# Jarisch-Herxheimer reaction as a complication of penicillin G and ceftriaxone treatment in neurosyphilis

**Authors:** Xin Feng, Junjun Yu, Xin Gu, Yilan Yang, Nanyan Jiang, Guixuan Wang, Danyang Zou, Meiping Ye, Pingyu Zhou

PMC · DOI: 10.1186/s12879-026-12683-2 · BMC Infectious Diseases · 2026-01-27

## TL;DR

This study finds that Jarisch-Herxheimer reaction occurs in about 10% of neurosyphilis patients treated with penicillin G or ceftriaxone, with similar rates but differing symptom timing.

## Contribution

The study compares JHR incidence and clinical features between penicillin G and ceftriaxone treatments in neurosyphilis patients.

## Key findings

- JHR occurred in 10.20% of neurosyphilis patients treated with penicillin G or ceftriaxone.
- Penicillin G caused earlier fever onset and faster resolution of fever compared to ceftriaxone.
- Neuropsychiatric symptoms occurred in JHR cases and resolved within 2–7 days.

## Abstract

Jarisch-Herxheimer reaction (JHR) is a complication of antibiotic treatment in neurosyphilis, and the profile of JHR in patients treated with different antibiotics remains unclear. This study investigates the incidence, clinical manifestations, and management of JHR in patients treated with penicillin G or ceftriaxone.

A retrospective study was conducted at the Shanghai Skin Disease Hospital, China, involving 1010 inpatients diagnosed with neurosyphilis, among whom 103 developed JHR. Statistical analyses included Student’s t-test or Mann-Whitney test for continuous variables and Fisher’s exact test for categorical data.

The overall incidence of JHR among neurosyphilis patients was 10.20% (103/1010), with rates varying from 0% − 25% across different subtypes. Incidence was similar in penicillin G-treated (10.20%, 92/902) and ceftriaxone-treated (10.19%, 11/108) cohorts. The 92 JHR cases of penicillin G group manifested as fever (98.91%, 91/92) and neuropsychiatric symptoms (25%, 23/92). All 11 cases of JHR in the ceftriaxone group presented with fever (100%, 11/11). Penicillin G treatment resulted in an earlier fever onset (8.92 ± 4.98 h vs. 14.00 ± 5.90 h, 95% CI: 1.861 to 8.303, P < 0.05) and a shorter time to defervescence (16.35 ± 5.48 h vs. 20.80 ± 3.79 h, 95% CI: 1.085 to 7.848, P < 0.05) than ceftriaxone. Management strategies included physical cooling, indomethacin suppositories, and supportive treatment for neuropsychiatric symptoms. Neuropsychiatric symptoms of JHR resolved within 2–7 days of initiating antibiotic therapy.

JHR is a notable complication of neurosyphilis treatment, presenting as febrile and neuropsychiatric symptoms. JHR frequency is comparable between penicillin G and ceftriaxone treatment. Penicillin G triggers an earlier febrile response of JHR compared to ceftriaxone. While generally mild and self-limiting, JHR can present with neuropsychiatric symptoms and severe conditions. This study contributes to the understanding of JHR and provides insights into the comparative effects of penicillin G and ceftriaxone treatment in neurosyphilis.

Not applicable.

## Linked entities

- **Chemicals:** penicillin G (PubChem CID 5904), ceftriaxone (PubChem CID 5479530)
- **Diseases:** neurosyphilis (MONDO:0004944)

## Full-text entities

- **Diseases:** Jarisch-Herxheimer reaction (MESH:D006967), neurosyphilis (MESH:D009494)
- **Chemicals:** penicillin G (MESH:D010400), ceftriaxone (MESH:D002443)

## Full text

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## Figures

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## References

4 references — full list in the complete paper: https://tomesphere.com/paper/PMC12918081/full.md

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Source: https://tomesphere.com/paper/PMC12918081