2438. Ceftolozane/tazobactam (C/T) against multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) infections: Clinical efficacy, and baseline and emergent resistance
Session: Poster Abstract Session: Treatment of AMR Infections
Saturday, October 6, 2018
Room: S Poster Hall
Background: Experience is mounting for C/T against MDR-Pa infections. More data are needed on efficacy for different infections, and baseline and emergent resistance.

Methods: We retrospectively reviewed pts receiving >48h of C/T for MDR-Pa infections. Clinical success was defined at 30d as survival, improved symptoms, and absence of recurrent infection. Microbiologic failures were defined as isolation of MDR-Pa following ≥7d of C/T. Minimum inhibitory concentrations (MICs) were determined by broth microdilution.

Results: 63 pts 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 13d (3 – 52). 58% of pts with pneumonia received concomitant inhaled antibiotics. 30% pts received concomitant intravenous antibiotics. Overall rates of clinical success and survival at 30d 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 pts receiving C/T mono- vs combination therapy (P=0.29). Among surviving pts (n=49), microbiologic failures occurred in 49% at a median of 23d (7 – 64) from C/T initiation. Micro failures were due to recurrent pneumonia (n=6) or colonization (n=18). 56% of patients survived at 90d. Median C/T MIC vs baseline MDR-Pa isolates was 2 µg/mL (range: 0.5 – >256); 10% of pts had C/T resistant isolates at baseline. Among pts 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 17d (6 – 53).

Conclusion: C/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.

Ryan K. Shields, PharmD, University of Pittsburgh, School of Medicine, Pittsburgh, PA, Ghady Haidar, MD, Infectious Disease, University of Pittsburgh Medical Center, Pittsburgh, PA, Brian A. Potoski, PharmD, University of Pittsburgh, Pittsburgh, PA, Yohei Doi, MD, PhD, University of Pittsburgh Medical Center, Pittsburgh, PA, Rachel V. Marini, PharmD, Pharmacy, UPMC Presbyterian Hospital, Pittsburgh, PA, M. Hong Nguyen, MD, Infectious Disease, University of Pittsburgh, Pittsburgh, PA and Cornelius J. Clancy, M.D., Infectious Diseases, University of Pittsburgh, Pittsburgh, PA

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 .

G. Haidar, None

B. A. Potoski, None

Y. Doi, None

R. V. Marini, None

M. H. Nguyen, Merck: Grant Investigator , Research grant . Astellas: Grant Investigator , Research grant .

C. J. Clancy, None

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