Fukushima Medical University and Nagasaki University conclude that treatment for Japanese spotted fever needs to be changed due to adverse events

A research group led by Professor Eiichiro Sando and Associate Professor Ikkoh Yasuda of the Department of General Internal Medicine and Clinical Infectious Diseases at Fukushima Medical University, in collaboration with Associate Professor Michiko Toizumi of the Institute of Tropical Medicine at Nagasaki University, has announced that they uncovered the risks of fluoroquinolone (FQ) combination therapy in the treatment of Japanese spotted fever. They found that combination therapy was associated with adverse events and did not improve mortality. The findings are expected to improve treatment methods and facilitate the appropriate use of antimicrobial agents and were published in the Journal of Antimicrobial Chemotherapy, an international academic journal, on June 12.

Japanese spotted fever is an infectious disease caused by tick-to-human transmission of rickettsia (Rickettsia japonica), a parasitic bacterial species found in ticks, through bites. Symptoms include headaches, a fever, skin rash, fatigue, arthralgia, and myalgia. The standard treatment for this disease is antibacterial therapy with tetracyclines (TCs). Some experts recommend the use of an FQ in addition to TCs, which has been practiced as combination therapy. However, there is no evidence that combination therapy improves mortality, and no studies of adverse events have been conducted.

In these findings, a retrospective cohort study was conducted using a database collected from hospitals in Japan. Specifically, 797 patients with a confirmed diagnosis of Japanese spotted fever were divided into those who received a TC alone (monotherapy group) and those who received a TC and an FQ (combination therapy group) to compare the mortality and complications such as convulsions. The results showed no significant differences in the mortality rates between the two groups after adjusting for age and severity, although the age and severity in the combination therapy group tended to be higher than those in the monotherapy group. Furthermore, the subgroup analysis suggested higher mortality rates in patients undergoing combination therapy with ciprofloxacin, a type of FQ.

Additionally, 27.7% of patients in the combination therapy group received antipyretic analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) along with FQs, and these patients were found to be at a significantly higher risk of convulsions. Given the likelihood of adverse events and lack of mortality improvements, they concluded that combination therapy with TCs and FQs should not be recommended for treating Japanese spotted fever.

Sando said, "Because Japanese spotted fever is a rare disease, it is difficult to compare treatment methods in a sufficient number of patients, and FQ combination therapy has been widely used without evidence of improving survival prognosis. We hope to use this study to provide information that will help clinicians determine the balance between benefits and disadvantages regarding appropriate use of antimicrobials."

Journal Information
Publication: Journal of Antimicrobial Chemotherapy
Title: Deleterious effects of a combination therapy using fluoroquinolones and tetracyclines for the treatment of Japanese spotted fever: a retrospective cohort study based on a Japanese hospital database
DOI: 10.1093/jac/dkae192