Antibiotic Resistance

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Global survey surfaces new information about overuse, resistance and need for faster diagnostics.

There’s an old adage, “You can take a horse to water but you can’t make it drink.” By recent accounts, it also seems you can take clinicians to a microbiology lab, but you can’t make them order the tests. Underutilization of microbiology labs and microbiologic diagnostics was one of the surprising findings that came out of the recent Global Point Prevalence Survey (GPPS) of more than 330 hospitals and more than 10,000 patients worldwide.

Funded by bioMerieux, the survey was conducted independently by investigators from University of Antwerp, Belgium, and provided a unique overview of antimicrobial consumption and resistance rates around the world. BioMerieux chose to step back while research was being done so as not to affect the intellectual discovery process; however, it did help recruit survey participants or point investigators to key opinion leaders in microbiology, due in part to maintaining hospital clients in more than 100 countries.

GPPS, a survey of patient samples taken at the various hospitals, examined a number of issues-such as how many patients were receiving antibiotics; what kinds of antibiotics were being administered and for how long a period; what kind of laboratory tests had been performed on those patients; what microbiologic tests had been utilized; and more.

Surprising Findings

The findings might be considered thirst-inducing for any clinical “horse” near a microbiology “stream.”

“A big surprise was how often the diagnosis of hospitalized patients involves the underuse of laboratories and how common it is to treat without microbiologic diagnostics or tests of any kind,” said Sam Bozzette, MD, PhD, vice-president, medical affairs-Americas for bioMerieux. It’s a daunting realization, given the rising global antibiotic resistance problem, and healthcare’s demonstrated willingness to supply antibiotics without microbiologically established reasons.

“Depending on the global region, one out of two or three hospitalized patients receive antibiotics-that’s a huge number,” explained Bozzette. “What the survey also confirmed is that overuse of antibiotics-and especially the overuse of secondary antibiotics, those that are usually reserved for serious infections-is very common across the globe. The particular drug varies by region. For example, in the U.S., vancomycin appears to be overused; whereas, in Asia, meropenem and carbapenem are overused. Accordingly, there is a strong association between the type of overuse and the type of resistance we see from region to region.”

“The GPPS found that only one in three cases get proper microbiologic testing to support the selection and appropriate use of antibiotics,” Bozzette said. He further noted that this is a particular problem in much of Asia. In the U.S., and the West in general, doctors very often feel pressured to prescribe antibiotics. In developing countries, access to adequate laboratories is an issue. According to additional information provided by bioMerieux, the longer the wait for a precise diagnosis and complete AST susceptibility profile, the longer it takes to get a patient onto optimal antimicrobial therapy.

“In the meantime, the therapy patients are on is either being misused or over-used, which is a primary driver of the emergence of the increasing number of resistance mechanisms in the microbial world. This is why so many medical organizations are no longer calling for just new antibiotics, but new antibiotics and new and faster diagnostics. The Infectious Disease Society of America, WHO, CDC and the White House have all called for a greater emphasis on the importance of diagnostics in controlling antimicrobial resistance.”

Growing Need for Rx and Dx

It would be difficult to overstate the urgent need for new antibiotics, diagnostics and companion diagnostics given an estimate of the expected toll that growing resistance may soon take on human life.

“According to a 2014 O’Neill report1 from the UK, drug resistant super bugs will cause more deaths than cancer by 2050,” said Bozzette. “The report noted that in Europe and the United States, antimicrobial resistance causes at least 50,000 deaths each year. And left unchecked, deaths would rise more than 10-fold by 2050.”

BioMerieux, one of the diagnostic companies represented at the White House Antibiotic Resistance Forum last year, made the point that optimal infectious disease selection can only happen with rapid diagnostic tools.

“If we only rely on new antibiotics, we will be in deep trouble,” said Bozzette. “These drugs are now used globally so the time it takes for resistance to first emerge and spread is very short. Consider MRSA as the classic example. In the 1950s, Staphylococcus aureus developed resistance to penicillin and spread quickly around the globe. Physicians responded with methicillin, which was immune to the staph enzyme that destroyed penicillin. But this victory was short-lived because we overused methicillin in the same way we did penicillin. By the 1960s, cases of methicillin-resistant MRSA had already emerged. Despite a growing body of literature and many MRSA outbreaks, hospitals dispensed more and more methicillin, making MRSA what it is today-a very serious public health threats.”

Asked why antibiotics are so liberally, and often inappropriately, dispensed, Bozzette paused then answered, “It’s called ‘clinical judgment,’ which can be fallible-and underuse of microbiology labs. But when appropriate tests are done, it makes a difference. In the U.S., clinicians sometimes order broad spectrum antibiotics hoping to hit the organism or they may treat a patient for something that is not a bacterial infection. Some of that is patient driven-demanding an unnecessary antibiotic. This all underscores the need for more rapid tests to detect pathogens and determine what an infection really is.”

Rapid Results Are Key

He added bioMerieux has focused on developing more rapid diagnostic tests for infectious diseases using the mantra, “Minutes, not hours; hours, not days.”

“We are working in this area. We have a biomarker, procalcitonin, that is shown to be elevated in cases of bacterial infection and is approved as a diagnostic aid in sepsis, for example, with results in about 45 minutes. We have mass spectroscopy for very rapid identification of organisms and are working to make antibiotic sensitivity testing faster. We also have a multiplex PCR-based technology called BioFire that determines the presence of 20-some pathogens and a variety of specimens-including blood cultures-also in 45 minutes.”

How can healthcare affect change, given the new information surfaced in GPPS?

“There are two major ways,” said Bozzette. “One is improving practice and the second is to advocate for change across health systems. Both overall and in specific regions, people need to identify their particular problems, use that information to help inform research and development, and undertake education.”

BioMerieux has also been partnering with various organizations and antibiotic resistance stewardship programs, presenting clinical microbiologic symposiums, making booklets available on antibiotic resistance and blood culture techniques, etc., and presenting educational webinars.

“Labs and lab directors must get involved in antibiotic stewardship, and antibiotic stewardship programs must involve the labs,” added Bozzette. “It will eventually be mandated that all facilities have some sort of antibiotic stewardship program in place. The role of laboratories is crucial. That’s where all of the information to inform treatment comes from.”


References:

  1. The Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. 2014.
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Valerie Neff Newitt
Valerie Neff Newitt

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