Pediatric Rocky Mountain Spotted Fever 

Updated: Apr 14, 2021
Author: Asif Noor, MD; Chief Editor: Russell W Steele, MD 

Overview

Practice Essentials

Rocky Mountain spotted fever (RMSF) is a tick-borne infection caused by an intracellular bacterium named Rickettsia rickettsii. RMSF is the most common rickettsial disease in the United States.[1]  The hallmark of disease process is vasculitis. RMSF is a serious infection with a case-fatality rate of about 10% if left untreated.

Under a magnification of 98X, this scanning electr Under a magnification of 98X, this scanning electron microscopic (SEM) image depicts the dorsal view of the head region from an American dog tick, Dermacentor variabilis, magnified 98X. D. variabilis is a known carrier of Rocky Mountain Spotted Fever (RMSF) caused by the bacterium, Rickettsia rickettsii. Courtesy of the Public Health Image Library (PHIL), CDC, photo credit Janice Haney Carr.

Signs and symptoms

Incubation period is 2-14 days, with a median of 4 days.

Most affected children are quite ill. The disease results from direct small vessel injury and presents as follows:

  • Fever (range of 40ºC or 104ºF is typical)
  • Severe headache
  • Characteristic rash
  • Myalgias
  • Severe malaise
  • Earlier in the disease course, gastrointestinal symptoms of nausea, vomiting, and abdominal pain may be predominant, suggestive of gastroenteritis or even a surgical abdomen

Physical findings include the following:

  • Rash: Appears in 90% of affected children between day 2 and 4 [2]
  • Conjunctival injection: Seen in 33% of cases
  • Altered mental status (33%)
  • Lymphadenopathy (29%)
  • Peripheral edema (25%)
  • Less common: Hepatosplenomegaly, meningismus, or coma

See Presentation for more detail.

Rocky Mountain Spotted Fever (RMSF) rash in a chil Rocky Mountain Spotted Fever (RMSF) rash in a child. It appears day 3-5 of illness, begins in ankles and wrists, and typically involves palms and soles. In early stages it is macular and later it is petechial. Courtesy of the Morbidity and Mortality Weekly Report (MMWR), CDC.

Diagnosis

Screening

Screening laboratory testing may reveal the following:

  • Complete blood cell count may show anemia and/or thrombocytopenia (observed in 5-30%)
  • Complete metabolic panel may show hyponatremia (50%)
  • Cerebrospinal fluid analysis may show pleocytosis in one third of the patients, with either lymphocytic or polymorphonuclear predominance

Confirmatory testing

The most widely used test is immunofluorescence assay (IFA). A 4-fold increase in titers is confirmatory between acute and convalescent stages (collected 2-6 weeks apart). A probable diagnosis can be made based on a single IFA titer of ≥1:64. The sensitivity is low in the first 10-12 days of illness. However, the test is 94% sensitive by 14-21 days.[3]

Real-time polymerase chain reaction (PCR) assay for RMSF is less established but is useful earlier in the disease course from blood or tissue samples.

Skin biopsy from the petechial rash during acute illness can be sent for immunohistochemistry; it is 100% specific and 70% sensitive.

See Workup for more detail.

Management

RMSF is a life-threatening illness, and antibiotic therapy should not be delayed in a child with consistent clinical features and epidemiology while awaiting confirmatory testing. Doxycycline is the treatment of choice for all ages. New evidence supports the use of doxycycline for a short course without the risk of teeth staining. Management with doxycycline before 5 days of illness significantly reduces hospitalization, ICU stay, and complications.

The majority of children defervesce within 1-2 days of starting doxycycline. Lack of improvement by 72 hours suggests the need to reconsider the diagnosis even in children with multiple organ involvement. Doxycycline should be continued for 3 days after improvement, and the usual course is 7-10 days.

See Treatment and Medication for more detail.

Background

Rocky Mountain spotted fever (RMSF) is the most common rickettsial infection and the second most commonly reported tick-borne disease (after Lyme disease) in the United States. RMSF is a member of the spotted fever group of rickettsial infections. RMSF gets its name from the initial epidemiological description in the Rocky Mountain region of the United States. It is a reportable disease in the United States to state or local health departments.

The causative agent is Rickettsia rickettsii (named after Howard T. Ricketts, the discoverer of the organism).

