Future of antibiotics worries infectious disease experts

At the Infectious Diseases Society of America meeting last fall, one of the issues that most riled the experts was antibiotics, specifically the lack of them.

Infectious disease experts have many worries. Pandemic viruses, inadequate infection control practices and other problems were discussed at the annual meeting of the Infectious Diseases Society of America (IDSA) in Philadelphia last fall, but one of the issues that most riled the experts was antibiotics, specifically the lack of them.

“We don't have new antibiotics,” warned John G. Bartlett, MACP, a professor at Johns Hopkins University School of Medicine in Baltimore, during a session on hot topics in infectious disease. “It's been spartan since 1970.”

A blend of regulatory and economic factors has kept drug manufacturers from developing antibiotics said Brad Spellberg MD of Harbor-UCLA Medical Center
A blend of regulatory and economic factors has kept drug manufacturers from developing antibiotics, said Brad Spellberg, MD, of Harbor-UCLA Medical Center.

In fact, he reported, a recent European analysis searched the Web for research on new molecular methods to fight gram-negative bacteria, and found absolutely nothing. Given the typical timeline for developing an antibiotic, the absence of drugs in the pipeline means that there won't be any new options for the next eight years, Dr. Bartlett said.

“Antibiotic development is dying,” agreed Brad Spellberg, MD, a member of IDSA's antimicrobial availability task force, at a press conference. A combination of economic and regulatory factors has pushed manufacturers to steer their research budgets away from antibiotic development, he said.

“Am I going to spend that money to develop the next drug that people take for seven days and then they're cured and stop? Or am I going to develop a drug that somebody's going to take every day for the rest of their life?” asked Dr. Spellberg, an assistant professor of medicine at Harbor-UCLA Medical Center in Torrance, Calif.

In addition, the regulatory process has gotten more difficult and complicated. “Congressional pressure in the aftermath of things like Vioxx has led to a morass at the regulatory level. Statisticians are dominating the conversation about what drug should be approved and clinicians have lost their voice,” Dr. Spellberg said.

To fix the problem, the IDSA is advocating for economic incentives to stimulate antibiotic development. Their efforts may have gotten a boost from a recent agreement signed in early November by President Obama and European leaders to form an international task force on antimicrobial resistance, the experts said.

Best use of available drugs

In the meantime, researchers are working to determine which current antibiotics work best to treat drug-resistant pathogens.

Karen R. Jacobson, MD, of Massachusetts General Hospital in Boston, presented a meta-analysis of treatments for extensively drug-resistant tuberculosis. “Worldwide, these strains are increasingly being seen and have significant death rates, especially among patients who are co-infected with HIV,” she said.

Among the 13 analyzed observational studies, in which 20% of patients died, treatment with late-generation fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin) was the one intervention that led to improved outcomes. There was a 4% increase in favorable outcomes for every additional 10% of patients who received the newer drugs. “It's an interesting signal that we're seeing and a potential intervention for a very deadly disease,” said Dr. Jacobson.

Researchers found a more problematic trend in the effectiveness of polymyxin to treat infections in the intensive care unit. Jason Kessler, MD, presented a study assessing the drug susceptibility of more than 3,000 specimens (of bacteria such as Klebsiella pneumoniae and Pseudomonas aeruginosa) collected at one hospital over two years.

“Although the prevalence of resistance to polymyxin in these bacteria species is currently at a relatively low level—around 6%—we noted over a two-year time frame that resistance to that agent increased by 50%. In addition, of all the isolates that we evaluated, more than 30% demonstrated resistance to at least five classes of antibiotics, meaning that most of those bacteria probably could only be treated with polymyxin,” said Dr. Kessler, a clinical fellow in the division of infectious diseases at Columbia University in New York, N.Y.

Experts at the IDSA meeting also presented data on another front in the war against drug resistance: reductions in antibiotic use. Dr. Bartlett discussed a French effort to decrease antibiotic prescriptions. The public information campaign (“Les antibiotiques c’est pas automatique”) reduced scripts by 26%, mostly in pediatric patients but across ages and geographic areas.

The cost-effectiveness of the 500-million-Euro effort is uncertain, but there are lessons for the U.S., Dr. Bartlett said. “It was doctors talking to doctors. This is something that we need to do.”

The use of electronic medical records, including computerized physician order entry, can also reduce antibiotic use, according to an abstract presented at the meeting. Researchers at Pitt County Memorial Hospital in Greenville, N.C., found that antimicrobial use declined 18% after their EMR was implemented. The hospital also had a 26% decrease in Clostridium difficile infections associated with the change.

Containing C. difficile

As one of the most problematic consequences of antibiotic use, C. difficile, and methods to stop its spread, were a hot topic at the meeting. One IDSA abstract found that small hospitals had higher rates of C. difficile while another study assessed rates of community-acquired infection, finding that patients who developed the disease in the community instead of the hospital were younger, healthier and mostly recent users of antibiotics.

“The majority impact of the disease remains in the hospital and long-term care, but it is an important disease in the community,” said study author Ghinwa Dumyati, MD, associate professor at the University of Rochester School of Medicine and Dentistry in Rochester, N.Y.

Meeting attendees collected some tips on stopping the spread of C. difficile in hospitals from William Rutala, PhD, a professor at the University of North Carolina School of Medicine in Chapel Hill, N.C. “The way patients acquire C. difficile is via contaminated environmental surfaces as well as shared instrumentation, hospital personnel's hands and infected roommates,” he said.

Removal of C. difficile spores from surfaces requires something more powerful than the usual low-level disinfectant, Dr. Rutala noted. Unlike viruses and bacteria, spores can survive on surfaces for up to five months, and bleach is the only really effective cleaner. “If you're in a unit with high endemic C. difficile infection rates, or an epidemic or outbreak setting, you may want to use a solution of sodium hydrochloride, such as a 1:10 solution,” Dr. Rutala said.

In addition to using the right product, a thorough cleaning job is important. “There are a number of papers in the literature now which suggest that there is a risk of acquiring pathogens…such as MRSA, VRE and C. difficile from prior room occupants,” Dr. Rutala said.

The results are not surprising given that other studies have found that only about half of the objects that are likely to spread disease get cleaned in an average discharge cleaning. “We validated this at UNC Health Care and I think probably every hospital in the country has similar data,” Dr. Rutala said.

Other methods of decontamination pose a possible solution to this problem. Ultraviolet light and hydrogen peroxide vapor have shown effectiveness comparable to chlorine at killing C. difficile. The vapor process does take a little longer to clean a room—one study found an average of 270 minutes to ready a room for a new patient versus 67 minutes with bleach.

Time may also pose an issue in the removal of C. difficile from health care workers' hands. Although many speakers at the IDSA lauded alcohol gels for the improvements they've caused in hand hygiene compliance, Dr. Rutala pointed out a limitation. “Soap and water remove C. difficile spores, but there's no antiseptic that can inactivate C. difficile spores at the concentrations that are usually employed.”

He recommended washing hands after contact with C. difficile patients, and posting a sticker on hand hygiene signs to remind clinicians that alcohol-based products are ineffective for this purpose.

That suggestion raised some debate among meeting attendees, with other experts noting that no evidence has shown an increase in C. difficile linked to the switch from soap and water to alcohol gels. Further research on the topic will likely be forthcoming, perhaps at a future IDSA meeting.