Pharmacodynamic Studies Of Florfenicol And It's Combinations In Vitro And In Vivo

Pharmacodynamics of flofenicol and it's combinations in vitro and in vivo were studied.Antimicrobial activity(MIC, MBC) of flofenicol and it's combinations against several common pathogens were described by the twofold dilution method or the "Chese-board"method. Killing-curves and post-antibiotic effect(PAE) of thiamphenicol, florfenicol and it's combinations were carried out using the viable counting method.The results of Killing activity of florfenicol, chloramphenicol and thiamphenicol against E.coli, S.pullorum, S. aureus and S. suis showed that florfenicol had an excellent potent against the tested pathogens and it's minimal inhibitory concentrations(MICs) or minimal bactericidal concentrations(MBCs) for the common nine pathogens were lowwer than or equal to 1.6Hg/ml.In killing-curves study, 105-106 colony form units(CFU)/ml E.coli or S. aureus were exposed to florfenicol or thiamphenicol at 1,2,4,8MIC. The killing curves of the two drugs showed that the bacterial growth were inhibited in the lowwer concentrations (1 or 2 MICs ), and Following the increase of drug concerntration from 2MICs to 8 MICs, the bacterials were gradually killed. In addition, the killing speed against E.coli was more rapid than against S. aureus(p<0.05). The PAEs of florfenicol and thiamphenicol against E.coli and S.s aureus were induced following exposure to the 2,4,8 times MICs concerntrations for 2 hours, and then the drugs were removed by a103 times dilution. PAEs of florfenicol against E.coli were 1.45±0.07h,1.92± 0.13h,2.07±0.05h ,respectively,and PAEs against S. aureus were0.48±0.02h, 0.69 ±0.09h, 1.18 ±0.10h ,respectively,Obviously, PAEs duration of florfenicol against the former were longer than that against the latter(p<0.05). But PAEs of thiamphenicol against the former(0.27 ± 0.02h,0.50 ± 0.04h,0.83 ± 0.15h ,respectively,)didn't longer than that against the latter(0.18± 0.01h, 0.29 ±0.09h, 0.53 ±0.01h respectively,) significantly.At last,florfenicol had a longer PAE than thiamphenicol against the same bacteria(p<0.05)and the PAEs of two agents increased with the increase of drug concentration from 2 to 8 times MICs(p<0.05).The sensitivity test of florfenicol combined with doxycycline against four different organisms were conducted, and the results were illustrated by frationalinhibitory concentration(FIC) that the combinations were indifference against the four organisms. But the results of killing-curves of combinations showed that they were synergistic against the organisms in 4 or 8 times MICs. Although the PAEs of the combinations were little longer than that of singles against the same organism, they illustrated indifference.Following treatment with three doses florfenicol(low dose 10mg/kg.b.w and middle dose 20mg/kg.b.w via intramuscular(IM), high dose 30mg/kg.b.w via oral) or two doses combinations ( middle dose 10mg/kg.b.w florfenicol plus 20mg/kg.b.w doxycycline, high dose 20mg/kg.b.w puls 40mg/kg.b.w by oral),the cure rates against Eschenichia.coli were 73.3%,76.3%,73.3%,76.7%,80%., and the efficacies were not significant different among the five varied regimens.