Combination Antimicrobial Effectiveness Against Streptococcus Suis Infection

Streptococcus Suis is an important zoonotic pathogen which is also an significant organism in animal husbandry industry.Swine and human are both host of S.suis,where the pathogen can live and survive for a long time in vivo.In addition,it is possible that swine and human are carrier for S.suis and do not cause any clinical symptoms normally.When climate changing,environment season alternating,decline of host immunity,it is high risk for an increase morbidity of S.suis infection disease.Although S.suis disease is sporadic,bacterial pathogenicity is quite strong.S.suis is capable of causing clinical symptoms like sow abortion,piglet diarrhea,meningitis,hematosepsis,arthrophlogosis,pneumonia,et.al.Farmers,butchers,and veterinarians can be infected by S.suis from swine.In this work,four S.suis strains,one standard ATCC 43765 and three isolates of GD2013-1025,GD 41,and GD 11,were used.Susceptibility of 13 antimicrobial agents against S.suis strains were tested by micro-dilution broth method,which shows that clinical isolates were resistant to tetracycline,chloramphenicol,clindamycin,compound sulfamethoxazole,and erythromycin;and susceptible to amp icillin,gentamicin,tiamulin,and florfenicol.The pairs of each two drugs were tested for antibacterial interactions by checkerboard method,and the Fraction inhibitory concentration index?FICI?were calculated.It is suggested that pairs of apramycin/ampicillin and spectinomycin/tiamulin are synergetic with FICI value under 0.5.In vitro time-killing curves of combination using of these two pairs drugs revealed that over 2-log₁₀CFU/mL colony counts was killed in combination groups,which was better than single drugs groups,accordingly.However,different killing effect was observed against different strains,like antibacterial effect was not satisfied against S.suis GD 41.In addition the pair of apramycin/ampicillin shows better antimicrobial activity against S.suis than that of spectinomycin/tiamulin combination.To confirm these findings,we also performed treatment trials in vivo using mouse thigh model.As expected,significant killing effects were observed in combination groups than single drug administrated groups?P<0.05?.Antimicrobial effectiveness were significant better given combination theropy against ATCC 43765 strains?P<0.001?.Although,it might be more complicated against wild strains than standard pathogen,combination use of Apramycin/Ampicillin or Spectinomycin/Tiamulin are still capable to perform a significant killing activity in vivo?P<0.05?.In conclusion,synergetic pairs of spectinomycin/tiamulin and apramycin/ampicillin were selected by checkerboard test.Combination antibacterial effectiveness were evaluated by in vitro time-killing curves and in vivo treatment,which suggested that these two pairs are effective to S.suis infection,and may put light on therapy of clinical S.suis diseases.