APPARENT FAILURE OF ONE INJECTION OF BENZATHINE PENICILLIN-G SYPHILISDURING PREGNANCY IN HUMAN IMMUNODEFICIENCY VIRUS-SERONEGATIVE AFRICANWOMEN

Background: Syphilis remains a major cause of premature birth, fetal a nd perinatal death, and congenital syphilis in South Africa despite sy stematic antenatal screening by rapid plasma reagin and treatment with 2.4 million U of benzathine penicillin G. Goal: To determine whether one injection of 2.4 million U of benzathine penicillin G,as recommend ed by the 1993 Centers for Disease Control and Prevention guidelines, is sufficient treatment for early syphilis during pregnancy. Study Des ign: Outcome of pregnancy was prospectively analyzed after zero to thr ee weekly intramuscular injections of benzathine penicillin G in 180 o f 212 human immunodeficiency virus-seronegative black urban women with syphilis in Pretoria, South Africa. Results: One hundred eight women receiving two or three weekly intra-gluteal injections of benzathine p enicillin G had a favorable pregnancy outcome, However, after only one injection, lower birth weight, increased immaturity, prematurity, and total preterm birth rate resulted. Total pregnancy loss and perinatal mortality were also increased. After exclusion of patients treated wi th oral penicillin derivatives and adjustment for the estimated durati on of treponemicidal levels at 3 weeks after injection, the perinatal outcome was reanalyzed. Treponemicidal coverage of 3 weeks or less res ulted in decreased birth weight (2748 vs. 3130 g, P = 0.004) compared with treponemicidal coverage Lasting longer than 3 weeks. In addition, the relative risks for prematurity (relative risk [RR], 8.5; 95% conf idence interval [CI95], 2.5-28), perinatal mortality (RR, 20.5; CI95, 2.3-184), and congenital syphilis (RR 2.0; CI95, 0.6-6.8) were increas ed when coverage was less then 3 weeks. These results were comparable to those obtained when no treatment was given. Most of the incompletel y treated women delivered at less than 4 weeks after they received the ir injection. These also had the worst neonatal outcome, Impaired outc ome due to short treatment clustered in early attenders of prenatal ca re (before the 28th week of gestation) and when the initial rapid plas ma reagin titer was higher than 16. Although numbers were small for a firm conclusion, incompletely treated and untreated women who had take n intercurrent oral ampicillin had an improved birth weight, lower pre maturity rate, and lower fetal mortality rate. Conclusions: One intram uscular injection of 2.4 million U benzathine penicillin G or treponem icidal concentrations lasting 3 weeks or less is not sufficient therap y for pregnant women with syphilis, Although fetal outcome is dearly i mproved at birth with more than one injection, without follow-up of th e neonates, complete cure cannot be predicted from these data. To obta in treponemicidal activity for longer then 3 weeks, the authors recomm end administration of two injections of 2.4 million U benzathine penic illin at least 1 week apart, if possible at 4 weeks or more before del ivery, This therapy is especially important for patients who attend pr enatal care before 28 weeks of pregnancy or when the rapid plasma reag in titer is higher than 16.