Friday, April 07, 2017

The infection-control industry is cleaning up

 The United States has no reliable means of tracking all superbug infections and deaths. Reuters found that, taken together, more than a dozen superbugs the CDC has labeled grave threats to public health continue to kill tens of thousands of people every year -- in addition to hundreds of thousands of nonfatal infections. Products like chlorhexidine wipes are big business. Global sales of antiseptics and disinfectants were an estimated $5.6 billion in 2015. And the total is projected to grow about 40 percent to $7.9 billion by 2020.

Sage Products has been generous to science, and science has been kind to Sage Products. Researchers published their findings in 2006: Used daily, they said, Sage’s wipes, soaked with a powerful germ-killing chemical called chlorhexidine, were more than twice as effective as sponge baths at preventing the spread of vancomycin-resistant Enterococcus. That’s a group of drug-resistant bacteria that infect thousands of hospital patients every year, killing hundreds. Shortly after, Rush received a $1 million donation from the family foundation of Sage’s founder, Vincent W. Foglia. The money was earmarked for research by the senior scientist on the study, Dr Robert A. Weinstein, an infectious-disease specialist at Rush. Since then, Sage has provided funding and millions of dollars in wipes for studies by Weinstein and his colleagues. And in that time, Weinstein and his colleagues have published 11 articles on six trials that endorse daily washing of patients with Sage’s patented wipes. Relationships like the one between Sage and researchers are common in the infection-control business. Such ties have helped propel the popularity of chlorhexidine products in hospitals and other healthcare settings where drug-resistant “superbugs” are a chronic problem. In 2014, sixty-three percent of hospitals surveyed by the federal Centers for Disease Control and Prevention (CDC) said they routinely bathed patients with chlorhexidine.

But as use of chlorhexidine products has grown, so have concerns about their effectiveness and safety — and about the role of industry-backed research in promoting them. The industry money funding chlorhexidine research muddies the message of the results, in the view of many health experts.

Dr Martin Blaser, a professor in New York University’s Department of Microbiology and chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, said it’s still impossible to tell whether washing patients daily with such a potent biocide is wise or effective. Indiscriminate use could trigger resistance in harmful bugs or kill off beneficial bacteria, with dangerous consequences, he said.We know antibiotic-resistant infections are out of control. We need something that works,” Blaser said. “But we want to know it works.” Weinstein sits on the same presidential advisory council that Blaser chairs.

 Washing of patients with Sage’s patented wipes is an “off-label” use, as the U.S. Food and Drug Administration (FDA) has approved the wipes only for cleaning patients before surgery. Chlorhexidine’s potential risks came to the fore in February, when the FDA issued a warning after registering a jump in reports of allergic reactions, including a couple of deaths, and other adverse events linked to the chemical.  And even chlorhexidine isn’t contamination-proof. In 2008 and again last year, Sage issued massive recalls of its chlorhexidine cloths that were tied, ironically, to dozens of infections by Burkholderia cepacia, a pathogen that wreaks havoc on hospital patients. The 2008 recall forced a temporary shutdown of a Sage-funded study, but not before six patients participating in the trial contracted the infection as a result of the contamination.

A 2013 article on that study, co-written by Weinstein and published in the New England Journal of Medicine, referred to the recall as a “treatment interruption” and concluded that the cloths were safe and effective without mentioning the six B. cepacia infections. References to the infections were removed from the original manuscript “for brevity” and because they didn’t directly relate to the wipes’ effectiveness in reducing drug-resistant infections, said Dr Michael W. Climo, lead author of the study.
Europe has been faster to recognize chlorhexidine’s potential risks. Studies from the region single out potentially fatal allergic reactions to the chemical as a serious, under-reported threat. Britain’s Medicines & Healthcare Products Regulatory Agency issued a warning about the dangerous reactions, called anaphylaxis, in 2012. The number of adverse events related to chlorhexidine reported to the agency increased from 14 in 2007 to 117 in 2016. In Europe, healthcare providers place greater emphasis on basic infection-control measures like consistent hand-washing and stringent housekeeping. 

