Meta-analysis supports CAZ/AVI as Tx option for OXA-48–producing CRE

A systematic review and meta-analysis conducted by researchers in Singapore support ceftazidime-avibactam (CAZ/AVI) as a primary therapeutic alternative for the treatment of OXA-48–producing carbapenem-resistant Enterobacterales (CRE).

The cohort included 514 patients with microbiologically confirmed OXA-48 Enterobacterales infection from five studies who had received IV CAZ/AVI or any best available therapy (BAT) alternative (including CAZ but not AVI). The primary outcome was 30-day all-cause mortality. Secondary outcomes included clinical success, defined as improvement in signs and symptoms (eg, defervescence, normalization of white blood cell counts, procalcitonin, and/or C-reactive protein) from baseline to end of therapy.

All five studies showed a lower 30-day mortality rate in the CAZ/AVI than in the BAT arm (22.5 percent vs 36.6 percent; odds ratio [OR], 0.46; p<0.05). This effect was sustained in the sensitivity analysis that excluded two studies with high risk of bias (p<0.05). [JAC Antimicrob Resist 2026;8:dlaf238]

Three of the five studies reporting data on the secondary outcome demonstrated a significantly higher rate of clinical success with CAZ/AVI vs BAT using a random-effects model with inverse-variance weighting (OR, 3.67; p<0.05).

CRE a public health concern

A meta-analysis found that mortality is twice as high in patients with CRE bacteraemia as opposed to those with carbapenem-susceptible Enterobacterales, with up to a 44 percent mortality rate due to carbapenem resistance. [Emerg Infect Dis 2014;20:1170-1175] “This underscores the significance of CRE as a public health concern,” the researchers highlighted.

There has been an upsurge in OXA-48 infections worldwide compared with other classical carbapenemases. [J Glob Infect Dis 2016;8:41-50] “In addition, OXA-48-producing isolates pose a significant challenge in laboratory diagnosis as they exhibit lower in vitro carbapenemase activity and may display susceptibility or lower minimum inhibitory concentrations to third-/fourth-generation cephalosporins and carbapenems,” the researchers explained.

CAZ is a third-generation cephalosporin, while AVI is a diazabicyclooctane non-β-lactam β-lactamase inhibitor that inhibits OXA-48 by forming a stable covalent complex. [Curr Opin Microbiol 2011;14:550-555] Initially approved by the FDA in 2015, CAZ/AVI is indicated for the treatment of infections for which no alternative treatment options are available, including complicated urinary tract infections, complicated intra-abdominal infections, and pneumonia (hospital- and ventilator-acquired). [https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf, accessed February 5, 2026]

“These findings lend further tentative support to current antibiotic use guidelines, [such as ESCMID* and IDSA**, regarding] the role of CAZ/AVI for the treatment of OXA-48–producing Enterobacterales infections, over BAT comprising older agents (eg, carbapenems, polymyxins, aminoglycosides) used alone or in combination [with other agents],” the investigators concluded.

However, they noted that the findings should be interpreted with caution due to the limited number of studies, moderate-to-high risk of bias, and the broad definitions of the population, intervention, and the comparator. The study included participants with microbiologically confirmed OXA-48–producing Enterobacterales infection, irrespective of site, who had received any CAZ/AVI-containing regimen or other BAT, instead of a specific alternative antibiotic.

“[Also,] mortality alone may not reflect treatment efficacy, as it can be influenced by various factors unrelated to antibiotic treatment, such as underlying patient comorbidities or non-infectious complications, which are often more complex in patients with CRE infections,” they added.

The researchers called for further studies to validate the findings and ascertain the role of CAZ/AVI in relation to other emerging new therapies.