL, range: 12.4-90.5) compared to the 95 patients who were malaria-free by Day 42 (median 47.6 ng/mL, range: 10.6-123.0).</p><p><strong>Conclusions: </strong>Although Pyramax® remains efficacious in treating P. falciparum, the lower pyronaridine concentrations in patients who had recrudescent malaria are worrisome and suggest that reduced pyronaridine exposure may be responsible for the Pyramax® treatment failures.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2630-2634"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835169","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":"Trends in antifungal use among hospitalized patients in the USA, 2018-23.","authors":"Dallas J Smith, Hannah R Murphy, Kaitlin Benedict, Natalie J M Dailey Garnes, Nancy N Vuong, Alyssa H Harris, Teny M John","doi":"10.1093/jac/dkaf269","DOIUrl":"10.1093/jac/dkaf269","url":null,"abstract":"<p><strong>Background and objectives: </strong>Fungal infections cause substantial morbidity and mortality. Monitoring antifungal use is a foundational aspect of antifungal stewardship, particularly as new disease-causing fungi emerge and antifungal resistance spreads. We assessed recent patterns in systemic antifungal medication use among hospitalized patients within a diverse convenience sample of academic medical centres and community hospitals in the USA.</p><p><strong>Methods: </strong>We conducted a multicentre retrospective cohort study using the Vizient® Clinical Data Base. We selected hospitalized patients who received ≥1 dose of systemic antifungal medication during 2018-23 and assessed antifungal days of therapy (DOT) per 1000 patient days. We stratified antifungal DOT by National Comprehensive Cancer Network (NCCN) cancer centre status to compare antifungal use at hospitals with an NCCN-designated cancer centre-some of which also include a main academic medical centre and non-cancer service lines-versus hospitals without an NCCN-designated cancer centre.</p><p><strong>Results: </strong>Among 39 956 873 discharges from 412 hospitals, the proportion of patients who received any systemic antifungal was 4.5%; azoles (3.8%) were the most common antifungal class, followed by echinocandins (0.9%). Overall antifungal DOT were 53.7 per 1000 patient days (114.5 among 25 NCCN hospitals and 43.2 among 387 non-NCCN hospitals).</p><p><strong>Conclusions: </strong>Substantial antifungal use occurs among hospitalized patients, particularly among those with cancer. The growing population susceptible to fungal infections (e.g. transplants, cancer and other immunosuppressing conditions) warrants consideration of antifungal stewardship and evaluation of appropriateness of antifungal use in the context of increasing resistance.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2659-2664"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835170","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":"Development of blood culture time-to-positivity as a pharmacodynamic indicator for monitoring antibiotic therapy against MDR Gram-negative bacteria.","authors":"Irene Zaghi, Monica Cricca, Jason A Roberts, Martina Brandolini, Claudia Colosimo, Sofia Montanari, Vittorio Sambri, Russell E Lewis","doi":"10.1093/jac/dkaf276","DOIUrl":"10.1093/jac/dkaf276","url":null,"abstract":"<p><strong>Objectives: </strong>We investigated the use of time-to-positivity (Tpos), a readily available parameter measured from automated blood culture incubators, as a surrogate marker for serum antimicrobial activity during antibiotic treatment against ESBL- and carbapenemase-producing Klebsiella pneumoniae.</p><p><strong>Methods: </strong>Banked human serum spiked with clinically representative concentrations of different antibiotics was injected into aerobic blood culture bottles containing 1 × 104 mL inoculum of K. pneumoniae isolates. The time required for the test inoculum to 'grow through' serum antibacterial activity (Tpos) was then measured over 24 h. Serum containing combinations of antibiotics were also tested using an 8 × 8 combination array to assess synergistic or antagonistic interactions.