Abstract
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 ~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.
Highlights
Streptococcus Suis, a facultatively anaerobic Gram-positive coccus, is an important swine pathogen worldwide and causes considerable economic losses within the swine industry (Haas and Grenier, 2017)
Twelve conventional antibiotics, which were commonly used for treatment of S. suis infections in veterinary clinic, were tested in total for the minimal inhibitory concentrations (MICs), including ampicillin (AMP), ceftiofur (CEF), enrofloxacin (ENR), apramycin (AP), spectinomycin (SPT), tetracycline (TET), erythromycin (ERY), chloramphenicol (CHL), florfenicol (FFN), tiamulin (TIA), trimethoprim/sulfamethoxazole (T/S), and clindamycin (CLI)
Broth micro-dilution method was performed in Mueller Hinton (MH) broth in triplicates regarding the guideline of Clinical and Laboratory Standards Institute (2013)
Summary
Streptococcus Suis, a facultatively anaerobic Gram-positive coccus, is an important swine pathogen worldwide and causes considerable economic losses within the swine industry (Haas and Grenier, 2017). S. suis is known as an emerging zoonotic agent since the first cases of human infection in 1986 (Perch et al, 1968). It is no doubt that S. suis is cause for increasing concern against the swine industry and human health. We try to find prospects to treat multi-drug resistant S. suis by employing combination therapy. One or two antimicrobial agents per each category were chosen for this study, which were conventional and widely used in Chinese veterinary clinic for treating S. suis diseases. The resistant characteristics of 11 S. suis isolates from diseased pigs were tested for MIC as phenotype and confirmed by genotype using
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