今日の臨床サポート

梅毒(感染症科)

著者: 谷崎隆太郎 市立伊勢総合病院 内科・総合診療科

監修: 上原由紀 聖路加国際病院 臨床検査科/感染症科

著者校正/監修レビュー済:2021/03/10
参考ガイドライン:
  1. アメリカ疾病予防管理センター(Centers for Disease Control and Prevention(CDC)):Sexually transmitted diseases treatment guidelines, 2015
患者向け説明資料

概要・推奨   

  1. 非トレポネーマ抗体検査は抗体価が病勢を反映することが有利な点であるが、さまざまな病態で偽陽性や偽陰性を示すため、梅毒トレポネーマ特異的抗体で確認することが必要である(推奨度1)
  1. 梅毒の症状は非常に多岐にわたり、積極的に疑うことが診断には必要である(推奨度1)
  1. 神経梅毒は後期梅毒の合併症とよく誤解されているが、実際にはあらゆる病期で起こり得る。何らかの神経症状のある場合(頭痛やめまいなど軽微な症状も含む)、HIV感染合併例、非トレポネーマ抗体価の高い症例(RPRで1:32以上)の場合には積極的に腰椎穿刺を行う(推奨度1)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
谷崎隆太郎 : 特に申告事項無し[2021年]
監修:上原由紀 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、妊婦における治療について加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 梅毒とは、梅毒トレポネーマ(Treponema pallidum subsp. pallidum)によって起こされる慢性の全身感染症であり、病期や宿主の状態により幅広い臓器に多彩な症状を引き起こす。
  1. 感染経路は主に性交渉・オーラルセックスによるが、まれに経皮感染や他の体液暴露による感染もあり得る。
  1. 母子感染により先天梅毒を起こすこともある。
  1. 病原体の培養が不可能なため、診断は臨床症状、病理所見、血清学的検査所見による。
  1. 妊娠中の女性における積極的な診断と治療は先天梅毒を防ぐために特に重要である。
  1. HIV陽性患者などでは、症状が非典型的になることも多く、合併感染症の治療も併せて専門家へのコンサルトを要する。
病歴・診察のポイント  
  1. 性行為感染症としての病歴聴取:
  1. ハイリスク性行為の有無(男性同性間の性交渉・肛門性交など)、複数の性行為パートナーの存在、コンドームの使用有無(性交時だけでなくオーラルセックスの際の使用も)、性産業従事者との接触など

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文献 

著者: Kimberly A Workowski, Gail A Bolan, Centers for Disease Control and Prevention
雑誌名: MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137.
Abstract/Text These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 30-May 2, 2013. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2010 (MMWR Recomm Rep 2010;59 [No. RR-12]). These updated guidelines discuss 1) alternative treatment regimens for Neisseria gonorrhoeae; 2) the use of nucleic acid amplification tests for the diagnosis of trichomoniasis; 3) alternative treatment options for genital warts; 4) the role of Mycoplasma genitalium in urethritis/cervicitis and treatment-related implications; 5) updated HPV vaccine recommendations and counseling messages; 6) the management of persons who are transgender; 7) annual testing for hepatitis C in persons with HIV infection; 8) updated recommendations for diagnostic evaluation of urethritis; and 9) retesting to detect repeat infection. Physicians and other health-care providers can use these guidelines to assist in the prevention and treatment of STDs.

PMID 26042815  MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137.
著者: Sam Ratnam
雑誌名: Can J Infect Dis Med Microbiol. 2005 Jan;16(1):45-51.
Abstract/Text Syphilis has several clinical manifestations, making laboratory testing a very important aspect of diagnosis. In North America, many unsuspected cases are discovered by laboratory testing. The etiological agent, Treponema pallidum, cannot be cultured, and there is no single optimal alternative test. Serological testing is the most frequently used approach in the laboratory diagnosis of syphilis. The present paper discusses the various serological and alternative tests currently available along with their limitations, and relates their results to the likely corresponding clinical stage of the disease. The need to use multiple tests is discussed, and the importance of quality control is noted. The complexity of syphilis serology means that the services of reference laboratories and clinical experts are often needed.

