475 Bioactivity of tetracycline antibiotic lock therapy in a model of catheter infection

Saturday, March 20, 2010
Grand Hall (Hyatt Regency Atlanta)
P. Brandon Bookstaver, PharmD, BCPS , South Carolina College of Pharmacy, USC Campus, Columbia, SC
S. Scott Sutton , South Carolina College of Pharmacy, USC Campus, Columbia, SC
Robert Sherertz, MD , Wake Forest University School of Medicine, Winston-Salem, NC
Background: Central line associated bloodstream infections (CLABSI) occur in up to 40% of tunneled central venous catheters (CVC).  National guidelines support the instillation of an antibiotic lock solution into the catheter as an adjunct to systemic antibiotics when the CVC is retained.  Minocycline possesses proven activity in a lock solution, supporting the investigation of alternative tetracycline antibiotics.   
Objective: This study evaluates the activity of tetracycline antibiotic lock solutions against clinical isolates from CLABSI using an in vitro model of intravenous catheter infection.
Methods: The following lock solutions were evaluated: tetracycline 3mg/mL, doxycycline 3mg/mL, EDTA 30mg/mL, and phosphate-buffered saline (PBS) as the control solution.  Gentamicin (Gent) 5mg/mL + heparin served as an active control.  The influence of variable saline concentrations (7% versus 18%) on microbial growth was also investigated (data not presented here).  Candidate lock solutions were tested with and without EDTA against the following organisms (isolated from CLABSI): methicillin-sensitive Staphylococcus aureus (MSSA), Staphylococcus epidermidis (CoNS), Pseudomonas aeruginosa (PSA), and Candida albicans (CA).  Analysis was performed on 1-cm silicone Hickman catheter segments incubated overnight at 37°C in inoculated tryptic soy broth.  The catheters were washed in PBS and incubated in the candidate lock solutions for periods of 0, 2, 4, and 24 hours.  After the specified period, the segments were removed and washed in PBS, sonicated for 3 minutes, and vortexed for 10 seconds.  The resulting solution was serial diluted and surface plated on blood agar.  After incubating for 24 hours, colony forming units (CFU) were counted and converted to log10.  Each condition was tested in quadruplicate and a geometric mean was determined.  Statistical analysis evaluated reduction in CFU by individual lock solutions compared to the control solution, PBS, at the 24 hour data point. 
Results:

Lock Solutions

Mean Log CFU Reduction at 24 h
MSSA
CoNS
PSA
CA
Tetracycline+EDTA1
3.73*
4.27*
2.66
0.18
Tetracycline
4.74*
4.73*
3.37*
1.08
Doxycycline+EDTA1
4.74*
4.98*
3.85*
3.75*
Doxycycline
3.79*
4.73*
4.32*
3.95*
EDTA
3.05*
3.96*
2.85
1.21
Gent+Heparin2
4.74*
5.24*
4.42*
3.95*
PBS (Control)
1.08
1.03
+0.08
+0.06
130 mg/mL; 21,000 units/mL;*p<0.05
Conclusions: Doxycycline, with and without EDTA in solution, significantly reduced the colony count of all isolates tested.  Given the potential as an alternative to minocycline, doxycycline deserves further investigation as a candidate lock solution.