Ceftolozane/tazobactam is a b-lactam/b-lactamase inhibitor combination indicated for complicated urinary tract/intra-abdominal infections and pneumonia. Although promising in-vitro activity has been demonstrated against carbapenem resistant Pseudomonas aeruginosa, clinical evidence supporting efficacy… Click to show full abstract
Ceftolozane/tazobactam is a b-lactam/b-lactamase inhibitor combination indicated for complicated urinary tract/intra-abdominal infections and pneumonia. Although promising in-vitro activity has been demonstrated against carbapenem resistant Pseudomonas aeruginosa, clinical evidence supporting efficacy of ceftolozane/tazobactam in treating bacteremia is limited. We report our experience using ceftolozane/tazobactam in P. aeruginosa bacteremia. Between January 2015 to December 2018, adults ( 18 years) with a positive blood culture for P. aeruginosa non-susceptible to meropenem at Baylor St. Luke’s Medical Center (Houston, Texas, USA) were examined. Clinical outcomes were compared for patients treated with ceftolozane/tazobactam or other agents (i.e., standard of care). Antibiotic/dosing selection was at the discretion of the attending medical teams. Appropriate empirical therapy was defined as administration within 24 h of index blood culture of an agent to which the isolate was susceptible on the final susceptibility report. The primary/secondary endpoints were 30-day and hospital (all-cause) mortality, respectively. P values of 0.05 were considered significant. Forty difficult-to-treat episodes of P. aeruginosa bacteremia were evaluated. Eleven patients (27.5%) received ceftolozane/tazobactam, while the remaining 28 patients (72.5%) received other agents (e.g., aztreonam, piperacillin/tazobactam, cefepime, meropenem, levofloxacin, amikacin, and colistin). One patient in the comparator group had 2 episodes in different years. Patient characteristics are shown in Table 1. All P. aeruginosa isolates from the ceftolozane/tazobactam group were multidrugresistant (MDR; resistant to 1 agent in 3 antipseudomonal antibiotic classes), as compared to 64.3% in the comparator group (p1⁄4 0.04). Patients who received ceftolozane/tazobactam had a significantly higher 30-day mortality (54.5% vs. 13.8%; p1⁄4 0.014), and hospital mortality (72.7% vs. 13.8%; p< 0.001) than the comparator group. These results were unexpected in view of promising in-vitro and clinical studies to date. As a retrospective study, we were unable to control for antimicrobial prescribing practice. Tumbarello et al. reported the association of 21-day mortality with MDR P. aeruginosa bacteremia. A greater MDR prevalence in the ceftolozane/tazobactam group (a plausible source of selection bias) could have contributed to the higher mortality rate observed. In addition, all patients given ceftolozane/tazobactam in our study were in the ICU, compared to only 72% of the comparator. The mortality difference could also be accounted for by sepsis incidence/severity, which was not specifically assessed (a possible study limitation). However, APACHE II scores between the two groups were not significantly different; suggesting the difference in illness severity (if any) was not captured by this metric. Ceftolozane/tazobactam was primarily (8 out of 11 patients) used as definitive therapy for MDR isolates, implying these patients had potentially failed empiric therapy. The mean time to start ceftolozane/tazobactam therapy was 6.2 days from the day of index culture. All patients except one received standard (1.5 g every 8 h or renally adjusted equivalents) instead of the more aggressive dosing (3 g every 8 h). Sepsis-induced pathophysiological changes affect antibiotic pharmacokinetics, complicating dose optimization. Aggressive dosing Correspondence to: Vincent H. Tam, Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Rd, Houston, TX 77204, USA. Email: [email protected]
               
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