Impact of ceftazidime/avibactam versus best available therapy on mortality from infections caused by carbapenemase-producing Enterobacterales (CAVICOR study).

BACKGROUND: Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown. METHODS: We conducted a multicentre retrospective observational study of patients who received ≥48 h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30 day crude mortality. Secondary outcomes were 21 day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30 day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis. RESULTS: The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2 days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20-0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18-1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08-1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21 day clinical response (OR 2.43, 95% CI 1.16-5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18-0.85; P = 0.02). CONCLUSIONS: Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.

Effectiveness of ceftazidime/avibactam as salvage therapy for treatment of infections due to OXA-48 carbapenemase-producing Enterobacteriaceae.

Background: Experience in real clinical practice with ceftazidime/avibactam is limited, and there are even fewer data on infections due to OXA-48-producing Enterobacteriaceae. Methods: We designed an observational study of a prospectively collected cohort of adult patients receiving ceftazidime/avibactam in our centre. Only the first treatment course of each patient was analysed. Efficacy and safety were evaluated as 14 and 30 day mortality, recurrence rate at 90 days, resistance development and occurrence of adverse effects. Results: Fifty-seven patients were treated with ceftazidime/avibactam. The median age was 64 years (range 26-86), 77% were male and the median Charlson index was 3. The most frequent sources of infection were intra-abdominal (28%), followed by respiratory (26%) and urinary (25%). Thirty-one (54%) patients had a severe infection (defined as presence of sepsis or septic shock). Most patients received ceftazidime/avibactam as monotherapy (81%) and the median duration of treatment was 13 days. Mortality at 14 days was 14%. In multivariate analysis, the only mortality risk factor was INCREMENT-CPE score >7 (HR 11.7, 95% CI 4.2-20.6). There was no association between mortality and monotherapy with ceftazidime/avibactam. The recurrence rate at 90 days was 10%. Ceftazidime/avibactam resistance was not detected in any case and only two patients developed adverse events related to treatment. Conclusions: Ceftazidime/avibactam shows promising results, even in monotherapy, for the treatment of patients with severe infections due to OXA-48-producing Enterobacteriaceae and limited therapeutic options. The emergence of resistance to ceftazidime/avibactam was not observed.