Caution still surrounds fluoroquinolone use in pediatrics

December 2006

In September, the American Academy of Pediatrics’ Red Book committee released updated recommendations on the use of fluoroquinolones in pediatric patients and asked that pediatricians be aware of fluoroquinolone-associated safety issues.

Fluoroquinolones are not recommended for patients younger than 18 years, with a few exceptions, but they continue to be used in the pediatric population, regardless. In fact, pediatricians wrote more than a half-million prescriptions for fluoroquinolones in 2002: 13,800 for children aged from 2 to 6 years and 2,750 for children younger than 2.

The recommendations are based on concerns about the risk of skeletal injury and toxicity to weight-bearing joints in children, which have been demonstrated in animal studies.

“The preponderance of the evidence has caused us to be reassured by the safety, but we are still not completely comfortable with it,” John Bradley, MD, director of infectious disease at Children’s Hospital and Health Center in San Diego, said in a previous interview.

“I would caution pediatricians to prescribe systemic fluoroquinolones only for children who really need them, in situations where there is no other alternative,” he said at the annual AAP conference.

The only currently FDA-licensed fluoroquinolone in the United States is ciprofloxacin (Cipro, Bayer). It is approved only for use in treating complicated urinary tract infections.

Fluoroquinolone-associated risks

Significant damage to joint cartilage has been shown in animal studies, but no study has yet determined a similar link in children.

The AAP committee wrote in the statement, “To date, most reported musculoskeletal adverse events associated with fluoroquinolones were of moderate intensity and were transient. Although there is no compelling evidence supporting the occurrence of sustained injury to developing joints in humans by fluoroquinolones, the possibility that it occurs infrequently has not been excluded.”

Additional adverse events may include: neurologic and cardiac conduction disorders, glucose homeostasis, changes in growth plate, blisters on the articular surface and more, which have been reported in animal studies.

“For each child, each infection and each different fluoroquinolone we use, we need to assess the potential risks of tendon and joint disorder with oral therapy vs. the risks of an intravenous or multiple-injection therapy,” Bradley said.

Another potential confounder is emerging resistance.

If fluoroquinolones are used inappropriately, it may lead to increased bacterial resistance to these agents, officials note.

“There is concern that authorizing the use of this class of drugs for respiratory infections and ear infections in children probably would result in a more rapid emergence of resistance,” Philip A. Brunell, MD, chief medical editor of Infectious Diseases in Children, said in a previously published commentary.

Recommendations for use

Pediatricians should report any cases of fluoroquinolone-associated toxicity, according to the AAP.

Bradley said there is also a need for further data on safety information for use in children, including more prospective, double-blind studies on adverse events.

“Physicians need to use fluoroquinolones intelligently, but [this risk] is not statistically significant. I have no statistical reason to tell you not to use fluoroquinolones,” Bradley said.

This year’s AAP recommendations were based on the FDA approval of ciprofloxacin for certain infections. The committee said they may be useful in treating infections caused by multidrug-resistant pathogens for which there is no alternative or parenteral therapy and no other safe, effective oral agent.

Appropriate uses include:

• Exposure to aerosolized Bacillus anthracis to decrease the incidence or progression of disease. The FDA has licensed this recommendation.
• Urinary tract infections caused by Pseudomonas aeruginosa or other multidrug-resistant, Gram-negative bacteria. The FDA has licensed fluoroquinolones for complicated E. coli UTIs and pyelonephritis attributed to E. coli in patients aged 1 to 17 years.
• Chronic suppurative otitis media or malignant otitis externa caused by P. aeruginosa.
• Chronic or acute osteomyelitis or osteochondritis caused by P. aeruginosa, but not for prophylaxis of nail puncture wounds to the foot.
• Exacerbation of pulmonary disease in patients with cystic fibrosis who have colonization with P. aeruginosa and can be treated in an ambulatory setting.
• Mycobacterial infections caused by isolates known to be susceptible to fluoroquinolones.
• Gram-negative bacterial infections in immunocompromised hosts in which oral therapy is desired or resistance to alternative agents is present.
• Gastrointestinal tract infection caused by multidrug-resistant Shigella species, Salmonella species, Vibrio cholerae or Campylobacter jejuni.
• Documented bacterial septicemia or meningitis attributable to organisms with in vitro resistance to approved agents or in immunocompromised infants and children in whom parenteral therapy with other appropriate antimicrobial agents has failed.
• Serious infections attributable to fluoroquinolone-susceptible pathogens in children with life-threatening allergy to alternative agents.