Bacterial killing by use of once daily gentamicin dosage in guinea pigs with Escherichia coli infection

Abstract

Objective - To determine whether the antibacterial activity of 6 mg of gentamicin/kg of body weight given SC once daily, is equivalent to the standard gentamicin dose of 2 mg/kg given SC every 8 hours. Animals - Guinea pigs with infected thigh wound: 5 in an untreated control group and 12 in 6 and 2 mg/kg gentamicin treatment groups. Procedure - Guinea pigs were inoculated with 109 Escherichia coll in the thigh muscle. Gentamicin treatment (2 mg/kg, SC, q 8 h or 6 mg/kg, SC, q 24 h) was begun 4 hours after E coli inoculation and continued for 72 hours. Four hours after the last gentamicin treatment, all guinea pigs were euthanatized and the cranial thigh muscle containing the entire inoculum was removed. Colony-forming units were counted to determine the E coli concentration in each thigh. Results - Mean ∓ SD Iog10 colony-forming units was 9.293 ∓ 0.074 in the control group, 8.161 ∓ 0.478 in the 2 mg/kg treatment group, and 7.796 ∓ 0.182 in the 6 mg/kg treatment group. One-way ANOVA revealed a significant (P < 0.05) difference between the control group and both treatment groups, and between both treatment groups. Conclusion - Bacterial killing did not differ between gentamicin given at a dosage of 6 mg/kg once daily, compared with 2 mg/kg every 8 hours in guinea pigs infected with E coli. Clinical Relevance - Gentamicin dosage regimens with high peak concentration and long dosing interval are as efficacious as divided dosage regimens. These data support the concept that once daily administration of gentamicin for treatment of E coli infection should be investigated clinically.