Apr. 24, 2002 COLUMBUS, Ohio - The two drugs most commonly used to treat anthrax in adults could cause unwanted side effects if used in children, according to an analysis of pediatric anthrax treatment options.
But the risks of using either medication pale in comparison to the risks of anthrax disease, said Milap Nahata, a professor and chair of pharmacy practice and administration at Ohio State.
"Anthrax can be fatal, and children may have the greatest risk for developing the disease in the event of a major bioterrorism attack," he said. "So the use of these antibiotics can be recommended despite the lack of adequate efficacy and safety studies in children." The researchers analyzed nearly 20 studies that examined the safety and efficacy of two medications - ciprofloxacin and doxycycline -- when used in children. The drugs are also often used to treat adults with the disease.
Past research links ciprofloxacin (or cipro) to bone deformations and doxycycline to bone growth inhibition and tooth discoloration in children.
Nahata conducted the study with Sandra Benavides, a postdoctoral fellow in pharmacy at Ohio State. Their analysis appears in a recent issue of The Annals of Pharmacology.
Anthrax infection is caused by Bacillus anthracis, a toxin-producing bacterium that can cause swollen lesions if it comes into contact with the skin or, if inhaled, internal bleeding and infection throughout the body. In rare cases, the bacteria can be ingested and cause serious gastrointestinal problems.
Even with antibiotic treatment, the risk of death from inhalation anthrax is nearly 100 percent for adults, Nahata said. Fatality from the cutaneous form of the disease is lower: 20 percent without antibiotic treatment and less than 1 percent with treatment. Children may have a greater chance of contracting the infection simply because they breathe faster than adults do and their skin is more permeable as well.
"We don't know the mortality rates in children," Nahata said. "Nor do we know the likelihood of cutaneous anthrax progressing into a systemic infection or, worse yet, meningitis."
The Centers for Disease Control and Prevention recommends using cipro to treat inhalation anthrax and doxycycline to treat the cutaneous form of the disease in adults and in children. The Food and Drug Administration hasn't approved the use of cipro in children younger than 18, unless inhalation anthrax is suspected. Doxycycline does not have approval for use in children younger than 8.
Doxycycline is a tetracycline - a group of drugs originally intended to treat respiratory tract infections and ear infections. Several studies in children and animals linked tooth discoloration to tetracycline, particularly in children younger than 2. Studies on doxycycline found fewer instances of tooth discoloration. One study linked bone growth inhibition in premature infants to the use of tetracyclines. Growth rates returned to normal, however, once tetracycline treatment was stopped.
"There haven't been any further reports of doxycycline-induced bone growth inhibition," Nahata said. "Also, the drug seems to have fewer adverse cosmetic effects on teeth than do older tetracyclines."
Although cipro studies in young animals have linked the drug to damage in the joints, similar complications in humans haven't been confirmed. Studies that included thousands of children who received cipro or a related drug showed no link between the drug and joint problems in healthy children. Nearly all of the children who had developed joint problems also had cystic fibrosis, a disease that causes such problems in 4 to 7 percent of patients.
A third drug, penicillin-derived amoxicillin, is also used to treat anthrax. Although this antibiotic can effectively treat anthrax, the bacteria sometimes produce a compound at the onset of disease that renders penicillin useless. Still, Nahata says, physicians have much more experience with amoxicillin than they do with either cipro or doxycycline.
A physician should first decide what form of anthrax a patient has contracted, and get it under control with either cipro or doxycycline. "It makes sense to use either drug at the onset of the disease," Nahata said. "Once the patient has undergone a short treatment regimen - say 14 days or less - it's probably safe to switch him to a drug like amoxicillin.
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