RMSF was first described in the late 1800s in the Bitterroot Valley of Idaho, and for several decades, the disease was thought to be limited to the Rocky Mountain area; however, it now has a high documented prevalence in the eastern United States. More than 60% of cases are reported in five states (North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri).

The disease is spread mainly through the bites of infected ticks. The dog tick, wood tick, and Lone Star tick are all potential vectors and are responsible for RMSF in different parts of the United States. The distribution of RMSF disease parallels tick activity during peak season.

RMSF has the highest mortality of any tick-borne illness in the United States (up to 30%). Because of this, the Rocky Mountain Laboratory was established in Hamilton, Montana, to help investigate the disease. This laboratory is now part of the National Institute of Allergy and Infectious Diseases (NIAID).

Early treatment is critical to the outcome in RMSF and must be started on the basis of clinical diagnosis. Consider the possibility of RMSF in any child with potential tick exposure who develops fever, myalgia, or headache, even if they do not have a rash. If suspected, promptly begin antibiotic (doxycycline) treatment even before confirmation of the diagnosis, as delay in the initiation of treatment is associated with significantly higher mortality.

For additional discussion of the disease, see Rocky Mountain Spotted Fever. For patient education information, see the Bites and Stings Center, as well as Ticks.

Pathophysiology

Rocky Mountain spotted fever is a diffuse, small-vessel vasculitis. R rickettsii is a small (0.1-0.3 μ) nonmotile gram-negative, obligate intracellular coccobacillus, with a tropism for human endothelial cells.The plasma membrane of mammalian cells, expresses Ku70, which serves as a receptor for the outer surface proteins of OmpA, OmpB and sca 1 for R rickettsii attachment and subsequent phagocytoses by the host cell. It resides in the cytosol and less commonly in the nuclei of the host cells and divides via binary fission. This bacterium causes membrane disruption and increased permeability.

Possible mechanisms for cellular injury include injury to the cell membrane, depletion of adenosine 5-triphosphate (which leads to failure of the sodium pump), and damage to the cell caused by toxic products of rickettsial metabolism.

Vascular lesions are responsible for the clinical manifestations, including rash, headache, alteration in the level of consciousness, heart failure, and shock. Vascular lesions can be found throughout the body, with highest predilection for the skin, gonads, and adrenal glands.

Profound hyponatremia is common. Several mechanisms have been postulated, including a shift in water from the intracellular spaces to the extracellular spaces; increased loss of sodium in the urine; and an exchange of sodium for potassium at the cellular level.[4]

Edema of the medulla oblongata may contribute to fatality in some patients.

Concentrations of antidiuretic hormone and aldosterone are increased in some patients.

Etiology

Ticks are the natural hosts, reservoirs, and vectors of R rickettsii. The species of tick acting as the vector varies by geographic location. R rickettsii is usually transmitted to humans by the bite of an infected tick. On occasion, transmission occurs by scratching or rubbing infectious tick feces into the skin.

Adult ticks transmit the disease to humans during feeding. At least 6 hours of tick attachment is needed for the transmission of R rickettsii.

Primary hosts of R rickettsii include the following {ref16-INVALID REFERENCE}

  • Dermacentor variabilis (dog tick) in the eastern United States and eastern Canada

  • Dermacentor andersoni (wood tick) in the western United States and western Canada

  • Amblyomma americanum (Lone Star tick) in the southwestern United States

  • Rhipicephalus sanguineus (brown dog tick) recently implicated as a vector in Arizona

  • Tick identification. (i) American dog tick (Dermac Tick identification. (i) American dog tick (Dermacentor variabilis), ii) Rocky Mountain wood tick (Dermacentor andersoni), and, iii) brown dog tick (Rhipicephalus sanguineus) iv) Lone star tick (Amblyomma americanum). Courtesy of the CDC.

Laboratory personnel can be infected by inoculation or inhalation of aerosolized infectious specimens. For this reason, only specially equipped laboratories should attempt to culture and isolate Rickettsia species. Transmission has occurred on rare occasions by blood transfusion.

Epidemiology

United States statistics

Rocky Mountain spotted fever has been a nationally notifiable condition since the 1920s under the category of Spotted Fever Rickettsiosis (SFR). It has been reported in almost every state in the continental United States, with an age-related annual incidence of 0.5-3 cases per million population.[5]  In 2000, 495 cases of SFR were reported, while in 2017, more than 6,248 cases were reported, a finding that has been attributed at least in part to increased awareness and testing for the disease, as the percentage of confirmed cases among the total reported, and the case-fatality rate, have both decreased.

