Multidrug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa, Acinetobacter species, and Klebsiella pneumoniae are emerging pathogens that are increasingly the cause of a variety of serious infections in hospitalized patients, particularly those in intensive care units. Therapeutic choices for these infections are severely limited since many of these MDR organisms have become resistant to all available antimicrobial agents. Colistin is often used as a last resort despite a lack of established breakpoints for susceptibility testing or good evidence for clinical efficacy. It is unclear if combination therapy leads to better patient outcomes when in vitro antimicrobial susceptibility testing shows resistance to one or more antimicrobial agents. This research proposal aims to survey and describe healthcare providers' knowledge, attitudes, and practices regarding their use of antimicrobial susceptibility data to choose and modify treatment regimens for MDR-Acinetobacter, Pseudomonas, and Klebsiella infections. We propose to investigate factors that lead providers to request certain susceptibility or synergy tests and whether different in vitro microbiology testing methods such as automated susceptibility testing, E-test, disk diffusion, agar dilution, or various synergy tests lead to different treatment choices, including altered dosing or route of administration of antimicrobial agents or the use of existing antimicrobials administered in regimens and combinations that are not FDA approved. Finally, we propose to investigate clinical outcomes including morbidity, mortality, cost and length of stay; microbiological outcomes; and time to clinical or microbiologic outcomes among patients who receive different treatment regimens. For each treatment regimen, we will analyze the pattern of antimicrobial susceptibility test results for isolates before, during, and after treatment; assess factors associated with clinical or microbiologic success or failure; and determine the effectiveness of different in vitro tests or testing strategies for predicting the observed outcomes. The goals of this project are to better understand how health care providers use in vitro susceptibility data to choose and modify antimicrobial treatment regimens for MDR- Acinetobacter, Pseudomonas, and Klebsiella infections and to determine which testing methods and treatment strategies correlate with clinical outcomes so that in vitro testing and therapeutic strategies for these infections can be optimized. Bacteria are becoming increasingly resistant to antibiotics and some bacteria are now resistant to all available antibiotic agents. This extent of antibiotic resistance severely limits healthcare providers' ability to treat patients infected with these organisms. This research is designed to better understand how providers use information from various microbiology laboratory testing methods to choose treatments and to identify strategies that lead to the best patient outcomes. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Infectious Diseases (CID)
Type
Research Project (R01)
Project #
5R01CI000530-02
Application #
7498041
Study Section
Special Emphasis Panel (ZCI1-TYM (15))
Program Officer
Hopkins, Andrew S
Project Start
2007-09-30
Project End
2010-09-29
Budget Start
2008-09-30
Budget End
2009-09-29
Support Year
2
Fiscal Year
2008
Total Cost
$299,510
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Maragakis, Lisa L; Perencevich, Eli N; Cosgrove, Sara E (2008) Clinical and economic burden of antimicrobial resistance. Expert Rev Anti Infect Ther 6:751-63
Maragakis, Lisa L; Perl, Trish M (2008) Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options. Clin Infect Dis 46:1254-63