PMID 18159528  Can J Infect Dis Med Microbiol. 2005 Jan;16(1):45-51.
著者: Rita Castro, Emília Simões Prieto, Filomena da Luz Martins Pereira
雑誌名: J Clin Lab Anal. 2008;22(4):257-61. doi: 10.1002/jcla.20254.
Abstract/Text The Venereal Disease Research Laboratory (VDRL) test has long been considered the best serological test for the diagnosis of neurosyphilis. The goal of this study was to find out if the Rapid Plasma Reagin (RPR) could be an alternative to the VDRL. Cerebrospinal fluid (CSF) and sera samples from patients in the following stages of syphilis were tested: 8 had symptomatic and 16 asymptomatic neurosyphilis, 4 were in the primary stage, 6 had secondary syphilis, and 92 were in the latent stage. We have also studied 61 samples from individuals with treated syphilis and 126 with other neurological diseases than neurosyphilis. All the CSF samples were studied with both RPR and VDRL tests. RPR and VDRL test results were mostly concordant. The specificity of these tests for current neurosyphilis was 99% for the VDRL and 99.3% for the RPR, whereas the sensitivity was 70.8 and 75%, respectively, for the VDRL and RPR. In view of these results it seems to us that the RPR could be an alternative to the VDRL in the diagnosis of neurosyphilis.

PMID 18623120  J Clin Lab Anal. 2008;22(4):257-61. doi: 10.1002/jcla.2・・・
著者: Christina M Marra, Clare L Maxwell, Stacy L Smith, Sheila A Lukehart, Anne M Rompalo, Molly Eaton, Bradley P Stoner, Michael Augenbraun, David E Barker, James J Corbett, Mark Zajackowski, Charles Raines, Judith Nerad, Romina Kee, Scott H Barnett
雑誌名: J Infect Dis. 2004 Feb 1;189(3):369-76. doi: 10.1086/381227. Epub 2004 Jan 27.
Abstract/Text OBJECTIVE: To define clinical and laboratory features that identify patients with neurosyphilis.
METHODS: Subjects (n=326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/ microL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result.
RESULTS: Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer > or =1 : 32 increased the odds of neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4+ T cell count < or =350 cells/ microL conferred 3.10-fold increased odds of neurosyphilis in HIV-infected subjects. Similar results were obtained when neurosyphilis was more stringently defined as a reactive CSF VDRL test result.
CONCLUSION: Serum RPR titer helps predict the likelihood of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis.

PMID 14745693  J Infect Dis. 2004 Feb 1;189(3):369-76. doi: 10.1086/38・・・
著者: Matthew R Golden, Christina M Marra, King K Holmes
雑誌名: JAMA. 2003 Sep 17;290(11):1510-4. doi: 10.1001/jama.290.11.1510.
Abstract/Text
PMID 13129993  JAMA. 2003 Sep 17;290(11):1510-4. doi: 10.1001/jama.290・・・
著者: A R Salkind, P G Cuddy, J W Foxworth
雑誌名: JAMA. 2001 May 16;285(19):2498-505.
Abstract/Text CONTEXT: Clinicians frequently withhold antibiotics that contain penicillin based on patients' self-reported clinical history of an adverse reaction to penicillin and the clinicians' own misunderstandings about the characteristics of a true penicillin allergy.
OBJECTIVES: To determine the likelihood of true penicillin allergy with consideration of clinical history and to evaluate the diagnostic value added by appropriate skin testing.
DATA SOURCES: MEDLINE was searched for relevant English-language articles dated 1966 to October 2000. Bibliographies were searched to identify additional articles.
STUDY SELECTION: We included original studies describing the precision of skin testing in diagnosis of penicillin allergy. We excluded studies that did not use both minor and major determinants, provide an explicit definition of penicillin allergy, or list the specific criteria necessary for a positive skin test result. Fourteen studies met the inclusion criteria.
DATA EXTRACTION: Three authors independently reviewed and abstracted data from all articles and reached consensus about any discrepancies.
DATA SYNTHESIS: Patients' self-reported history has low accuracy for diagnosis of true penicillin allergy. By evaluating studies comparing clinical history to the skin test for penicillin allergy among patients with and without a positive history for penicillin allergy, positive and negative likelihood ratios were calculated. History of penicillin allergy had a positive likelihood ratio of 1.9 (95% confidence interval [CI], 1.5-2.5), while absence of history of penicillin allergy had a negative likelihood ratio of 0.5 (95% CI, 0.4-0.6).
CONCLUSIONS: Only 10% to 20% of patients reporting a history of penicillin allergy are truly allergic when assessed by skin testing. Taking a detailed history of a patient's reaction to penicillin may allow clinicians to exclude true penicillin allergy, allowing these patients to receive penicillin. Patients with a concerning history of type I penicillin allergy who have a compelling need for a drug containing penicillin should undergo skin testing. Virtually all patients with a negative skin test result can take penicillin without serious sequelae.

