2395. Mechanism-based-susceptibility testing (MBST) using disc diffusion assays (DDA) to Guide Treatment of Multidrug- and Extensively Drug Resistant Pseudomonas aeruginosa (MDR-XDR-Pa) in a Cystic Fibrosis (CF) Lung Transplant Recipient; are we ready for combination therapy vs. MDR-XDR-Pa?
Session: Poster Abstract Session: Treatment of AMR Infections
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • Yasmin_Abbo_Draft_IDweek_9_29_18 .pdf (402.3 kB)
  • Background:

    Lung infections with MDR-XDR-Pa in patients with CF are challenging due to the emergence of antibiotic resistance. We applied MBST with DDA to guide combination antibiotic therapy in an 18-year-old woman with CF. We investigated if this approach can assist in choosing effective regimens.

    Methods:

    Consecutive Pa respiratory isolates were collected between 12/16 and 3/18 and typed with MLST. After automated antibiotic susceptibility (AST) and Kirby-Bauer testing, we performed double or triple DDAs. Combinations were based on mechanisms (MBST) of anti-pseudomonal antibiotics (e.g., targeting of penicillin-binding proteins, β-lactamase inhibition, and cell membrane disruption).

    Results:

    During therapy, 1859 antibiotic-days were administered. Fifteen Pa isolates, (9 sequence type (ST) 2100 and 1 ST463) with varying AST patterns were found (Figure). MBST with DDA revealed active combinations for isolates resistant to individual antibiotics (Table). These combinations led to a microbiological response permitting lung transplantation. Antibiotic regimens were also informed by allergies, clinical and radiologic findings.

    Conclusion:

    Strains with evolving resistance profiles recapitulate the dynamic nature of respiratory infections in CF. Double or triple DDAs identified potential treatment options e.g. vs. MDR-XDR Pa. MBST can support the management of challenging infections.   

    Table:   Antimicrobial combinations reflecting zones of inhibition by strain and date.

    CZA: ceftazidime-avibactam; C/T: ceftolozane-tazobactam; TOB: tobramycin; PMB: polymyxin B; FOF: fosfomycin; TZP: piperacillin-tazobactam; CIP: ciprofloxacin; IPM: imipenem; MEM: meropenem.

    Bold: largest zone  

     

     

    Combinations + inhibition zones (mm)

    Strain

    Date

    Combo 1

    Combo 2

    Combo 3

     

    1

    2-23-17

     CZA + TOB 35

    PMB + IPM 38

    FOF 40+

    2

    4-8-17

     CZA + TOB 31

    FOF + CZA 35

    PMB + C/T + MEM 39

    3

    5-27-17

    FOF + TZP 40

    C/T + TOB 37

    PMB + CZA 33

    4

    6-7-17

    FOF + TZP 15

    PMB + CZA + IPM 22

    C/T + IPM 24

    5

    8-3-17

       FOF + TZP 18

    PMB + CZA + IPM 38

    C/T + IPM 42

    6

    8-7-17

       FOF + TZP 19

    PMB + IPM 21

     

    7

    8-21-17

       FOF + TZP 32

    FOF + CZA 26

    CZA + TOB 22

    8

    8-24-17

       FOF + TZP 28

    PMB +I PM 35

    C/T + IPM 39

    9

    10-15-17

    FOF + IPM 30

    PMB + IPM 30

    C/T + IPM 30

    10

    11-30-17

       PMB+CIP 19

    PMB + CZA + IPM 25

    PMB + FOF + IPM 25

    11

    12-9-17

    FOF + TZP 30

    PMB + IPM 25

     

    12

    1-15-18

    PMB + IPM 23

     

     

    13

    1-25-18

    PMB + IPM 26

     

     

    14

    2-21-18

    FOF + TZP 20

    PMB + CIP 21

     

    15

    3-4-18

    C/T + IPM 21

    CZA + IPM 23

     

     

     

    Lilian M. Abbo, MD1, Mohamad Yasmin, MD2, Steven H. Marshall, MS3, Federico Perez, MD, MS4, Mónica Corzo-Pedrosa, MD5, Jose F. Camargo, MD6, Jacques Simkins, MD6, Laura Aragon, PharmD, BCPS-AQ ID7, Shweta Anjan, MD8, Michele I Morris, MD, FIDSA, FAST6, Nicolas Brozzi, MD9, Mathias Loebe, MD9, Jesse Fulmer, MD10, Neeraj Sinha, MD10, Octavio Martinez, PhD11, Armando Perez-Cardona, BS12, Andrew Colin, MD10, Christina Cloke, MD13 and Robert A. Bonomo, MD3, (1)Infectious Disease, University of Miami-Jackson Health System, Miami, FL, (2)Infectious Diseases, Case Western Reserve University, Cleveland, OH, (3)Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, (4)Louis Stokes Cleveland VA Medical Center, Cleveland, OH, (5)Pediatrics, Pulmonary Medicine, University of Miami, Holtz Children’s Hospital, Miami, FL, (6)Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, (7)Pharmacy, Jackson Memorial Hospital, Miami, FL, (8)Infectious Disease, Jackson Memorial Hospital-University of Miami Miller School of Medicine, Miami, FL, (9)Cardiothoracic Surgery, University of Miami-Jackson Memorial Hospital, Miami, FL, (10)University of Miami, Holtz Children’s Hospital, Miami, FL, (11)Pathology, University of Miami Miller School of Medicine, Miami, FL, (12)Jackson Memorial Hospital, Miami, FL, (13)Infectious Disease, University of Miami-Jackson Memorial Hospital, Miami, FL

    Disclosures:

    L. M. Abbo, Roche Diagnostics: Scientific Advisor , Consulting fee .

    M. Yasmin, None

    S. H. Marshall, None

    F. Perez, None

    M. Corzo-Pedrosa, None

    J. F. Camargo, None

    J. Simkins, None

    L. Aragon, None

    S. Anjan, None

    M. I. Morris, Chimerix: Investigator and Scientific Advisor , Consulting fee and Research support . Merck: Investigator , Research grant .

    N. Brozzi, None

    M. Loebe, None

    J. Fulmer, None

    N. Sinha, None

    O. Martinez, None

    A. Perez-Cardona, None

    A. Colin, None

    C. Cloke, None

    R. A. Bonomo, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.