An international team of investigators this week published phase 3 clinical trial data supporting aztreonam-avibactam as a potential therapeutic option for patients with serious gram-negative bacterial infections with limited treatment options.

Jointly developed by Pfizer and Abbvie, aztreonam-avibactam is a beta-lactam/beta-lactamase inhibitor combination that restores aztreonam's activity against gram-negative bacteria that carry two defense mechanisms—metallo-beta-lactamase (MBL) and beta-lactamase enzymes—that confer resistance to nearly all currently available antibiotics. It was approved in April by the European Medicines Agency based on the results of two phase 3 clinical trials that evaluated its efficacy in treating several types of multidrug-resistant infections.

The results of the open-label REVISIT trial, published in The Lancet Infectious Diseases, show that aztreonam-avibactam had similar clinical cure rates as meropenem in 422 patients with either complicated intra-abdominal infection (76.4% vs 74.0%, respectively) or hospital-acquired/ventilator-associated pneumonia (HAP-VAP) (45.9% vs 41.7%) caused by gram-negative bacteria. The investigators also found that overall all-cause mortality rates at 28 days were relatively low, and similar between both treatment groups for each infection type (2% for aztreonam-avibactam vs 3% for meropenem in patients with complicated intra-abdominal infection and 11% vs 19% in patients with HAP-VAP).

Aztreonam-avibactam was generally well-tolerated, with safety findings that were consistent with the known safety profile of aztreonam.

"These phase 3 efficacy and safety data provide support for aztreonam-avibactam as a potential therapeutic option for complicated intra-abdominal infection or HAP-VAP caused by Gram-negative bacteria," the investigators wrote.

Trial limitations

The investigators add, however, that while the trial was conducted in a region where MBL-producing gram-negative pathogens are prevalent, few patients in the trial had infections caused by MBL-producing bacteria, highlighting the need for more data on the drug's efficacy against such pathogens. That concern is echoed in a commentary by infectious disease experts from the University of Maryland School of Pharmacy and the University of Pittsburgh.

"Ultimately, the small number of patients with metallo-β-lactamases in the study restricts the ability to draw conclusions about the utility of aztreonam-avibactam in eradicating these difficult-to-treat pathogens," Emily Heil, PharmD, and Erin McCreary, PharmD wrote.

A study of long-term care (LTC) facilities in Massachusetts found that residents with a documented penicillin allergy were 95% less likely to receive beta-lactam antibiotics, researchers reported yesterday in Antimicrobial Stewardship & Healthcare Epidemiology.

For the study, researchers from Tufts University and the Massachusetts Department of Public Health analyzed data on antibiotic prescriptions and penicillin allergies at 20 LTC facilities across the state. The aim of the study was to measure the impact of documented penicillin allergies on the prescribing patterns of beta-lactam antibiotics in LTC facilities, where an estimated 50% to 75% of residents receive at least on antibiotic annually. Previous research has shown that penicillin allergy labels are frequently inaccurate and can result in the selection of broader-spectrum antibiotics, which contribute to antimicrobial resistance and have an increased risk of side effects.

"Inaccurate penicillin allergy labeling poses a critical health threat in this vulnerable population because older individuals are more susceptible to mortality from multidrug-resistant infections and adverse effects from broad-spectrum antibiotics," the study authors wrote.

Penicillin allergy delabeling efforts needed in LTCs

Among 2,345 LTC residents, 449 (19.1%) received an antibiotic, and 156 of the antibiotic recipients (34.7%) had a documented penicillin allergy. The primary indications for antibiotic prescriptions were urinary tract infections (UTIs) (45.4%), respiratory tract infections (RTIs) (29.2%), and skin and soft-tissue infections (SSTIs) (18.5%). Beta-lactams accounted for 45.5% of all antibiotic prescriptions.

Inaccurate penicillin allergy labeling poses a critical health threat in this vulnerable population because older individuals are more susceptible to mortality from multidrug-resistant infections and adverse effects from broad-spectrum antibiotics.

Multivariable regression analysis revealed that residents with a documented penicillin allergy were significantly less likely to be receiving beta-lactam antibiotics for all infections (adjusted odds ratio [aOR], 0.05; 95% confidence interval [CI], 0.03 to 0.09), UTIs (aOR, 0.03; 95% CI, 0.01 to 0.08), RTIs (aOR, 0.05; 95% CI, 0.02 to 0.13), and SSTIs (aOR, 0.11; 95% CI 0.03 to 0.38).

The authors say the findings underscore the need to improve penicillin allergy assessments and delabeling strategies in LTC settings.