Approach

Antibiotic therapy should be started as soon as the diagnosis is reasonably considered, without waiting for the results of tests to confirm the diagnosis. Outcomes are best when antirickettsial therapy is initiated within the first 5 days of illness.[1]

First-line antibiotic therapy

Doxycycline is the preferred agent for the treatment of Rocky Mountain spotted fever (RMSF) in patients of all ages due to its efficacy, twice-daily dosing, low cost, and favorable safety profile.[1][19]

Although repeated courses of tetracycline were associated with staining of permanent teeth in young children, no evidence suggests that doxycycline causes any such tooth staining.[23][24][25]

Alternative antibiotic therapy

Chloramphenicol is an alternative agent for treatment of RMSF and was once considered the drug of choice for children <8 years of age. However, for several reasons doxycycline is preferred over chloramphenicol for both adults and children with suspected RMSF:[1]

  • Patients treated with chloramphenicol for RMSF have an increased case fatality rate compared to those treated with doxycycline.

  • Doxycycline is effective for treatment of human monocytic ehrlichiosis and granulocytic anaplasmosis, and other spotted fever group rickettsioses that clinically mimic RMSF, whereas chloramphenicol may not be.

  • Chloramphenicol is associated with numerous adverse effects, and the oral formulation is no longer available in the US.

CDC emphasizes that the use of antibiotics other than doxycycline increases the risk of patient death. The care of patients with a doxycycline allergy should be undertaken in consultation with an infectious diseases specialist.[19]

Pregnant women

The care of pregnant women with suspected RMSF should be undertaken in consultation with an infectious disease specialist.[19] Pregnant women should be counseled on the potential risks and benefits when making a treatment decision.[26]

  • Tetracyclines are generally contraindicated in pregnant women, due to their potential toxicity to both fetus and mother.[1]

  • The safety of doxycycline has not been assessed in controlled studies in pregnant women; however, one review concluded that the risk of teratogenicity is unlikely, although data were insufficient to conclude that no risk exists.[27] Doxycycline has been used successfully to treat rickettsial disease in pregnant women without adverse effects; however, follow-up to assess toxicity was limited.[1]

  • Chloramphenicol has traditionally been considered the preferred agent for treatment of RMSF in pregnant women. However, this recommendation is being reconsidered, given the accumulating data on the safety of doxycycline in pregnancy, the greater efficacy of doxycycline for RMSF, limited availability of chloramphenicol in the US, and the potential toxicity of chloramphenicol to the fetus.

Other bacterial infections

For those whose presentation may be consistent with a serious different bacterial infection, therapy needs to begin presumptively, and empiric antibiotics are indicated until blood cultures or clinical course rule out the alternative diagnosis. An antibiotic active against Neisseria meningitidis, such as a parenteral third-generation cephalosporin, is also appropriate for other bacterial infections that can rarely mimic RMSF (e.g., pneumococcal bacteremia in asplenic hosts). If sepsis or toxic shock syndrome caused by Staphylococcus aureus cannot be excluded, empiric therapy is appropriate. 

Patients with RMSF who receive therapy within the first week of illness will generally show signs of improvement, including defervescence, within 72 hours of initiating doxycycline therapy; lack of improvement suggests the need to search for an alternative diagnosis.[1][14]

Critically ill patients

Patients with RMSF who are ill enough to be hospitalized may require aggressive supportive care interventions. Fluid balance and serum electrolytes should be monitored closely. Some patients may need transfusions of packed red blood cells or platelets. Critically ill patients might require adjunctive therapies for seizures, intracranial hypertension, shock, acute respiratory distress syndrome, renal failure, or other complications.[1][13]

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