Efficacy of several antibiotic combinations against Brucella melitensis Rev 1 experimental infection in BALB/c mice

• Published in: Journal of antimicrobial chemotherapy 2006-09, Vol.58 (3), p.622-626
• Main Authors: Grilló, M. J., De Miguel, M. J., Muñoz, P. M., Marín, C. M., Ariza, J., Blasco, J. M.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; antimicrobial therapy; B. melitensis Rev 1 vaccine strain; Bacterial diseases; Biological and medical sciences; Brucella melitensis; Brucella melitensis - drug effects; Brucella melitensis - growth & development; Brucellosis - drug therapy; Disease Models, Animal; Drug Resistance, Multiple, Bacterial - drug effects; Drug Therapy, Combination; Female; Human bacterial diseases; Human brucellosis; Infections; Infectious diseases; Medical sciences; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Miscellaneous; Pharmacology; Pharmacology. Drug treatments; Rodents; Treatment Outcome
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkl289

Objectives: The objective of the present study was to compare the efficacy of gentamicin given alone or combined with doxycycline with that of standard combination therapies in BALB/c mice experimentally infected with the Brucella melitensis vaccine strain Rev 1. Methods: A standard broth microdilution method was applied to determine the susceptibility of strain Rev 1 to the clinically most relevant aminoglycosides. Eight groups of BALB/c mice were inoculated intraperitoneally (ip) with 1 × 106 cfu/mouse of strain Rev 1. While one group remained untreated, the other seven groups were treated 10 days later once a day for 14 days with (i) doxycycline given orally at 2 mg/day; (ii) streptomycin given ip at 0.4 mg/day; (iii) gentamicin given ip at 0.4 mg/day; (iv) rifampicin given orally at 0.5 mg/day; (v) doxycycline plus streptomycin; (vi) doxycycline plus gentamicin; and (vii) doxycycline plus rifampicin. The number of cfu per spleen and clearance of Rev 1 were assessed 34 days after inoculation. Results: With the exception of streptomycin, strain Rev 1 was susceptible to all aminoglycosides tested. As expected, the combination doxycycline/streptomycin was ineffective against Rev 1 infection. In contrast, the combinations doxycycline/gentamicin and doxycycline/rifampicin were effective in the clearance of Rev 1 infection, but only the former improved significantly the therapeutic efficacy as compared with that of the antibiotics given alone. Conclusions: Gentamicin may be used along with doxycycline when the classical combination is considered the first choice in the treatment of patients with brucellosis due to B. melitensis vaccine strain Rev 1.