</p><p><strong>Results: </strong>Tpos increased from <10 to >24 h with increasing serum antibiotic concentrations for all drug-isolate combinations tested with the EC50 Tpos of ∼17 h for all isolates. The EC50 for ceftazidime/avibactam (4:1) ranged from 5.73 mg/L (95% CI, 5.60-5.37) for a WT strain (MIC 0.125 mg/L) to 377 mg/L (95% CI, 356.26-398.41) for a resistant KPC-3-producing isolate (MIC 16 mg/L). Variation in observed Tpos was linked to isolate MIC (R2 = 0.94). Antibiotic combinations marginally increased serum Tpos (1-3 h) for most isolates with the exception of ceftazidime/avibactam + meropenem or aztreonam against KPC-3-producing isolates (increase of 10.36-11.61 h) or ceftazidime/avibactam + aztreonam against an NDM-2 isolate (increase of 10.33 h).</p><p><strong>Conclusions: </strong>Tpos is a simple, reproducible marker of serum antibiotic activity against ESBL- and carbapenemase-producing K. pneumoniae. With further clinical validation, Tpos could be developed as a complementary surrogate marker for early detection of inadequate antimicrobial therapy in patients receiving antibiotic therapy for bloodstream infections caused by MDR Gram-negative bacteria.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2705-2713"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144846594","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":"Molecular characterization of fluoroquinolone resistance in invasive clinical isolates of Streptococcus pneumoniae susceptible to delafloxacin.","authors":"Emilia Cercenado, Mercedes Marín, Manuel Iglesias, Laura Jiménez, Marta Pérez-Abeledo, Juan Carlos Sanz","doi":"10.1093/jac/dkaf308","DOIUrl":"10.1093/jac/dkaf308","url":null,"abstract":"<p><strong>Background: </strong>Delafloxacin is a dual-targeting fluoroquinolone against topoisomerase IV and DNA gyrase that could decrease resistance selection by diminishing the likelihood of multiple mutational events in both enzymes.</p><p><strong>Objectives: </strong>To determine the activity of delafloxacin against invasive Streptococcus pneumoniae isolates resistant to levofloxacin (LEV-R), compare delafloxacin MICs for LEV-R isolates with those of susceptible strains, and analyse mutations in QRDRs.</p><p><strong>Methods: </strong>A total of 130 S. pneumoniae isolates (2014-20) were studied. The isolates were distributed according to levofloxacin MICs: high-level LEV-R (n = 46; MIC > 32 mg/L), low-level LEV-R (n = 36; MIC range 3-12 mg/L) and susceptible (LEV-S; n = 48; MIC ≤2 mg/L). We considered delafloxacin-resistant to be MIC ≥ 0.12 mg/L (EUCAST epidemiological cut-off). MICs were determined by gradient diffusion (control strain S. pneumoniae ATCC 49619). All isolates were subjected to PCR and sequencing of parC, parE, gyrA and gyrB genes.</p><p><strong>Results: </strong>All LEV-S isolates showed delafloxacin MICs of ≤0.008 mg/L, and did not show mutations in QRDRs. Isolates with levofloxacin MICs of 3-12 mg/L showed delafloxacin MICs of <0.12 mg/L, with 3 (8.3%) presenting mutations in gyrA, and 11 (30.6%) in parC previously related to resistance. Isolates with levofloxacin MICs of >32 mg/L showed two to four mutations in QRDRs and 11 (24%) were delafloxacin resistant, presenting at least two mutations in gyrAS81F/L/V + parCS79F; four accumulated three mutations, and two showed four mutations in QRDRs.</p><p><strong>Conclusions: </strong>Among LEV-R pneumococci, 71 (87%) were susceptible to delafloxacin, indicating that it maintains its activity despite the presence of mutations in gyrA + parC that lead to high-level resistance to levofloxacin.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2834-2843"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955212","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 course of patients with bloodstream infections enrolled in the BALANCE clinical trial.","authors":"Sean W X Ong, Ruxandra Pinto, Asgar Rishu, Steven Y C Tong, Robert A Fowler, Nick Daneman","doi":"10.1093/jac/dkaf294","DOIUrl":"10.1093/jac/dkaf294","url":null,"abstract":"<p><strong>Objectives: </strong>There is a lack of data describing the longitudinal clinical trajectories of vital signs and laboratory tests in patients with bloodstream infection (BSI). The BALANCE trial, which randomly assigned patients with BSI to receive 7 or 14 days of antibiotic treatment, provided rich daily data to describe these trajectories.</p><p><strong>Methods: </strong>As part of the BALANCE trial, we collected several daily parameters (temperature, heart rate, mean arterial pressure, systolic blood pressure, respiratory rate, WBC count, C-reactive protein, platelet count and SOFA score) until Day 14 of illness, discharge or death. In this post hoc descriptive sub-study, we described trajectories of these parameters, stratified by treatment group allocation and by the primary outcome of 90-day all-cause mortality.