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Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.

Tsai MS, Yang CJ, Lee NY, Hsieh SM, Lin YH, Sun HY, Sheng WH, Lee KY, Yang SP, Liu WC, Wu PY, Ko WC, Hung CC - J Int AIDS Soc (2014)

Bottom Line: 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).Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.

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.

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Related in: MedlinePlus

Time to the Jarisch-Herxheimer reaction during the first 24 hours after starting syphilis treatment according to the regimen (BPG, benzathine penicillin G).
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Figure 0001: Time to the Jarisch-Herxheimer reaction during the first 24 hours after starting syphilis treatment according to the regimen (BPG, benzathine penicillin G).

Mentions: The overall incidence of the Jarisch-Herxheimer reaction was 30.0% (95% CI, 25.2–35.2). Patients receiving benzathine penicillin G experienced a higher incidence of the Jarisch-Herxheimer reaction than those receiving azithromycin (56.3% vs. 14.1%; odds ratio [OR], 3.98; 95% CI, 2.73–5.81). The median time between treatment administration and development of the Jarisch-Herxheimer reaction was 4 hours [interquartile range (IQR), 3 to 6 hours] for the penicillin group, which was significantly shorter (8 hours) than that for the azithromycin group (IQR, 5–19 hours, p<0.001) (Figure 1). The symptoms such as fever or skin rash subsided spontaneously or with antipyretics and antihistamines within 24 hours.


Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.

Tsai MS, Yang CJ, Lee NY, Hsieh SM, Lin YH, Sun HY, Sheng WH, Lee KY, Yang SP, Liu WC, Wu PY, Ko WC, Hung CC - J Int AIDS Soc (2014)

Time to the Jarisch-Herxheimer reaction during the first 24 hours after starting syphilis treatment according to the regimen (BPG, benzathine penicillin G).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150017&req=5

Figure 0001: Time to the Jarisch-Herxheimer reaction during the first 24 hours after starting syphilis treatment according to the regimen (BPG, benzathine penicillin G).
Mentions: The overall incidence of the Jarisch-Herxheimer reaction was 30.0% (95% CI, 25.2–35.2). Patients receiving benzathine penicillin G experienced a higher incidence of the Jarisch-Herxheimer reaction than those receiving azithromycin (56.3% vs. 14.1%; odds ratio [OR], 3.98; 95% CI, 2.73–5.81). The median time between treatment administration and development of the Jarisch-Herxheimer reaction was 4 hours [interquartile range (IQR), 3 to 6 hours] for the penicillin group, which was significantly shorter (8 hours) than that for the azithromycin group (IQR, 5–19 hours, p<0.001) (Figure 1). The symptoms such as fever or skin rash subsided spontaneously or with antipyretics and antihistamines within 24 hours.

Bottom Line: 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).Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.

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.

Show MeSH
Related in: MedlinePlus