February 1997
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Serial MRIs of the left knee of a 9-year-old boy with CF
before and after a three-month course of ciprofloxacin and at follow-up five and
15 months later. No pathologic findings were seen.
ACAPULCO, Mexico — Currently, fluoroquinolones are not indicated for pediatric use because of concerns of musculoskeletal toxicity, which have occurred in juvenile animal models. Data presented here, however, indicated that the effects seen in animals may not necessarily be seen in humans.
At the First World Congress of Pediatric Infectious Diseases here, Urs B. Schaad, MD, presented long-term data of quinolone use in children. "It is important to realize that all quinolones induce cartilage toxicity in experimental investigations in juvenile animals," said Schaad, professor and chairman of pediatrics at the University of Basel.
"It is not just one toxic effect of one component among the class of quinolones. All the agents, all the older and newer quinolones show this effect in the animal experiments," he said. However, those effects have not been seen in children.
The typical pathology observed in animals includes limb and joint swelling, and formation of blisters, fissures and erosions. These effects were seen primarily in dog pups and rabbit kits. "The clinical correlate is swelling," he explained. "There is effusion in the joint, and they develop a limp, which means the animal is experiencing pain when walking."
Magnesium deficiency produces the same pathological picture as quinolone use in juvenile animals.
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With these concerns, why even consider quinolone use in children? Schaad said the agents offer many benefits, and for some children, especially those with cystic fibrosis, they are reasonable medications to consider. Quinolones have activity against a broad spectrum of gram-positive and gram-negative aerobic and anaerobic bacteria, favorable pharmacodynamics, good clinical experience and can be prescribed as sequential intravenous and oral therapy. (Two quinolones, ciprofloxacin [Cipro, Bayer] and ofloxacin [Floxin, McNeil], are available in the United States in both IV and oral formulations.)
"For us clinicians, what is the message for all of this? We have to be careful. We should be aware that this toxicity observed in animals could also happen in the setting in the use of children," he said.
Experience so far with the quinolones, especially ciprofloxacin, which has been on the market for a considerable time, does not support this concern. Schaad said there is good documentation of use in more than 3,000 pediatric cases and more than 300 pregnant women. "In all of these cases, there has not been a proven case of cartilage toxicity produced so far in humans," he said.
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Light microscopic picture of normal articular cartilage of beagle
pup.
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Light microscopic picture of articular cartilage of beagle pup
after two-week quinolone administration: formation of blister containing
necrotic cartilage.
Schaad took a look at specific data on file about ciprofloxacin. The data reports on more than 2,000 courses of medication. Although most of the cases were children between 13 and 17 years old, younger children were also given the medication. Most of the children suffered from respiratory infections, and many had cystic fibrosis (CF). Although most of the children took the oral formulation, some used the IV or a combination of the two. Most of the patients received daily dosages of between 20 mg/kg and 40 mg/kg body weight for one to three weeks. Some children, however, received medication for much longer, and most of the IV courses tended to be between one and two weeks, he said.
Monitoring was done with his topathology, MRI, sonography and/or clinical experience. The most common adverse effects were gastrointestinal tract effects. Some mild skin reactions were also seen. Musculoskeletal complaints were low, only 1.7%, and most of these were arthralgic symptoms in children with CF.
"With the exception of arthropathy, these adverse events in children were the same as seen in adults," Schaad said. "I think it is important to stress that the majority of these cases of arthralgia occurred in adolescent patients with cystic fibrosis where the problem of arthritis, as those of you who take care of such patients know, this problem is quite common with these patients and probably has nothing to do with any toxicities of the medication.
"Based on the data, I think there are clinical uses for quinolones in pediatrics," he added.
For more information:
- Schaad UB. Use of quinolones in pediatrics: indications and restrictions in pediatric patients. Presented at the First World Congress of Pediatric Infectious Diseases. Dec. 6, 1996. Acapulco, Mexico.
Editor's Note: Physician safety is as much a of a problem as patient safety. Using this drug which has been associated with a common symptom — joint complaints — appears to be foolhardy when the package insert says it should not be used in those under 18 years of age. This is not to say there are situations in which you may be forced to use it as there is no alternative. In these situations, it should be discussed with the parents, the patient, where appropriate, and a note of the conversations should be made in the patient's chart. — P. Brunell
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