KNUDSEN JD, SKOV RL, GERNER-SMIDT P, PALLESEN LV, FRIMODT-MOLLER N; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. A-2091.

Statens Serum Institut, Copenhagen, Denmark

BACKGROUND: Human infections with food-borne agents such as Salmonella Tyhimurium are an in-creasing problem, and treatment is increasingly impeded by multi-resistance in these strains. Treatment failures with ciprofloxacin in infections caused by S. Typhimurium with MICs of 0.1-1 mg/L for cipro-floxacin have been described. The correlation between MICs and the ED50s for ciprofloxacin for strains of S. Typhimurium DT104 with different susceptibility to ciprofloxacin, was studied in the mouse peri-tonitis/sepsis model. METHODS: We studied the effect of ciprofloxacin in the mouse peritonitis model (CF1 outbred mice) against three clinical isolates of S. Typhimurium DT104 with the following MICs of ciprofloxacin, ST-A: 0.023 mg/L, ST-B: 0.125 mg/L, and ST-C: 0.19 mg/L, respectively. Both ST-B and ST-C have point mutations in the gyrA-gen. The mice were inoculated i.p. with 107cfu, a 100% lethal dose within 2 days for all three strains. One hour after the inoculation a single dose of ciprofloxacin, varying from 0.1 to 100 mg/kg was given s.c. to groups of at least 5 mice. RESULTS: The single dose ED50s increased with increasing MICs: ST-A: 27 mg/kg, ST-B: 54 mg/kg, and ST-C: 85 mg/kg. The ED90 for ST-A was 92 mg/kg, but the ED90-values for ST-B and ST-C were not obtained within the dosing range used, e.g. above 100 mg/kg. When extrapolated to humans, this would mean doses higher than 8 g ciprofloxacin. The AUC/MIC (h) at the ED50 were for ST-A: 411, ST-B: 151, and for ST-C: 157. CONCLUSION: Minor changes in MICs of ciprofloxacin for strains of S. Typhimurium within the NCCLS breakpoint for susceptibility, induced major changes in the effective doses in mouse peritonitis model. These findings confirm the doubt about using ciprofloxacin in treatments of infections caused by S. Ty-phimurium not fully susceptible to ciprofloxacin.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Area Under Curve
• Ciprofloxacin
• Humans
• Mice
• Microbial Sensitivity Tests
• Salmonella
• Salmonella Infections
• Salmonella typhimurium

Other ID:

• GWAIDS0030576

UI: 102270213

From Meeting Abstracts