Combination of anti-staphylococcal β lactam with standard therapy compared to standard therapy alone for the treatment of MRSA bacteraemia: a post hoc analysis of the CAMERA2 trial using a desirability of outcome ranking (DOOR) approach

Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints. We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). Participants were randomly assigned to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). Each participant was assigned a DOOR category, within which they were further ranked according to their hospital length of stay (LOS) and duration of intravenous antibiotic treatment. We calculated the probability and the generalized odds ratio of participants receiving combination therapy having worse outcomes than those receiving standard therapy. Participants assigned combination therapy had a 54.5% (95% CI 48.9-60.1; p=0.11) probability and a 1.2-fold odds (95% CI 0.95–1.50; p=0.12) of having a worse outcome than participants on standard therapy. When further ranked according to LOS and duration of antibiotic treatment, participants in the combination group had a 55.6% (95% CI 49.5-61.7; p=0.07) and 55.3% (95% CI 49.2-61.4; p=0.08) probability of having a worse outcome than participants in the standard treatment group, respectively. When considering both efficacy and safety, treatment of MRSAB with a combination of standard therapy and a β-lactam likely results in a worse clinical outcome than standard therapy. However, a small benefit of combination therapy cannot be excluded. Most likely the toxicity of combination therapy outweighed any benefit from faster clearance of bacteraemia.