Infections associated with indwelling medical devices, particularly catheters account for about half of nosocomial infections in the United States. These infections prolong hospital stay and result in substantial morbidity and mortality. Bacterial colonization and formation of biofilm around the surface of the implanted device are prelude for clinical infection. Many antimicrobial agents, although may be effective against planktonic pathogens, have minimal or no effect against biofilm-embedded organisms. Thus, there is a pressing need to explore the approach of using compounds that can interfere with the biofilm that accommodates these pathogenic organisms. N-acetyl cysteine (NAC), a derivative of amino acid cysteine and a potent antioxidant, commonly used as a systemic remedy against toxicity with acetaminophen, is also used for inhalation therapy in patients with chronic bronchitis by breaking up the mucus. This mucolytic property may be a valuable tool in preventing the formation of biofilm or removing biofilms formed on medical devices. By elimination of the biofilm, antimicrobial agents become more effective against causative pathogens. Therefore, combination of NAC and an antibiotic may prove to be instrumental in combating catheter colonization and treating device-associated infection. In this proposal we plan to study the utilization of this combination to impregnate vascular catheters in order to prevent their bacterial colonization when implanted in patients. Furthermore, we would like to study the use this combination as a catheter lock solution to treat indwelling colonized catheters.

Public Health Relevance

This project examines the possibility of using a combination of a chemical agent that breaks the network that pathogens can attach to when a medical device (i.e. catheter) is placed in a patient and an antimicrobial agent to prevent or treat infection of catheters. Although we will only experiment this model in the laboratory and with animals at this stage, this project mainly targets hospitalized patients who depend on intravenous means to receive drugs or nutrition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI074010-02
Application #
7860317
Study Section
Special Emphasis Panel (ZRG1-IDM-M (12))
Program Officer
Korpela, Jukka K
Project Start
2009-06-05
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2012-05-31
Support Year
2
Fiscal Year
2010
Total Cost
$191,875
Indirect Cost
Name
Baylor College of Medicine
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Ashong, Chester N; Hunter, Andrew S; Mansouri, M David et al. (2017) Adherence to clinical practice guidelines for the treatment of candidemia at a Veterans Affairs Medical Center. Int J Health Sci (Qassim) 11:18-23
Mansouri, Mohammad D; Hull, Richard A; Stager, Charles E et al. (2013) In vitro activity and durability of a combination of an antibiofilm and an antibiotic against vascular catheter colonization. Antimicrob Agents Chemother 57:621-5
Mansouri, Mohammad D; Opperman, Timothy J; Williams, John D et al. (2012) In vitro potency and in vivo efficacy of a novel bis-indole antimicrobial compound in reducing catheter colonization. Antimicrob Agents Chemother 56:2201-4
Mansouri, Mohammad D; Awan, Leah; Darouiche, Rabih O (2011) In vitro efficacy of antimicrobial-treated drainage catheters in preventing bacterial colonization in biological fluids. Infect Control Hosp Epidemiol 32:731-2
Mansouri, M D; Cadle, R M; Agbahiwe, S O et al. (2011) Impact of an antibiotic restriction program on antibiotic utilization in the treatment of community-acquired pneumonia in a Veterans Affairs Medical Center. Infection 39:53-8
Mansouri, M D; Ramanathan, V; Al-Sharif, A H et al. (2010) Efficacy of trypsin in enhancing assessment of bacterial colonisation of vascular catheters. J Hosp Infect 76:328-31