MINOCYCLINE AND CEFOTAXIME IN THE TREATMENT OF EXPERIMENTAL MURINE VIBRIO-VULNIFICUS INFECTION

We conducted an in vivo study with the mouse model of Vibrio vulnificu s infection to evaluate the efficacies of therapy with minocycline or cefotaxime alone and in combination. V. vulnificus was introduced subc utaneously into the area over the right thigh. The inoculum size range d from 1.0 x 10(3) to 1.2 x 10(8) CFU from experiment to experiment bu t was constant for all animals in the same experiment. Antibiotics wer e given intraperitoneally 2 h after the bacteria were inoculated. In e xperiments 1 to 4, the standard dose for humans was used to treat the infection, while in experiment 5, five times the standard dose for hum ans was used to treat the infection. In experiment 1, with a small ino culum of 5 x 10(3) CFU, all mice in the saline-treated control group a nd the cefotaxime-, minocycline-, and combined antibiotic-treated grou ps survived, In experiment 2, with a moderate inoculum of 1.2 x 10(5) CFU, all the mice in the three antibiotic-treated groups survived, whi le only two of nine mice in the control group survived, In experiment 3, with a large inoculum of 8.0 x 10(7) CFU, six of nine mice in the c ombined antibiotic-treated group survived, while only one of nine mice in the cefotaxime-treated group and none of the mice in the control a nd minocycline-treated groups survived, In experiment 4, with a large inoculum of 1.2 x 10(8) CFU, 8 of 20 mice in the combined antibiotic-t reated group survived, while none of the 20 mice in the control group, the group treated with cefotaxime alone, and the group treated with m inocycline alone survived. In experiment 5, in which mice were infecte d with a large inoculum of 6.6 x 10(7) CFU and treated with five times the standard human dose of antibiotics, 10 of 12 mice in the combined antibiotic-treated group survived, while only 4 of 12 mice in the min ocycline-treated group, 1 of 12 mice in the cefotaxime-treated group, and none of the mice in the control group survived. In experiments 3 t o 5, the difference in the survival rates between the combined antibio tic-treated and minocycline-treated groups was statistically significa nt (P < 0.05), These results indicate that combination therapy with ce fotaxime and minocycline is distinctly more advantageous than therapy with the single antibiotic regimen for the treatment of severe experim ental V. vulnificus infections.