AAP endorses fluoroquinolones, with reservation

October 2006

The recent FDA approval of ciprofloxacin and a growing body of safety evidence has led the AAP to recommend the use of systemic fluoroquinolones for certain infections.

“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 & Health Center in San Diego, said in an interview.

Bradley is a member of the AAP Committee on Infectious Diseases, which issued a recent policy statement on the use of systemic fluoroquinolones that was published in Pediatrics.

“I would caution pediatricians to prescribe systemic fluoroquinolones only for children who really need them, in situations where there is no other alternative,” Bradley said. “We are going to keep looking to see if there’s a safety issue. If pediatricians see a problem, we would ask that they inform the FDA and the Red Book committee.”

Although the approved uses of systemic fluoroquinolones are limited in patients younger than 18 years to complicated urinary tract infections, pyelonephritis and postexposure treatment for inhalation anthrax, approximately 520,000 prescriptions were written in the United States in 2002. Of these, 13,800 were written for children aged 2 to 6 years, and 2,750 were written for children younger than 2 years.

Risks

Fluoroquinolones that are FDA approved for use in the United States have been shown to cause arthrotoxicity in juvenile animals and have been associated with reversible musculoskeletal events in both children and adults.

Other adverse events associated with fluoroquinolones include central nervous system disorders, photosensitivity, disorders of glucose homeostasis, prolongation of QT interval with rare cases of torsade de pointes, hepatic dysfunction and rashes.

Ciprofloxacin (Cipro, Bayer) has been associated with muscoskeletal events in children despite statements to the contrary, according to the policy statement. In one study of ciprofloxacin use in the treatment of Escherichia coli UTIs in patients aged 17 years or younger, musculoskeletal adverse events were reported in 9.3% of treated patients compared with 6% of controls.

“To date, most reported musculoskeletal events associated with fluoroquinolones were of moderate intensity and were transient,” the committee wrote in the statement. “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.”

Recommended uses

The AAP committee also noted that the inappropriate use of fluoroquinolones in children and adults is likely to be associated with increased bacterial resistance to these agents.

Fluoroquinolones inhibit two enzymes that are essential for bacterial DNA replication. “It basically shuts down the DNA synthesis and the bacteria die,” Bradley said. “It can provide an oral alternative to the current IV regimens, but it is not for treating sore throats.”

In light of the evidence, the AAP has made the following recommendations:

Circumstances in which fluoroquinolones may be useful include those in which 1) the infection is caused by multidrug-resistant pathogens for which there are no safe and effective alternatives, and 2) parenteral therapy is not feasible and no other effective oral agent is available.

Appropriate uses should be limited to the following:

• Exposure to aerosolized Bacillus anthracis to decrease the incidence or progression of disease. The FDA has licensed this recommendation (evidence grade III).
• UTIs 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 (evidence grade II-2).
• Chronic suppurative otitis media or malignant otitis externa caused by P. aeruginosa (evidence grade II-3).
• Chronic or acute osteomyelitis or osteochondritis caused by P. aeruginosa, but not for prophylaxis of nail puncture wounds to the foot (evidence grade III).
• Exacerbation of pulmonary disease in patients with cystic fibrosis who have colonization with P. aeruginosa and can be treated in an ambulatory setting (evidence grade II-2).
• Mycobacterial infections caused by isolates known to be susceptible to fluoroquinolones (evidence grade III).
• Gram-negative bacterial infections in immunocompromised hosts in which oral therapy is desired or resistance to alternative agents is present (evidence grade II-1).
• Gastrointestinal tract infection caused by multidrug resistant Shigella species, Salmonella species, Vibrio cholerae, or Campylobacter jejuni (evidence grade II-2).
• 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 (evidence grade III).
• Serious infections attributable to fluoroquinolone-susceptible pathogens in children with life-threatening allergy to alternative agents (evidence grade III).

For more information:

• Powell KR, Baltimore RS, Bernstein H, et al. The use of systemic fluoroquinolones. Pediatrics. 2006;118:1287-1292.