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Weekly Digest: Risk perception drives antibiotic prescription; Pediatric MDR-TB burden in United States underestimated

A weekly roundup of news on drug resistance and other topics in global health.

Fuzzy-trace theory applied to clinician decisions about antibiotics. Clinicians who weigh the risks of antibiotic-associated adverse effects and antibiotic resistance against the likelihood of benefit are less likely to prescribe them than clinicians who focus just on the potential benefits of antibiotics. These two “gists”—“antibiotics may be harmful” and “why not take a risk”—capture the essence of clinician decision-making processes, as defined by fuzzy-trace theory, and are predictive of prescribing patterns.  In research reported in The Journal of General Internal Medicine, CDDEP researchers and colleagues—including fuzzy-trace theory developer Dr. Valerie Reyna—surveyed 69 emergency department clinicians about how they frame their decisions to prescribe antibiotics. They then matched up the survey responses with their actual antibiotic prescribing practices for patients with acute respiratory infections over 17 months, starting in 2014. Clinicians were true to their gists: the “why not take a risk” group was about fifty percent more likely to prescribe antibiotics than the “antibiotics may be harmful” group. This was most pronounced for patients with conditions that, according to prescribing guidelines, do not actually require antibiotics. These findings could improve antibiotic stewardship strategies and educational tools that aim to encourage responsible prescribing and preserve the effectiveness of antibiotics. [JGIM, CDDEP, CIDRAP]

U.S. pediatric MDR TB burden underestimated. Multidrug-resistant tuberculosis (MDR TB) in children (under age 15) in the United States may be more prevalent than officially recorded, according to the Centers for Disease Control and Prevention (CDC). CDC researchers, reporting in Clinical Infectious Diseases, compared National TB Surveillance System reports—which require culture confirmation—with the much higher number of clinically diagnosed cases treated for MDR TB in six states reporting the highest number of cases from 1993 through 2014.  Limiting official counts to culture-confirmed cases led to an undercount of 42 to 55 percent. Better estimates are needed to improve TB control in children, particularly MDR TB. [CIDRAP, Clinical Infectious Diseases]

AMR stewardship programs highly effective in reducing infections. Antibiotic stewardship programs can reduce rates of antibiotic-resistant infections and colonization, and of Clostridium difficile, in hospitals, according to a meta-analysis of 32 studies published between 1992 and 2014. The review, published in The Lancet Infectious Diseases, included studies from the United States, Europe, Asia, and Latin America, covering more than 9 million patient-days. The most common stewardship components across the studies were antibiotic cycling, education, and use of implementing guidelines. Rates of all important resistant pathogens were reduced, including a halving of multi-drug resistant Gram-negative infections and one-third reductions in MRSA and C. difficile infections and colonization. The measures are even more effective when implemented along with infection control and prevention programs, particularly improved hand hygiene. In an accompanying Comment, Debra Goff and Marc Mendelson speak to the need for implementation of stewardship and infection control, especially in low- and middle-income countries. “[I]t is fine to talk the talk, but countries and the global community now need to step up and walk the walk when it comes to financing national action plans.” [CIDRAP, Lancet ID study, Lancet ID Comment]

Testing for flu alone may be enough for rational antibiotic use in patients with respiratory illnesses. Testing for influenza in patients with respiratory illnesses during flu season does influence antiviral and antibiotic prescription practices, but testing for other viruses simultaneously may not. The study, reported in the Journal of Infectious Diseases was conducted over three annual flu seasons in a tertiary care hospital in Montreal. Eight hundred adult patients who were admitted for acute respiratory illnesses were tested for 12 viruses, including influenza. About half the patients were positive for influenza, and clinicians were 1.4 times more likely to stop earlier prescribed antibiotics than for flu-negative patients. The findings suggest that expensive multiplex virus tests are not necessary for a positive impact on antibiotic stewardship. CIDRAP, Journal of Infectious Diseases]

The search for novel antibiotics. Paleontologist Seth Herzon is determined to find an efficient and economical way to produce pleuromutilin, an antibacterial molecule produced by a mushroom local to northern temperate areas. The substance has been used to make animal antibiotics, but has been passed over by the pharmaceutical industry because it has proven difficult to formulate into a safe and effective substance. Herzon has pioneered a modular assembly approach that could change the outlook for pleuromutilin and derivatives. CDDEP Director Ramanan Laxminarayan states, “This is the kind of work we need to move things forward. It’s not going to enter clinical trials tomorrow, but unless we’re constantly looking out for new antibiotics, we’re not going to be able to replace the ones that are no longer working.” [STAT+, Science]

Identifying synergistic drug pairings to slow antibiotic resistance. Pairing two or more antibiotics can be more effective than using single drugs, and Is an established strategy to slow the development of resistance to the drugs. Finding effective synergistic pairings, however, has proven difficult., Researchers from the University of Utah report in PLOS Biology on a method they developed, which they call the overlap2 method (O2M), which makes it easier to identify drugs that can work synergistically to fight multidrug-resistant bacterial infections. Study co-author Morgan Wambaugh explained “It uses the idea that if you have a synergistic pair, it will elicit a response in a bacterial mutant. Then, if you get this response in that same mutant with other drugs that are also known to synergize with that input, you can keep going faster and faster, looking for any drug that elicits the same response in that mutant.” [PLOS Biology, CIDRAP]

India plans to eliminate TB by 2025 but cuts funding. India has the largest tuberculosis burden globally, with 3 million cases and almost half a million deaths reported in 2015. In February this year, India announced a goal of eliminating TB by 2025. Yet in the  national budget for 2017-18, TB program funding is reduced by $2 million compared with 2016, write Pranay Sinha at Yale-New Haven Hospital and Scott K. Heysell from the University of Virginia, in The New York Times. Not only is the program underfunded, the domestic contribution is much smaller than in other high-burden countries like South Africa. The many technical shortcomings and inadequate scale of the program also contribute to slow progress. The authors suggest that elimination by 2025 is no more than a pipe dream without the resources to make it happen. [New York Times]