PMID 11368703  JAMA. 2001 May 16;285(19):2498-505.
著者: Khalil G Ghanem, Emily J Erbelding, Walter W Cheng, Anne M Rompalo
雑誌名: Clin Infect Dis. 2006 Mar 15;42(6):e45-9. doi: 10.1086/500406. Epub 2006 Feb 8.
Abstract/Text BACKGROUND: Doxycycline is the preferred recommended second-line agent for the treatment of syphilis, although efficacy data from controlled trials are lacking. We compared the serological responses of patients with early syphilis treated with doxycycline with the responses of patients treated with benzathine penicillin G (BPG).
METHODS: All patients who received a diagnosis of early syphilis attending 2 public sexually transmitted disease clinics in Baltimore, Maryland, who were treated with doxycycline (100 mg orally, twice daily for 14 days) between October 1993 and June 2000 were eligible. Patients treated with BPG (a single dose of 2.4 million units intramuscularly) were selected as the control group. Inclusion criteria included a clinician-recorded diagnosis of primary, secondary, or early latent syphilis with reactive serological test results at the time of diagnosis and at least 1 follow-up serological test titer. Serological failure was defined as lack of a 4-fold drop in rapid plasma reagin titer 270-400 days after treatment, or a 4-fold increase in titer 30-400 days after therapy.
RESULTS: During the study period, 1558 patients were treated for early syphilis, and 87 received doxycycline. Of those treated with doxycycline, 34 met the inclusion criteria. Seventy-three patients from a randomly selected group of 200 age-matched individuals treated with BPG met the inclusion criteria. There were 4 patients with serological failure in the BPG group (5.5%; 95% confidence interval [CI], 1.6%-13.8%) and 0 patients with serological failure in the doxycycline group (0%; 95% CI, 0%-10.3%; P=.2). The median times to successful serological responses for patients in the doxycycline and BPG groups were 106 days (95% CI, 75-149 days) and 137 days (95% CI, 111-172 days), respectively (P=.6).
CONCLUSION: Doxycycline appears to be an effective agent for the treatment of early syphilis.

PMID 16477545  Clin Infect Dis. 2006 Mar 15;42(6):e45-9. doi: 10.1086/・・・
著者: Tom Wong, Ameeta E Singh, Prithwish De
雑誌名: Am J Med. 2008 Oct;121(10):903-8. doi: 10.1016/j.amjmed.2008.04.042.
Abstract/Text BACKGROUND: Benzathine penicillin G is the treatment of choice for infectious syphilis, but tetracycline and doxycycline are believed to be effective second-line treatments. The objective of this study was to assess the serological response from treatment of primary syphilis with benzathine penicillin compared with doxycycline or tetracycline.
METHODS: We examined rapid plasma reagin serological test results of all first-time primary syphilis patients in Alberta, Canada from 1980 to 2001 and compared treatment with single dose of penicillin with 14-day course of oral doxycycline (100 mg twice a day) or oral tetracycline (500 mg 4 times a day). Serological treatment success was defined as a minimum 4-fold decrease in baseline rapid plasma reagin test antibody titer within 6 months, or > or =8-fold decrease within 12 months, or > or =16-fold decrease by 24 months. The median time to successful response was estimated, and factors associated with treatment success were identified by unadjusted logistic regression.
RESULTS: Of the 445 primary syphilis cases with available treatment outcome data, 420 (94.4%) received penicillin and 25 (5.6%) received doxycycline/tetracycline. The serological treatment success rate was 97.4% in the penicillin group (409/420) and 100% in the doxycycline/tetracycline group (25/25), and not significantly different. The estimated median time to serological treatment success was 72.0 days (mean=101.7, range 10-603) in penicillin and 43.0 days (mean=78.6, range 15-334) in doxycycline/tetracycline-treated patients; however, this difference was not statistically significant (P=0.16).
CONCLUSION: Doxycycline/tetracycline had a similarly high serological treatment success rate when compared with penicillin in the treatment of primary syphilis.

