2003. Ceftazidime/avibactam and ceftolozane/tazobactam in treatment of pulmonary infections by Imipenem resistant Pseudomonas aeruginosa.
Session: Poster Abstract Session: Antimicrobial Resistance Mechanisms
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • idweekv2 Alina.pdf (788.7 kB)
  • Background:

    Recently, ceftolozane/tazobactam (Zerbaxa) and ceftazadime/avibactam (Avycaz) became available to clinicians to meet the rising need for therapeutics to treat multidrug resistant (MDR) organisms. Phase 3 clinical trials investigating efficacy of these agents compared to Carbapenems in nosocomial pneumonia are currently in progress. However, data regarding their role in treatment of pulmonary infections caused by Imipenem resistant Pseudomonas (Psa) is still lacking.

    We identified patients with Imipenem resistant Psa pneumonia and treated them with ceftolozane/tazobactam or ceftazadime/avibactam. Genetic analyses of Psa isolates were performed to understand the molecular basis for the emergence of this resistance phenotype in our institution.

    Methods:

    Patients’ characteristics, severity of illness and outcomes were reviewed. Multilocus sequence typing (MLST) was performed to evaluate Psa strain relatedness. PCR was done to screen for presence of blaKPC and metallo-beta-lactamase (MBL) genes. OprD genes was sequenced and analyzed. Expasy Swiss modeling server was used to construct models of OprD porin.

    Results:

    Demographics, treatment, and outcomes are summarized in Table 1.  In all three cases microbiologic eradication was achieved. Two out of three patients survived. Psa isolates were not related by MLST typing and did not possess blaKPC or MBL genes. All isolates had mutations in the oprD gene resulting in early stop codons. Modelling of these OprD channels showed significantly truncated proteins.

    STRAIN

    INFXN

    DRUG

    CCI*

    APACHEII

    F/u cultures

    Clincal Resolution

    Death

    1

    HCAP

    Zerbaxa+ tobramycin

    1

    13

    -

    +

    -

    2

    HCAP

    Zerbaxa

    3

    N/A

    -

    +

    -

    3

    HCAP+bacteremia

    Avycaz

    10

    17

    -

    -

    +

    *CCI Charlson comorbidity index

    Conclusion:

    Our early experience demonstrates ceftazidime/avibactam and ceftolozane/tazobactam are promising therapeutic options for the treatment of Imipenem resistant Psa pulmonary infections. Our genetic analysis indicates that Imipenem resistance in these isolates was partly mediated by OprD porin mutations, causing truncated, likely non-functional protein. 

    Analysis of additional cases is needed to delineate the role of these novel cephalosporin/beta-lactamase inhibitor combinations in treatment of MDR Psa infections.

    Alina Iovleva, MD, Internal Medicine, University Hospitals Case Medical Center, Cleveland, OH; Internal Medicine, Louis Stokes VA Medical Center, Cleveland, OH, Federico Perez, MD, Louis Stokes Cleveland VA M, Cleveland, OH, Steve H. Marshall, MS, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, Andrea M. Hujer, BS, Case Western Reserve University, Cleveland, OH, Michael R. Jacobs, MD, PhD, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH, Usha Stiefel, M.D., Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, Amy Ray, MD, MPH, Infectious Diseases, University Hospitals Case Medical Center, Cleveland, OH and Robert A. Bonomo, MD, Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, OH

    Disclosures:

    A. Iovleva, None

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

    S. H. Marshall, None

    A. M. Hujer, None

    M. R. Jacobs, None

    U. Stiefel, None

    A. Ray, Merck: Speaker's Bureau , Speaker honorarium

    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

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