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- Title
In vitro and in vivo activity of combination antimicrobial agents on Haemophilus ducreyi.
- Authors
Josée E. Roy-Leon; Wallace D. Lauzon; Baldwin Toye; Neera Singhal; D. William Cameron
- Abstract
Objectives: Development of single dose antibiotic treatments for chancroid has been followed by drug-resistant Haemophilus ducreyi in endemic areas. We examined the activity and interactions of antimicrobial agents and combinations against H. ducreyi.Methods: We evaluated the in vitro susceptibility of three virulent strains of H. ducreyi to ceftriaxone, azithromycin, rifabutin and streptomycin, and each two-drug combination by the agar dilution method. We then tested each two-antibiotic combination for activity by the chequerboard method. Lastly, we chose the antibiotic combination with the lowest fractional inhibitory concentration index (FICI) and tested combined sub-therapeutic doses, the highest doses which had no effect alone on lesion healing compared with controls, for in vivo interaction in the temperature-dependent rabbit model of H. ducreyi infection.Results: Each H. ducreyi strain was susceptible in vitro to each antibiotic and two-antibiotic combination, and combined ceftriaxone and streptomycin had the lowest FICI at 0.63. In five treated animals versus three untreated controls, combined sub-therapeutic doses of ceftriaxone (0.05 mg/kg) and streptomycin (10 mg/kg) reduced mean (SD) duration of culture positivity from 7.3 (1.1) to 2.6 (1.7) days (P < 0.001), time to 50% reduction in lesion size from 9.7 (1.5) to 5.8 (0.8) days (P < 0.005), and time to resolution of ulcer from 11.7 (2.3) to 6.6 (1.7) days (P < 0.05).Conclusions: Ceftriaxone and streptomycin have in vivo synergic interaction against H. ducreyi lesions in the temperature-dependent rabbit model of infection. Antibiotic combinations may be evaluated clinically as single-dose therapy for chancroid.
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2005, Vol 56, Issue 3, p552
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dki270