Combination Therapy Strategies Against Multiple-Resistant Streptococcus Suis

Streptococcus suis is a major swine pathogen, an emerging zoonotic agent responsible for meningitis, endocarditis and septicaemia followed by deafness in humans The development of antimicrobial resistance in S suis increases the risk for therapeutic failure in both animals and humans In this study, we report the synergism of combination therapy against multi-resistant S suis isolates from swine Twelve antibiotic profiles were determined against 11 S suis strains To investigate their synergistic/antagonistic activity, checkerboard assay was performed for all the possible combinations In-vitro killing curves and in-vivo treatment trials were used to confirm the synergistic activity of special combinations against S suis dominant clones In this study, 11 S suis isolates were highly resistant to erythromycin, clindamycin, trimethoprim/sulfamethoxazole, and tetracycline with ratios of 80-100%, and the resistance percentages to enrofloxacin, florfenicol, and spectinomycin were similar to 50% The checkerboard data identified two combination regimens, ampicillin plus apramycin and tiamulin plus spectinomycin which gave the greatest level of synergism against the S suis strains In-vitro kill-curves showed a bacterial reduction of over 3-logCFU with the use of combination treatments, whilst the application of mono-therapies achieve less than a 2-logCFU cell killing In-vivo models confirm that administration of these two combinations significantly reduced the number of bacterial cells after 24 h of treatment In conclusions, the combinations of ampicillin plus apramycin and tiamulin plus spectinomycin showed the greatest synergism and may be potential strategies for treatment of multi-resistant S suis in animal.