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Front. Microbiol. | doi: 10.3389/fmicb.2019.02430

In Vitro and In Vivo Synergistic Effects of Florfenicol and Thiamphenicol in Combination against Swine Actinobacillus pleuropneumoniae and Pasteurella multocida

 Porjai Rattanapanadda1, Hung-Chih Kuo2, Thomas W. Vickroy3, Chi-Hsuan Sung1, Tirawat Rairat1, Tai-Lu Lin1, Sze -Yu Yeh1 and  Chi-Chung Chou1*
  • 1Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taiwan
  • 2Department of Veterinary Medicine, College of Veterinary Medicine, National Chiayi University, Taiwan
  • 3Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, United States

Potential synergism between florfenicol (FF) and thiamphenicol (TAP) was investigated for in vitro efficacy against Actinobacillus pleuropneumoniae and/or Pasteurella multocida as well as in vivo efficacy in swine. Among isolates of A. pleuropneumoniae (n=58) and P. multocida (n=79) in Taiwan that were tested, high percentages showed resistance to FF (52% and 53%, respectively) and TAP (57% and 53%, respectively). Checkerboard microdilution assay indicated that synergism (fractional inhibitory concentration index (FICI) ≤ 0.5) was detected in 17% of A. pleuropneumoniae (all serovar 1) and 24% of P. multocida isolates. After reconfirming the strains showing FICI ≤ 0.625 with time kill assay, the synergism increased to around 32% against both bacteria and the number could further increase to 40% against resistant A. pleuropneumoniae and 65% against susceptible P. multocida isolates. In vivo study in pigs against P. multocida showed that the FF+TAP dosage at ratios correspondent to their MIC deduction was equally effective to the recommended dosages. Further on the combination, the resistant mutation frequency is very low when A. pleuropneumoniae is grown with FF+TAP and similar to the exposure to sub-inhibitory concentration of FF or TAP alone. The degree of minimum inhibitory concentration (MIC) reduction in FF could reach 75% (1/4 MIC) or more (up to 1/8 MIC for P. multocida, 1/16 for A. pleuropneumoniae) when combined with ¼ MIC of TAP (or 1/8 for A. pleuropneumoniae). The synergism or FICI ≤ 0.625 of FF with oxytetracycline (47%), doxycycline (69%), and erythromycin (56%) was also evident, and worth further investigation for FF as a central modulator facilitating synergistic effects with these antimicrobials. Taken together, synergistic FF+TAP combination was effective against swine pulmonary isolates of A. pleuropneumoniae and P. multocida both in vitro and in vivo. Thus, this study may offer a potential alternative for the treatment of A. pleuropneumoniae and P. multocida infections and has the potential to greatly reduce drug residues and withdrawal time.

Keywords: Pasteurella multocida, Actinobacillus pleuropneumoniae, Thiamphenicol, Florfenicol, Synergism

Received: 17 Jun 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Rattanapanadda, Kuo, Vickroy, Sung, Rairat, Lin, Yeh and Chou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Chi-Chung Chou, National Chung Hsing University, Department of Veterinary Medicine, College of Veterinary Medicine, Taichung, Taiwan, ccchou@nchu.edu.tw