Journal of Antimicrobial Chemotherapy最新文献

Objective: From 2017 to 2024, there were 16 cases of ceftriaxone-resistant gonorrhoea in Canada, 8 of which were isolated in 2024, including one XDR case. We describe the clinical and demographic details of all 16 cases and examine the phenotypic and molecular characteristics of each case. To investigate the relatedness of the cases both to each other and to international isolates, a phylogenetic tree was constructed.

Methods: All 16 ceftriaxone-resistant isolates underwent WGS and were compared to the international isolates. Antimicrobial susceptibility testing was completed by agar dilution following the CLSI protocol.

Results: Ceftriaxone MICs for the 16 isolates range between 0.25 and 2 mg/L. All cases were isolated from genital sites, and four cases were probable treatment failures. Ten of the cases were linked to international travel.Seven of the isolates were part of the NG-STAR ST 233 clonal complex. All 16 cases have penA alleles associated with cephalosporin resistance, including penA 60.001, penA 121.002, penA 237.001 and penA 294.002.

Conclusion: We summarize 16 cases of ceftriaxone-resistant gonorrhoea that were isolated in Canada from 2017 to 2024. We determined the penA allele type for each case and detected molecular markers associated with cephalosporin resistance. Local public health investigations and the genomic data for each case indicate that the strains did not spread further in the population. To date, ceftriaxone remains an effective treatment for gonorrhoea, but continued surveillance is required to ensure detection and thus prevent the further spread of ceftriaxone-resistant Neisseria gonorrhoeae in Canada.

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 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.

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.