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July 21, 2021

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Zeina A. Kanafani, MD, MS, FIDSA.jpgAddition of Aztreonam to Ceftazidime-avibactam Improves Outcomes in Some Drug-resistant Gram-negative Infections

By Manie Beheshti, MD

Antimicrobial resistance continues to remain a top health threat according to the World Health Organization and the Centers for Disease Control and Prevention. Difficult-to-treat gram-negative infections, such as those caused by metallo-β-lactamase (MBL) producing Enterobacterales, lead to increased complications and worsened outcomes and pose a challenge for providers. Effective antibiotics for such infections are limited, and combinations of existing antibiotics have been previously investigated.

A report in the June 1 issue of Clinical Infectious Diseases demonstrates that the addition of aztreonam (ATM) to ceftazidime-avibactam (CAZ-AVI) for infections due to MBL-producing Enterobacterales leads to better outcomes. In this prospective, observational study out of Greece and Italy, 30-day mortality, the main study outcome, was compared between patients receiving CAZ-AVI with ATM (CAA) and those receiving other active antibiotics (OAAs). 

Therapeutic decisions were made by five independent ID physicians based on sensitivity data. The 30-day mortality was 19.2% in the 52 CAA patients compared to 44% in the OAA group (P = .007). In 82 and 20 patients, resistance was due to New Delhi metallo-β-lactamase and Verona integron encoded metallo-β-lactamase, respectively. Improvement in secondary outcomes was also noted. Clinical failure at 14 days was lower in the CAA group (hazard ratio, 0.30; 95% confidence interval [CI], 0.14-0.65, P = 0.002). Length of stay was also shorter in the CAA group (subdistributional hazard ratio, 0.49; 95% CI, 0.30-0.82; P =.007). Clinical characteristics were largely similar. However, ICU care was more frequent in the CAA group, whereas immunosuppressive therapy and acquisition of infection in a surgical ward were more prevalent in the OAA group. 

Though this is an observational, nonrandomized study with a small sample size, it does provide an added strategy for infections where therapeutic options are few. The authors attempted to address these limitations and provide data that could help with antibiotic selection and, ultimately, improve patient outcomes. Until novel, effective antibiotics are readily available, further studies like this will be needed to help us better understand how to approach these difficult-to-treat infections with the limited available antimicrobials.

(Falcone et al. Clin Infect Dis. 2021;72(7):1871-1878.)

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