Open AccessIn Vitro Pharmacodynamic Analyses Help Guide the Treatment of Multidrug-Resistant Enterococcus faecium and Carbapenem-Resistant Enterobacter cloacae Bacteremia in a Liver Transplant Patient
Author(s) -
Eric Wenzler,
Maressa Santarossa,
Kevin A. Meyer,
Amanda Harrington,
Gail Reid,
Nina M. Clark,
Fritzie S Albarillo,
Zackery P. Bulman
Publication year - 2020
Publication title -
open forum infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.546
H-Index - 35
ISSN - 2328-8957
DOI - 10.1093/ofid/ofz545
Subject(s) - enterococcus faecium , linezolid , medicine , daptomycin , enterobacter cloacae , vancomycin resistant enterococcus , bacteremia , pharmacodynamics , enterococcus , intensive care medicine , vancomycin , microbiology and biotechnology , antibiotics , pharmacology , klebsiella pneumoniae , biology , pharmacokinetics , staphylococcus aureus , genetics , escherichia coli , bacteria , gene
Background Infections due to multidrug-resistant pathogens are particularly deadly and difficult to treat in immunocompromised patients, where few data exist to guide optimal antimicrobial therapy. In the absence of adequate clinical data, in vitro pharmacokinetic (PK)/pharmacodynamic (PD) analyses can help to design treatment regimens that are bactericidal and may be clinically effective. Methods We report a case in which in vitro pharmacodynamic analyses were utilized to guide the treatment of complex, recurrent bacteremias due to vancomycin-, daptomycin-, and linezolid-resistant Enterococcus faecium and carbapenem-resistant Enterobacter cloacae complex in a liver transplant patient. Results Whole-genome sequencing revealed unique underlying resistance mechanisms and explained the rapid evolution of phenotypic resistance and complicated intrahost genomic dynamics observed in vivo. Performing this comprehensive genotypic and phenotypic testing and time-kill analyses, along with knowledge of institution and patient-specific factors, allowed us to use precision medicine to design a treatment regimen that maximized PK/PD. Conclusions This work provides a motivating example of clinicians and scientists uniting to optimize care in the era of escalating antimicrobial resistance.