In Vitro Susceptibility of Treponema pallidum subsp. pallidum to Doxycycline

Abstract

Doxycycline is regarded as an effective therapy for early syphilis, and there is also increasing interest in using doxycycline for prophylaxis of this infection. However, the minimum inhibitory concentration (MIC) of doxycycline for Treponema pallidum subsp. pallidum has not been reported previously. In this study, an in vitro culture system was utilized to determine that the MIC of doxycycline is 0.06 to 0.10 μg/ml for four strains of T. pallidum subsp. pallidum (Nichols, SS14, UW231B, and UW249B). The Nichols strain cultured in vitro with doxycycline was also tested for infectivity in rabbits, and the minimum bactericidal concentration (MBC) was found to be ≤ 0.1 μg/ml using this method. The low MIC and MBC values are consistent with the previously demonstrated clinical efficacy of doxycycline for the treatment of early syphilis. This study represents the first report of the in vitro susceptibility of T. pallidum to doxycycline, and the resulting information may be useful in the consideration of doxycycline for use in prevention of syphilis.

Parameters Affecting Continuous In Vitro Culture of Treponema pallidum Strains

“…Approaches such as metabolomics may indicate the compounds or activities that Sf1Ep cells are providing, potentially leading to the ultimate development of axenic culture conditions. Overall, the T. pallidum culture system has been shown to be highly reproducible and robust, and our group and other laboratories have begun to apply this system to other aspects of T. pallidum biology, including antimicrobial susceptibility ( 43 ), isolation of clonal populations, propagation of organisms from patient samples, and genetic manipulation.…”

A large screen identifies beta-lactam antibiotics which can be repurposed to target the syphilis agent

“…We note that while doxycycline has been shown to kill T. pallidum , but it is not effective at 5 nM (Fig. 2a ) 20 . Relative efficacy differences notwithstanding, both groups of β-lactams were highly variable (Fig.…”

“…3 ). Nonetheless, all candidates were extremely effective and produced MIC values 10–100 times lower than doxycycline 20 .…”

Pharmacokinetics of single dose doxycycline in the rectum, vagina, and urethra: implications for prevention of bacterial sexually transmitted infections

“…The 90% minimum inhibitory concentration (MIC 90 ) of doxycycline for C. trachomatis and T. pallidum used in this analysis was 0.064 and 0.1 μg/mL, respectively. 19 , 20 MIC values for tetracycline determined by standardized methods were used for N. gonorrhea susceptibility to doxycycline because they closely resemble MIC values for doxycycline. 21 Tetracycline-sensitive N. gonorrhoeae were classified as having an MIC less than 0.25 μg/mL and tetracycline-resistant N. gonorrhoeae were classified as having an MIC greater than 2 μg/mL.…”