Journal of Antimicrobial Chemotherapy最新文献

Objectives: To clarify the relationship between acute kidney injury (AKI) and vancomycin use in patients with renal impairment and to establish a risk score for AKI.

Methods: In this retrospective, multicentre, observational cohort study, trough and peak blood samples were collected from patients who initiated vancomycin therapy. The cumulative incidence of AKI within 14 days was compared among three groups classified according to renal function (estimated glomerular filtration rate ≥ 60, 30-59 and <30 mL/min/1.73 m2). The risk score and predicted probability of AKI incidence were calculated. AKI was defined in accordance with the Kidney Disease Improving Global Outcomes criteria.

Results: The incidence of AKI was 11.7% (99/847). No statistically significant difference was detected in the cumulative incidence of AKI among the three groups (P = 0.103). Cox proportional hazard analysis showed that the use of tazobactam/piperacillin [HR: 3.3, 95% CI (2.18-4.99), 2 points], vasopressors/inotropes [HR: 3.0, 95% CI (2.02-4.51), 2 points] and area under the concentration-time curve (AUC) on Day 2 [500-600 µg·h/mL: HR, 2.4, 95% CI (1.50-3.89), 1 point; >600 µg·h/mL: HR, 4.4, 95% CI (2.62-7.37), 3 points] were significantly related to the development of AKI. The predicted probabilities of AKI incidence were <5% (low-risk), 5% to <20% (moderate-risk), 20% to <40% (high-risk) and 40% to 67% (very high-risk), with total points of 0, 1-2, 3-4 and ≥5, respectively.

Conclusions: A risk prediction model was developed for AKI based on AUC exposure and concomitant medications, and no difference in AKI risk was observed across renal function categories.

Background: Emergence and spread of carbapenem-resistant Acinetobacter baumannii (CRAB) producing metallo-β-lactamases (MBLs), especially New Delhi MBLs (NDMs), are concerning due to resistance to last-resort antibiotics.

Methods: PubMed and Scopus were queried for studies published between 2020 and 2024 reporting MBL prevalence in CRAB isolates. Risk of bias was assessed across the population, setting and measurement domains. Binomial-Normal mixed-effects models were applied to estimate regional and country-specific weighted MBL and NDM prevalence proportions in CRAB. Subgroup and meta-regression analyses were performed to investigate heterogeneity.

Results: Two hundred thirty-three studies reporting 58 676 CRAB isolates were analysed. The global MBL prevalence in CRAB was 5.3% [95% confidence interval CI), 3.3%-8.2%]. Regional variability explained a substantial portion of heterogeneity in meta-regression (R2 = 35%). MBL prevalence in CRAB was highest in the Eastern Mediterranean (42.1%; 95% CI, 28.7%-56.8%) and African (36.1%; 95% CI, 12.2%-69.8%) regions, moderately high in South-East Asia (17.9%; 95% CI, 9.6%-30.9%), and low (<1%) in Europe, the Americas and the Western Pacific region. MBL prevalence in CRAB was higher in studies conducted during 2020-2024 than during 2012-2019 (7.2% versus 4.2%; adjusted odds ratio 2.3, P = 0.024). NDM was the dominant MBL in CRAB, with a global prevalence of 1.7% (95% CI, 1.1%-2.7%) in 218 studies.

Conclusions: Although its global prevalence is low, MBL-producing CRAB is common in specific regions and countries, threatening the utility of new antibiotics. Sustained surveillance, rigorous infection control and antimicrobial stewardship are required to preserve the activity of last-resort antimicrobials.

Background: People with HIV have a greater risk of cardiovascular disease than the general population. Current literature suggests that some ARTs may exacerbate this risk.

Objectives: To estimate the risk of hypertension in treatment-naïve people with HIV receiving integrase strand transfer inhibitor (INSTI)/tenofovir alafenamide (TAF) or INSTI/non-TAF versus NNRTI/non-TAF regimens.

