Is prophylactic ciprofloxacin effective in delaying biliary stent blockage?

BACKGROUND: Late stent blockage is a major complication of endoscopic stent insertion for malignant obstructive jaundice. Stents block as a result of bacterial infection and biofilm formation. We report a randomized but unblinded study using an animal model to evaluate the effect of prophylactic ciprofloxacin, which selectively suppresses gram-negative bacteria, in an attempt to prolong stent patency. METHOD: Ten adult cats underwent surgical implantation of 5F polyethylene stents through common bile duct strictures created around the choledochotomy, with the tip of the stent left in the duodenum. Five animals received intravenous ciprofloxacin perioperatively and were then maintained on oral ciprofloxacin 25 mg twice daily. Control cats were not given antibiotics. The animals were sacrificed when signs of biliary obstruction or cholangitis persisted for more than 3 days or at the end of the 16-week study period. Stents were removed and examined for patency. In addition, the stents were cultured to recover the adherent bacteria. RESULTS: All control animals developed stent blockage within 4 weeks. Two ciprofloxacin-treated cats developed stent blockage at 21 and 42 days, respectively, whereas the other 3 cats had patent stents for the entire study period. There was a significant difference between the median stent patency of 112 days for the ciprofloxacin group versus 16 days for the control group (p < 0.02). Bacteriologic cultures showed that the bile and blocked stents from the control group had predominantly gram-negative bacteria, whereas the bile and stents of the ciprofloxacin group had gram-positive and anaerobic bacteria, with an absence of gram-negative bacteria (p < 0.01). CONCLUSION: Ciprofloxacin prophylaxis eliminates gram-negative bacterial infection in bile and minimizes sludge formation and may have a potential benefit in delaying stent blockage.

Lipopolysaccharide induced acute red eye and corneal ulcers.

Using a new animal model, the aims of this study were to assess the role played by purified lipopolysaccharide (LPS) and neutrophils in the pathogenesis of acute red-eye reactions (ARE) and corneal ulcers. In addition, IL-1 alpha was assessed for its implications in the formation of corneal ulcers. Following corneal abrasion, eyes of rabbits underwent single or double exposures to various doses of LPS from Pseudomonas aeruginosa or Serratia marcescens. This protocol induced ARE symptoms, and their severity depended on the dosage, number of LPS exposures, and type of LPS used (LPS from S. marcescens showing highest virulence). Corneal ulcers were induced by delivering a high dose of Serratia LPS (100 micrograms) followed by a low dose (10 micrograms). Histopathological examination revealed that both ARE and corneal ulceration were associated with prominent neutrophil infiltration. In addition, many lymphocytes and other monocytic cells infiltrated ulcerated ocular tissue. Tear fluids obtained from ulcerated eyes contained high concentrations of a protein recognized by anti-rabbit IL-1 alpha antibodies as demonstrated by immunoblotting studies. The results indicate that LPS can induce ARE and corneal ulceration in the absence of any live bacteria. Moreover, the findings implicate the accumulation of neutrophils and IL-1 alpha-related proteins in the pathogenesis of ARE and corneal ulcers.

Use of tilmicosin for treatment of pasteurellosis in rabbits.

