Evaluation of clinical and microbiological factors related to mortality in patients with Gram-negative bacterial infections treated with ceftazidime-avibactam: A prospective multicentric cohort study.

OBJECTIVES: This study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime-avibactam for carbapenem-resistant Gram-negative bacterial infections. METHODS: This multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime-avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. RESULTS: Of the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.6%) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28-4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24-3.78, P < 0.01). Only one patient developed resistance to ceftazidime-avibactam during treatment. CONCLUSIONS: Treatment with ceftazidime-avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.

Vancomycin and creatinine determination in dried blood spots: Analytical validation and clinical assessment.

This study aims to develop a liquid chromatography tandem-mass spectrometry (LC-MS/MS) method for vancomycin and creatinine measurement in dried blood spots (DBS) and to evaluate its clinical application. The analytes were extracted from DBS and analyzed by LC-MS/MS. Vancomycin and creatinine DBS and plasma concentrations were compared in 54 and 35 samples, respectively, from 29 patients. Accuracy was 94.4-102.6%, intra-assay precision was 2.1-5.6%, and inter-assay precision was 3.5-7.0%. Patients vancomycin plasma to DBS concentration ratios were highly variable (1.148-5.022), differently from creatinine (0.800-1.283). The assay has adequate analytical performance. Plasma concentrations can be satisfactorily predicted from DBS measurements for creatinine, but not for vancomycin, which limits its clinical application.