Antimicrobial resistance is a common problem of great clinical and public health significance due to the associated increase in morbidity and mortality. Antimicrobial use is a critical factor in the development of antimicrobial resistance. Antimicrobial cycling-sequential use of antimicrobial agents with cycle periods of several months-has had mixed results in studies aiming to decrease antimicrobial resistance. Mathematical modeling studies suggest that diversity of use of antimicrobials, essentially a cycling period of zero, would be optimal to limit antimicrobial resistance. We are performing an interventional study to test the hypothesis that an increase in antimicrobial diversity of agents typically used to treat Pseudomonas infections (antipseudomonals) will lead to a decrease in Pseudomonas aeruginosa antimicrobial resistance. We will determine the effect of a diversity of use of anti-Pseudomonal agents on the prevalence of phenotypic anti-Pseudomonal resistance (to any anti-Pseudomonal) in P. aeruginosa clinical isolates obtained from clinical cultures. Our study will also determine the effect of a diversity use of anti-Pseudomonal antimicrobials on the prevalence of specific mechanisms of anti-Pseudomonal resistance. We will utilize a quasi-experimental study design with multiple pre- and post-intervention observations hospital-wide in an intervention hospital versus two control hospitals. The intervention will increase the diversity of anti-Pseudomonal agent use by increasing the evenness of use of available anti-pseudomonals. The results of our study will be used as preliminary data to propose a cluster-randomized controlled trial to further investigate this intervention. If our current and future studies demonstrate that diversity of antimicrobial use limits antimicrobial resistance, it will affect antimicrobial prescribing for all hospitalized patients and be a wedge against the thus far inexorable rise in antimicrobial resistance. Diversity of Antimicrobial Use and Emergence of Resistance in Pseudomonas Public Health Statement Antimicrobial resistance in hospitalized patients is a common problem of great clinical and public health significance due to the associated increase in morbidity and mortality. We hypothesize that increasing the diversity of antimicrobials used in the treatment of hospitalized patients will lead to a decrease in Pseudomonas aeruginosa antimicrobial resistance. The results of our study will be generalizable to inpatients in tertiary acute care centers everywhere. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI075303-02
Application #
7500794
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Taylor, Christopher E,
Project Start
2007-09-30
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2010-08-31
Support Year
2
Fiscal Year
2008
Total Cost
$193,134
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Cluzet, Valerie C; Lautenbach, Ebbing; Nachamkin, Irving et al. (2015) Risk factors for gyrA and parC mutations in Pseudomonas aeruginosa. Infect Control Hosp Epidemiol 36:387-93