OBJECTIVES: To determine tilmicosin concentrations in serum and tissues of rabbits given a single dose of 25 mg of tilmicosin/kg of body weight. To examine the effects of tilmicosin treatment (25 mg/kg, s.c.) in rabbits with pasteurellosis. PROCEDURE: After receipt of tilmicosin, healthy New Zealand White female rabbits (n = 3 at each time) were euthanatized at 2, 4, 8, 24, 48, and 72 hours for collection of blood samples and tissue specimens; 4 rabbits served as untreated controls. Rabbits (male and female) with pasteurellosis (n = 42) also were treated. Tilmicosin concentration was determined in serum, lung, and uterine tissues. Rabbits with pasteurellosis were treated with tilmicosin. Response was monitored, using bacteriologic culturing and antibiotic resistance and susceptibility testing, and by scoring clinical signs of disease. RESULTS: Serum tilmicosin concentration reached 1.91 +/- 0.18 micrograms/ml after 2 hours, decreased to 0.77 +/- 0.07 microgram/ml by 8 hours, and was below minimum inhibitory concentrations for Pasteurella multocida at 24 hours. Terminal half-life in serum was 5.97 hours. Lung and uterus concentrations were 14.43 +/- 1.34 and 11.57 +/- 0.09 ppm at 2 hours, and were 5.10 +/- 1.05 and 8.87 +/- 1.66 ppm at 24 hours, respectively. 69% (29/42) of rabbits with pasteurellosis responded favorably in 3 days. Second treatment was required in 31% (13/42), and 5 of these rabbits had clinical signs on day 6; 2 of these 5 had improved. Treatment success rate was 93% (39/42). Of the rabbits that were culture positive on day 0, 35% (6/ 17) remained positive on day 3. 1 of 6 rabbits was culture positive on day 6. CONCLUSION: Tilmicosin (25 mg/kg, s.c.) was an effective treatment for pasteurellosis in New Zealand White rabbits. CLINICAL RELEVANCE: Tilmicosin treatment of pasteurellosis in rabbits is useful in research rabbits and in those destined for meat production. A single dose of antibiotic minimizes stress-associated handling.

Comparative evaluation of fleroxacin, ampicillin, trimethoprimsulfamethoxazole, and gentamicin as treatments of catheter-associated urinary tract infection in a rabbit model.

Fleroxacin, ampicillin, trimethoprim-sulfamethoxazole, and gentamicin were comparatively evaluated for effectiveness in treating experimentally induced catheter-associated urinary tract infection and bacteriuria in a rabbit model with a closed drainage system. Fleroxacin, ampicillin and gentamicin effectively eliminated a lactose-negative, streptomycin-resistant uropathogenic strain of Escherichia coli (WE6933) from bag urine and catheter port urine, while trimethoprim-sulfamethoxazole only marginally reduced urine bacterial counts when compared to rabbits that received no antibiotic therapy. Fleroxacin eliminated E. coli from the catheter surfaces and from tissues adjacent to the catheter. Ampicillin or gentamicin therapy also eliminated biofilm bacteria from the catheter surfaces, but did not eliminate th residual bacteria from tissue adjacent to the septic catheters despite achieving urine levels of antibiotics substantially higher than minimum bactericidal concentrations for this pathogen. Trimethoprim-sulfamethoxazole was ineffective in eliminating E. coli from the catheter surfaces and the adjacent tissues. The ability of fleroxacin to effectively eliminate biofilm bacteria from catheter surfaces and tissues adjacent to such medical devices in the urinary tract may prove useful in the treatment of catheter-associated urinary tract infection and bacteriuria in mammals and humans.

Therapeutic efficacy of fleroxacin for eliminating catheter-associated urinary tract infection in a rabbit model.

The efficacy of fleroxacin as therapy for experimentally induced catheter-associated urinary tract infection (CAUTI) was examined. A rabbit model of CAUTI using a closed urinary catheter drainage system and the mutant strain of Escherichia coli (WE 6933) were used to examine three dosage regimens (30 mg/kg q8h i.v.; 20 mg/kg q8h i.v.; and 10 mg/kg q8h++i.v.) of fleroxacin administered intravenously for 4 days. Quantitative bacterial counts, urinary concentrations of fleroxacin and desmethylferoxacin, histopathologic changes, and electron microscopic evaluation of catheter-associated biofilm and mucosal biofilm were performed. The results indicated that the bacterial biofilm on the urinary catheter could be eliminated by fleroxacin at 30 mg/kg q8h i.v. and 20 mg/kg q8h i.v. Fleroxacin concentrations in urine exceeded the levels necessary to destroy E. coli. Viable bacteria were eliminated with the third regimen (10 mg/kg q8h i.v.), but electron microscopy demonstrated remnants of bacterial biofilm. Histopathologic changes were significantly reduced in all fleroxacin-treated rabbits, and scanning electron microscopy showed deterioration of the bacterial biofilm on the surface of the Foley catheter in treated animals. These data suggest that fleroxacin may be useful for treating catheter-related infections because these therapeutic dosages limited ascending infections of the urethra and bladder, eliminated catheter-associated biofilms, and killed planktonic bacteria in urine.