Hemodialysis catheter-associated bacteremia (HCAB) is a significant cause of nosocomial morbidity and mortality in patients with end stage renal disease (ESRD) and incurs additional health care costs. Most infections of tunneled hemodialysis catheters arise from a bacterial biofilm on the luminal catheter surface. Biofilms, which comprise of sessile bacteria within an extracellular polysachharide matrix (EPS), are difficult to eradicate with antibiotics alone, and thus, biofilm-associated infections generally necessitate catheter removal. N-acetylcysteine (NAC) decreases EPS production and promotes biofilm disruption. We initially showed in vitro that NAC acts synergistically with tigecycline against biofilm-embedded organisms. We subsequently demonstrated in a single-arm, open-label pilot trial that a catheter lock solution (CLS) consisting of NAC, tigecycline and heparin can be safe and effective when used for catheter salvage in patients with HCAB. We plan to further investigate in vitro the mechanisms leading to the anti-biofilm effect of NAC by evaluating organism viability, cell detachment, and amount of EPS in the presence of different concentrations of NAC. Additionally, we plan to study in rabbits the efficacy of NAC-containing catheter lock solution in preventing colonization and infection of vascular catheters in vivo. We will also perform a prospective, randomized, double-blind clinical trial to evaluate the use of a CLS that contains NAC, tigecycline, and heparin in the treatment of ESRD subjects with HCAB. The candidate, an Assistant Professor in the section of Infectious Diseases at Baylor College of Medicine (BCM), is applying for a K23 award to enable her to pursue advanced patient-oriented research training with the goal of becoming an independent clinical investigator and academic infectious disease physician. Dr. Aslam's career development plan includes didactic training through the Clinical Scientist Training Program at BCM that would earn her a Master's degree in Clinical Investigation, formal mentoring by her scientific advisory committee, and conducting the research plan as outlined above.

Public Health Relevance

An increasing number of ESRD patients use tunneled vascular catheters for hemodialysis access. If the NAC/tigecycline/heparin catheter lock solution proves successful, it will represent a breakthrough in the treatment of infections of hemodialysis catheters and possibly other types of tunneled vascular catheters. It is anticipated that the work proposed here would have significant impact on public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK078828-06
Application #
8492073
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2009-07-17
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
6
Fiscal Year
2013
Total Cost
$149,278
Indirect Cost
$11,058
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Aslam, Saima; Darouiche, Rabih O (2011) Role of antibiofilm-antimicrobial agents in controlling device-related infections. Int J Artif Organs 34:752-8
Narasimhan, Supriya; Aslam, Saima; Lin, Peter H et al. (2010) Bacterial translocation across ePTFE vascular graft surfaces. J Infect 60:486-90
Aslam, Saima; Darouiche, Rabih O (2010) Mechanical integrity of hemodialysis catheters after exposure to a novel catheter lock solution. Infect Control Hosp Epidemiol 31:1124-9
Aslam, Saima; Hernandez, Maria; Thornby, John et al. (2010) Risk factors and outcomes of fungal ventricular-assist device infections. Clin Infect Dis 50:664-71