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Research on Doxycycline and Tooth Staining

Highlights

  • Doxycycline is the most effective antibiotic for the treatment of suspected rickettsial infections, including Rocky Mountain spotted fever (RMSF).Misperceptions about the use of doxycycline for children prevent kids from getting lifesaving treatment.
  • Delay in treatment of rickettsial diseases may lead to severe illness or death. Children are five times more likely than adults to die from RMSF.
  • Misperceptions about the use of doxycycline for children prevent kids from getting lifesaving treatment.
  • Doctors often avoid prescribing doxycycline to young children because of a warning that tooth staining may occur when used in children less than 8 years old.
  • In a new study, experts at the CDC and Indian Health Service (IHS) found that short courses of the antibiotic doxycycline can be used in children without causing tooth staining or weakening of tooth enamel.

Background on doxycycline and older tetracycline antibiotics

doctor holding medicine bottle Tetracycline antibiotics are broad-spectrum antibiotics in use since the 1940s. Older tetracycline-class antibiotics have been linked to cosmetic staining of permanent teeth when used in children before the age of 8 years. As a result, in 1970 a warning label was attached to all tetracycline-class antibiotics advising against the use in children under the age of 8 years.

In 1967 doxycycline was introduced as a newer tetracycline-class antibiotic. Doxycycline binds less readily to calcium and has not been shown to cause the same tooth staining. Several studies have previously been published showing the lack of staining of permanent teeth when doxycycline was used in children. The warning, currently present on all tetracycline-class antibiotics, including doxycycline, continues to mention the concern regarding dental staining.

Doxycycline and rickettsial diseases

Doxycycline is the most effective treatment of all rickettsial diseases including Rocky Mountain spotted fever, ehrlichiosis and anaplasmosis.  It is the antibiotic recommended by the American Academy of Pediatrics (AAP) and CDC for the treatment of suspected rickettsial diseases in patients of all ages. Studies have shown that other antibiotics are less effective and are associated with a higher number of deaths (case fatality rate).

In a 2012 national survey, 80% of clinicians correctly selected doxycycline as the treatment of choice for suspected RMSF in persons 8 years or older, however, only 35% of clinicians correctly chose doxycycline as the treatment of choice for suspected RMSF in children under 8 years. This hesitation may contribute to the increased fatality rate among children. Children under the age of 10 years represent <6% of RMSF cases, but they represent 22% of deaths. The same disproportionate case fatality rate in children has been observed for ehrlichiosis and other serious rickettsial infections.

Case Fatality Rate of Spotted Fever Rickettsiosis by Age Group, 2008-2013

Case Fatality Rate of Spotted Fever Rickettsiosis by Age Group

Case fatality rate by age-group for spotted fever rickettsioses (including RMSF) in the United States, 2008-2012.

Case Fatality Rate of Spotted Fever Rickettsiosis by Age Group, 2008-2013
Age Group at Onset (years) Case Fatality Rate (%)
0-4 1.95
5-9 1.30
10-19 0.30
20-29 0.15
30-39 0.10
40-49 0.45
50-59 0.40
60-69 0.25
70+ 0.65

Case Fatality Rate of Ehrlichia chaffeensis by Age Group, 2008-2013

Case Fatality Rate of Ehrlichia chaffeensis by Age Group

Case fatality rate by age-group for ehrlichiosis in the United States, 2008-2012.

Case Fatality Rate of Ehrlichia chaffeensis by Age Group, 2008-2013
Age Group at Onset (years) Case Fatality Rate (%)
0-4 2.95
5-9 0
10-19 0
20-29 0
30-39 0.35
40-49 0.40
50-59 0.40
60-69 0.60
70+ 2.40

Rickettsial diseases begin with non-specific symptoms, such as fever, headache, and gastrointestinal illness. A rash may develop around 2-5 days after the start of symptoms. This disease progresses rapidly into severe illness requiring hospitalization, or even death. Rickettsia can cause damage to the blood vessels leading to organ failure, amputation of extremities from lack of blood flow, and neurological deficits (such as hearing loss, paralysis, and encephalopathy). More than 20% of untreated cases of RMSF are fatal, with the average time from the beginning of symptoms to death being only 8 days.

Digital necrosis in hand with untreated Rocky Mountain Spotted Fever

Digital necrosis in hand with untreated Rocky Mountain Spotted Fever Digital necrosis may occur with untreated RMSF. Median time to death is only 8 days.

Rocky Mountain Spotted Fever rash on foot

Rocky Mountain Spotted Fever rash on foot Rash can occur with RMSF, but may start later in illness. Never wait for a rash to begin doxycycline.

Doxycycline is most effective when given within the first 5 days of illness. Because there is no rapid test to diagnose rickettsial diseases, clinicians must diagnose and treat based on clinical suspicion alone. It is important that concern about dental staining not cause providers to use other antibiotics, or delay the start of treatment in children.

The newest evidence

child smiling In 2013, researchers from the CDC and IHS began looking into the issue of dental staining following doxycycline usage, to better understand if this is an issue. This study was performed to look at whether or not doxycycline, in the dose and duration used to treat suspected RMSF, caused dental staining in children less than 8 years. The study took place in a community which has suffered from high rates of RMSF since 2003, where a large number of people, including children, were treated with doxycycline.

Dentists inspected the permanent teeth of children who had received doxycycline for suspected RMSF prior to their 8th birthday and those who had not. Blinded dentists (without knowing which children had received the drug) looked for tooth staining, evaluated tooth color, and looked for evidence of weakness in the tooth enamel for all children in the study. No differences were found between children who had received doxycycline and those who had not.

This study provides the largest sample size and best evidence to date that short courses of doxycycline (such as those used to treat rickettsial diseases) do not cause dental staining when given to children under the age of 8 years.

The current label allows for the use of doxycycline in pediatric rickettsial patients because other antibiotics are not likely to be effective for treatment.  However, clearer language on the drug label may help avoid hesitation in prescribing life-saving doxycycline to children, and reinforce CDC and AAP RMSF treatment recommendations. 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.

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