PMID 18823862  Am J Med. 2008 Oct;121(10):903-8. doi: 10.1016/j.amjmed・・・
著者: Gabriele Riedner, Mary Rusizoka, Jim Todd, Leonard Maboko, Michael Hoelscher, Donan Mmbando, Eleuter Samky, Eligius Lyamuya, David Mabey, Heiner Grosskurth, Richard Hayes
雑誌名: N Engl J Med. 2005 Sep 22;353(12):1236-44. doi: 10.1056/NEJMoa044284.
Abstract/Text BACKGROUND: Pilot studies suggest that a single, 2-g oral dose of azithromycin may be an alternative to a 2.4-MU intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis. We evaluated the efficacy of treatment with azithromycin in a developing country.
METHODS: A total of 328 subjects, 25 with primary and 303 with high-titer (a titer of at least 1:8 on a rapid plasmin reagin [RPR] test) latent syphilis, were recruited through screening of high-risk populations in Mbeya, Tanzania, and randomly assigned to receive 2 g of azithromycin orally (163 subjects) or 2.4 million units of penicillin G benzathine intramuscularly (165 subjects). The primary outcome was treatment efficacy, with cure defined serologically (a decline in the RPR titer of at least two dilutions by nine months after treatment) and, in primary syphilis, by epithelialization of ulcers within one or two weeks.
RESULTS: The average age of participants was 27.0 years, 235 (71.6 percent) were female, and 171 (52.1 percent) were seropositive for human immunodeficiency virus. Cure rates were 97.7 percent (95 percent confidence interval, 94.0 to 99.4) in the azithromycin group and 95.0 percent (95 percent confidence interval, 90.6 to 97.8) in the penicillin G benzathine group (95 percent confidence interval for the difference, -1.7 to 7.1 percent), achieving prespecified criteria for equivalence. Cure rates were also similar three and six months after treatment in the two groups and in all subgroups. Cure rates at three months were 59.4 percent (95 percent confidence interval, 51.8 to 67.1) in the azithromycin group and 59.5 percent (95 percent confidence interval, 51.8 to 67.3) in the penicillin G benzathine group and at six months were 85.5 percent (95 percent confidence interval, 79.4 to 90.6) and 81.5 percent (95 percent confidence interval, 74.8 to 87.4), respectively.
CONCLUSIONS: Single-dose oral azithromycin is effective in treating syphilis and may be particularly useful in developing countries in which the use of penicillin G benzathine injections is problematic. However, recent reports of azithromycin-resistant Treponema pallidum in the United States indicate the importance of continued monitoring for resistance.

