Synergistic Effect of a Pleuromutilin Derivative with Tetracycline against Streptococcus suis In Vitro and in the Neutropenic Thigh Infection Model.

Abstract

Tetracycline (TET) has been widely used in the treatment of Streptococcus suis (S. suis) infection. However, it was found that the efficacy of many antibiotics in S. suis decreased significantly, especially tetracycline. In this study, GML-12 (a novel pleuromutilin derivative) was used in combination with TET against 12 S. suis isolates. In the checkerboard assay, the TET/GML-12 combination exhibited synergistic and additive effects against S. suis isolates (n = 12). In vitro time-killing assays and in vivo therapeutic experiments were used to confirm the synergistic effect of the TET/GML-12 combination against S. suis strains screened based on an FICI ≤ 0.5. In time-killing assays, the TET/GML-12 combination showed a synergistic effect or an additive effect against three isolates with a bacterial reduction of over 2.4-log10 CFU/mL compared with the most active monotherapy. Additionally, the TET/GML-12 combination displayed potent antimicrobial activity against four isolates in a mouse thigh infection model. These results suggest that the TET/GML-12 combination may be a potential therapeutic strategy for S. suis infection.

• Authors: Fang Chen, Meng-Chao Wei, Yi-Dan Luo, Zhen Jin, You-Zhi Tang
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 15 (Aug 01 2020) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 32752180 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Diterpenes
• Polycyclic Compounds
• Tetracycline

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage, toxicity)
• Bacterial Zoonoses (drug therapy, microbiology)
• Disease Models, Animal
• Diterpenes (administration & dosage, toxicity)
• Drug Synergism
• Drug Therapy, Combination
• Female
• Humans
• In Vitro Techniques
• Mice
• Mice, Inbred ICR
• Microbial Sensitivity Tests
• Neutropenia (drug therapy, microbiology)
• Polycyclic Compounds (administration & dosage, toxicity)
• Streptococcal Infections (drug therapy, microbiology)
• Streptococcus suis (drug effects, isolation & purification)
• Swine
• Swine Diseases (drug therapy, microbiology)
• Tetracycline (administration & dosage)
• Pleuromutilins