Despite all the promising study results, the number of hospital-acquired drug-resistant infections has remained stubbornly high. In 2009, the federal government launched a campaign to reduce bloodstream infections by the notorious superbug methicillin-resistant Staphylococcus aureus (MRSA) in hospital patients 25 percent by 2013. That failed. The new goal: Halve infection rates by 2020. A Reuters analysis of federal data found that after a small decline in the rate of MRSA infections in hospital patients from 2013 to 2014, the rate increased slightly the following year. The CDC confirmed the increase and said it “is being followed closely” as new data become available. 

Hospitals are understandably eager to find ways to beat back the infections, which waste time, money — and lives. But hospitals tend to “like these mass-produced, one-size-fits-all solutions,” said Blaser.
Dr Didier Pittet, director of the World Health Organization’s Collaborating Centre on Patient Safety, said that in the United States, “the marketing behind the use of chlorhexidine is huge.”

Weinstein said Sage’s support hasn’t deterred him from publishing negative results about its products. He has produced one such critique, he said. It involved a small trial at Rush in 2006, which appeared as a brief report in a European journal in 2010. The report said daily bathing with the wipes was no better than soap and water at reducing infections from central-line catheters in a surgical intensive care unit.
Cindy V. Salgado claimed Sage fired her from her job as a medical liaison in 2014 after she objected to the company’s tactics to market its chlorhexidine wipes. The federal lawsuit, filed in the Southern District of California, accused Sage of spending “a considerable amount of resources” to influence speakers and researchers to promote universal daily bathing of patients.  In exchange for free Sage products for two large studies, Dr Susan S. Huang of the University of California Irvine agreed to arrange for instructions on daily chlorhexidine bathing to be posted on the website of the federal Agency for Healthcare Research and Quality (AHRQ) after publication. A Sage manager then told sales staff to direct customers to the AHRQ website

Corporate ties to infection-control research extends beyond chlorhexidine. Manufacturers of diagnostic tests have financially supported scientists whose studies found that testing and treating patients upon hospital admission significantly reduced MRSA infections. Hospital garment makers have helped to fund scientists who found gowns and gloves highly effective in combating MRSA. Researchers involved in those studies have said that the companies were not involved in the trials and that their support did not influence the results.

 ChloraPrep is a pre-surgical chlorhexidine applicator previously marketed by CareFusion and now by Becton, Dickinson & Co (BD). In 2014, the U.S. Justice Department announced that CareFusion had paid $40.1 million to settle allegations that it gave $11 million in kickbacks to Dr Charles Denham to promote its ChloraPrep applicator. The company admitted no liability. Denham was co-chair of the safe practices committee of the National Quality Forum, a nonprofit healthcare industry group that endorses standards of care. CareFusion allegedly paid him to influence the organization’s 2010 endorsement of an antiseptic formulation for surgical sites that described ChloraPrep’s patented mix, according to federal records. After a competitor complained, the National Quality Forum conducted a review and removed the reference to a specific preparation. Denham in 2015 agreed to pay a $1 million settlement, without admitting liability, according to federal records. The investigation of CareFusion included allegations that the company generated “enormous growth” in sales by illegally marketing ChloraPrep as a product that could prevent infections, federal records say.  The FDA-approved label says only that ChloraPrep reduces the number of bacteria present, not the number of infections.

Since 2007, the U.S. Veterans Administration has combined active surveillance of patients for MRSA and strict staff adherence to basic infection-control protocols throughout the VA healthcare system. In January, the agency published a study showing an 80 percent drop in MRSA infections system wide since the program began. “The reason we’ve had the success we’ve had is because everybody’s engaged,” said Dr Martin E. Evans, lead author of the study. “Even though it’s more work and more expense, it’s a benefit to the patients.”

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