Copyright 2005 Massachusetts Medical Society.
PMID 16177249  N Engl J Med. 2005 Sep 22;353(12):1236-44. doi: 10.1056・・・
著者: Yuping Cao, Xiaohong Su, Qianqiu Wang, Huazhong Xue, Xiaofeng Zhu, Chuanfu Zhang, Juan Jiang, Shuzhen Qi, Xiangdong Gong, Xiaofang Zhu, Min Pan, Hong Ren, Wenlong Hu, Zhiping Wei, Meihua Tian, Weida Liu
雑誌名: Clin Infect Dis. 2017 Oct 30;65(10):1683-1688. doi: 10.1093/cid/cix611.
Abstract/Text Background: The aim of this study was to assess the efficacy of ceftriaxone and benzathine penicillin G (BPG) in nonpregnant, immunocompetent adults with early syphilis because there is a lack of clinical evidence supporting ceftriaxone as an alternative treatment for early syphilis without an human immunodeficiency virus coinfection.
Methods: A randomized, open-label controlled study evaluating the efficacy of ceftriaxone and BPG was conducted in 4 hospitals in Jiangsu Province. Treatment comprised either ceftriaxone (1.0 g, given intravenously, once daily for 10 days) or BPG (2.4 million units, given intramuscularly, once weekly for 2 weeks). A serological response was defined as a ≥4-fold decline in the rapid plasma reagin (RPR) titer.
Results: In all, 301 patients with early syphilis were enrolled in this study; 230 subjects completed the follow-ups. The serological response at 6 months of follow up was observed in 90.2% in ceftriaxone group and 78.0% in BPG group (P = .01). There was no significant difference between treatment groups in patients with primary or early latent syphilis, but among patients with secondary syphilis the difference was highly significant (95.8% vs 76.2%; P < .01). Moreover, patients exhibiting a Jarisch-Herxheimer reaction after treatment might have a shorter period before a serological response (P = .03).
Conclusions: In this study, ceftriaxone regimen was noninferior to the BPG regimen in nonpregnant, immunocompetent patients with early syphilis.
Clinical Trials Registration: ChiCTR-TQR-13003624.

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PMID 29020150  Clin Infect Dis. 2017 Oct 30;65(10):1683-1688. doi: 10.・・・
著者: Pingyu Zhou, Kang Li, Haikong Lu, Yihong Qian, Xin Gu, Weiming Gong, Joseph D Tucker, Myron S Cohen
雑誌名: Sex Transm Dis. 2010 Nov;37(11):726-9. doi: 10.1097/OLQ.0b013e3181e2c753.
Abstract/Text BACKGROUND: Azithromycin has been used to treat primary and secondary syphilis and as prophylaxis for sexual partners. We evaluated syphilis treatment failure in patients who received azithromycin therapy.
METHODS: Patients who did not respond to azithromycin therapy were referred to Shanghai Skin Disease and sexually transmitted disease hospital. Treatment failure was defined as follows: (1) persistent ulcers or cutaneous or mucosal lesions 1 month after therapy; or (2) detection of spirochetes in dark-field microscopy examination of a lesion at least 1 week after treatment; or (3) failure of rapid plasma reagin titers to decrease 4-fold at 3 months after treatment.
RESULTS: A total of 132 patients with primary and secondary syphilis who failed azithromycin therapy were referred to our hospital between January 2001 and October 2008. Of 132 patients, 42 (31.8%) had primary syphilis and 90 (68.2%) had secondary syphilis. Twenty-six patients with primary syphilis developed multiple lesions or secondary syphilis, or persistent ulcers despite using azithromycin. The skin or mucosal lesions did not resolve in 37 patients with secondary syphilis after azithromycin treatment. Ten patients had a positive dark-field examination for Treponema pallidum (T. pallidum) after treatment. The serum rapid plasma reagin titers studied in all cases had failed to decrease 4-fold at 3 months after therapy. The doses of azithromycin used for treatment ranged from 4 to 30 g.
CONCLUSIONS: The failure of azithromycin to cure a substantial number of patients with primary and secondary syphilis in Shanghai suggests that azithromycin has limited therapeutic value in this setting.

