Infection Control: April 2017
The news service Reuters is reporting on relationships between industry and researchers in the infection control space, relating to ties that "have helped propel the popularity of chlorhexidine products in hospitals and other healthcare settings where drug-resistant superbugs are a chronic problem," the article says. The authors of the investigative piece continue, "In 2014, 63 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
Sage Products has been generous to science, and science has been kind to Sage Products.
This happy relationship blossomed more than a decade ago, when Sage funded a study at Rush University Medical Center in Chicago to test the efficacy of the company’s new antibacterial wipes on hospital patients.
Researchers published their findings in 2006: Used daily, they said, Sage’s wipes, soaked with 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 — an “off-label” use, as the U.S. Food and Drug Administration (FDA) has approved the wipes only for cleaning patients before surgery.
Europe has been faster to recognise 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 the United States, the FDA’s chlorhexidine warning in February came after a similar spike in incidents reported to the agency’s Federal Adverse Event Reporting System. Under the system, drug manufacturers are required to report when their products are suspected of causing illness or injury.
A Reuters analysis of FDA data found that chlorhexidine was listed as the primary suspect in an average of 85 adverse events a year reported from 2007 through 2014. Then, in 2015, the number jumped to 183, and then to 226 in 2016. The FDA said that a reported event is not necessarily due to the product, and that the agency does not receive reports for every adverse event that occurs.
Anaphylaxis or shock was cited in the FDA’s adverse event reports 120 times. Skin irritation, rashes and burns were mentioned 325 times. The tally included 48 life-threatening events and seven deaths.
About a third of the serious allergic reactions were attributed to ChloraPrep, a pre-surgical chlorhexidine applicator previously marketed by CareFusion and now by Becton, Dickinson & Co.
A spokesman for BD, which acquired CareFusion for $12.2 billion in 2015, said in an email that adverse events like anaphylaxis are “rare occurrences” compared to the “BILLIONS of uses” of the product since it entered the market in 2000.
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.
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.
The BD spokesman said the company acquired CareFusion in 2015, after the settlements. “CareFusion took great care to address the potential concerns raised in the settlement and this continues at BD,” he said.
In response to the FDA’s new guidance on chlorhexidine, Sage will add an allergy warning to labels on its wipes, according to a spokeswoman for Stryker Corp, which acquired Sage Products last year in a deal valuing the company at $2.78 billion. Stryker does not break out Sage’s sales. It told analysts this year that it expects Sage to continue to show exponential sales growth.
Products like chlorhexidine wipes are big business. Global sales of antiseptics and disinfectants were an estimated $5.6 billion in 2015, according to BCC Research. And the total is projected to grow about 40 percent to $7.9 billion by 2020.
The FDA approved the wipes only for cleansing skin before surgery. Sage is prohibited from marketing them for off-label uses, including universal daily bathing. It’s even required to include a warning on the product label against using the cloths as a “general skin cleanser.”
However, Sage is not prohibited from informing medical professionals of scientific studies that tout the virtues of its wipes for off-label uses, leaving it up to the customer to decide whether or not to use them.
In Europe, healthcare providers place greater emphasis on basic infection-control measures like consistent hand-washing and stringent housekeeping. That behavioural approach recently received dramatic support from a U.S. Veterans Administration initiative paid for with federal funds.
Since 2007, the agency 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 systemwide 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.”
Weinstein, the Rush infectious-disease specialist who received Sage support, dismissed the criticisms of the “REDUCE MRSA” study. Plenty of studies show chlorhexidine works, and millions of people are benefiting from reduced risk of infection, he said.
“As long as people are benefiting…you use it,” Weinstein said. “If resistance emerges, well, maybe there'll be a new product.”