Annual incidence (per million persons) for Spotted Annual incidence (per million persons) for Spotted Fever Rickettsiosis (SFR) in the United States, 2017. Courtesy of the CDC.

The term Rocky Mountain spotted fever is a misnomer because the disease is relatively rare in the Rocky Mountain states. States reporting the highest rate of disease include North Carolina, Missouri, Tennessee, Oklahoma, and Arkansas; these states have accounted for more than half the total cases.

About 90% of cases occur between April and September, the time of the year when ticks have maximal activity and when people participate in outdoor recreational activities.

International statistics

Rocky Mountain spotted fever is also found in Canada, Mexico, Central America, and South America. However, the arthropod vector differs by location. Other rickettsial illnesses similar to Rocky Mountain spotted fever are also found worldwide (see the table below).

Table 1. Human Disease Around the World Caused by Spotted Fever Group Rickettsiae. (Open Table in a new window)

Organism

Disease or Presentation

Geographic Location

Rickettsia rickettsii

Rocky Mountain spotted fever

North, Central and South America

Rickettsia akari

Rickettsialpox

Worldwide

Rickettsia conorii

Mediterranean spotted fever, boutonneuse fever, Israeli spotted fever, Astrakhan fever, Indian tick typhus

Europe, Asia, Africa, India, Israel, Sicily, Russia

Rickettsia sibirica

Siberian tick typhus, North Asian tick typhus

Siberia, People's Republic of China, Mongolia, Europe

Rickettsia australis

Queensland tick typhus

Australia

Rickettsia honei

Flinders Island spotted fever, Thai tick typhus

Australia, South Eastern Asia

Rickettsia africae

African tick-bite fever

Sub Saharan Africa, Caribbean

Rickettsia japonica

Japanese or Oriental spotted fever

Japan

Rickettsia felis

Cat flea rickettsiosis, flea borne typhus

Worldwide

Rickettsia slovaca

Necrosis, erythema, lymphadenopathy

Europe

Rickettsia heilongjaiangensis

Mild spotted fever

China, Asian region of Russia

Rickettsia parkeri

Mild spotted fever

US

Race-, sex-, and age-related differences in incidence

Prior to 2000, Native Americans had rates of Rocky Mountain spotted fever similar to those of other races in the United States.[6] From 2001-2005, rates increased disproportionately (16.8 cases per million vs 0.5-4.2 cases per million for other races). The highest rates were in Oklahoma (113.1 cases per million).[7]

Darker-skinned individuals tend to have a worse clinical course, probably due to delays in recognizing the rash. Native American have higher rates of incidence, as well as worse outcomes. The annual incidence of Rocky Mountain spotted fever was 277.2 cases per million in the Southern plains, 104.6 cases per million in the East, and 49.4 cases per million in the Southwest regions.[8] Rates described through the national surveillance network are approximately 5-fold lower than those described in the review by Folkema et al.

The incidence is higher in males than in females, with a male-to-female ratio of 1.7:1. Children are at greater risk of acquiring Rocky Mountain spotted fever than are adults. The highest incidence occurs in children aged 5-9 years. However, the highest mortality is in those aged 50 years or older.

Prognosis

Outcomes can vary from complete resolution to death. The mortality rate during the preantibiotic era was as high as 30%; however, the mortality rate now ranges from approximately 2% in children to 9% in elderly persons.

The outcome greatly depends on the early start of appropriate treatment. The case-fatality rate is higher (6.2%) for persons whose treatment begins more than 3 days after onset of symptoms than for those treated within the first 3 days of illness (1.3%).

The importance of early treatment may help explain the poorer prognosis in African Americans. Rocky Mountain spotted fever may be diagnosed later in Blacks than in people with lighter skin because of the difficulty in detecting the early macular rash. In addition, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency tend to have a severe course of Rocky Mountain spotted fever, and the prevalence of G6PD deficiency in Black males is 12%.

Severe disease may result in long-term sequelae, such as the following:

  • Partial paralysis of the lower extremities

  • Gangrene requiring amputation of fingers, toes, arms, or legs

  • Hearing loss

  • Blindness

  • Loss of bowel or bladder control

  • Movement disorders

  • Speech disorders

Patient Education

Rocky Mountain spotted fever (RMSF) is a bacterial disease spread through the bite of an infected tick.

