Combination Therapy Strategies Against Multiple-Resistant Streptococcus Suis

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.

Ginkgetinin vitro and in vivoreducesStreptococcus suisvirulence by inhibiting suilysin activity

“…Facing the increasingly serious problem of bacterial resistance, we are in an unfortunate situation that the development of new antibiotics cannot catch up with the rate of bacterial resistance (Escaich ; Seitz et al ). Similarly, the drug resistance of S. suis is becoming an increasing worrisome, and multiple types of drug‐resistant S. suis strains, including strains with resistance to erythromycin, clindamycin, trimethoprim (Yu et al ) and cephalosporins (Zhang et al ), have been isolated. The development of antivirulence strategies is considered effective and promising for addressing the challenges posed by the increases in bacterial resistance to drugs (Rasko and Sperandio ).…”

“…Over the past two decades, cases of S. suis infection have been reported worldwide. The incidence has substantially increased (Yu et al ), particularly in 2005, when hundreds of people were infected with S. suis and more than 30 people died (Yu et al ), which has resulted in widespread panic and concern throughout society.…”

Antibacterial mechanism of rhodomyrtone involves the disruption of nucleoid segregation checkpoint in Streptococcus suis

“…Zoonotic transmission of this pathogen to human occurs via direct contact with the sick pigs or consumption of contaminated meat and pork products (Segura et al 2014;Wertheim et al 2009). Similar to Streptococcus pneumoniae infections, penicillin and ampicillin previously were the mainstay of treatment of S. suis infections (Lakkitjaroen et al 2011;Yu et al 2018;Zhang et al 2015). To date, the efficacy of these antibiotics was seriously compromised as evidenced by the frequent isolation of ampicillin-resistant S. suis strains from infected swine and human (Yu et al 2018;Zhang et al 2015).…”

Antibacterial mechanism of rhodomyrtone involves the disruption of nucleoid segregation checkpoint in Streptococcus suis

“…Zoonotic transmission of this pathogen to human occurs via direct contact with the sick pigs or consumption of contaminated meat and pork products (Segura et al 2014;Wertheim et al 2009). Similar to Streptococcus pneumoniae infections, penicillin and ampicillin previously were the mainstay of treatment of S. suis infections (Lakkitjaroen et al 2011;Yu et al 2018;Zhang et al 2015). To date, the e cacy of these antibiotics was seriously compromised as evidenced by the frequent isolation of ampicillin-resistant S. suis strains from infected swine and human (Yu et al 2018;Zhang et al 2015).…”

“…Similar to Streptococcus pneumoniae infections, penicillin and ampicillin previously were the mainstay of treatment of S. suis infections (Lakkitjaroen et al 2011;Yu et al 2018;Zhang et al 2015). To date, the e cacy of these antibiotics was seriously compromised as evidenced by the frequent isolation of ampicillin-resistant S. suis strains from infected swine and human (Yu et al 2018;Zhang et al 2015). Therefore, novel and effective antimicrobial agents are indeed needed for the management of S. suis infection.…”