THURSDAY, Feb. 8 (HealthDay News) -- While scientists have believed for years that excessive antibiotic use leads to microbes gaining resistance to those drugs, a new study offers up much-needed proof.

"A lot of studies have shown an association between antibiotic use and resistance," said Dr. Herman Goossens, lead author of the report in the Feb. 10 issue of The Lancet. "But all those studies are based on indirect evidence. There have been no randomized, placebo-controlled, double-blind studies. Ours is the first study to show directly that antibiotic use leads to resistance," he said.

The study was performed at University Hospital Antwerp in Belgium, where Goossens is professor of medical microbiology.

The study showed that "antibiotics will have a tremendous effect on normal flora [microbes] which will exist for at least six months," Goossens said. It also showed that different antibiotics in the same famil y can have strikingly different effects on these bugs.

In the study, healthy volunteers were given either azithromycin or clarithromycin, members of the macrolide family of antibiotics, while a third group received a placebo.

The researchers periodically tested samples of the Streptococcus family of bacteria, obtained from individuals in each group, to see if they had developed any resistance to the macrolide drugs.

As expected, resistance levels rose in the two groups given the antibiotics -- by 50 percent after eight days in the clarithromycin group, and by more than 53 percent after four days in the azithromycin group. There was no increase in antibiotic resistance among people who took the placebo.

And while azithromycin caused a slightly greater increase in bacterial resistance over the short term, clarithromycin seemed to favor the survival of bacteria carrying a gene called erm(B), which appears to confer high-level resistance to macrolide antibiotics.

Both drugs also affected the levels of naturally occurring, harmless bacteria in the mouth, an effect that was still evident after 180 days.

"Other studies have shown that resistance genes can spread among bacteria," Goossens noted. "They can spread to pathogens causing such problems as ear infections and sore throats. Then these become very difficult to treat."

According to the researchers, the study's take-home message is one experts have preached for years: "Physicians should take into account the striking ecological effects of antibiotics when prescribing such drugs to their patients."

However, differences in resistance patterns between the two closely related antibiotics also invites further study, they added.

The report fills in an important gap in knowledge, said Dr. Stephanie Dancer, a consultant microbiologist at Southern General Hospital in Glasgow, Scotland. She wrote an accompanying editorial in the journal.

"Microbiologists knew this anyway, but it's so nice to see direct evidence," Dancer said. "It's what we have needed."

"I do feel very, very strongly, as my colleagues do, that we are running out of [effective] antibiotics," Dancer said. "This study is so nice, because it gives concrete evidence underpinning everything we have suspected."

More information

There's more on the threat of antibiotic resistance at the Alliance for the Prudent Use of Antibiotics .