Comparison of 3 Treatment Regimens for Latent Syphilis of Late or Unknown Duration Using Public Health Surveillance...

The Centers for Disease Control and Prevention recommends treating latent syphilis of late/unknown duration (LSUD) with 3 doses of intramuscular benzathine penicillin G (BPG) or 28 days of oral doxycycline. This recommendation lacks high-quality evidence.

Using public health surveillance data from King County, Washington, we conducted a retrospective cohort study comparing rates of serological cure (≥2-titer reactive plasma reagin [RPR] decline) among persons with LSUD following receipt of 1 of 3 regimens: 1 dose of BPG, 3 doses of BPG, and 28 days of doxycycline. Subjects included persons diagnosed in 2007 to 2020 with an initial RPR ≥1:2 and follow-up RPR testing 1 to 36 months after treatment. We stratified initial RPRs into high and low titer (≥1:32, <1:32) and compared outcomes using Cox proportional hazards.

The study population included 761 persons with median time from treatment to last RPR/serological cure of 219 days (interquartile range, 114-488 days). Among high-titer persons, serological cure occurred in 36 of 41 (88%), 330 of 376 (88%), and 58 of 64 (88%) receiving single-dose BPG, 3-dose BPG, and doxycycline, respectively. Among low-titer persons, serological cure occurred in 4 of 13 (31%), 114 of 235 (49%), and 14 of 30 (47%) receiving single-dose BPG, 3-dose BPG, and doxycycline, respectively. Controlling for initial RPR, serological cure did not differ between high-titer persons receiving 1- and 3-dose BPG (adjusted hazard ratio, 0.89; 95% confidence interval, 0.63-1.26) or 1-dose BPG and 28 days of doxycycline (adjusted hazard ratio, 1.03; 95% confidence interval, 0.68-1.58).

Serological outcomes in high-titer LSUD after 1 dose of BPG, 3 doses of BPG, and 28 days of doxycycline are similar.