Delayed Minocycline Initiation from Symptom Onset and Severe Outcomes in Japanese Spotted Fever: A Single-Center...

Japanese spotted fever (JSF) is an endemic tick-borne rickettsiosis in Japan that can cause severe illness and organ failure. Because early tetracycline therapy is crucial for improving outcomes, clarifying the clinical profile of JSF in endemic communities with an aging population and quantifying the impact of treatment delay are clinically important. We aimed to describe the clinical characteristics of patients with polymerase chain reaction (PCR)-confirmed JSF in an endemic region and to evaluate whether delays from symptom onset to minocycline initiation were associated with severe outcomes.

We conducted a retrospective cohort study in patients with PCR-confirmed JSF admitted to a tertiary hospital in eastern Hiroshima Prefecture between 2011 and 2023. Time intervals were calculated using calendar dates, with same-day events coded as 0 days. The primary outcome was severe JSF, defined as the need for invasive mechanical ventilation and/or renal replacement therapy. Logistic regression was used to assess associations between onset-to-minocycline delay and severe outcomes, adjusting for age and sex.

Forty-two patients (median age, 73.5 years) were included. Severe outcomes occurred in 13 patients (31.0%), and 6 patients (14.3%) died during hospitalization. The median onset-to-minocycline interval was longer in severe cases than in non-severe cases (6.0 vs. 4.0 days; p = 0.035). In multivariable analysis, each 1-day delay in minocycline initiation was associated with higher odds of severe outcomes (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.81; p = 0.043).

In this region with endemic JSF and with an older patient population, longer delays from symptom onset to minocycline initiation were associated with severe outcomes. Strategies to shorten onset-to-treatment intervals, including timely clinical examination and empiric tetracycline therapy when JSF is suspected, may improve outcomes in older communities with endemic JSF.