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Infectious disease expert addresses controversies. (Mixing Antibiotics with Escherichia Coli).

SAN FRANCISCO -- It's no secret that the field of pediatric infectious diseases is fraught with its share of controversies, Dr. Charles Prober said at a meeting on clinical pediatrics sponsored by the University of California, San Francisco.

Dr. Prober, a member of the American Academy of Pediatrics Red Book Committee, brought his perspective to four arguments in the field that he described as "modestly pessimistic":

1. Antibiotics plus Escherichia coli cause hemolytic uremic syndrome. E. coli 0157:H7 is the undisputed leader in causing hemolytic uremic syndrome. "We used to treat E. coli bloody diarrhea with antibiotics," but people kept asking if it was a good or bad thing to do, said Dr. Prober, also of the department of pediatrics at Stanford (Calif.) University.

A recent study followed 71 children who were infected with E. coli 0157:H7 (N. Engl. J. Med. 342[26]:1930-36, 2000). Nine were treated with antibiotics; the remaining 62 were not. Study participants were between 4 and 5 years of age and 80%-90% of them had bloody stools. Both groups had B. coli-positive stools for about 5 days.

The frequency of hemolytic uremic syndrome was 78% (7 out of 9 patients) in those treated with antibiotics, compared with 11% (7 out of 62 patients) in those who did not receive antibiotics; this was a statistically significant difference.

"These data are tantalizing," Dr. Prober remarked. "They suggest that there may be an association, but I don't think they absolutely prove it because the number of observations is small. So I'm not sure we know for sure that antibiotics are bad when you mix them with E. coli."

2. Ibuprofen is poisonous. There are 7,600 deaths attributable to patients on ibuprofen in the United States each year. "Some of these are related to gastritis with bleeding and perforation of the GI tract," said Dr. Prober, who is also a professor of pediatrics and of microbiology and immunology at Stanford University.

These are mostly adverse events that occur among adult subjects rather than among the pediatric population. Nonetheless, this drug has the potential for causing some substantial downsides.

For example, aseptic meningitis has been described in association with ibuprofen, as have renal toxicity and immune modulation. Ibuprofen downregulates different parts of the immune system, which may result in enhanced susceptibility to infection.

That may be a significant problem, Dr. Prober said. It also may result in altered clinical assessment because you're trying to judge whether the patient has pain and what some of the other symptoms are.

In addition, some clinicians argue that necrotizing fasciitis and varicella are potentiated by the administration of ibuprofen, "although the data are not clear in my mind," he said. "There are enough concerns out there, that at least you should think about whether this would be a good drug or not in a child with chickenpox."

3. Dormitories are hazardous because of meningococcal infections. The rate of meningococcal disease per 100,000 among freshmen in dormitories is 4.6, compared with 1.5 for controls aged 18-23 years. It would cost $1.4-$2.9 million to prevent an estimated 15-30 cases each year, and $7-$20 million to prevent an estimated 1-3 deaths per year from infection.

"It would not be cheap to prevent one death... , but that's an issue for the economy of health care in the [country]," he said.

"Vaccine types C and Y are becoming more important," he said. The current vaccine is a quadrivalent vaccine for types A, C, Y, and W-135. It's 85%-95% effective in preventing meningitis.

4. Vaccines cause all things bad. For years, some have claimed that hepatitis B vaccine causes demyelinating disease and that measles, mumps, and rubella vaccine causes autism.

Results from a recent randomized, controlled study suggest that there was no significant increase in demyelinating disease in infants through 14-year-olds who received the hepatitis B vaccine, compared with those who didn't (N. Engl. J. Med. 344[5]:327-32, 2001).

Dr. Prober challenged the validity of the argument that MMR vaccine causes autism. "Autism is thought to be genetically based," and the claims are based in a small number of observations.

A population-based study from London evaluated all 498 cases of autism diagnosed since 1979. No increase in cases of autism have been reported since MMR was introduced in England in 1988 (Lancet 353[9169]:2026-29, 1999).
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Title Annotation:Charles Prober
Author:Brunk, Doug
Publication:Pediatric News
Geographic Code:1USA
Date:Dec 1, 2001
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