Q fever endocarditis is a serious and often fatal condition caused by the gram-negative bacterium Coxiella burnetii. Nonspecific cardiac findings, evidence of infection and detection of specific antibodies on blood culture confirm the diagnosis. Eradicating C. burnetii is difficult, making Q fever endocarditis fatal in 25 to 60 percent of patients. Combination therapy with tetracycline and a quinolone increases survival, but patients often must take the medication for the rest of their lives. This treatment regimen is the longest of any bacterial disease. Raoult and associates compared the effectiveness of the standard combination therapy with that of doxycycline and hydroxychloroquine to assess whether the latter resulted in a shorter period of treatment.
Patients with confirmed C. burnetii infection and endocarditis were enrolled in the 10-year study. During the first five years, patients were given combination therapy consisting of 100 mg of doxycycline twice daily and 200 mg of ofloxacin three times daily. During the next five years, patients received the same dosage of doxycycline and 200 mg of hydroxychloroquine three times a day. Patients were evaluated monthly for overall physical condition, blood chemistry and plasma levels of hydroxychloroquine, and dosages were adjusted accordingly. Patients were considered cured, and treatment was discontinued when their IgG antibodies to C. burnetii were lower than 1/800, and their IgM and IgA antibodies were lower than 1/50. Follow-up was performed at specified intervals after treatment was discontinued.
Thirty-five patients were enrolled in the study, 14 of whom were given doxycycline and ofloxacin. Of these patients, one died, seven experienced a relapse and were either re-treated or switched to the new regimen, five were cured and one was undergoing evaluation. All patients reported photosensitivity during the summer months. The mean duration of treatment for patients considered cured was 55 months. No patients treated for longer than four years experienced a relapse, and only one patient experienced a relapse after three years of treatment.
Twenty-one patients received the combination of doxycycline and hydroxychloroquine. Of these, two had increased IgG antibodies and discontinued treatment within 10 months. However, both experienced relapses within six months and were re-treated. At that time, treatment for all patients was extended to a minimum of 18 months. Fifteen patients were cured with no relapse, two experienced a relapse and were re-treated and cured, two were still being treated, one was being evaluated and one died. These patients also reported photosensitivity. The mean duration of treatment for patients considered cured was 31 months. Only two patients were treated for longer than four years.
Mortality rates, the need for valve surgery, and drug tolerance were similar between groups. However, patients in the doxycycline-hydroxychloroquine group had a shorter period of treatment and experienced fewer relapses. Patients treated with the standard combination for more than 48 months were still undergoing treatment and, of the four patients who switched to the doxycycline-hydroxychloroquine regimen, three were cured.
The authors conclude that treatment with doxycycline-hydroxychloroquine was more effective and resulted in a shorter duration of treatment than the standard regimen. Doxycycline and ofloxacin should be given for at least four years, whereas doxycycline-hydroxychloroquine requires a period of no less than 18 months but no longer than four years.