Prevention

There is no vaccine to prevent RMSF. Avoidance of illness is by preventing tick bites, preventing ticks on your pets, and preventing ticks in your yard.

Know where to expect ticks. Ticks live in grassy, brushy, or wooded areas, or even on animals, so spending time outside camping, gardening, or hunting will bring you in close contact with ticks.

Treat clothing and gear with products containing permethrin.

Use Environmental Protection Agency (EPA)-registered insect repellents containing DEET, picaridin, IR3535, oil of lemon eucalyptus (OLE), or 2-undecanone. Do not use products containing OLE or para-menthane-diol (PMD) on children under 3 years old.

After you come indoors, check your clothing for ticks and perform a full body check of yourself and your child's body, particularly at the following areas:

  • Under the arms
  • In and around the ears
  • Inside the belly button
  • At the back of the knees
  • In and around the hair
  • Between the legs
  • Around the waist

Remove the attached tick as soon as you notice it by grasping with tweezers, as close to the skin as possible, and pulling it straight out.

Watch for signs of illness. Most people who get sick with RMSF will have a fever, headache, and rash. RMSF can be deadly if not treated early with the right antibiotic. Timely initiation of doxycycline in children in essential to reduce the risk of morbidity and mortality. A short course of doxycycline is safe even in children younger than 8 years of age.

 

Presentation

History

The incubation period for Rocky Mountain spotted fever (RMSF) is 2-14 days after the tick bite. A history of tick bite is present in only two thirds of cases.

Symptoms can begin gradually or abruptly. Fever, headache, rash, myalgia, and mental confusion are the major clinical manifestations.

The patient's body temperature usually exceeds 38.8°C (101.8°F). Headache is the most common neurologic manifestation. In older children and adults, the headache may be intractable and may be ongoing day and night. Young children may not complain of headache.

Nausea, vomiting, and abdominal pain may occur. Conjunctival hyperemia and photophobia may be observed.

Rash

The rash of Rocky Mountain spotted fever is an important pathognomonic feature of the disease and is present in 80-90% of patients. Rash begins as blanching maculopapular lesions. These lesions become petechial or purpuric in approximately one half of patients, accounting for the disease’s former name of black measles.[9]

The rash first appears peripherally on the wrists and ankles. It spreads centripetally over the next 2-3 days. Involvement of the palms and soles is an important diagnostic feature.

In most patients, rash usually appears by the second or third day. However, it may be delayed until the sixth day.

Early recognition of the blanching macular eruption is vital, because the classic petechial rash does not typically appear until 6 days or so after the initial symptoms become apparent.

Physical Examination

Body temperature exceeds 38.8°C (101.8°F). The patient may have a toxic appearance. The characteristic skin rash is present in 80-90% of infected individuals. Hepatomegaly and splenomegaly are present in approximately 33% of patients. Signs of meningoencephalitis include restlessness, irritability, mental confusion, and delirium.

Meningismus may occur. Findings may include neck stiffness, photophobia, a positive Kernig sign (pain on knee extension when the hip is flexed to 90°), and a positive Brudzinski sign (knee and hip flexion when the neck is flexed).

Ataxia may be present. Spastic paralysis may occur. Sixth nerve palsy may be observed. Muscle tenderness is a common feature.

Complications

Complications may include the following:

  • Meningitis

  • Renal failure

  • Pulmonary involvement

  • Liver impairment with development of jaundice

  • Splenomegaly

  • Myocarditis

  • Thrombocytopenia

 

DDx

Diagnostic Considerations

Rocky Mountain spotted fever (RMSF) is a life-threatening disease. Therefore, it is important to consider the possibility of RMSF in any patient whose clinical presentation is consistent with the disease. Clinicians should have a low threshold for treatment if RMSF is clinically suspected.

Signs and symptoms can mimic those of other diseases. Therefore, a history of traveling to endemic areas, having tick bites, or having exposures to ticks is an important clue. Absence of a history of tick bites should not exclude the diagnosis if the index of clinical suspicion is high.

The differential diagnosis of RMSF includes other infections with fever and rash, especially those involving rash including palms and soles, such as the following:

An enteroviral infection is typically seen in summer months, the child is relatively well-appearing, and the screening laboratory tests usually do not reveal significant derangements. In a sexually active individual, secondary syphilis can present with fevers and rash, including on the palms and soles. Invasive West Nile virus infection causes maculopapular rash with a petechial component. Sepsis, especially meningococcemia, should be considered in a toxic-appearing child who presents with fever and a purpuric rash. Toxin-mediated gram-negative sepsis should be considered in an immunocompromised host with fever and rash.

