Approach

The most difficult aspect of treating a rickettsial infection is considering that the patient may have a rickettsial infection in the first place. Therefore it is important to start appropriate empirical antibiotic therapy as soon as rickettsial infection is reasonably considered in the differential, without waiting for the results of tests to confirm the diagnosis. Prompt treatment is essential as it results in improved outcomes.​

Antibiotic therapy

The first-line treatment for all rickettsial diseases in people of all ages is doxycycline (a tetracycline class antibiotic).[22] Doxycycline can be given as oral or intravenous therapy depending on the severity of symptoms. A clinical response, including abatement of fever, should be evident in 48 to 72 hours.[29] Doxycycline should be continued for at least 3 days after clinical improvement is seen, with a typical course being 5 to 7 days.[22] Tetracycline may also be used; however, doxycycline has a more convenient dosing schedule and is the preferred option.

If the patient is allergic to tetracyclines, an infectious disease consultant and/or an allergy and immunology specialist should be consulted. Azithromycin is a suitable alternative in patients with scrub typhus and a severe doxycycline allergy.​[30]​​ Low-quality evidence suggests that it is as effective as doxycycline and tetracycline for the treatment of scrub typhus in terms of treatment failure and time to defervescence.[31] Rifampicin is an alternative option for patients with scrub typhus and a severe doxycycline allergy.[30]​ Chloramphenicol is another option, but is generally not recommended as it is associated with numerous adverse effects.[22] Chloramphenicol was associated with the highest cure rate for scrub typhus in children in one network meta-analysis.[32]​​

Commonly used antibiotics (e.g., penicillins and cephalosporins) do not work against rickettsiae because of the unusual chemical nature of their bacterial cell wall, and sulfonamides have been associated with an increased disease severity and death.[22]

Treatment in children

Doxycycline is the drug of choice for children with rickettsial infections.[22] 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.[33][34][35] Tetracycline may also be used in children >8 years of age; however, doxycycline has a more convenient dosing schedule and can be used in younger children, so is the preferred option. CDC: research on doxycycline and tooth staining Opens in new window

Treatment in pregnant or breastfeeding women

The care of pregnant women with rickettsial infection should be undertaken in consultation with an infectious disease consultant. Maternal infection with scrub typhus has been associated with poor maternal and neonatal outcomes (including high miscarriage rates).[5]

Tetracyclines as a group are generally contraindicated in pregnant women, due to their potential toxicity to both fetus and mother.[22] However, a review of the evidence suggested that the safety profile of doxycycline is significantly different to other tetracyclines and that there was no correlation between use of doxycycline and teratogenic effects.[35] Low levels of doxycycline are excreted in breast milk. The use of a short course (5 to 7 days) of doxycycline typically recommended for treatment of rickettsial diseases is probably safe during lactation.[22]

There are limited data to support the use of other antimicrobial agents in the treatment of tick-borne rickettsial diseases during pregnancy. Treatment alternatives for pregnant women may include azithromycin, chloramphenicol, or rifampicin; however, a specialist should decide the most appropriate regimen on a case by case basis. Caution is advised when using chloramphenicol late in the third trimester of pregnancy due to a theoretical risk of grey baby syndrome.[22]​​

Critically ill patients

Some patients with rickettsial infection may be extremely unwell and close to death. This is particularly true of patients with scrub typhus (caused by Orientia tsutsugamushi). Intensive medical support in the intensive care unit is urgently required, including appropriate antibiotics. 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, or disseminated intravascular coagulation.[22][36]

Other bacterial infections

For patients whose presentation may be consistent with a serious, different bacterial infection, therapy needs to begin presumptively, and empirical 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 occasionally mimic rickettsial spotted fevers (e.g., pneumococcal bacteraemia in asplenic hosts).[22] If sepsis or toxic shock syndrome caused by Staphylococcus aureus cannot be excluded, empirical therapy is appropriate.

Patients with rickettsial infection who receive therapy within the first week of illness will generally show signs of improvement, including abatement of fever, within 72 hours of initiating doxycycline therapy. Lack of improvement suggests the need to search for an alternative diagnosis.[22][37]

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