Promising Hospital Anti-infection Strategy Probably Won’t Work

Hospital patients increasingly face tenacious bacterial infections because microbes found in hospitals acquire resistance to commonly prescribed antibiotics. A recent strategy alternating the most commonly used antibiotics has sparked hope of stopping the spread of antibiotic resistance.

But a new model shows that the practice of cycling – alternating between two or more classes of antibiotics as often as every few months – probably will not work. It is an unexpected finding at a time when clinical tests of the practice with real patients are in progress.

“We were really surprised. We expected to find a number of cases where it would work, and it was the exact opposite,” said Carl Bergstrom, a University of Washington assistant professor of biology.

Instead of cycling, Bergstrom said, hospitals could probably help patients more by prescribing a variety of antibiotics, a method known as mixing. That means instead of having a standard, rotating antibiotic that is used routinely within a single unit, such as intensive care, or even throughout the hospital, a more effective strategy would be to have two or more generally prescribed antibiotics being administered randomly. Two people sharing a room could routinely receive different antibiotics.

Bergstrom noted that antibiotic mixing already is relatively common, not as a conscious strategy but rather because individual doctors develop preferences for the types of medications they prescribe. That can instigate the same type of antibiotic variety as mixing would introduce.

The theory behind antibiotic cycling is that, just as a pathogen strain begins to adapt to a particular antibiotic, a new antibiotic is introduced and the pathogen must start from scratch in building resistance. However, the model implies that pathogens actually encounter new antibiotics more frequently when hospitals use antibiotic mixing than when they use cycling, so cycling is unlikely to reduce resistance levels.

“If the cycling trials that are underway don’t work, we’ll know why they don’t,” Bergstrom said. “And if they do work, the people conducting the trials are going to have to do further investigation on why they are working, because the rationale that we’ve been using for cycling doesn’t hold true.”

The study is based on numerical models that examined the mechanics of how microbial infections spread in hospitals and how the microbes build resistance to antibiotics. Bergstrom is the lead author of a paper detailing the work, which is being published in the Proceedings of the National Academy of Sciences and will appear online the week of Aug. 9. Co-authors are Monique Lo and Marc Lipsitch of the Harvard University School of Public Health.

Another implication of the work, Bergstrom said, is that cycling actually could be detrimental to patients, “so the studies need to be very carefully monitored to make sure we are not causing additional harm in the hospital.”

He likened a hospital to a disease-ridden island in the middle of a relatively healthy river. As people get well and leave the island, they can carry with them the antibiotic-resistant organisms developed on the island and the pathogen can spread. That can make things worse when the patients carrying the resistant pathogens return to the hospital-island, as they often do.

“When you release resistant bacteria into the community, I think it’s a lot like polluting an ocean,” Bergstrom said. “At first you don’t notice, but then it starts to creep up on you and you have a real problem. And then it’s hard, maybe even impossible, to go back and fix it.”