Mediterranean Spotted Fever (Boutonneuse Fever) Treatment & Management

Updated: Sep 15, 2021
  • Author: D Matthew Shoemaker, DO, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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Approach Considerations

The course of Mediterranean spotted fever (MSF), also known as boutonneuse fever (BF), can be shortened with appropriate antibiotics. The illness sometimes takes a malignant form—for instance, in people who are immunocompromised or elderly. Although in a study of 142 patients hospitalized with MSF, 5% of patients presented with malignant MSF.

Doxycycline is considered first-line antibiotic of choice for MSF. Clinical response is typically observed after 2-4 days of first-line therapy, as noted by the decrease in fever and the slow resolution of the maculopapular rash. Patients already in good health are usually discharged home to complete a total of 7 days of antibiotic therapy.

A recent randomized clinical trial demonstrated that clarithromycin is an acceptable alternative to doxycycline for MSF. [32]  Based on this, it is extrapolated that azithromycin would be a suitable alternative, especially in pregnant women and young children for whom doxycycline is contraindicated.

Single-dose azithromycin can be used for prophylaxis of MSF following a tick bite in an endemic area. [33]

Chloramphenicol is an acceptable alternative but adverse drug reactions, particular blood dyscrasias and gray baby syndrome in pregnancy, and lack of commercial availability in the United States limit its use.

Fluoroquinolones may have a deleterious effect as demonstrated in an analysis of risk factors for malignant MSF. [34]

Because the differential diagnosis for MSF includes many rare diseases, consultations with a dermatologist and an infectious disease specialist should be considered.


Pharmacologic Therapy

Patients with the benign form of MSF are usually treated with antibiotics for 7 days; those with the malignant form of MSF are usually treated with antibiotics for 2 weeks.

The preferred drug is doxycycline (100 mg PO q12hr).

Other effective treatments include the following:

  • Chloramphenicol (50-60 mg/kg/day PO in 4 divided doses)
  • Azithromycin (500 mg PO once daily) or 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. [33]
    • 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). [32]
  • Chloramphenicol (50-60 mg/kg/day PO in 4 divided doses)
  • Children with malignant MSF, 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 MSF, 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.
  • Pregnant women should receive azithromycin or clarithromycin.
    • Josamycin, a newer macrolide antibiotic which is not currently commercially available in the United States, seems to be effective against malignant MSF (when available).
    • Some have suggested that it may be the drug of choice for malignant MSF in pregnant women. [35, 36, 37]
  • 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 for tick borne infections and appears to be safe.
  • Fluoroquinolones may have a deleterious effect as demonstrated in an analysis of risk factors for malignant MSF. [34]


To prevent infection by rickettsiae, precautions should be taken to avoid exposure to ticks.

Protective clothing should be worn, preferably impregnated with permethrin or another pyrethroid. Topical repellents such as DEET or permethrin can be used on any exposed skin. Topical repellents have a short duration of effect and frequent application is therefore recommended. During travel, daily self-checks and removal of any ticks found should be performed.

Additionally, care should be taken to avoid close contact with ticks’ animal vectors (eg, dogs, goats, and sheep) when in endemic areas.

There is no vaccine for MSF.