Comparing 7-Day Versus 6-8-Day Penicillin Treatment Intervals Among Pregnant People With Syphilis of Late or Unknown Duration: No Difference Found in Incidence of Congenital Syphilis

Kelly A Johnson; Nicole O Burghardt; Robert E Snyder; Rosalyn E Plotzker; Brandon M Imp; Ryan Murphy; Kathleen Jacobson; Eric C Tang

doi:10.1093/ofid/ofad300

Comparing 7-Day Versus 6-8-Day Penicillin Treatment Intervals Among Pregnant People With Syphilis of Late or Unknown Duration: No Difference Found in Incidence of Congenital Syphilis

Open Forum Infect Dis. 2023 Jun 8;10(6):ofad300. doi: 10.1093/ofid/ofad300. eCollection 2023 Jun.

Authors

Kelly A Johnson^{1

2}, Nicole O Burghardt¹, Robert E Snyder¹, Rosalyn E Plotzker^{1

3}, Brandon M Imp⁴, Ryan Murphy¹, Kathleen Jacobson¹, Eric C Tang¹

Affiliations

¹ Sexually Transmitted Diseases Control Branch, Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond, California, USA.
² Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, USA.
³ Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
⁴ Department of Medicine, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA.

Abstract

Background: Guidelines recommend that pregnant patients with syphilis of late/unknown duration be treated with benzathine penicillin G, dosed as 3 weekly intramuscular injections (BPGx3) given ideally at strict 7-day intervals. Given limited pharmacokinetic data, it is unknown whether more flexible BPG treatment intervals might be effective in preventing congenital syphilis (CS).

Methods: We used California surveillance data to identify birthing parent/infant dyads wherein the pregnant parent had syphilis of late/unknown duration between January 1, 2016 - June 30, 2019. We divided the dyads into 3 groups based on prenatal treatment: (1) BPGx3 at strict 7-day intervals, (2) BPGx3 at 6-8 day intervals, and (3) no/inadequate treatment. We then compared CS incidence among infants in each group.

Results: We analyzed 1,092 parent/infant dyads: 607 (55.6%) in the 7-day treatment group, 70 (6.4%) in the 6-8 day treatment group, and 415 (38.0%) in the no/inadequate treatment group. The incidence proportion of infants meeting CS criteria in each group was, respectively, 5.6%, 5.7%, and 36.9%. Compared with BPGx3 at 7-day intervals, the odds of CS were 1.0 [95% CI 0.4-3.0] in the 6-8 day group and 9.8 [95% CI 6.6-14.7] in the no/inadequate treatment group.

Conclusions: Prenatal BPGx3 at 6-8 days was no more likely to lead to CS in infants than 7-days. These findings hint that 6-8-day intervals might be adequate to prevent CS among pregnant people with syphilis of late/unknown duration. Consequently, it is possible that CS evaluation beyond an RPR at delivery may be unnecessary in asymptomatic infants whose parents received BPGx3 at 6-8 days.

Keywords: congenital syphilis; sexually transmitted infections (STIs); syphilis in pregnancy; syphilis prevention; syphilis treatment intervals.