Lack of antimicrobial activity of sodium heparin for treating experimental catheter-related infection due to Staphylococcus aureus using the antibiotic-lock technique

175

129

Intravascular catheter-associated bloodstream infections significantly increase rates of morbidity and hospital costs. Microbial colonization and development of biofilms, which are known to be recalcitrant to antibiotic therapy, often lead to the loss of otherwise patent vascular access systems. We evaluated a new taurolidine-and citrate-based catheter lock solution (Neutrolin; Biolink Corporation, Norwell, Mass.) for its activity against planktonic microbes, antimicrobial activity in a catheter model, and biofilm eradication activity. In studies of planktonic microbes, after 24 h of contact, 675 mg of taurolidine-citrate solution per liter caused >99% reductions in the initial counts of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Entercoccus faecalis. A solution of 13,500 mg/liter was cidal for Candida albicans. Ports and attached catheters inoculated with 50 to 600 CFU of these bloodstream isolates per ml were locked with heparin or the taurolidine-citrate solution. After 72 h, there was no growth in the taurolidine-citrate-treated devices but the heparin-treated devices exhibited growth in the range of 6 ؋ 10 2 to 5 ؋ 10 6 CFU/ml. Biofilms were developed on silicone disks in modified Robbins devices with broth containing 6% serum (initial counts, 10 6 to 10 8 CFU/cm 2 ). The axenic biofilms were treated for 24 h with taurolidine-citrate or heparin. Taurolidine-citrate exposure resulted in a median reduction of 4.8 logs, whereas heparin treatment resulted in a median reduction of 1.7 logs (P < 0.01). No significant differences in the effects of the two treatments against P. aeruginosa and C. albicans were observed. These findings suggest that taurolidine-citrate is a promising combination agent for the prevention and treatment of intravascular catheter-related infections.

Section: Discussionmentioning

confidence: 92%

Antimicrobial Activity of a Novel Catheter Lock Solution

Shah

Mittelman²,

Costerton

et al. 2002

175

129

“…The concentrations of fluoroquinolones tested in our study against preformed S. maltophilia biofilms are generally higher than those reached in serum when applied by the intravenous or oral route. Nevertheless, data from our study might have clinical significance because these concentrations are easily achievable when standard dosages of drugs are infused through the vascular catheters in the "antibiotic lock" technique (5,14,18). Further, topical application may be possible.…”

Section: Vol 48 2004mentioning

confidence: 86%

Biofilm Formation by Stenotrophomonas maltophilia : Modulation by Quinolones, Trimethoprim-Sulfamethoxazole, and Ceftazidime

Bonaventura¹,

Spedicato²,

D’Antonio

et al. 2004

153

128

We investigated the in vitro effects of seven fluoroquinolones (ciprofloxacin, grepafloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, and rufloxacin), compared to those of trimethoprim-sulfamethoxazole (SXT) and ceftazidime on total biomass and cell viability of Stenotrophomonas maltophilia biofilm. S. maltophilia attached rapidly to polystyrene, within 2 h of incubation, and then biofilm formation increased over time, reaching maximum growth at 24 h. In the presence of fluoroquinolones at one-half and one-fourth the MIC, biofilm biomass was significantly (P < 0.01) reduced to 55 to 70% and 66 to 76% of original mass, respectively. Ceftazidime and SXT did not exert any activity. Biofilm bacterial viability was significantly reduced by all antibiotics tested at one-half the MIC. At one-fourth the MIC all antibiotics, except levofloxacin, significantly reduced viability. Treatment of preformed biofilms with bactericidal concentrations (500, 100, and 50 g/ml) of all fluoroquinolones caused, except for norfloxacin, significant reduction of biofilm biomass to 29.5 to 78.8, 64.1 to 83.6, and 70.5 to 82.8% of original mass, respectively. SXT exerted significant activity at 500 g/ml only. Ceftazidime was completely inactive. Rufloxacin exhibited the highest activity on preformed biofilm viability, significantly decreasing viable counts by 0.6, 5.4, and 17.1% at 500, 100, and 50 g/ml, respectively. Our results show that (i) subinhibitory (one-half and one-fourth the MIC) concentrations of fluoroquinolones inhibit adherence of S. maltophilia to polystyrene and (ii) clinically achievable concentrations (50 and 100 g/ml) of rufloxacin are able to eradicate preformed S. maltophilia biofilm.The use of synthetic materials for temporary or permanent implantation-i.e., central venous catheters, urinary catheters, intraocular lenses, and prosthetic heart valves-has been accompanied by the emergence of implant-associated infection. The bacterial infections following colonization and biofilm formation on these prosthetic materials represent the principal cause of morbidity in patients undergoing prosthetic implantation (6). The production of extracellular slime or glycocalyx is a crucial factor in the adherence of bacteria and their protection from host defense mechanisms and effects of antimicrobial agents. It has become clear that biofilm-grown cells express properties distinct from those of planktonic cells, one of which is an increased resistance to antimicrobial agents. Standard antimicrobial treatments typically fail to eradicate biofilms, which can result in chronic infection and the need for surgical removal of afflicted areas.Stenotrophomonas maltophilia is being reported with increasing frequency as an important nosocomial pathogen. It is an opportunistic pathogen colonizing patients in intensive care settings, especially those with underlying debilitating conditions such as immunosuppression, malignancies, and implantation of foreign devices (catheters, respiratory therapy equipment, etc.). Bacterial adherenc...

“…However, heparin has been shown to have no antimicrobial activity (5,29) and, more recently, has been shown to stimulate S. aureus biofilm formation (37). On the other hand, EDTA, a known chelator, has been shown in vitro and clinically to have anticoagulant activity equivalent to that of heparin (3,28).…”

Section: Discussionmentioning

confidence: 99%

Optimal Antimicrobial Catheter Lock Solution, Using Different Combinations of Minocycline, EDTA, and 25-Percent Ethanol, Rapidly Eradicates Organisms Embedded in Biofilm

Raad

Hanna

Dvorak

et al. 2007

139

102

Antimicrobial lock solutions may be needed to salvage indwelling catheters in patients requiring continuous intravenous therapy. We determined the activity of minocycline, EDTA, and 25% ethanol, alone or in combination, against methicillin-resistant Staphylococcus aureus and Candida parapsilosis catheter-related bloodstream infection strains in two established models of biofilm colonization. Biofilm-colonized catheter segments from a modified Robbins device and a silicone disk biofilm colonization model were exposed to these antimicrobial agents for 15 or 60 min, respectively. After exposure, segments were sonicated and cultured. To determine regrowth after incubation at 37°C, following the brief exposure to the antimicrobial agents, an equal number of segments were washed, reincubated for 24 h, and then sonicated and cultured. The triple combination of minocycline-EDTA (M-EDTA) in 25% ethanol was the only antimicrobial lock solution that completely eradicated S. aureus and C. parapsilosis in biofilm of all segments tested in the two models, and it completely prevented regrowth. In addition, M-EDTA in 25% ethanol was significantly more effective in rapidly eradicating the growth or regrowth of methicillin-resistant S. aureus and C. parapsilosis biofilm colonization in the two models than the other solutions-minocycline, EDTA, M-EDTA, 25% ethanol, and EDTA in ethanol. We conclude that M-EDTA in 25% ethanol is highly effective at rapidly eradicating S. aureus and C. parapsilosis embedded in biofilm adhering to catheter segments.