Methods: Post hoc pooled analysis evaluating data from US participants in five Phase 3 randomized studies. Adjusted prevalence of Stage 1 and 2 hypertension (American College of Cardiology/American Heart Association criteria) and conditional odds of higher blood pressure ratios were estimated using proportional odds mixed-effect regression through 108 weeks after ART initiation. Time to incident hypertension through 96 weeks was modelled using Cox proportional-hazards regression.

Results: In total, 2411 participants were included (528, 749 and 1134 received NNRTI/non-TAF, INSTI/non-TAF and INSTI/TAF regimens, respectively). Nearly half of participants had hypertension (Stage ≥1) at baseline. The Week 96 adjusted estimates of risk of hypertension (95% CI) were 1.06 (0.99, 1.13) and 1.12 (0.98, 1.27) for Stages ≥1 and ≥2 hypertension, respectively, for NNRTI/non-TAF versus INSTI/non-TAF, and 1.01 (0.95, 1.08) and 1.02 (0.91, 1.17) for Stages ≥1 and ≥2 hypertension, respectively, for NNRTI/non-TAF versus INSTI/TAF. There were no significant differences in conditional odds of high blood pressure between treatment groups. No significant differences were identified in time to incident composite hypertension for INSTI/non-TAF and INSTI/TAF versus NNRTI/non-TAF regimens; estimated hazard ratios (approximate 95% CI) were 0.88 (0.66, 1.17) and 0.98 (0.75, 1.28), respectively.

Conclusions: Results suggest the risk of hypertension is not significantly different across INSTI/TAF, INSTI/non-TAF and NNRTI/non-TAF regimens.

Background and objective: Stenotrophomonas maltophilia is an emerging multidrug-resistant opportunistic pathogen, frequently recovered from deep sites in immunocompromised or critically ill patients. Its clinical relevance is difficult to distinguish from colonization, particularly in polymicrobial infections. To describe the management of patients with deep-site S. maltophilia isolates and to identify factors associated with 28-day mortality.

Methods: We conducted a bicentric retrospective study including all patients with at least one deep-site S. maltophilia isolates in two Paris academic hospitals between 2018 and 2020. Demographic, clinical, microbiological and therapeutic data were collected. Appropriate therapy was defined upon in vitro susceptibility. Propensity score weighting was applied to adjust for confounding when assessing the association between appropriate therapy and 28-day mortality.

Results: A total of 131 patients were included (67% male; median age 61 years); 63% were immunocompromised and 31% admitted to intensive care. Isolates originated mainly from urine (41%), blood (32%) and respiratory samples (21%); 57% of cultures were polymicrobial. Appropriate therapy was administered to 53% of patients, predominantly trimethoprim/sulfamethoxazole or fluoroquinolones. Overall 28-day mortality was 20%. Mechanical ventilation was independently associated with mortality (HR 4.13, P = 0.001). After propensity score weighting, appropriate therapy was not significantly associated with improved survival.

Conclusion: Targeted therapy against S. maltophilia did not reduce 28-day mortality after adjustment, suggesting that patient condition and infection severity may outweigh the effect of targeted treatment. Given the modest sample size, potential confounding, and the secondary nature of this analysis, these findings should be interpreted with caution. Careful clinical evaluation is warranted before initiating specific S. maltophilia therapy.

Objectives: The aim of this study was to investigate the fluctuations in isavuconazole concentrations and to identify influencing factors in Chinese patients with haematological malignancies.

Methods: A retrospective analysis was conducted on patients with haematological malignancies who received their first standard dose of isavuconazole treatment in 2024. Statistical analysis of trough concentrations of isavuconazole, demographics and clinical characteristics over 60 days of treatment was performed. A nomogram was constructed based on independent risk factors to predict isavuconazole trough concentrations > 7 mg/L.

