Ceftazidime-avibactam and aztreonam combination for Carbapenem-resistant Enterobacterales bloodstream infections with presumed Metallo-β-lactamase production: a systematic review and meta-analysis

ABSTRACT

Introduction

Carbapenem-resistant Enterobacterales (CRE) due to Metallo-β-lactamase (MBL) production are treated with either polymyxins or the novel combination of ceftazidime-avibactam and aztreonam (AA). This study aims to evaluate the 30-day mortality of AA in patients with BSI caused by MBL-CRE infections.

Methodology

In this systematic review and meta-analysis, all articles up to June 2023 were screened using search terms like ‘CRE’, ‘MBL’, ‘AA’ and ‘polymyxins’. The risk ratio for AA vs polymyxins was pooled using a random-effect model, and the results were represented by a point estimate with a 95% confidence interval.

Results

After removing the duplicates, the titles and abstracts of 455 articles were screened, followed by a full-text screening of 50 articles. A total of 24 articles were included for systematic review, and four comparative studies were included in the meta-analysis. All four studies had a moderate or serious risk of bias. The pooled risk ratio for 30-day mortality for AA vs. polymyxins was 0.51 (95%CI: 0.34–0.76), p < 0.001. There was no significant heterogeneity.

Conclusion

The meta-analysis from studies with a high risk of bias shows that AA is associated with lesser 30-day mortality when compared to polymyxins in patients with MBL-producing CRE BSI. Registration with PROSPERO- CRD42023433608.

KEYWORDS:

• Aztreonam
• ceftazidime-avibactam
• polymyxin
• hospital-acquired infection
• bloodstream infection
• NDM
• metallobetalactamase

Article highlights

• Bloodstream infections (BSI) by Metallo-β-lactamase (MBL) producing Carbapenem-resistant Enterobacterales (CRE) are commonly treated with either polymyxins or the novel combination of ceftazidime-avibactam and aztreonam (AA).

• In this systematic review, a total of 24 articles were included after screening 512 articles.

• Of the 42 cases with BSI in which AA was used and mortality was reported, 19% of the patients died. Of the 42 cases in two single-arm studies, the 30-day mortality was 26%.

• From the four comparative studies, the pooled 30-day mortality with AA was 26%, while it was 55% for polymyxins.

• The pooled risk ratio for 30-day mortality for AA vs. polymyxins was 0.51 (95%CI: 0.34-0.76), p<0.001. All the studies had moderate or serious risk of bias, but there was no significant heterogeneity.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14787210.2024.2307912

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.