</p><p><strong>Results: </strong>Among 3608 patients included, median age was 70 years and 46.7% were female. At enrolment, 55.0% were admitted in the ICU and 21.2% required mechanical ventilation. Longitudinal trajectories of vital signs, laboratory tests and SOFA scores were almost identical comparing the two treatment groups, including from Day 7 after treatment divergence. These trajectories were markedly different when comparing survivors (3034 patients; 84.7%) and non-survivors (547 patients; 15.3%), with non-survivors demonstrating a slower recovery course throughout the 14-day period.</p><p><strong>Conclusions: </strong>Among hospitalized patients with BSI, recovery trajectories were similar in patients assigned to 7- versus 14-day antibiotic treatment durations but were different comparing survivors versus non-survivors. These data could be used to inform daily clinical management, formulate predictive risk scores or clinical decision rules, and guide future research into individualized therapeutic strategies.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2752-2758"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775430","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}

{"title":"In vivo activity of ceftibuten-ledaborbactam oral combination against serine-β-lactamase-producing Enterobacterales: an assessment in the pyelonephritis and cystitis murine model.","authors":"Christina Koenig, Fan Yi, David P Nicolau, Tomefa E Asempa","doi":"10.1093/jac/dkaf277","DOIUrl":"10.1093/jac/dkaf277","url":null,"abstract":"<p><strong>Background: </strong>Ledaborbactam is an investigational oral β-lactamase inhibitor that restores ceftibuten's activity against strains of Enterobacterales expressing ESBLs and serine carbapenemases, offering a potential oral therapeutic option for cUTIs.</p><p><strong>Objectives: </strong>To characterize the activity of ceftibuten-ledaborbactam human simulated regimens (HSRs) against β-lactamase-producing Enterobacterales in a murine urinary tract infection (UTI) model assessing infection in both the kidney and bladder.</p><p><strong>Methods: </strong>Ten urogenic Enterobacterales (ceftibuten-ledaborbactam MIC ≤0.03 to 4 mg/L; ESBL, KPC, OXA-48) were assessed. Murine HSRs for oral ceftibuten (400 mg q8 h and 600 mg q12 h) alone and combined with oral ledaborbactam (400 mg q8 h and 600 mg q12 h) were developed. Activity was assessed by absolute bacterial burden (log10 cfu) in kidneys and bladders after 24 h of treatment.</p><p><strong>Results: </strong>Mean (±SD) bacterial burdens in kidneys and bladders of mice at the start of dosing (0 h control) were 5.54 ± 0.22 and 2.95 ± 0.39 log10 cfu/tissue, respectively, which increased to >9 and >5.5 log10 cfu/tissue after 24 h. Ceftibuten monotherapy demonstrated similar growth compared to saline-dosed controls. Ceftibuten-ledaborbactam activity resulted in bacterial burden ranging from 3.56 to 6.44 log10 cfu/kidney for the q8 h regimen and 4.09-5.94 log10 cfu/kidney for the q12 h regimen across nine isolates with MIC ≤ 0.5 mg/L. In bladders, a bacterial burden of 2.00-3.92 log10 cfu was observed across treatment groups. As anticipated, the high MIC strain (4 mg/L), displayed only a moderate bacterial burden reduction in the kidney and bladder after treatment.</p><p><strong>Conclusion: </strong>HSR exposures of ceftibuten-ledaborbactam administered q8 h and q12 h resulted in similar and marked bacterial reduction in an upper (kidney) and lower (bladder) UTI model caused by a variety of multi-drug resistant Enterobacterales.