The term rickettsial diseases refers to diseases caused by a diverse group of bacterial organisms which share the properties of obligate intracellular parasitism of their host and which are transmitted by an intermediate vector, often a biting tick (although lice and fleas are other notable vectors).

Examples of rickettsial diseases include scrub typhus (caused by Orientia tsutsugamushi), spotted fevers such as Rocky Mountain spotted fever (RMSF - caused by Rickettsia rickettsiae), and epidemic typhus-like infections such as murine typhus (caused by Rickettsia typhi).

In order to appropriately treat rickettsial diseases, one must usually have first considered their possibility. This is because the specific antibiotics which treat rickettsia are seldom routine empirical choices, this being especially true if the presentation is severe. Need for consideration of the diagnosis is not precluded by the commonly used non-specific diagnostic tests such as blood cultures, as these will not identify rickettsia. Thus, it is not possible to accidently make the diagnosis, which is important as the rickettsial diseases mentioned above have a considerable associated mortality.

Despite the diversity of rickettsial infections (both geographically and in terms of the phylogeny of the pathogens), certain epidemiological, historical, or clinical clues may suggest a rickettsial pathogen. A history of travel to an area where rickettsial diseases are recognised, a tick bite, an eschar (a black scab at the bite mark which appears later), and a particular constellation of symptoms may point to the clinical diagnosis. Additionally, non-response to a conventional first-line antibiotic, such as a beta-lactam, which are inactive against these infections, may suggest the diagnosis by exclusion.

Rickettsia of all types tend to be sensitive to the tetracycline class of antibiotic, of which doxycycline is the most widely used and has the best documented efficacy. Reports of resistance of rickettsia to these antibiotics have been very few, and newer evidence casts doubt on these. Doxycycline resistance should not pose a clinical concern for treating physicians. Concern about adverse effects of doxycycline in pregnancy, and in young children, have been found to be negligible in comparison to the significant morbidity and mortality associated with the disease. As such, doxycycline is the go-to treatment, unless truly contraindicated or an alternative with known equivalence is available in consultation with guidelines or expert advice.

Alternatives with proven efficacy include macrolide antibiotics (in particular azithromycin), which may prove to be equivalent in activity against certain rickettsia but inferior against others, such as Rickettsia typhi. Beta-lactam antibiotics (e.g. penicillins, cephalosporins, carbapenems) are inactive against the significant rickettsial pathogens mentioned above and should not be used for their treatment. The quinolones (e.g. ciprofloxacin) and chloramphenicol have variable activity and should only be considered when doxycycline or other alternatives cannot be used, and only in consultation with guidelines or expert advice.