Konstantinos Pontikis, Ilias Karaiskos, Aikaterini Sakagianni, Eleni Mouloudi, Evdoxia Tsigou, Aikaterini Gkoufa, Sofia Michelidou, Kristina Mouratidou, Alexandra Gavala, Christina Routsi, Stamatis Karakonstantis, Stavroula Michalea, Sevasti Ampelioti, Theodora Katsarou, Athanasios G. Papathanasiou, Maria Pirounaki, Charalambos Anastogiannis, Antonia Koutsoukou, Helen Giamarellou, George L. Daikos, on behalf of the DESPAIR Study Group
(PDR-AB) causes severe infections and constitutes a threat in several geographic regions. Little is known about the differential effectiveness of last-resort regimens, frequently used in this setting. We compared the effectiveness of two literature-proposed regimens against PDR-AB infections consisting of colistin, ampicillin-sulbactam, and either meropenem (regimen A) or tigecycline (regimen B). This is a retrospective analysis of prospectively collected data from 12 centers on adult patients with hospital-acquired pneumonia (HAP) or bloodstream infection (BSI), who had received definitive treatment with either regimen A or regimen B. The primary outcome was clinical failure, defined as any of the following occurring by day 14 from infection onset: death, initiation of salvage treatment, treatment withdrawal due to toxicity, persistent bacteremia for BSI patients and failure to improve oxygenation for HAP patients before and after propensity matching. Eighty-three patients were included in the primary analysis; 60 had received regimen A and 23 regimen B. Regimen B was significantly associated with clinical failure before and after propensity matching (odds ratios [OR]: 3.11; 95% confidence interval [CI]: 1.10-8.84 vs OR: 3.83; 95% CI: 1.26-11.63), respectively. Salvage therapy and treatment discontinuation due to toxicity were more frequent in patients treated with regimen B. In multivariable analysis, regimen B was independently associated with 28-day mortality before (hazard ratio [HR]: 2.53; 95% CI: 1.08-5.94) but not after propensity matching (HR: 2.64; 95% CI: [0.99-7.02]). Treatment with colistin, ampicillin-sulbactam, and meropenem against severe PDR-AB infections was associated with favorable outcomes compared to colistin, ampicillin-sulbactam, and tigecycline.