Comparative in vitro killing activities of enrofloxacin when used alone and in combination with doxycycline against E. coli isolates from dogs and cats

Abstract

Enrofloxacin (ENR) exhibits bactericidal activity while doxycycline (DOX), a drug of choice for Ehrlichia canis (E. canis), demonstrates bacteriostatic effect. When Gram-negative bacteria and E. canis co-infection occurs, using enrofloxacin concurrently with doxycycline is inevitable. The objectives of this study were to compare in vitro killing activities and killing times of enrofloxacin when used alone with those of its combination with doxycycline against ten Escherichia coli (E. coli) isolates from dogs and cats using time-kill curves. The combination treatment was administered either simultaneously (ENR+DOX at t=0 hr) or separately (DOX at t=0 followed by ENR at t=12 hr). The best killing activity was found with enrofloxacin alone, with a log reduction of 3.96 ± 0.49 (97.96-100.00% kill) within 2 hr of drug administration, followed by the simultaneous combination with a log reduction of 3.78 ± 0.37 (98.73-100.00% kill) within 6 hr, and the separated combination with a log reduction of 3.51 ± 0.47 (99.19-100.00% kill) within 12 hr. Comparing time to 3 log reduction (T3K), the separated combination killed E. coli significantly slower than enrofloxacin alone (8.04 ± 0.94 vs 2.47 ± 0.40 hr; p < 0.05), which was consistent with time to elimination (TE) (14.97 ± 1.35 vs 5.83 ± 0.58 hr; p < 0.05). This study establishes that the killing activities of enrofloxacin were reduced and delayed when used in combination with doxycycline, especially with 12-hour doxycycline pre-treatment, suggesting the antagonistic interaction between enrofloxacin and doxycycline when concurrently used against E. coli from dogs and cats.