Efficacy of Ceftazidime/Avibactam in the Treatment of Infections Caused by Carbapenemase-Producing Enterobacteria

Patient Population and Evaluated Parameters

A total of 339 adult patients (mean age 70 years) hospitalized between June 2014 and December 2019 with urinary tract infections (n = 129; 38.1%), bloodstream infections (n = 111; 32.7%), intra-abdominal infections (n = 60; 17.7%), or pneumonia (n = 39, including 15 ventilator-associated cases; 11.5%) were enrolled in the Spanish multicenter retrospective observational study CAVICOR. The etiology involved infections caused by carbapenemase-producing enterobacteria. A total of 189 (55.8%) of these patients were treated with the combination of ceftazidime/avibactam, while the remaining 150 (44.2%) received BAT as decided by the attending physician..

The primary parameter evaluated was 30-day mortality, with secondary parameters being clinical response (i.e., absence of symptoms of persistent infection or its relapse) and microbiological response (i.e., negative culture of biological material collected at least 5 days after starting therapy) after 21 days of treatment.

Findings

Overall 30-day mortality was 17.4% (n = 59), being highest in patients with pneumonia (28.2%) and lowest in patients with intra-abdominal infections (10%). Specifically, it was also lower in the group treated with the combination of ceftazidime/avibactam compared to those receiving BAT (13.7% vs. 22%; p = 0.04; odds ratio [OR] 0.41; 95% confidence interval [CI] 0.20–0.80; p = 0.01). The SOFA score (Sequential Organ Failure Assessment; OR 1.20; 95% CI 1.08–1.34; p = 0.001) and INCREMENT-CPE > 7 (OR 2.57; 95% CI 1.18–5.58; p = 0.01) emerged as independent risk factors for mortality. 

Clinical response was achieved after 21 days of therapy in 84.9% of patients, more frequently in those treated with the combination of ceftazidime/avibactam compared to those receiving BAT (89.4% vs. 79.3%; p = 0.01; OR 2.43; 95% CI 1.16–5.12; p = 0.02).

Repeat cultures of biological material were performed on a total of 192 patients, with microbiological eradication achieved in 78.1%. This was more common in patients treated with the combination of ceftazidime/avibactam (83.3% vs. 69.4%; p = 0.02; OR 0.40; 95% CI 0.18–0.85; p = 0.02).

Adverse events related to antibiotic therapy were reported in a total of 12.1% of patients, less frequently in those treated with the combination of ceftazidime/avibactam (5.8% vs. 20%; p < 0.001). The most common adverse events were renal failure (43.9%) and diarrhea (21.9%), with two cases of clostridial enterocolitis in patients treated with the combination of ceftazidime/avibactam.

Conclusion

Ceftazidime/avibactam appears to be an effective alternative for treating infections caused by carbapenemase-producing enterobacteria, particularly in patients with an INCREMENT-CPE score > 7 points. However, these findings should be confirmed by randomized controlled trials in the future.

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Source: Castón J. J., Cano A., Pérez-Camacho I. et al. Impact of ceftazidime/avibactam versus best available therapy on mortality from infections caused by carbapenemase-producing Enterobacterales (CAVICOR study). J Antimicrob Chemoter 2022; 77 (5): 1452–1460, doi: 10.1093/jacPdkac049.