Fosfomycin in bacteraemic urinary tract infection due to multidrug-resistant Escherichia coli: insights of post hoc DOOR analysis of the FOREST trial.

Purpose: A post hoc analysis of data from a previously published clinical trial was conducted using the desirability of outcome ranking (DOOR) methodology with the aim provide additional information on the use of fosfomycin for the treatment of bacteraemic urinary tract infection (BUTI) caused by multi-drug-resistant (MDR) E. coli.

Methods: Three DOOR systems with five, six and seven categories, respectively were developed. Safety and efficacy were prioritised in all rankings, but step down to oral therapy and exposure to antibiotics with lower ecological impact were also considered in DOOR-6 and DOOR-7. The probability that a patients assigned to fosfomycin was classified into a more desirable outcome category was calculated for the three DOOR definitions. Subgroups analyses and an ordinal logistic regression model were also performed.

Results: Data from 143 participants were analysed. The probability of having a more desirable outcome after treatment with fosfomycin versus the comparators was 0.44 (95% CI 0.36 - 0.52) for DOOR-5; 0.50 (95% IC 0.42 - 0.58) using DOOR-6 and 0.61 (95% CI 0.53-0.69) with DOOR-7. In subgroups, the highest probability of having a better DOOR with fosfomycin was seen in the clinically evaluable population and among patients without chronic heart disease or renal insufficiency for the DOOR-7 definition.

Conclusions: DOOR analysis could be applied to the FOREST trial data; the results were somehow different for the different DOOR systems used. Overall, fosfomycin was favoured when oral step-down treatment and use of antibiotics with lower ecological impact were included.