PMID 20644500  Sex Transm Dis. 2010 Nov;37(11):726-9. doi: 10.1097/OLQ・・・
著者: Takeshi Nishijima, Kei Kawana, Ichio Fukasawa, Naoko Ishikawa, Melanie M Taylor, Hiroshige Mikamo, Kiyoko Kato, Jo Kitawaki, Tomoyuki Fujii, Women’s Health Care Committee, Japan Society of Obstetrics and Gynecology
雑誌名: Emerg Infect Dis. 2020 Jun;26(6):1192-1200. doi: 10.3201/eid2606.191300.
Abstract/Text We conducted a nationwide retrospective study in Japan to evaluate the effectiveness of oral amoxicillin or ampicillin as alternatives to injectable benzathine penicillin G for treating pregnant women with syphilis and preventing congenital syphilis (CS). We investigated 80 pregnant women with active syphilis treated with amoxicillin or ampicillin during 2010-2018. Overall, 21% (15/71) had pregnancies resulting in CS cases, and 3.8% (3/80) changed therapies because of side effects. Among 26 patients with early syphilis, no CS cases occurred, but among 45 with late syphilis, 15 (33%) CS cases occurred. Among 57 patients who started treatment >60 days before delivery, 8 (14%) had CS pregnancy outcomes. We found oral amoxicillin potentially ineffective for preventing CS cases among pregnant women with late syphilis but potentially effective in those with early syphilis. Prospective studies are needed to definitively evaluate the efficacy of amoxicillin for the treatment of pregnant women with syphilis to prevent CS.

PMID 32441638  Emerg Infect Dis. 2020 Jun;26(6):1192-1200. doi: 10.320・・・
著者: A2058G Prevalence Workgroup
雑誌名: Sex Transm Dis. 2012 Oct;39(10):794-8. doi: 10.1097/OLQ.0b013e31826f36de.
Abstract/Text BACKGROUND: The 23S rRNA A2058G point mutation in Treponema pallidum is associated with macrolide antibiotic treatment failure. Its prevalence and potential association with a molecular subtype within the United States are unknown.
METHODS: During 2007 to 2009, 11 clinics across the United States sent samples from genital ulcers to the Centers for Disease Control and Prevention. Molecular techniques were used to identify T. pallidum DNA sequences, the A2058G mutation, and subtype of T. pallidum. Accompanying epidemiologic information was abstracted from medical records.
RESULTS: A total of 141 samples with T. pallidum were collected from individuals whose median age was 33 years (range, 13-68 years): 118 were male (69% reported as men having sex with men [MSM]). The A2058G mutation was carried in 75 samples (53%) with T. pallidum, with samples from MSM (versus women and other men) more likely carrying the A2058G mutation (65/82 samples versus 8/57 samples; prevalence ratio, 5.7; 95% confidence interval, 2.9-10.8). Of 98 strain-typed samples, 61 (62%) were the 14d9 subtype of T. pallidum, which was also associated with samples with T. pallidum from MSM (prevalence ratio, 3.5; 95% confidence interval, 1.9-6.5). However, among T. pallidum from MSM, the A2058G mutation was not associated with the 14d9 subtype.
CONCLUSIONS: The A2058G mutation and 14d9 subtype of T. pallidum were present throughout the United States. Both were more commonly found in T. pallidum from MSM compared with women or other men but were not associated with each other. Treating syphilis with azithromycin should be done cautiously and only when treatment with penicillin or doxycycline is not feasible.

PMID 23001267  Sex Transm Dis. 2012 Oct;39(10):794-8. doi: 10.1097/OLQ・・・
著者: E C Tramont
雑誌名: JAMA. 1976 Nov 8;236(19):2206-7.
Abstract/Text The isolation of Treponema pallidum from cerebrospinal fluid (CSF) obtained from two adult patients, both of whom had normal CSF values except for positive fluorescent treponemal antibody-absorption (FTA-ABS) tests and both of whom had received currently recommended courses of penicillin, raises important considerations in the treatment of neurosyphilis in adults.

PMID 789927  JAMA. 1976 Nov 8;236(19):2206-7.
著者: R E Morrison, S M Harrison, E C Tramont
雑誌名: Genitourin Med. 1985 Dec;61(6):359-62.
Abstract/Text A serum amoxycillin concentration of 0.11 g/l was established as being treponemicidal in a rabbit model with orchitis. Seventeen patients treated with amoxycillin 2 g by mouth three times a day plus 500 mg probenecid twice a day attained treponemicidal CSF amoxycillin concentrations. Thus amoxycillin by mouth offers an effective alternative method for treating patients with neurosyphilis.

