Leeds Institute for Molecular Medicine, University of Leeds, Leeds LS2 9JT, UK.
J Antimicrob Chemother. 2013 Sep;68(9):2078-82. doi: 10.1093/jac/dkt160. Epub 2013 Jun 11.
Previous work suggests oritavancin may be inhibitory to Clostridium difficile spores. We have evaluated the effects of oritavancin exposure on C. difficile spore germination, outgrowth and recovery.
Germination and outgrowth of C. difficile spores exposed to different concentrations of oritavancin, vancomycin, or metronidazole (0.1-10 mg/L) were monitored at 0, 2, 4, 6, 24 and 48 h using phase-contrast microscopy. Recovery of antimicrobial-exposed spores was determined by viable counting on Brazier's modified CCEYL agar. Persistence of oritavancin activity on spores after washing was determined by measuring activity against a Staphylococcus aureus lawn.
Oritavancin, vancomycin and metronidazole exposure did not prevent germination of phase-bright spores to phase-dark spores, but did inhibit further outgrowth into vegetative cells. The inhibitory effect of oritavancin persisted after washing, whereas the inhibitory effects of vancomycin and metronidazole did not. Oritavancin exposure affected spore recovery; fewer spores were recovered after washing following oritavancin exposure than vancomycin exposure. The extent of this effect was dependent on PCR ribotype, with recovery of ribotype 078 spores completely prevented, but recovery of ribotype 001 spores only slightly affected. Spores exposed to oritavancin, but not vancomycin, retained antimicrobial activity after washing, indicating adherence of oritavancin, but not vancomycin, to the spore surface
Oritavancin may adhere to spores, potentially causing early inhibition of germinated cells, preventing subsequent vegetative outgrowth and spore recovery. This may prevent some recurrences of symptomatic C. difficile infection that are due to germination of residual spores following antibiotic therapy.
先前的研究表明，奥他凡星可能对艰难梭菌孢子具有抑制作用。我们评估了奥他凡星暴露对艰难梭菌孢子发芽、生长和复苏的影响。
使用相差显微镜在 0、2、4、6、24 和 48 小时监测不同浓度奥他凡星、万古霉素或甲硝唑（0.1-10 mg/L）暴露下艰难梭菌孢子的发芽和生长。通过在 Brazier 改良的 CCEYL 琼脂上进行活菌计数来确定暴露于抗菌药物的孢子的复苏情况。通过测量奥他凡星对金黄色葡萄球菌菌苔的活性来确定洗涤后奥他凡星活性在孢子上的持久性。
奥他凡星、万古霉素和甲硝唑暴露不能阻止相亮孢子向相暗孢子的发芽，但确实抑制了进一步向营养细胞的生长。奥他凡星的抑制作用在洗涤后仍然存在，而万古霉素和甲硝唑的抑制作用则不存在。奥他凡星暴露影响孢子的复苏；与万古霉素暴露相比，洗涤后从奥他凡星暴露的孢子中回收的孢子较少。这种影响的程度取决于 PCR 核糖体型，核糖体型 078 孢子的复苏完全被阻止，但核糖体型 001 孢子的复苏仅受到轻微影响。暴露于奥他凡星但未暴露于万古霉素的孢子在洗涤后仍保留抗菌活性，表明奥他凡星而不是万古霉素与孢子表面结合。
奥他凡星可能与孢子结合，可能导致发芽细胞的早期抑制，从而阻止随后的营养生长和孢子复苏。这可能防止了一些由于抗生素治疗后残留孢子发芽引起的有症状的艰难梭菌感染的复发。
