What's worse than getting exposed to a kind of bacteria that modern antibiotics can't kill? Getting exposed to more than one - because they may work together to cause an infection, new research suggests.

And trying different antibiotics to control one such "superbug" may only encourage others lurking nearby, according to new findings made in hundreds of nursing home patients by a team from the University of Michigan.

In fact, the researchers say it's time to think about such bacteria as members of an antibiotic-resistant ecosystem in health care environments - not as single species that act and respond alone.

Forty percent of the 234 frail elderly patients in their study had more than one multidrug-resistant organism, or MDRO, living on their bodies. Patients who had specific pairs of MDROs were more likely to develop a urinary tract infection involving an MDRO.

The researchers created a map of interactions among bacteria and classes of antibiotics, which they've published with their findings in the Proceedings of the National Academy of Sciences journal.

Eventually, that kind of mapping could help health care providers. For instance, they could choose to treat a patient with a specific antibiotic not just because of its ability to kill one MDRO, but also for its potential downstream impact on other MDROs that may be lurking on the patient, or nearby.

But that will take time, and more research in the laboratory and in health care facilities, say the researchers, led by systems biologist Evan Snitkin of the U-M Medical School Department of Microbiology and Immunology.

So in the meantime, they hope their new findings will give healthcare providers and patients even more reason to avoid using antibiotics in the first place unless they're truly necessary - because "superbugs" evolve in response to them.

The researchers used detailed data from a long-term study of nursing home patients led by U-M geriatrician Lona Mody, the Amanda Sanford Hickey Collegiate Professor of Internal Medicine, who studies infection transmission and prevention in nursing homes. The team also included Betsy Foxman of the U-M School of Public Health, a longtime researcher in the epidemiology of antibiotic resistance and urinary tract infections.

Nearly two-thirds of the patients studied were treated with one or more of 50 different antibiotics during the study period. All the patients in the study used a urinary catheter to empty their bladders for at least three days during the study period. This allowed the researchers to look at patterns of urinary tract infections, which in nursing home and hospital patients often arise from bacteria entering the bladder along a catheter.

The findings showed that colonization of such patients' skin, noses and throats with common MDROs was not random.

"We observed a complex network of interactions, with acquisition of each of six different MDRO species being influenced by different sets of antibiotics, and primary MDRO colonization in turn increasing the risk of acquisition and infection by other MDROs," said lead author Joyce Wang, a postdoctoral fellow in Snitkin's lab who led the analysis.

Colonization with one MDRO increased the risk of acquiring other MDROs - but not all others. It was as if they were interacting very specifically with other species. And treatment of a patient with any given antibiotic increased their chances of being colonized with an MDRO - which in turn altered their risk of becoming colonized with another MDRO later.

The researchers focused on two of the most dangerous MDROs - vancomycin resistant Enterococcus (VRE), and methicillin-resistant Staphylococcus aureus (MRSA) - as well as four Gram-negative bacteria that have evolved resistance to two powerful antibiotics.

One of the four, Proteus mirabilis, causes many catheter-associated UTIs and can form biofilms that invol