Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis

Azithromycin versus benzathine penicillin G therapy

Mao Song Tsai, Chia Jui Yang, Nan-Yao Lee, Szu Min Hsieh, Yu Hui Lin, Hsin Yun Sun, Wang Huei Sheng, Kuan Yeh Lee, Shan Ping Yang, Wen Chun Liu, Pei Ying Wu, Wen-Chien Ko, Chien Ching Hung

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Abstract

Introduction: The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated. Methods: In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance. Results: The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p <0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted. Conclusions: Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.

Original languageEnglish
Article number18993
JournalJournal of the International AIDS Society
Volume17
DOIs
Publication statusPublished - 2014 Jan 1

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Penicillin G Benzathine
Azithromycin
Syphilis
HIV
Treponema pallidum
Macrolides
Reagins
Therapeutics
Odds Ratio
Confidence Intervals
Polymerase Chain Reaction
23S Ribosomal RNA
Neurosyphilis
Mutation
Incidence
Taiwan
Point Mutation
Penicillins
Restriction Fragment Length Polymorphisms
Pregnant Women

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Tsai, Mao Song ; Yang, Chia Jui ; Lee, Nan-Yao ; Hsieh, Szu Min ; Lin, Yu Hui ; Sun, Hsin Yun ; Sheng, Wang Huei ; Lee, Kuan Yeh ; Yang, Shan Ping ; Liu, Wen Chun ; Wu, Pei Ying ; Ko, Wen-Chien ; Hung, Chien Ching. / Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis : Azithromycin versus benzathine penicillin G therapy. In: Journal of the International AIDS Society. 2014 ; Vol. 17.
@article{7ce0881c47f4484c96f426acf61e94de,
title = "Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: Azithromycin versus benzathine penicillin G therapy",
abstract = "Introduction: The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated. Methods: In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance. Results: The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1{\%} vs. 56.3{\%}, p <0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95{\%} CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95{\%} CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3{\%}) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted. Conclusions: Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.",
author = "Tsai, {Mao Song} and Yang, {Chia Jui} and Nan-Yao Lee and Hsieh, {Szu Min} and Lin, {Yu Hui} and Sun, {Hsin Yun} and Sheng, {Wang Huei} and Lee, {Kuan Yeh} and Yang, {Shan Ping} and Liu, {Wen Chun} and Wu, {Pei Ying} and Wen-Chien Ko and Hung, {Chien Ching}",
year = "2014",
month = "1",
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doi = "10.7448/IAS.17.1.18993",
language = "English",
volume = "17",
journal = "Journal of the International AIDS Society",
issn = "1758-2652",
publisher = "International AIDS Society",

}

Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis : Azithromycin versus benzathine penicillin G therapy. / Tsai, Mao Song; Yang, Chia Jui; Lee, Nan-Yao; Hsieh, Szu Min; Lin, Yu Hui; Sun, Hsin Yun; Sheng, Wang Huei; Lee, Kuan Yeh; Yang, Shan Ping; Liu, Wen Chun; Wu, Pei Ying; Ko, Wen-Chien; Hung, Chien Ching.

In: Journal of the International AIDS Society, Vol. 17, 18993, 01.01.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis

T2 - Azithromycin versus benzathine penicillin G therapy

AU - Tsai, Mao Song

AU - Yang, Chia Jui

AU - Lee, Nan-Yao

AU - Hsieh, Szu Min

AU - Lin, Yu Hui

AU - Sun, Hsin Yun

AU - Sheng, Wang Huei

AU - Lee, Kuan Yeh

AU - Yang, Shan Ping

AU - Liu, Wen Chun

AU - Wu, Pei Ying

AU - Ko, Wen-Chien

AU - Hung, Chien Ching

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Introduction: The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated. Methods: In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance. Results: The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p <0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted. Conclusions: Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.

AB - Introduction: The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated. Methods: In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance. Results: The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p <0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted. Conclusions: Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.

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