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TOPLINE:

Ceftazidime-avibactam plus aztreonam, initiated within 24 hours of detecting metallo-beta-lactamase (MBL)-producing Enterobacterales bacteremia, reduced 30-day mortality and clinical failure rates more effectively than other active antibiotics and was associated with fewer adverse events.

METHODOLOGY:

• Ceftazidime-avibactam plus aztreonam is recommended as first-line therapy for infections caused by MBL-producing Enterobacterales; however, clinical evidence supporting the effectiveness of this combination remains limited.
• Researchers emulated a retrospective target trial across 17 hospitals in Argentina to assess the effectiveness and safety of ceftazidime-avibactam plus aztreonam vs other active antibiotics in patients with confirmed MBL-type carbapenemase-producing Enterobacterales bacteremia from January 2016 to October 2024.
• Among 243 patients, 93 received ceftazidime-avibactam plus aztreonam (median age, 62 years) and 150 received other active antibiotics, including colistin, meropenem, fosfomycin, aminoglycosides, and tigecycline (median age, 56 years) within 24 hours of MBL detection and 96 hours of blood culture collection.
• The primary outcome was 30-day all-cause mortality, and secondary outcomes included clinical failure (relapse, complications, or death) and adverse events.

TAKEAWAY:

• Treatment with ceftazidime-avibactam plus aztreonam resulted in a lower 30-day mortality rate than treatment with other active antibiotics (35% vs 47%; P < .01).
• Clinical failure was 46% (95% CI, 35-56) and occurred at a median of 11 days in patients treated with ceftazidime-avibactam plus aztreonam vs 53% in patients treated with other active antibiotics (95% CI, 44-61), who experienced failure at a median of 6 days (P = .03).
• Adverse events were also less frequent in patients treated with ceftazidime-avibactam plus aztreonam (9.6%) than in those treated with other active antibiotics (22.8%; P = .014).
• Likewise, new acute kidney injury was less common, and no cases of thrombocytopenia were reported in the ceftazidime-avibactam plus aztreonam group.

IN PRACTICE:

“These findings further emphasize the efficacy and safety profile of CAZAVI + ATM [ceftazidime-avibactam plus aztreonam] in the treatment of severe, multidrug-resistant infections,” the authors wrote.

SOURCE:

This study was led by Ivan Alfredo Huespe, Hospital Italiano de Buenos Aires in Buenos Aires, Argentina. It was published online on July 5, 2025, in The Lancet Regional Health - Americas.

LIMITATIONS:

As this was a retrospective study, treatments were not randomized, and despite adjustments for known confounders, residual confounding by unmeasured variables could not be entirely ruled out. Synergy testing for ceftazidime-avibactam-aztreonam was unavailable in several hospitals. The retrospective design prevented the assessment of patient-reported outcomes or clinician acceptability. Heterogeneity within the comparator group and limited data on adverse events such as C difficile-associated diarrhea hindered more detailed analysis.

DISCLOSURES:

No specific funding was provided for this study. Three authors disclosed receiving payment, honoraria, or travel support or participating on a data safety monitoring board or advisory board for pharmaceutical organizations, including Pfizer, Bago, and BD.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.