PMID 3910544  Genitourin Med. 1985 Dec;61(6):359-62.
著者: Ryutaro Tanizaki, Takeshi Nishijima, Takahiro Aoki, Katsuji Teruya, Yoshimi Kikuchi, Shinichi Oka, Hiroyuki Gatanaga
雑誌名: Clin Infect Dis. 2015 Jul 15;61(2):177-83. doi: 10.1093/cid/civ270. Epub 2015 Mar 31.
Abstract/Text BACKGROUND: Intramuscular benzathine penicillin G (BPG) is widely used for the treatment of syphilis. However, BPG is not available in some countries. This study examined the effectiveness and safety of high-dose oral amoxicillin plus probenecid for the treatment of syphilis in patients with human immunodeficiency virus type 1 (HIV-1).
METHODS: This retrospective observational study included 286 HIV-infected male patients with syphilis (median age, 36 years; median CD4 count, 389 cells/µL) who were treated with oral amoxicillin 3 g plus probenecid. Syphilis was diagnosed by both serum rapid plasma reagin (RPR) titers ≥8 and positive Treponema pallidum hemagglutination test. Patients with neurosyphilis diagnosed by cerebrospinal fluid examination were excluded. Successful treatment was defined as a at least 4-fold decrement in RPR titer.
RESULTS: The overall treatment efficacy was 95.5% (95% confidence interval [CI], 92.4%-97.7%; 273/286 patients), and efficacy for primary, secondary, early latent, late latent, and unknown duration syphilis was 93.8% (95% CI, 68.1%-99.8%; 15/16), 97.3% (95% CI, 92.9%-99.2%; 142/146), 100% (95% CI, 90.5%-100%; 37/37), 85.7% (95% CI, 58.6%-96.4%; 18/21), and 92.4% (95% CI, 81.9%-97.3%; 61/66), respectively. Treatment duration was mostly 14-16 days (49.7%) or 28-30 days (34.3%), with efficacy of 94.4% (134/142) and 95.9% (94/98), respectively; 96.3% of successfully treated patients achieved a ≥4-fold decrement in RPR titer within 12 months. Adverse events were noted in 28 (9.8%) patients, and 25 of these (89.3%) were successfully treated. Only 6% of patients underwent lumbar puncture.
CONCLUSIONS: The combination of oral amoxicillin 3 g plus probenecid was highly effective and tolerable for the treatment of syphilis in patients with HIV-1 infection.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID 25829004  Clin Infect Dis. 2015 Jul 15;61(2):177-83. doi: 10.1093・・・
著者: Motoyuki Tsuboi, Takeshi Nishijima, Takahiro Aoki, Katsuji Teruya, Yoshimi Kikuchi, Hiroyuki Gatanaga, Shinichi Oka
雑誌名: J Clin Microbiol. 2018 Nov;56(11). doi: 10.1128/JCM.01003-18. Epub 2018 Oct 25.
Abstract/Text The usefulness of an automated latex turbidimetric rapid plasma reagin (RPR) assay, compared to the conventional manual card test (serial 2-fold dilution method), for the diagnosis of syphilis and evaluation of treatment response remains unknown. We conducted (i) a cross-sectional study and (ii) a prospective cohort study to elucidate the correlation between automated and manual tests and whether a 4-fold decrement is a feasible criterion for successful treatment with the automated test, respectively, in HIV-infected patients, from October 2015 to November 2017. Study i included 518 patients. The results showed strong correlation between the two tests (r = 0.931; P < 0.001). With a manual test titer of ≥1:8 plus a positive Treponema pallidum particle agglutination (TPPA) test as the reference standard for diagnosis, the optimal cutoff value for the automated test was 6.0 RPR units (area under the curve [AUC], 0.998), with positive predictive value (PPV) of 92.5% and negative predictive value (NPV) of 99.4%. Study ii enrolled 66 men with syphilis. Their RPR values were followed up until after 12 months of treatment. At 12 months, 77.3% and 78.8% of the patients achieved a 4-fold decrement in RPR titer by the automated and manual test, respectively. The optimal decrement rate in RPR titer by the automated test for a 4-fold decrement by manual card test was 76.54% (AUC, 0.96) (PPV, 96.1%; NPV, 80.0%). The automated RPR test is a good alternative to the manual test for the diagnosis of syphilis and evaluation of treatment response and is more rapid and can handle more specimens than the manual test without interpersonal variation in interpretation.

