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SAN FRANCISCO — So many children with group A [beta]-hemolytic streptococcal tonsillopharyngitis failed treatment with amoxicillin or penicillin that neither drug should be used for this indication alone, investigators reported at two separate poster presentations at the annum Interscience Conference on Antimicrobial Agents and Chemotherapy.
Among 1,080 children aged 2-18 years who were treated for confirmed strep throat, 25% of 591 children treated with amoxicillin and 36% of 28 patients treated with penicillin returned to a doctor’s office with recurrent symptoms and bacteriologic failure within a month of diagnosis, failure rates that were significantly higher than those seen in patients treated with one of seven other antibiotics, reported Dr. Janet R. Casey and Dr. Michael E. Pichichero of the University of Rochester (N.Y.). Half of patients treated with either of these drugs for recurrent symptoms failed therapy, Dr. Casey added.

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In comparison, among 420 children treated with cephalexin or cefadroxil, 18% failed clinically and bacteriologically within a month, according to the findings of the retrospective study. The most effective treatments were [beta]-lactamase-stable antibiotics, including amoxicillin-clavulanate, cefprozil, cefuroxime, cefdinir, or cefpodoxime, which resulted in clinical failure in 5% of 41 children.
Dr. Casey is an adviser to Abbott Laboratories, which makes cefdinir. Dr. Pichichero has received honoraria and other funding from Abbott Laboratories and is a consultant to many companies that make antibiotics.
Numerous previous studies of strep throat have reported increasing failure rates with amoxicillin and penicillin since the 1980s, but other pediatricians commonly told Dr. Casey that they weren’t seeing this trend in their practices, which prompted the study.
More than a fourth of children who relapsed in the current study were back in clinicians’ offices within 5 days of completing therapy, but recurrent symptoms were milder and less numerous, Dr. Casey explained. “When they do recur, sometimes they fly under the radar screen, and they’re back at school infecting all of their buddies,” she said.
She has changed her pediatric practice to make her first-line treatment for strep throat cephalexin, a generic first-generation cephalosporin with a relatively narrow spectrum that is palatable and can be given twice a day.
She still uses amoxicillin or penicillin in some patients with strep throat, such as a child with concomitant ear infection, because cephalexin doesn’t penetrate into the middle ear space. “Those patients need to come back for a checkup to make certain that they have cleared the organism and to make sure that they are not having mild symptoms,” she said.
Clinical guidelines list amoxicillin as a first-line treatment for pediatric strep throat, and those guidelines need to change, said Dr. Pichichero, professor of microbiology and immunology, pediatrics, and medicine at the university.
In a separate poster presentation by Dr. Pichichero and his associates, amoxicillin eradicated Streptococcus pyogenes in only 65% of children and penicillin eradicated the organism in 68% in a randomized, controlled study of 566 patients. Those surprisingly poor efficacy rates fall below the minimum 85% eradication rate called for by the Food and Drug Administration, he noted at the meeting, which was sponsored by the American Society for Microbiology.
“These therapies should be abandoned as treatment for strep throat in children. Abandoned,” Dr. Pichichero said.
His investigator-blinded study randomized 566 children with strep throat to treatment with 7 days of an experimental sprinkle formulation of amoxicillin that’s given once daily or 10 days of four-times-daily oral penicillin VK. Pharmacodynamic analysis of the results showed that increasing the dosage would not improve cure rates because blood levels of the drugs were above the minimum concentration needed to kill the bacteria 60%-70% of the time between doses, well above the standard of 40% of the time, he noted.
Advancis Pharmaceutical Corp., which makes the amoxicillin sprinkle, will not pursue the product for pediatric strep throat but will be applying for approval for use in adults with strep throat based on other studies showing an 85% cure rate, meeting the minimum standard, Dr. Pichichero said.
The difference between children and adults in these cases is that children’s mouths are laden with [beta]-lactamase–producing normal flora that can inactivate amoxicillin or penicillin in the throat, he explained.
Dr. Pichichero also has switched to cephalexin (Keflex) as first-line therapy in children with strep throat. If they don’t improve, he uses the third-generation cephalosporin cefdinir (Omnicef).
BY SHERRY BOSCHERT
San Francisco Bureau
COPYRIGHT 2006 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning