Are cefiderocol or sulbactam/durlobactam better than alternative best available treatment for infection by carbapenem-resistant A. baumannii? A systematic literature review.

Objective: Cefiderocol (CFDC) and sulbactam/durlobactam (SUL/DUR) are new treatment options against infections by carbapenem-resistant A. baumannii (CRAB). However, whether they outperform contemporary alternative best available therapy (BAT), currently consisting of high-dose ampicillin/sulbactam (AMP/SUL)-based regimens, is unclear.

Methods: A systematic review was conducted in PubMed and clinical trial registries to assess regimens used in comparator arms in studies comparing CFDC or SUL/DUR to alternative treatment regimens.

Results: Only 1 relevant study was found for SUL/DUR (the registrational Phase 3). Almost all (98%) patients enrolled had pneumonia and the comparator arm was colistin/imipenem, a regimen not recommended for treatment of CRAB infections, especially pneumonia. With regards to CFDC, subgroup analyses (with significant limitations) from 2 randomized trials were disappointing showing higher mortality in CREDIBLE-CR compared to colistin-based treatment and similar mortality in APEKS-NK compared to high-dose meropenem among patients with CRAB infections. The rest (n = 11) of the trials were observational, predominantly single-center (82%) and retrospective (82%), and all but one were conducted in Italy (91%). Although meta-analyses of observational studies suggest better outcomes with CFDC, the comparator arm was colistin-based in all cases and only a minority of patients had received high-dose AMP/SUL.

Conclusions: High-quality evidence supporting use of either CFDC or SUL/DUR in favor of high-dose AMP/SUL-based regimens is lacking. This has important stewardship implications. Additionally, both CFDC and SUL/DUR are much more expensive than AMP/SUL, an important consideration especially for low-/mid-income countries. Studies comparing CFDC- and SUL/DUR-based treatments to contemporary alternative BAT are needed.