Copyright © 2018 American Society for Microbiology.
PMID 30135229  J Clin Microbiol. 2018 Nov;56(11). doi: 10.1128/JCM.010・・・
著者: A F Luger, B L Schmidt, M Kaulich
雑誌名: Int J STD AIDS. 2000 Apr;11(4):224-34. doi: 10.1258/0956462001915750.
Abstract/Text Our objective is to assess the specificity and sensitivity, and thus elaborate the relevance, of different laboratory findings for the diagnosis of neurosyphilis. One hundred and fourteen HIV-negative pairs of serum and cerebrospinal fluid (CSF) samples were examined by the Venereal Disease Research Laboratory (VDRL) test, a fluorescent treponemal antibody-absorption (FTA-ABS) test, microhaemagglutination assay with Treponema pallidum antigen (MHA-TP) test (serum) and Treponema pallidum haemagglutination assay (TPHA) test (CSF); further, albumin, total protein, and total IgG were determined and, in the CSF, cell count was performed. The donors were 60 patients with active neurosyphilis and 54 healthy persons with a former history of syphilis and with persisting positive results in the T. pallidum haemagglutination tests (serum: MHA-TP, CSF: TPHA), who supplied specimens for control. Albumin quotient, IgG index, TPHA index, modified TPHA index, Intrathecally produced T. pallidum Antigen (ITpA) index, its 2 modifications and, in 12 samples, the adenovirus group antibody (AVGA)/TPHA index were ascertained. The specificity and sensitivity of the TPHA index were 100% and 98.3%, of the modified TPHA index 50.0% and 96.7%, of the ITpA index 42.6% and 90.0%, of the modified ITpA indices 51.8% and 68.3% (first modification) and 53.7% and 63.3% (second modification). The AVGA/TPHA index yielded a specificity of 91.7% (11/12). The CSF VDRL test was positive in 55/60 (91.7%) of samples from patients with neurosyphilis and in none of the controls (0/54). A CSF-TPHA titre greater than 1:320 was observed in 59/60 (98.3%) of the neurosyphilis specimens and in none of the controls (0/54). A TPHA index above an outcome of 70, a positive CSF-TPHA test at a titre greater than 1:320 and, with lower sensitivity, the criteria of the Centers for Disease Control (CDC) guidelines yield the most reliable results for laboratory support to a diagnosis of neurosyphilis. The modified TPHA index, the ITpA index, and its 2 modifications produce results of minor sensitivity and poor specificity. Observations on the AVGA/THPA index are too limited yet for judgement. The diagnostic significance of a CSF-TPHA titre above 320 needs further confirmation on a greater number of observations made by different laboratories.

PMID 10772085  Int J STD AIDS. 2000 Apr;11(4):224-34. doi: 10.1258/095・・・
著者: Alfredo Franco, Lucia Aprea, Chiara Dell'Isola, Francesco Saverio Faella, Francesca Maria Felaco, Elio Manzillo, Fiorella Martucci, Teresa Pizzella, Matilde Sansone, Francesco Simioli, Stefania Simioli, Crescenzo Maria Izzo
雑誌名: Infez Med. 2007 Sep;15(3):187-90.
Abstract/Text A 47-year-old woman was pricked accidentally with a needle previously used for a neurosyphilitic man. At day 0 she had no positive laboratory results for the infection, while the source, at day 1, had TPHA positive, but no post-exposure prophylaxis (PEP) against syphilis was prescribed. The subject missed the day 30 follow-up, and underwent our visit at day 90, when she showed no clinical signs, but she seroconverted (VDRL = positive 1/2; TPHA = positive 1/320; FTA-Abs IgG and IgM = present). She started antibiotic therapy, and currently her serological status is VDRL = positive 1/2, TPHA = positive 1/160, FTA-Abs IgM = negative.

PMID 17940403  Infez Med. 2007 Sep;15(3):187-90.

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