Belgian researchers have dispelled any doubt that antibiotic use causes rapid resistance. Their randomized, controlled trial of two types of macrolides showed the emergence of resistant microorganisms in just a few days. What’s more, the effect persisted for months.

Researchers at University Hospital Antwerp in Belgium gave 224 healthy volunteers either clarithromycin for seven days, faster-acting azithromycin for four days, or a placebo. Pharyngeal swabs were taken before the drugs were started—at the end of each course (day 8 for clarithromycin, day 4 for azithromycin), and after two weeks, four weeks, six weeks, and six months. The proportion of resistant bacteria was measured each time.

Resistant organisms rose significantly with each swab compared with placebo. They peaked on the day after each drug course was completed, with a mean increase of 50% among those taking clarithromycin and an increase of 53% among those taking azithromycin. The resistant strains were still evident after six months (Lancet. 2007;369:482-490).

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The study “provides a robust challenge to ambivalence over the consequences of inappropriate and uncontrolled antibiotic prescribing,” wrote Stephanie J. Dancer, MD, in an introductory commentary. An expert on antibiotic resistance, Dr. Dancer is affiliated with the microbiologydepartment at Southern General Hospital in Glasgow, but she was not involved in the research.

“The basic message is that treating a patient with an antibiotic will cause a dramatic change of his normal [bacterial] flora and select for resistant genes that can spread to a true pathogen,” said lead researcher Herman Goossens, MD, PhD in a Lancet podcast interview.

“We followed the volunteers for six months and realized we’d still not reached a baseline,” said Dr. Goossens. “The changes in flora are dramatic and persist probably for just under a year.”

To avoid treatment failure, the study suggests, clinicians should not prescribe macrolides if the patient has taken them within the previous six months. The researchers also warn that, because of structural genetic similarities, clarithromycin may also cause resistance to lincosamides, streptogramin B, and tetracyclines.