Doxycycline for Rocky Mountain Spotted Fever: Safe for All Ages

Rocky Mountain Spotted Fever

I'm Dr Casey Barton Behravesh, with the Rickettsial Zoonoses Branch at the Centers for Disease Control and Prevention (CDC). I am here to discuss Rocky Mountain spotted fever (RMSF) and the new research on doxycycline showing that it is safe to use in children at any age.

First, let's review some clinical characteristics of this serious disease. RMSF is caused by Rickettsia rickettsii, an intracellular bacterium transmitted through the bite of an infected tick. Early manifestations, within the first 4 days of illness, are typically nonspecific, with such symptoms as fever, headache, myalgia, and gastrointestinal illness. However, RMSF progresses rapidly to severe illness. Around 2-5 days after illness onset, a macular rash may develop on the wrists and ankles before spreading centrally.

After day 5, illness severity increases dramatically with the development of late-stage petechial rash as well as hypotension and respiratory distress. Permanent, life-altering sequelae may result from vascular damage during acute illness, leading to neurologic deficits (such as hearing loss, paralysis, and encephalopathy) and the need to amputate extremities.

Owing to the rapid progression of this disease, empiric treatment with doxycycline, the frontline drug for treatment of RMSF, is critical for anyone at any age and should be initiated in patients with suspected RMSF before laboratory diagnosis is obtained. Delay of doxycycline treatment past day 5 of illness is associated with increased risk for hospitalization and death. Death can occur rapidly in patients who do not receive appropriate treatment. The average time from onset of symptoms to death is only 8 days.

Between 2008 and 2012 in the United States, 13,635 cases of RMSF were reported.^[1] About 6% of cases were among children younger than 10 years of age; however, this same age group represented almost one quarter of all deaths. Children younger than 10 years are five times as likely to die from RMSF compared with any other age group. Therefore, we looked at data from a 2012 national survey of clinicians on prescribing practices for suspected RMSF. We found that 80% of responding clinicians correctly selected doxycycline as the treatment of choice for suspected RMSF in patients aged 8 years or older; however, only 35% correctly chose doxycycline as the treatment of choice for suspected RMSF in children younger than 8 years of age.^[2]

Safety of Doxycycline in Children

This points to a concerning gap in the treatment of pediatric RMSF. We suspect that one reason for the hesitation to prescribe doxycycline to pediatric patients is the warning about dental staining on all tetracycline-class antibiotics. Doxycycline, a newer tetracycline antibiotic, binds less readily to calcium during tooth development and has not been shown to cause tooth discoloration. Confidence in an antibiotic's safety is essential in clinicians' prescribing practices, so CDC scientists conducted a study to evaluate the potential for tooth staining in pediatric RMSF patients treated with doxycycline.

In 2013, the CDC conducted a retrospective review of children in a community with high rates of RMSF.^[3] We compared children who had received doxycycline before the age of 8 years in the treatment of suspected RMSF with children who had never received doxycycline. Licensed dentists, blinded to exposure status, performed quantitative and qualitative evaluations of tooth color and enamel hypoplasia. The study showed no evidence of subjective tetracycline-like staining, no difference in the rate of enamel defects, and no difference in tooth shade between the children who had received doxycycline and those who had not. This study provides the best evidence to date that short courses of doxycycline do not cause dental staining when given to children under the age of 8 years.

Doxycycline is the first-line therapy for the treatment of suspected rickettsial infections in patients of all ages, recommended by the CDC as well as the American Academy of Pediatrics (AAP).^[4] The current label allows for the use of doxycycline in pediatric patients with RMSF because other antibiotics are not likely to be effective for treatment. However, clearer language on the drug label is needed to avoid hesitation in prescribing life-saving doxycycline to children and to reinforce CDC and AAP recommendations for the treatment of RMSF. Despite the current label warning, it is important for healthcare providers to know that doxycycline has not been shown to cause tooth staining in the dose and duration used to treat rickettsial diseases. Early administration of doxycycline in adults and children can prevent severe illness and save lives. For up-to-date information about RMSF and doxycycline, please visit our website.

Casey Barton Behravesh MS, DVM, DrPH, DACVPM, is Chief of the Epidemiology Activity in the Rickettsial Zoonoses Branch, Division of Vector-borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC). She is a Commander in the United States Public Health Service. Dr Barton Behravesh currently serves as a subject matter expert on the diagnosis, treatment, management, and epidemiology of tickborne rickettsial diseases. From 2006 to 2014 Dr. Barton Behravesh focused her efforts on investigating outbreaks of human illnesses caused by enteric pathogens, including Salmonella and Escherichia coli O157:H7, that are foodborne and waterborne, as well as through contact with animals and their environments. Dr Barton Behravesh is a huge advocate of using an interdisciplinary One Health approach involving human, animal, and environmental health to protect public health.

Dr Barton Behravesh holds a master of science degree in veterinary parasitology from Texas A&M University. She received her doctor of veterinary medicine degree from Texas A&M University and a doctor of public health degree from the University of Texas Health Science Center at Houston, School of Public Health, both in 2005. She was an Epidemic Intelligence Service (EIS) Officer from 2006 to 2008, with the Enteric Diseases Epidemiology Branch at the CDC. She is board certified in American College of Veterinary Preventive Medicine.