Infectivology Xagena

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Antibiotics: changes in the composition of the beneficial microbial species of the gut caused by repeated Ciprofloxacin use


A study, published in the Proceedings of the National Academy of Sciences ( PNAS ), has examined the effects of Ciprofloxacin ( Cipro ), an antibiotic that is widely prescribed for intestinal, urinary and a variety of systemic infections.

An earlier, short-term study, had concluded that people's intestinal microbial communities seem to bounce back reasonably well within weeks after a five-day regimen of Ciprofloxacin. This new study involved two courses of antibiotic administration, six months apart, and it revealed more-subtle, long-term effects of Ciprofloxacin use, such as the replacement of multiple resident bacterial species by other, closely related varieties and the occasional complete eradication of a species.

The infrequent occurrence of easily visible side effects such as bloating and diarrhea from Ciprofloxacin use has given rise to an assumption that the drug spares most beneficial gut-dwelling bacteria. Overall similarities between pre-regimen gut bacterial strains and their post-regimen replacements explain why such side effects aren't typically seen after Ciprofloxacin use.

Still, the more nuanced differences between the pre-existing communities and those that appear in the wake of this repeated disturbance present a new set of problems. A bacterial species whose presence was lost or diminished may have been performing a valuable job, for example, secreting a protein that's toxic to a particular pathogen, that is shirked by its replacement. The abandoned function might not be noticed until, perhaps, years later when the pathogen in question invaded the person's gut.

While the study's findings shouldn't be interpreted to mean that Ciprofloxacin is dangerous and should be avoided, they do raise questions about possible long-term effects of antibiotic administration, in addition to concerns about spurring the evolution of drug-resistant organisms.



Twice during this 10-month period, the researchers perturbed their subjects' gut ecosystems by giving them five-day courses of Ciprofloxacin at a standard dose. During the first course, overall bacterial populations in each subject, which had previously waxed and waned but, on the whole, been quite stable, plummeted and remained depressed for about a week. Roughly one-third to one-half of the resident species' populations declined, with some disappearing entirely. A few originally less-abundant species grew in number, as they filled in the ecological niche abandoned by bugs adversely affected by the drug.


The second course of antibiotic administration produced a stronger effect. Even the one subject whose gut bacterial community fully recovered after the first Ciprofloxacin course experienced an incomplete recovery after the second one. The communities in the other two subjects partially recovered from the second course, but never returned to their original state. In essence, each subject's community of gut-dwelling microbes shifted to a new, alternative state and remained in that state for at least two months after the second antibiotic course had been completed.

Ecologists have found that an ecosystem, such as a wildlife refuge, that is quite capable of rebounding from even huge occasional perturbations may yet be undone by too rapid a series of such perturbations; in the same way, recurring antibiotic use may produce a cumulative effect on our internal microbial ecosystems with potentially debilitating, if as yet unpredictable, consequences.

The precise counts of gut-dwelling microbes in this study were made possible by a new technique, pioneered in recent years. The older method, growing the microbes in culture, simply doesn't work for many species and, even when it does, rare species are often swamped by more common ones and don't get counted. The new technique reads short, telltale DNA snippets that distinguish microbes both from human cells and one from another. This allowed the researchers to assess both the total number of different microbial varieties and the relative size of each variety's population.


Source: Stanford University Medical Center 2010