AUTHOR=Rattanapanadda Porjai , Kuo Hung-Chih , Vickroy Thomas W. , Sung Chi-Hsuan , Rairat Tirawat , Lin Tsai-Lu , Yeh Sze-Yu , Chou Chi-Chung 

TITLE=In vitro and in vivo Synergistic Effects of Florfenicol and Thiamphenicol in Combination Against Swine Actinobacillus pleuropneumoniae and Pasteurella multocida

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02430

DOI=10.3389/fmicb.2019.02430

ISSN=1664-302X

ABSTRACT=<p>Potential synergism between florfenicol (FF) and thiamphenicol (TAP) was investigated for <italic>in vitro</italic> efficacy against <italic>Actinobacillus pleuropneumoniae</italic> and/or <italic>Pasteurella multocida</italic> as well as <italic>in vivo</italic> efficacy in swine. Among isolates of <italic>A. pleuropneumoniae</italic> (<italic>n</italic> = 58) and <italic>P. multocida</italic> (<italic>n</italic> = 79) from pigs 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 <italic>A. pleuropneumoniae</italic> (all serovar 1) and 24% of <italic>P. multocida</italic> 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 <italic>A. pleuropneumoniae</italic> and 65% against susceptible <italic>P. multocida</italic> isolates. A challenge-treatment trial in pigs with <italic>P. multocida</italic> 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 <italic>A. pleuropneumoniae</italic> 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 <italic>P. multocida</italic>, 1/16 for <italic>A. pleuropneumoniae</italic>) when combined with 1/4 MIC of TAP (or 1/8 for <italic>A. pleuropneumoniae</italic>). 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 <italic>A. pleuropneumoniae</italic> and <italic>P. multocida</italic> both <italic>in vitro</italic> and <italic>in vivo.</italic> Thus, this study may offer a potential alternative for the treatment of <italic>A. pleuropneumoniae</italic> and <italic>P. multocida</italic> infections and has the potential to greatly reduce drug residues and withdrawal time.</p>