2438. Ceftolozane/Tazobactam (C/T) Against Multidrug-Resistant Pseudomonas aeruginosa (MDR-Pa) Infections: Clinical Efficacy, and Baseline and Emergent Resistance

Abstract

BackgroundExperience is mounting for C/T against MDR-Pa infections. More data are needed on efficacy for different infections, and baseline and emergent resistance.MethodsWe retrospectively reviewed patients receiving >48 hours of C/T for MDR-Pa infections. Clinical success was defined at 30 days as survival, improved symptoms, and absence of recurrent infection. Microbiologic failures were defined as isolation of MDR-Pa following ≥7 days of C/T. Minimum inhibitory concentrations (MICs) were determined by broth microdilution.Results63 patients were included. Median age was 58 (range: 23–91), 54% were men, and median Charlson score was 4 (0–12). 35% were transplant recipients. At onset of infection, median APACHE II and SOFA scores were 21 (2–49) and 5 (0–17), respectively. Infections included pneumonia (n = 45), tracheobronchitis (n = 4), intra-abdominal (n = 4), skin/soft tissue (n = 3), urinary tract (n = 3), bacteremia (n = 2), endocarditis and empyema (n = 1 each). Median duration of C/T was 13 days (3–52). 58% of patients with pneumonia received concomitant inhaled antibiotics. 30% patients received concomitant intravenous antibiotics. Overall rates of clinical success and survival at 30 days were 57% and 78%, respectively. Failures were due to death (n = 14), recurrent infection (n = 7), lack of clinical improvement (n = 5), or early discontinuation of C/T (n = 1). Rates of success and survival for pneumonia were 53% and 71%, respectively. Success rates were 67% and 51% among patients receiving C/T mono- vs. combination therapy (P = 0.29). Among surviving patients (n = 49), microbiologic failures occurred in 49% at a median of 23 days (7–64) from C/T initiation. Micro failures were due to recurrent pneumonia (n = 6) or colonization (n = 18). 56% of patients survived at 90 days. Median C/T MIC vs. baseline MDR-Pa isolates was 2 µg/mL (range: 0.5–>256); 10% of patients had C/T resistant isolates at baseline. Among patients with microbiologic failures infected by C/T susceptible isolates at baseline (n = 21), 38% developed resistance. The median duration of treatment prior to the emergence of resistance was 17 days (6–53).ConclusionC/T was effective for treatment of various MDR-Pa infections. MDR-Pa cannot be assumed to be C/T susceptible at baseline, and MICs should be measured before treatment and following microbiologic failure.Disclosures R. K. Shields, Allergan: Grant Investigator, Research grant. Pfizer: Consultant and Scientific Advisor, Speaker honorarium. Shionogi: Scientific Advisor, Consulting fee. Roche: Grant Investigator, Research grant. Venatorx: Grant Investigator, Research grant. Medicines Company: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Accelerate Diagnostics: Scientific Advisor, Consulting fee. M. H. Nguyen, Merck: Grant Investigator, Research grant. Astellas: Grant Investigator, Research grant.