In vitro and in vivo activity of combination antimicrobial agents on Haemophilus ducreyi.
OBJECTIVE
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.
Roy-Leon
Josée E
JE
Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Lauzon
Wallace D
WD
Toye
Baldwin
B
Singhal
Neera
N
Cameron
D William
DW
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002602:Chancroid / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D006191:Haemophilus ducreyi / Q000187:drug effects*; D008297:Male; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D016896:Treatment Outcome
D000890:Anti-Infective Agents