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Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.
J Int AIDS Soc. 2014; 17:18993.JI

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.

Authors+Show Affiliations

Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan.Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.Center for Infection Control, National Taiwan University Hospital, Taipei, Taiwan.Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.Center for Infection Control, National Taiwan University Hospital, Taipei, Taiwan.Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan.Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; China Medical University, Taichung, Taiwan.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

25174641

Citation

Tsai, Mao-Song, et al. "Jarisch-Herxheimer Reaction Among HIV-positive Patients With Early Syphilis: Azithromycin Versus Benzathine Penicillin G Therapy." Journal of the International AIDS Society, vol. 17, 2014, p. 18993.
Tsai MS, Yang CJ, Lee NY, et al. Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy. J Int AIDS Soc. 2014;17:18993.
Tsai, M. S., Yang, C. J., Lee, N. Y., Hsieh, S. M., Lin, Y. H., Sun, H. Y., Sheng, W. H., Lee, K. Y., Yang, S. P., Liu, W. C., Wu, P. Y., Ko, W. C., & Hung, C. C. (2014). Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy. Journal of the International AIDS Society, 17, 18993. https://doi.org/10.7448/IAS.17.1.18993
Tsai MS, et al. Jarisch-Herxheimer Reaction Among HIV-positive Patients With Early Syphilis: Azithromycin Versus Benzathine Penicillin G Therapy. J Int AIDS Soc. 2014;17:18993. PubMed PMID: 25174641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: 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, Y1 - 2014/08/28/ PY - 2013/12/09/received PY - 2014/06/15/revised PY - 2014/07/17/accepted PY - 2014/9/2/entrez PY - 2014/9/2/pubmed PY - 2015/3/5/medline KW - immunomodulation KW - macrolide resistance KW - macrolides KW - sexually transmitted diseases KW - spirochetal disease SP - 18993 EP - 18993 JF - Journal of the International AIDS Society JO - J Int AIDS Soc VL - 17 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. SN - 1758-2652 UR - https://www.unboundmedicine.com/medline/citation/25174641/Jarisch_Herxheimer_reaction_among_HIV_positive_patients_with_early_syphilis:_azithromycin_versus_benzathine_penicillin_G_therapy_ L2 - https://doi.org/10.7448/IAS.17.1.18993 DB - PRIME DP - Unbound Medicine ER -