Results: A total of 63 patients with a median age of 54 (39-63) years and 390 isavuconazole plasma concentrations with a median value of 5.68 mg/L (range 1.24-16.49 mg/L) were included. The median intra- and inter-individual coefficients of variation were 15.0% and 43.3%, respectively. In univariate and multivariate analysis, isavuconazole levels > 7 mg/L on day 7 were significantly associated with body mass index (BMI) and albumin (ALB). Compared to patients with a BMI > 21.0 kg/m2, those with a BMI ≤ 21.0 kg/m2 exhibited a 15.88-fold increased risk of isavuconazole trough concentrations > 7 mg/L. Similarly, patients with ALB ≥ 36.4 g/L showed a 4.71-fold higher risk of elevated isavuconazole levels than those with ALB < 36.4 g/L. A nomogram model for effectively predicting the risk of isavuconazole concentrations exceeding 7 mg/L based on BMI and ALB results was successfully established.

Conclusions: Patients with haematological malignancies treated with isavuconazole show modest plasma concentration variability. However, for patients with a BMI ≤ 21.0 kg/m2 and/or an ALB ≥ 36.4 g/L, we propose that therapeutic drug monitoring may assist in ensuring medication safety. Additionally, for the first time, a nomogram was developed to predict isavuconazole levels > 7 mg/L using BMI and ALB, though further validation is warranted.

Background: Teicoplanin exhibits complex pharmacokinetics with substantial inter-patient variability. Therapeutic drug monitoring (TDM) is recommended to ensure adequate exposure, yet contemporary data on real-world prescribing practices are scarce. We evaluated current teicoplanin dosing and monitoring practices across UK and Irish hospitals.

Methods: We conducted a multicentre, retrospective cohort study (Teicoplanin in UK: Study of Hospital Practice; TUcK-SHOP) across 21 hospitals. Adults receiving ≥5 days of intravenous/intramuscular teicoplanin with at least one TDM sample were included. Primary outcome was adherence to local or national dosing guidelines. Secondary outcomes included initial trough level attainment (≥20 mg/L) and laboratory-confirmed toxicity. Multivariable linear regression identified predictors of first trough concentrations.

Results: A total of 391 patients met inclusion criteria (median age 69 years; 57.5% male). Guideline adherence was 66% overall but varied widely between sites (5%-100%). Most patients received three-dose loading (61.3%) with median maintenance dosing of 10.6 mg/kg daily (IQR 7.3-12.1). Median first trough level was 24.6 mg/L (IQR 17.9-33.2); only 40.8% of patients on 6 mg/kg maintenance achieved ≥20 mg/L versus 86.6% on 12 mg/kg (P < 0.001). Independent predictors of higher trough levels included lower creatinine clearance, longer time to TDM sampling, higher loading and maintenance doses, and greater body weight (adjusted R2 = 0.26, P < 0.001). Dose adjustments were required in 30% of patients.

Conclusions: Teicoplanin prescribing demonstrates significant variation across UK and Irish hospitals. Higher maintenance dosing (10-12 mg/kg) predicts therapeutic target attainment. These real-world data support the need for standardized dosing protocols to optimize teicoplanin therapy.

Introduction: Risk of transmission of HIV through breastfeeding is minimal in case of maternal viral suppression due to antiretroviral therapy. However, to what extent antiretroviral drugs transfer into breastmilk is not fully understood. Data are especially lacking for relatively newer drugs-such as bictegravir-that only recently was approved to use in pregnancy. Therefore, the aim of this study is to determine infant exposure to bictegravir through breastmilk.

Materials and methods: Concentrations of bictegravir were measured in plasma and breastmilk of healthy, lactating women without HIV after a single dose of bictegravir 50 mg (co-formulated with tenofovir alafenamide 25 mg and emtricitabine 200 mg). Concentrations were measured using validated LC-MS/MS assays and pharmacokinetic parameters were calculated using non-compartmental analysis. Breastmilk to maternal plasma ratio, daily infant dosage and relative infant dose were established to determine infant exposure to bictegravir through breastmilk.

Results: Twelve volunteers participated in the study. The geometric mean (CV%) area under the curve based on the last measured concentration was 52.17 (22.6) mg*h/L in plasma and 0.44 (32.0) mg*h/L in breastmilk, resulting in a geometric mean (CV%) breastmilk to maternal plasma ratio of 0.009 (26.6). The median (IQR) daily infant and relative infant doses with an intake of 150 or 200 mL/kg/day were 0.034 mg/kg/day (0.026-0.060) and 0.046 (0.035-0.080) mg/kg/day and 0.68 (0.53-1.00) % and 0.90% (0.71-1.33), respectively.

