The course of boutonneuse fever (BF), also known as Mediterranean spotted fever (MSF), can be shortened with appropriate treatment (ie, antibiotics). The illness sometimes takes a malignant form—for instance, in people who are elderly and especially in those who are immunocompromised. In a study of 142 patients hospitalized with BF, 5% of patients presented with malignant BF.
Tetracyclines, along with chloramphenicol and quinolones, may be considered first-line antibiotics for BF. After 2-4 days of first-line therapy, the fever decreases and the rash usually disappears. Patients already in good health are usually discharged after 7-8 days of treatment. Single-dose azithromycin can be used for prophylaxis of BF.
Because the differential diagnosis for BF includes many rare diseases, consultations with a dermatologist and an infectious disease specialist should be considered.
Patients with the benign form of BF are usually treated with antibiotics for 7 days; those with the malignant form of BF are usually treated with antibiotics for 2 weeks.
The preferred drug is doxycycline (100 mg PO q12hr). Other effective treatments include the following:
Ciprofloxacin (200 mg IV q12hr or 750 mg PO q12hr)
Levofloxacin (500 mg PO once daily)
Chloramphenicol (50-60 mg/kg/day PO in 4 divided doses)
Macrolides such as azithromycin (500 mg PO once daily) and clarithromycin (500 mg PO q12h) - These have been shown to be efficacious in children  and can be used as alternatives to doxycycline in adults, including pregnant women. A small randomized trial in children and adults showed a similar time to resolution of fever and other symptoms among those treated with clarithromycin versus doxycycline (or doxycycline plus josamycin in children). 
For children with malignant BF, tetracyclines (especially doxycycline) should be considered first; these are the most effective drugs for this potentially life-threatening disease. A single short (≤1 week) course of doxycycline should not result in cosmetically significant staining of teeth. In malignant BF, there is a narrow window of time during which effective antibiotic therapy delivered in an extremely efficient way can substantially reduce the risk of an unfavorable outcome.
In pregnant women, erythromycin should be administered; however, it is not as effective as the tetracyclines are.
In an analysis of risk factors for malignant BF, researchers noted that fluoroquinolones may have a deleterious effect. 
Josamycin, a newer macrolide antibiotic, seems to be effective against malignant BF (when available). Some have suggested that it may be the drug of choice for malignant BF in pregnant women. [28, 29, 30]
Rifampin, though designated by the US Food and Drug Administration (FDA) as a category C drug in pregnancy and tuberculosis, has also been used extensively in this setting and appears to be safe.
To prevent infection by rickettsiae, precautions should be taken to avoid exposure to ticks, in particular by refraining from close contact with ticks’ animal vectors (eg, dogs, goats, and sheep) when in endemic areas.
Protective clothing should be worn, preferably impregnated with permethrin or another pyrethroid. Topical repellents can be used on any exposed skin; however, these agents have a short duration of effect (~1-2 hours per application), and frequent application is therefore recommended. During travel, daily self-checks and removal of any ticks found should be performed.
At present, there is no vaccine for BF.
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