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2714-2718"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835162","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":"Long-acting cabotegravir and rilpivirine for the treatment of people with HIV: current landscape and challenges ahead.","authors":"Luis Buzón-Martín, Alfonso Cabello, Alberto Díaz de Santiago, María J Galindo, Carmen Hidalgo-Tenorio, Alberto Romero-Palacios, Jesús Troya","doi":"10.1093/jac/dkaf246","DOIUrl":"10.1093/jac/dkaf246","url":null,"abstract":"<p><p>Long-acting injectable cabotegravir plus rilpivirine (LAI CAB + RPV) represents an important advance in HIV treatment, offering an alternative to daily oral antiretroviral therapy (ART) for people with HIV (PWH) who are virologically suppressed. This narrative review aims to (i) evaluate the effectiveness and safety of LAI CAB + RPV in real-world clinical practice; (ii) assess outcomes in key subgroups, including women, older adults, people with elevated BMI, transgender people, and those with adherence challenges; and (iii) discuss practical and implementation considerations relevant to routine care. We synthesized the most up-to-date evidence from peer-reviewed publications and major international HIV conferences. Recent real-world cohort studies consistently report high rates of virological suppression (typically >90%) and low rates of confirmed virological failure, even in diverse populations and those with complex social or medical needs. Injection site reactions are common but rarely lead to discontinuation, and overall tolerability is high. Evidence suggests that LAI CAB + RPV can be successfully implemented in clinical practice, including among individuals with a history of non-adherence, provided that appropriate support systems are in place. However, current data are limited by short follow-up periods and relatively small sample sizes, especially in underrepresented groups such as women, older adults, people with high BMI, or transgender people. Further research is needed to clarify long-term outcomes and optimize patient selection. In summary, LAI CAB + RPV is a promising and well-tolerated option for maintaining virological suppression in routine care, with the potential to address important unmet needs across a broad spectrum of PWH. Ongoing studies will help define its optimal use and long-term benefits in real-world settings.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2565-2586"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835165","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":"Model-informed individualized administration of ceftazidime-avibactam in critically ill patients: population pharmacokinetics studies and a parametric time-to-event analysis.","authors":"Tingting Wu, Qin Ding, Shuqi Huang, Shengnan Zhang, Ruwei Yang, Yuanfang Qin, Jingjing Liu, Qi Pei","doi":"10.1093/jac/dkaf275","DOIUrl":"10.1093/jac/dkaf275","url":null,"abstract":"<p><strong>Objectives: </strong>Ceftazidime-avibactam is effective against resistant Gram-negative bacteria but associated with a risk of acute kidney injury (AKI), with incidence rates ranging from 13.3% to 33.0%. This study developed a population pharmacokinetic (PopPK) model for ceftazidime-avibactam in critically ill Chinese adults, identified AKI risk factors using a time-to-event (TTE) model, and optimized dosing.</p><p><strong>Methods: </strong>The PopPK model was developed using non-linear mixed-effects modelling (31 patients; 104 samples) and validated with 59 samples (32 patients). A TTE model identified AKI risk factors, and Monte Carlo simulations optimized dosing strategies based on these risks.</p><p><strong>Results: </strong>Both ceftazidime and avibactam were best described by a one-compartment model. Creatinine clearance (CrCL) affected clearance of both, while avibactam clearance decreased with increasing C-reactive protein. AKI patients had higher exposure. The TTE analysis identified ceftazidime AUCss,24 h and mechanical ventilation (MV) as risk factors for AKI. Simulations supported a dual-objective optimization (efficacy, AUCss,24 h ≥ 784 μg·h/mL; safety, MV ≤ 1200 μg·h/mL, non-MV ≤ 2000 μg·h/mL) and renal function-stratified dosing recommendations [CrCL > 80 mL/min, 2.5 g q8h for MV/non-MV; CrCL 50-80, 1.25 g q8h for MV/non-MV; CrCL 30-50, 0.94 g q12h (MV) versus 1.25 g q8h (non-MV); CrCL 15-30, 0.94 g q24h (MV) versus 0.94 g q12h/q24h (non-MV); CrCL 6-15, 0.94 g q48h (MV) versus 0.94 g q24h/q48h (non-MV)].</p><p><strong>Conclusions: </strong>The PopPK model for ceftazidime-avibactam was developed for critically ill Chinese adults. TTE analysis identified ceftazidime AUCss,24 h and MV as AKI risk factors. Renal function-guided dosing optimizes efficacy and safety.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2693-2704"},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835166","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}