Aztreonam-avibactam cures serious infections due to Gram-negative bacteria

Treatment with aztreonam in combination with avibactam (ATM-AVI) results in favourable clinical response and is well tolerated in patients with complicated intra-abdominal infection (cIAI) and hospital-acquired or ventilator-associated pneumonia (HAP/VAP) due to Gram-negative bacteria, according to the results of the REVISIT study.

In addition, the efficacy of the combined treatment was comparable to that of meropenem with or without colistin (MER ± COL).

“These data support [the] potential use of ATM-AVI for the treatment of serious infections caused by susceptible Gram-negative bacteria,” said co-author Dr Francis Arhin, director of developmental microbiology at Pfizer, Inc, Manitoba, Canada, who presented the findings at IDWeek 2023.

Arhin and his colleagues conducted REVISIT to examine the efficacy and safety of ATM-AVI in the treatment of cIAI or HAP/VAP due to Gram-negative bacteria, including metallo-β-lactamase (MBL)-producing multidrug resistant pathogens, with limited or no treatment options.

REVISIT was a phase III, prospective, randomized, multicentre, open-label, central assessor-blinded study in adults hospitalized due to a serious infection. These patients were randomly assigned in a 2:1 ratio to receive either ATM-AVI (with or without metronidazole [MTZ]; cIAI patients only) or MER ± COL for 5 to 14 (cIAI patients) or 7 to 14 days (HAP/VAP patients).

The primary endpoints were clinical cure at the test-of-cure visit in the intent-to-treat and clinically evaluable analysis sets. Other endpoints assessed were microbiological responses at test-of-cure visit, 28-day mortality, and safety.

Cure rates

A total of 422 patients were analysed, of whom 282 were treated with ATM-AVI ± MTZ and 140 with MER ± COL. Overall, the adjudicated clinical cure rates were similar between the two treatment arms (ATM-AVI: 193/282, 68.4 percent; MER ± COL: 92/140, 65.7 percent). [IDWeek 2023, abstract 2893]

Likewise, no significant difference was observed in terms of favourable microbiological response rates at test-of-cure visit: 75.7 percent for ATM-AVI vs 73.9 percent for MER ± COL.

The rates for 28-day all-cause mortality in cIAI and HAP/VAP were 1.9 percent (4/208) and 10.8 percent (8/74) for ATI-AVI and 2.9 percent (3/104) and 19.4 percent (7/36) for MER ± COL, respectively. Higher mortality rates were seen for HAP/VAP than cIAI, consistent with higher severity of illness.

In the safety analysis set, Arhin and his team recorded several adverse events (AEs), including anaemia, increased ALT, diarrhoea, hypokalaemia, increased AST, and pyrexia, among others. Majority of these AEs were mild to moderate in severity.

“Looking specifically at treatment-related adverse events … there were no new findings beyond what [is expected],” Arhin said. “There were no treatment-related serious AEs in the ATM-AVI group.”

Additionally, no cases of Hy’s law were reported, and no treatment-related deaths occurred.

“So based on these results, we conclude that ATM-AVI was effective in treating patients with cIAI and HAP/VAP, displaying similar efficacy to MER ± COL,” Arhin said. “From the safety results, ATM-AVI was generally well tolerated, with no new safety findings.”

Further studies will focus on MBL-producing pathogens, according to the researchers.