Combination Dangers

Every week U.S. physicians are being bombarded with samples and ads of prefabricated antibiotic combinations--penicillin with novobiocin, neomycin with bacitracin, oleandomycin with tetracycline, and dozens more. In addition, antibiotics are offered in combination with the sulfas or with unrelated items--anti-histamines, hormones, vitamins. Just how good are these package drugs?

Very good indeed, holds one school, led by Henry Welch, a microbiologist with the Food and Drug Administration. Dr. Welch and some physicians insist that treatment with combinations is no "oldfashioned 'shotgun' approach, but a calculated, rational method of attacking the problem of resistant organisms."

Research physicians, by and large, take the opposite view. In a series of scathing editorials in recent medical journals, several groups have attacked the combination drugs. In the A.M.A.'s Archives of Internal Medicine, nine doctors list and refute the claims made for the combinations. With the most widely agreed answers, these are:

CLAIM: mixed infections caused by two kinds of bacteria may need mixed antibiotics. ANSWER: such infections are rare, except in wounds, and can best be treated then by proper choice of drugs in the right amounts--not by trusting to luck that a manufacturer's choice of items and dosage will turn out to be right.

CLAIM: when a patient's life is in danger, and there has not been time to identify the disease-causing bacteria, two or more drugs provide insurance. ANSWER: this is true only if both are used in full doses--the danger is that in a fulminating infection a patient will get a packaged combination containing only half doses of each antibiotic.

CLAIM: two antibiotics may be synergistic; i.e., have a combined effect greater than the sum of their separate effects. ANSWER: no proof of this in patients (except those with heart inflammation caused by the enterococcus and a few other microbes).

CLAIM: a second antibiotic may delay the emergence of bacteria which are resistant to the first antibiotic. ANSWER: this may be true in-test tubes, but generally there is no proof that it works in human patients.

Experts agree that three combinations are justified: 1) streptomycin with other drugs (such as isoniazid) to discourage the appearance of resistant tubercle bacilli; 2) penicillin with streptomycin for inflammation of the heart lining (endocarditis); 3) tetracycline (or related antibiotics) with nystatin, not routinely but in some cases, to guard against secondary infection with the fungus monilia. Granting exceptions such as these, the Archives' editorialists conclude: "It is our firm conviction that the promotion and sale of such combinations should be discouraged."

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