Effect of amoxicillin exposure before penicillin administration on Jarisch-Herxheimer incidence in people with early syphilis: a retrospective study

Background Jarisch-Herxheimer reaction (JHR) is a potential adverse effect of penicillin treatment in patients with syphilis, occurring more frequently when treatment is administered during the early stages of infection. We aimed to assess whether prior exposure to amoxicillin, an antibiotic effective against Treponema pallidum, reduces the incidence of JHR in patients with early syphilis.Methods In this retrospective observational study, individuals with early syphilis were categorized as exposed or unexposed to amoxicillin on the basis of whether they received a >= 24-h course of treatment in the 7 days preceding penicillin administration. JHR was defined as the occurrence of fever, chills, headache, myalgia, or rash within 24 h of penicillin administration. Logistic regression analyses were performed to evaluate the association between prior amoxicillin exposure and JHR occurrence in patients with early syphilis.Results The study included 347 participants, of whom 210 had early syphilis and were included in the analysis. Most patients (75.2%) received amoxicillin before penicillin administration. A total of 16 cases of JHR were recorded (7.6%; 95% CI: 4.0-11%), with fever being the most common symptom (62.5%). After adjusting for age, sex assigned at birth and rapid plasma reagin titer, amoxicillin exposure was significantly associated with reduced odds of JHR (adjusted odds ratio 0.24, 95% CI: 0.08-0.68; P = 0.008).Conclusions Exposure to amoxicillin prior to penicillin treatment may reduce the risk of JHR in patients with early syphilis.