2036. Ceftolozane-Tazobactam (C/T) for Severe Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Poster IDWeek2016MUNITA Oct_22_2016.pdf (474.8 kB)
  • Background: Ceftolozane/tazobactam (C/T) is a novel antibiotic combination with potent in vitro activity against multidrug-resistant P. aeruginosa. However, data to support the clinical use of C/T to manage these infections are limited. We describe a case series of patients from 5 US centers that received C/T to treat carbapenem-resistant P. aeruginosa (CR-PAE) infections.

    Methods: We reviewed all patients treated off-label for ≥ 72 h with C/T for a CR-PAE infection. All relevant clinical and demographic data were extracted. Identification of isolates and susceptibility testing were performed by standard methods at each participating center. Susceptibility to C/T was determined by Etest.

    Results: C/T was used to treat CR-PAE infections in 35 patients (median age 55 years; 23% female). Eighteen (51%) cases had hospital-associated pneumonia, 3 of which were complicated with empyema. Overall, 6 patients had secondary bacteremia. A summary of the infection types is depicted in Fig. 1. Antipseudomonal antibiotics were given prior to the start of C/T to 30 (86%) patients. Most isolates were resistant to ciprofloxacin and b-lactams while remaining susceptible to colistin (Fig. 2A). Of note, despite the absence of previous exposure to C/T, 4 isolates were non-susceptible to the antibiotic (Fig. 2A). C/T was used as monotherapy in 27 (77%) patients and combined with an inhaled (n=5) or systemic (n=3) anti-pseudomonal agent in the remaining 8 cases. The approved C/T dose (1.5g Q8h) was used in 11/18 patients with normal renal function (≥ 70 mL/min), while the remaining 7 received 3g Q8h. C/T dosing among 7 patients with a creatinine clearance of 30-50 mL/min ranged from 0.375g to 3g Q8h. Patients on intermittent hemodialysis (HD, n=3) received 0.375g Q8h and subjects undergoing continuous HD (n=7) were dosed from 0.375g to 1.5g Q8h. Clinical success was achieved in 26 (74%) cases. A total of 9 patients were considered to have failed therapy (Fig. 3). All patients infected with C/T non-susceptible P. aeruginosa (n=4) failed therapy (Fig. 2B). Major adverse effects were not reported.

    Conclusion: C/T may become an important alternative for the treatment of CR-PAE infections. Resistance resulting in poor clinical outcomes was observed. Hence, routine C/T susceptibility testing should be done prior to use of this agent

    Jose Munita, MD1, Samuel Aitken, PharmD2, Federico Perez, MD3, Rossana Rosa, MD4, Rupali Jain, Pharm.D.5, Masayuki Nigo, MD6, Audrey Wanger, PhD7, Rafael Araos, MD, MMSc8, Truc Tran, PharmD9, Frank P. Tverdek, PharmD10, Luis Shimose, MD11, Paola Lichtenberger, MD12, Javier Adachi, MD, FIDSA13, Lilian Abbo, MD, FIDSA11, Robert Rakita, MD14, Samuel Shelburne, MD, PhD, FIDSA15, Robert A. Bonomo, MD16 and Cesar Arias, MD, PhD, FIDSA1,17, (1)University of Texas Medical School at Houston, Houston, TX, (2)1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, TX, (3)Louis Stokes Cleveland VA M, Cleveland, OH, (4)Department of Medicine, Jackson Memorial Hospital-University of Miami Miller School of Medicine, Miami, FL, (5)Dept of Pharmacy/Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, (6)Division of Infectious Disease, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, (7)Department of Pathology and Lab Medicine, McGovern Medical School, Houston, TX, (8)Instituto de Ciencias e InnovaciĆ³n en Medicina, Clinica Alemana, Universidad del Desarrollo, Santiago, Chile, (9)Internal Medicine, University of Texas McGovern Medical School at Houston, Houston, TX, (10)Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, (11)Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, (12)Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, (13)Dept. of Infectious Diseases, Infection Control and Employee Health, The University of Texas - MD Anderson Cancer Center, Houston, TX, (14)Allergy and Infectious Disease, University of Washington, Seattle, WA, (15)Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX, (16)Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, OH, (17)Univ. El Bosque, Houston, TX

    Disclosures:

    J. Munita, None

    S. Aitken, Astellas: Scientific Advisor , Consulting fee

    F. Perez, Pfizer: Grant Investigator , Grant recipient
    Actavis: Consultant , Consulting fee

    R. Rosa, None

    R. Jain, None

    M. Nigo, None

    A. Wanger, None

    R. Araos, None

    T. Tran, None

    F. P. Tverdek, Astellas: Scientific Advisor , Consulting fee

    L. Shimose, None

    P. Lichtenberger, None

    J. Adachi, None

    L. Abbo, None

    R. Rakita, None

    S. Shelburne, None

    R. A. Bonomo, Merck: Grant Investigator and Scientific Advisor , Consulting fee and Research grant
    Actavis: Invited Speaker , Speaker honorarium
    Allergan: Grant Investigator , Research grant
    Wockhardt: Grant Investigator , Research grant
    GlaxoSmithKline: Grant Investigator , Research grant
    AstraZeneca: Grant Investigator , Research grant

    C. Arias, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.