2022 年 10 巻 3 号 p. 77-79
Aim: We evaluated the effect of oral aminobenzylpenicillin (OA) for syphilis during pregnancy in terms of treatment duration.
Methods: In August 2021, we requested 2,146 obstetrical facilities to provide information on syphilis treatment in pregnant women.
Results: There were 45 pregnant women who received OA for active syphilis. Among these women, the median duration of OA treatment was 12 weeks, and four (9%) had been prescribed OA for more than 24 weeks.
Conclusion: It takes a long time to adequately treat syphilis with OA during pregnancy.
Our previous study in 20161) found that an estimated 250 (1/4,022) pregnant women per year were infected with syphilis in Japan. Syphilis is easy to cure in early stages. Penicillin G is administered parenterally as a preferred drug in cases of syphilis in all stages,2) for example, a single intramuscular injection of long-acting benzathine penicillin G (2.4 million units) is effective for curing primary, secondary, or early latent syphilis. During pregnancy, parenteral penicillin G is the only recommended therapy with documented efficacy.2) Penicillin antibiotics have been shown to be effective for treating syphilis, and no penicillin-resistant bacteria have been reported. Penicillin G for intramuscular injection, however, had not been approved in Japan until 2021 due to previous reports of anaphylactic shock events. In Japan, a routine examination for syphilis using two methods (a non-specific test and specific test for Treponema pallidum) is performed in pregnant women, which is covered by Japanese public funds. For pregnant women with active syphilis, oral aminobenzylpenicillin (OA: ampicillin or amoxicillin: 500 mg×3/day, 2–12 weeks) is prescribed in order to prevent congenital syphilis.3) Syphilis is considered cured when the value of non-specific antibodies is reduced to about half the pretreatment value using the automated method, or by one-fourth using the 2-fold serial dilution method.4,5) If antibody values do not decrease sufficiently, a possibility of inappropriate dosing should be considered, along with possibilities of reinfection, neurosyphilis, and immunodeficiency. Nishijima et al.6) recently observed cases in which OA was ineffective for preventing congenital syphilis in pregnant women with late syphilis. Against this backdrop, the present study evaluated the effect of OA in terms of the duration of treatment for syphilis during pregnancy.
The protocol for this study was approved by the Ethics Committee of the Japan Association of Obstetricians and Gynecologists (JAOG).
In August 2021, we requested 2,146 obstetrical facilities that are members of the JAOG to provide information on syphilis treatment in pregnant women between April 2020 and March 2021. Requested data included the duration of OA treatment required to cure syphilis according to the guidelines mentioned above.4,5)
In total, 1,459 (67.8%) of the 2,146 obstetrical facilities responded with possible statistical analysis information on a total of approximately 590,000 deliveries. There were 45 pregnant women who received OA for active syphilis.
Figure 1 shows the duration of OA treatment among the 45 pregnant women. The median duration of OA treatment was 12 weeks. Four (9%) women had been prescribed OA for more than 24 weeks.
Duration of oral aminobenzylpenicillin treatment in 45 pregnant women with active syphilis.
In recent years, the number of individuals with syphilis has dramatically increased in Japan.7) In particular, the number of young women with syphilis is on the rise, and the prevalence of congenital syphilis is also increasing. However, since the number of clinical cases has been low, the diagnosis and treatment of syphilis have been confusing due to the recent status in Japan.
In the present study, although the suitability and effectiveness of OA prescription were not examined, the median duration of treatment of 12 weeks suggests a considerably long period of time required to adequately treat syphilis during pregnancy. This finding is consistent with the report by Nishijima et al.6) We previously reported that roughly 21% of pregnant women with syphilis were diagnosed during the second or third trimester of pregnancy, and that 25% were infected during pregnancy.1) In Japan, treatment of syphilis with OA has been common even though some issues exist regarding treatment duration and/or treatment failure. The therapeutic effect of OA depends on the patient’s adherence to the treatment, e.g., whether OA is taken as instructed when symptoms disappear.8) In addition, it takes a lot of patience to continue taking OA for a long period of time without missing doses. In the future, a prospective study will be necessary to evaluate the efficacy of OA for syphilis.
In 2022, the clinical reintroduction of parenteral penicillin G (single dose) was approved in Japan. A shift in therapeutic approaches (to use penicillin G instead of OA) should be considered, especially for syphilis infections during late pregnancy. In addition, a future study on the therapeutic effect of penicillin G is warranted.
The authors thank the 2,146 member facilities of the Japan Association of Obstetricians and Gynecologists (JAOG) for providing information.
None of the authors declare conflicts of interest relevant to this article.
