Antibiotics can lead to bacterial drug resistance in a patient up to a year after treatment, according to a study published in the British Medical Journal Wednesday.

The literature review of 24 earlier studies found bacteria's resistance to antibiotics was strongest in the month following treatment, but could last up to 12 months afterward.

"This goes on for quite a lot longer than we had thought," Dr. Alastair Hay, lead author of the study and a physician and lecturer in health care at the NIHR National School for Primary Care Research in Bristol, UK, told DOTmed News.

The study was the first major review of the literature known to the researchers to check how long after therapy drug resistance in patients lasts, Hay said.

The review looked over earlier studies to find the effects on an individual's bacterial drug resistance after treatment with several common antibiotics in the respiratory tract, urinary tract; and MRSA infections. It found that the greater number of courses before treatment, the greater the likelihood researchers would extract bacteria in the patients resistant to the antibiotics.

For two of the most commonly prescribed first-line antibiotics, amoxicillin and trimethoprim, the researchers said they found evidence of a dose-response relationship, meaning the greater the dose, the greater the subsequent resistance.

Resistance happens as antibiotic exposure kills off susceptible bacteria, artificially creating a favorable environment for resistant bacteria to flourish, Hay said. But the state isn't stable. In a randomized, controlled study Hay said was among the best-designed of the ones looked at, resistance was highest in the week after treatment but declined over time. The odds ratio for resistance fell from around 12 after the first week, to around 6 at one month, and 2.2 after half a year.

"Being a resistant bacteria is harder work than being a susceptible one," he said. "If there's no other environmental pressure, the bacteria will slowly revert back to being susceptible. It's their most energy-efficient state."

RESISTANCE COSTS

This antibiotic resistance has serious costs. In an editorial accompanying Hay's article, researchers from Duke University in North Carolina and Uppsala University in Sweden point out treating hospital-acquired infections derived from just six bacteria cost the United States around $1.9 billion a year, more than the costs for treating the flu. Costs from the European Union add another nearly $1.9 billion to the global total.

The hit is not just monetary. In an analysis also published in the BMJ, researchers say multi-drug resistant bacteria claim 25,000 lives in the EU every year.

CONVINCING COMPANIES TO FIND NEW DRUGS

In November, the EU and the United States set up a task force to look at the issue of drug-resistant germs, prompting the Infectious Diseases Society of America to call for creating 10 new antibacterial drugs by 2020, according to the BMJ editorial by Anthony D So, Neha Gupta and Otto Cars.

The trouble is convincing companies to undertake the research. A mere 1.6 percent of all drugs in development by the world's 15 largest drug companies in 2004 were antibiotics, Chantal Morel, a research fellow at the London School of Economics and Political Science, wrote in her accompanying analysis.

One reason for the low rate of development is antibiotics are often less profitable for drug companies, Morel said. For one, they cure disease instead of managing symptoms for chronic conditions over a long time, she said. Also, generic antibiotics are used for most infections, with newer ones used infrequently, often saved for tougher cases. Plus, researchers lack reliable point-of-care diagnostic methods and good models for developing antibiotic treatment studies, she said.

In her article, co-written with Elias Mossialos, a professor of health policy at LSE, Morel cites a Current Opinions in Microbiology piece showing the risk-adjusted net value of an antibiotic is only one-third that of a cancer drug, and one-tenth that of a musculoskeletal drug.

To entice companies to develop new antibiotics for drug-resistant pathogens, Morel believes governments can offer grants and tax incentives, and even require researchers working on publicly funded projects to share findings via open-access libraries to make collaborative biomedical work possible. Government groups can even look to orphan drug legislation, which provides various exemptions or incentives to researchers working on treatments for rare diseases, to see if offering limited exclusivity extensions spurs development.

"Pricing and reimbursement levels right now minimally reflect the actual therapeutic benefits or cost savings that antibiotics provide," Morel told DOTmed News by email. "The promise of higher prices goes far in luring developers to antibiotics."

IMPROVING THE CONVERSATION

While drug development would be years away, Hay hopes in the near term his work can help primary care doctors and nurses when they discuss the subject with patients.

"If you talk to people about antibiotic resistance, they think it's somebody else's problem," Hay said.

In general, he and his fellow researchers recommend that if a patient has received one or more courses of antibiotics in the past year, a different antibiotic should be given for certain future infections. And Hay thinks antibiotics often shouldn't be prescribed for many everyday respiratory tract infections, sore throats and even simple chest infections, where evidence suggests they rarely help people feel better or get well faster.

"When [antibiotics] were first developed, they were such miraculous drugs, we still hanker after the good old days," he said. "We've sort of diluted their effectiveness by using them for less and less serious infections."

Hay said he and his colleagues are now conducting a pilot study to see how critical these effects are: if hospital admissions with infections are more likely to be resistant if the patient had a large number of antibiotic courses beforehand from primary care.

"We're looking at not just the minor end of the spectrum of coughs and colds at an ambulatory care center," Hay said, "but rather something that's a little bit more serious for a patient that means they're ill enough to require treatment."