In vitro evaluation of disease-modifying antirheumatic drugs against rheumatoid arthritis associated pathogens of the oral microflora

体外评价抗风湿药物对口腔菌群类风湿关节炎相关病原体的作用

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作者:Manuel Kussmann, Markus Obermueller, Kathrin Spettel, Stefan Winkler, Daniel Aletaha

Conclusion

Methotrexate, sulfasalazine and aurothiomalate showed antimicrobial activity against a broad spectrum of RA associated pathogens of the oral microflora. While methotrexate showed relevant antimicrobial activity, and to a more limited extent aurothiomalate, sulfasalazine was active only at far supratherapeutic systemic concentrations. Nevertheless, given the highly species-dependent antimicrobial activity and the multiple ways it can affect the human microbiome, our results suggest a link between antimicrobially active antirheumatic drugs and their potential effect in the treatment of RA.

Methods

DMARDs were screened for antimicrobial activity against bacteria that are associated with the pathogenesis of the disease and/or frequently isolated from the oral microflora of patients with RA. Screening was done by an agar diffusion assay and minimum inhibitory concentrations (MICs) of antimicrobial active substances were then determined by broth dilution.

Results

Aurothiomalate and sulfasalazine demonstrated broad-spectrum antimicrobial activity, but with MICs ranging from 18 to >280 µg/mL and 150 to >600 µg/mL, respectively, only at supratherapeutic concentrations. Methotrexate showed antimicrobial activity only against Fusobacterium nucleatum and Viridans streptococci. The corresponding MICs were 3.75 to >30 µg/mL and 0.5-15 µg/mL, respectively, thus at least for streptococci, within the therapeutically achievable range. No other DMARD tested showed antimicrobial activity in the agar diffusion screening assay.

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