Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients.

OBJECTIVES: The primary objective was to describe clinical features, treatment and outcomes in patients with carbapenemase-producing Enterobacteriaceae (CPE) bacteremia. Additionally, patients treated with ceftazidime/avibactam (study group) were compared to the rest of the patients (comparator group) to determine the influence of the treatment in both crude mortality and clinical cure. METHODS: Multicenter and retrospective study that included patients with hematologic malignancies who had CPE bacteremia. A bivariate analysis was performed to compare the clinical variables between the study group and the control group. RESULTS: 31 patients were included. Bacteremia was considered primary in 14 (45%) patients. Overall crude mortality at 30days was 45.2% (n=14). Mortality was more frequent when septic shock (78.6% vs 11.8%; p>0.001) and higher Pitt score (6+14 vs 1.5+4; p<0.01) were present. 8 patients (25.8%) received treatment with ceftazidime/avibactam. No significant differences in crude mortality were found between study and comparator groups (p=0.19). In contrast, patients in study group had higher clinical cure rates than the comparator group within 14days of initiating treatment (85.7% vs. 34.8%, respectively, p=0.031). CONCLUSIONS: CPE bacteremia is associated with high mortality in patients with hematologic malignancies. Ceftazidime/avibactam may be an effective alternative for treating these patients.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.