Other tick-borne infections, such as monocytic ehrlichiosis and granulocytic anaplasmosis, can present strikingly similarly to RMSF.  However, ehrlichiosis usually is associated with leucopenia; thrombocytopenia and rash are often absent. It should be kept in mind that tick-borne co-infections are possible in the same patient bitten by the same tick.

Other infectious and inflammatory entities that may have clinical features that can be confused with those of RMSF include the following:

  • Infectious mononucleosis
  • Parvovirus infection
  • Roseola
  • Scarlet fever
  • Leptospirosis
  • Kawasaki disease
  • Typhoid fever and dengue should be in the differential if the patient has a history of travel
  • The new Phlebovirus (Heartland virus) seen mostly in Missouri, and a new rickettsial species ( Rickettsia amblyommii) seen in North Carolina, may present similarly to infection with R rickettsii        
  • Fever and rash can also be present with noninfectious conditions, such as drug reactions, and vasculitis

Differential Diagnoses

 

Workup

Approach Considerations

Laboratory findings may be nonspecific in Rocky Mountain spotted fever (RMSF). On the complete blood cell count, the total leukocyte count may be normal, elevated, or decreased but usually shows a left shift.

Mild anemia and thrombocytopenia of less than 150 × 109/L (< 150 × 103/µL) occur in approximately one third of patients. Severe thrombocytopenia of less than 20 × 109/L (< 20 × 103/µL) occurs in approximately 10% of patients.

On a comprehensive metabolic panel, the following may be noted:

  • Hyponatremia (serum sodium < 130 mEq/L) in 20% of patients

  • The serum alanine aminotransferase level is usually increased

  • Serum albumin values may be low

  • The blood urea nitrogen (BUN) level is increased

Results of cerebrospinal fluid (CSF) analysis are generally normal. However, mild pleocytosis may be present, and approximately 50% of patients have a predominance of polymorphonuclear cells. An elevated CSF protein level may also be observed.

Serologic assays to detect anti–R rickettsii immunoglobulin G (IgG) antibodies are usually performed for definitive diagnosis.[10] Testing of acute-phase and convalescent-phase sera is recommended to demonstrate a 4-fold or higher increase in the titer.

Enzyme immunoassays (EIAs) and immunoglobulin M (IgM) antibody-capture immunoassays are new serologic tests that potentially allow for early diagnosis.

In research laboratories, isolation of rickettsiae from tissues or direct detection of rickettsiae in tissues by means of direct immunofluorescence is used to confirm the diagnosis. Polymerase chain reaction tests have been developed but are not widely available.

Imaging Studies

CT imaging is typically normal, whereas MRI seems more sensitive at revealing abnormalities. Published findings include diffuse edema, effacement of the sulci, arterial infarctions, prominent perivascular spaces, and enhancement of the meninges (ie typical findings of meningoencephalitis). In a case series of 3 pediatric cases of Rocky Mountain spotted fever (RMSF) with encephalitis, scattered nonenhancing punctate lesions were described throughout the cerebral white matter, visible on T2- and diffusion-weighted MRI.[11, 12, 13]

 

Treatment

Approach Considerations

Early treatment is critical to the outcome in Rocky Mountain spotted fever (RMSF) and must be started on the basis of clinical diagnosis.[2] Consider the possibility of RMSF and promptly begin antibiotic treatment in any patient with potential tick exposure who develops fever, myalgia, or headache, even if they do not have a rash.

Never delay treatment while awaiting a confirmatory laboratory diagnosis or the development of a rash. The best outcomes are achieved when treatment is started within 5 days of symptom onset, and the classic petechial rash may not appear until day 6.

Doxycycline

Doxycycline is considered to be first-line treatment for both adults and children and should be started as soon as RMSF is suspected.[14] The use of any other antibiotics has been associated with a higher risk of death (see Table 2, below).

Doxycycline treatment is most effective at preventing death if it is started within the first 5 days after symptoms begin. As a result, doxycycline treatment should be started before the return of laboratory results and before the manifestation of severe symptoms, such as petechiae. If the patient is treated within the first 5 days of disease, fever generally subsides within 24-72 hours.[14]

The recommended dosage of doxycycline is 2.2 mg/kg body weight twice daily for children less than 45 kg (100 lb). For adults, the dosage is 100 mg every 12 hours. Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Standard duration of treatment is 7-14 days.

