Teicoplanin Suppresses Vegetative Clostridioides difficile and Spore Outgrowth

Abstract

In recent decades, the incidence of Clostridioides difficile infection (CDI) has remained high in both community and health-care settings. With the increasing rate of treatment failures and its ability to form spores, an alternative treatment for CDI has become a global priority. We used the microdilution assay to determine minimal inhibitory concentrations (MICs) of vancomycin and teicoplanin against 30 distinct C. difficile strains isolated from various host origins. We also examined the effect of drugs on spore germination and outgrowth by following the development of OD600. Finally, we confirmed the spore germination and cell stages by microscopy. We showed that teicoplanin exhibited lower MICs compared to vancomycin in all tested isolates. MICs of teicoplanin ranged from 0.03–0.25 µg/mL, while vancomycin ranged from 0.5–4 µg/mL. Exposure of C. difficile spores to broth supplemented with various concentrations of antimicrobial agents did not affect the initiation of germination, but the outgrowth to vegetative cells was inhibited by all test compounds. This finding was concordant with aberrant vegetative cells after antibiotic treatment observed by light microscopy. This work highlights the efficiency of teicoplanin for treatment of C. difficile through prevention of vegetative cell outgrowth.

Effects of Different Bacteriostats on the Dynamic Germination of Clostridium perfringens Spores

“…While D-isoascorbic acid and potassium sorbate could not stop spore germination, they could decrease spore survival rates and increase protein and nucleic acid leakage during germination (Figure 4). This could be because these bacteriostats also compromised the cell membrane's integrity and increased cellular permeability, causing the contents of the cell to flow out [9,23,38,39]. The inhibitory effects of nitrite and ε-polylysine hydrochloride on C. perfringens spores could be attributed to the effect of these compounds on the cell membrane of propagules, enzyme activity, and energy metabolism, thus impairing bacterial metabolism [10,11,40].…”

“…The diameter of the inhibition zone was used to assess the antibacterial activity of the bacteriostat. An inhibition zone with a diameter of >9 mm indicated antibacterial activity of the bacteriostat, and the larger the diameter of the inhibition zone, the stronger was the antibacterial activity of the bacteriostat [23]. Subsequently, the inhibitory effects of various bacteriostats on C. perfringens were compared, and the outcomes are presented in Table 1.…”

“…Studies have indicated that the resistance of spores varies with the chemicals [21]. Some oxidants have been found to damage the inner membrane of the spores, rupturing the inner membrane during germination [22], while other compounds, such as nitrous acid and formaldehyde, can kill spores through DNA damage [7,23]. Moreover, the mechanism by which some compounds kill spores is still unknown.…”

С. difficile infection: clinical and pharmacoeconomic assessment of treatment regimens in antibiotic-associated diarrhea

“…Более того, в недавно проведенном исследовании при экспериментальном сравнении минимально пода вляющих концентраций (МПК) у 30 штаммов С. difficile, полученных из различных источников, тейкопланин оказался примерно на порядок активнее ванкомицина (МПК 0,03-0,25 и 0,5-4,0 мг/л соответственно), хотя оба препарата в равной степени подавляли превраще ние спор в вегетативную форму [24].…”

Introduction to the Special Issue on Clostridioides difficile

“…Regarding the therapeutic approaches to CDI, a contribution by Ojha et al highlighted that teicoplanin, an antimicrobial agent approved for the treatment of other bacterial infections, prevents the outgrowth of CD vegetative cells [16].…”