Conclusion: Exposure to bictegravir through breastmilk is very low, with a relative infant dose below 1%. Even though metabolizing capacity in newborns is not yet fully developed, it is not expected to cause infant toxicity.

Introduction: Selection and dosing of surgical antimicrobial prophylaxis (SAP) to prevent surgical site infections (SSIs) is variable and often inappropriate in clinical settings resulting in increased risk of SSI. We therefore developed and implemented a novel computer decision-support tool to improve appropriate SAP selection specific to each patient's procedure and clinical context.

Methods: The intervention, performed at a multi-site tertiary hospital network, was a computer decision-support tool programmed within the hospital's electronic health record (EHR) to provide patient-specific SAP recommendations based on four variables: procedure name, patient's beta-lactam allergy status, MRSA status and weight. Safety of cefazolin prophylaxis among patients with self-reported beta-lactam allergy was established in the pre-operative clinic using a validated simple two-item questionnaire. Before each operation, a best practice SAP recommendation alert was provided to the anaesthesiologist based on the inputs from the four aforementioned variables.

Results: In the post-intervention period of 2 years, a total of ∼110 recommendation alerts were logged. A random sample audit of 408 surgical encounters were selected from the pre- and post-intervention periods. Overall, appropriate antibiotic administration rose from 77% (161/208) to 92.5% (185/200) (χ2 = 18.0, P < 0.001) post-intervention. Significant improvements were made for procedure-specific antibiotic selection (80.5% versus 94.5%; χ2 = 19.3, P < 0.001) and weight-based dosing (92.5% versus 98.4%; χ2 = 7.45, P = 0.006). Using National Surgical Quality Improvement Program (NSQIP) auditing of 21 912 surgeries showed a significant decline in SSIs following the implementation of the intervention in June 2022.

Conclusion: In this first-ever intervention designed to direct SAP prescribing based on patient-specific variables, we significantly improved appropriate SAP selection and reduced SSIs across a comprehensive list of surgical procedures.

Objectives: Pseudomonas aeruginosa is a common microorganism in chronic infections due to biofilm formation and antibiotic resistance. This study aimed to compare the synergistic effects of antibiotic combinations against carbapenem-resistant P. aeruginosa (CRPA) in planktonic and biofilm-embedded states.

Methods: Twelve CRPA bloodstream isolates from the Asian Bacterial Bank (2016-2018) were analysed. The minimum biofilm eradication concentrations (MBECs) were determined using the peg lid system, and antimicrobial interactions were assessed using biofilm checkerboard assays, testing three double combinations (colistin-rifampin, colistin-imipenem, and rifampin-ceftazidime/avibactam) and two triple combinations (colistin-rifampin-imipenem and colistin-rifampin-ceftazidime/avibactam).

Results: The MBEC values of all four antimicrobial agents (rifampin, colistin, imipenem, and ceftazidime/avibactam) were significantly higher than their corresponding minimum inhibitory concentration values (P < 0.001). Although single agents required markedly elevated concentrations to eradicate CRPA biofilms, approximately half of the double and triple antimicrobial combinations demonstrated synergistic activity. In the biofilm phase, synergism rates were comparable between triple combinations (colistin-rifampin-ceftazidime/avibactam, 50%; colistin-rifampin-imipenem, 66%) and double combinations (colistin-rifampin, 42%; rifampin-ceftazidime/avibactam, 42%; colistin-imipenem, 66%). The triple combinations showed lower FBEC indices (colistin-rifampin-imipenem: median 0.17; colistin-rifampin-ceftazidime/avibactam: 0.34) than the corresponding double combinations (colistin-rifampin: 0.53; colistin-imipenem: 0.20; rifampin-ceftazidime/avibactam: 0.78), although these differences were not statistically significant.

Conclusions: Our study provides experimental evidence that antimicrobial combination therapy may offer advantages over single agents for CRPA biofilm eradication, supporting further investigation into the role of such regimens in biofilm-associated infections.