The recommended dosage of doxycycline for RMSF has not been shown to cause staining of permanent teeth.[15]

Chloramphenicol was previously recommended for the treatment of children younger than 9 years. In national surveillance data, however, patients treated with chloramphenicol were more likely to die than those treated with a tetracycline. Staining of teeth caused by one or more courses of tetracyclines (particularly doxycycline) is negligible.

Some authors have advocated the use of adjunctive corticosteroids, but the specific therapeutic benefits of these drugs are not known. Physicians should be aware that sulfonamide treatment given empirically in a febrile child can worsen Rocky Mountain spotted fever.

Other supportive measures (eg, intravenous administration of fluids, oxygenation, correction of electrolyte impairments, management of disseminated intravascular coagulation) should be provided according to the patient's clinical situation.

Patients with RMSF should be treated in consultation with an infectious disease specialist.

Deterrence and Prevention

Avoidance of tick-infested areas is the first line of defense against RMSF. If tick-infested areas cannot be avoided, wearing light-colored shirts and trousers that fit tightly around the waist and ankles can minimize the risk of being bitten.

Exposed areas of the skin should be covered with insect repellents containing N -N -diethyl-M -toluamide (DEET). In children, insect repellents should be used carefully on exposed skin. Application to the face and hands should be avoided.

After people leave an endemic area, they should inspect their bodies for attached ticks, with particular attention to areas containing hair.

If ticks are found, any of several commercial removal devices should be used if possible. Otherwise, ticks should be removed by grasping them with fine tweezers at the point of attachment and by pulling them out slowly and steadily. The aim is to remove the tick's mouthparts from the site of insertion without damaging the body of the tick.

After the tick is removed, the skin should be disinfected. Check to make sure that the head of the tick is not still embedded.

Some have recommended keeping the removed tick in a jar along with a dampened paper towel in the refrigerator for a month. This way, if the person later develops symptoms, the tick may be used to help identify what (if any) infection it may have transmitted.

Burning the tick, smothering it in alcohol or petroleum jelly (or another substance), or twisting or rubbing it off is not recommended. These methods have not been shown to decrease the time the tick remains embedded. In addition, they may pose of risk breaking the body of the tick open and releasing bacteria that were otherwise contained within it.

After a tick bite occurs, use of antimicrobial prophylaxis has no role in the prevention of RMSF.

Table: Specific Recommended Treatment

Table 2. Doxycycline Treatment for Rocky Mountain Spotted Fever (Open Table in a new window)

  • Doxycycline is first-line treatment for both adults and children; antibiotics other than doxycycline increase the risk of death[14]

  • Dosage for children < 45 kg (100 lb): 2.2 mg/kg body weight given twice a day

  • Dosage for adults: 100 mg every 12 hours

  • Treatment is most effective at preventing death if doxycycline is started within the first 5 days of symptoms; if treatment occurs within 5 days, fever generally subsides within 24-72 hours

  • Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement; the standard duration of treatment is 7-14 days - "Fever plus 3, at least a week"

 

Medication

Medication Summary

The best outcomes in Rocky Mountain spotted fever (RMSF) are achieved when treatment is started within 5 days of symptom onset. Doxycycline is the antibiotic of choice.

Chloramphenicol was previously recommended for the treatment of children younger than 9 years. In national surveillance data, however, patients treated with chloramphenicol were more likely to die than those treated with a tetracycline. Chloramphenicol poses a risk of permanent aplastic anemia and should be avoided if at all possible.

Antibiotic Agents

Class Summary

Tetracyclines are the drugs of choice. Although tetracyclines should not be routinely prescribed to children younger than 8 years, the benefits far exceed the risks in RMSF. Doxycycline is the agent of choice because the risk of dental staining is less with this agent than with other tetracyclines.

Doxycycline (Adoxa, Doxy 100, Vibramycin, Monodox)

Doxycycline is the drug of choice for RMSF. It is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. When given orally, it is almost completely absorbed.

It concentrates in bile and is excreted in urine and feces as a biologically active metabolite in high concentrations. This agent is the only tetracycline that does not need dosing adjustment in renal failure.

Doxycycline inhibits protein synthesis and, therefore, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl transfer RNA (tRNA) from ribosomes, arresting RNA-dependent protein synthesis.