APUA Highlights: November 2015
APUA HEADQUARTERS IN ACTION
APUA HEADQUARTERS IN ACTION
APUA also signed on to a letter of thanks to House and Senate appropriators for giving high priority to the antimicrobial resistance line-items in the FY 2016 budget. The letter urges members of Congress to work towards a deal that reduces sequestered spending caps and fully funds the president’s original budget request.
A letter to Congressmen Boustany (R-LA) and Thompson (D-CA) expressed concern about the alarming rise of antibiotic-resistant infections and urged support for their bipartisan efforts to build upon the success of the 2012 Generating Antibiotic Incentives Now (GAIN) Act. While the GAIN Act would add 5 years of “exclusivity” for new antibiotic or antifungal drugs that treat serious or life threatening infections, the READI Act 2015 (Reinvigorating Antibiotic and Diagnostic Innovation), proposed by Boustany and Thompson, would provide assistance to a company during the costly and risky drug development process. The combination of these two (“push and “pull”) incentives is viewed by economists as an important stimulus for the R & D of new antibiotics and urgently needed new diagnostics for guiding appropriate antibiotic use, rapid identification of outbreaks, and identifying eligible patients for antibiotic clinical trials. The letter received support from 40 commercial companies and non-profit institutions.
APUA has also supported a letter spearheaded by Keep Antibiotics Working and directed to USDA Acting Commissioner Ostroff. The letter requests that the USDA, FDA and CDC fulfill their commitment to collect needed data on how antibiotics are used on the farm.
Addressing the deficit in quantitative data on antibiotic use in food will “1) assess the rate of adoption of changes outlined in the FDA's GFI #213; 2) help gauge the success of antibiotic stewardship efforts and guide their continued evolution and optimization; and 3) assess associations between antibiotic use practices and resistance.” To meet current needs, the letter requests that data collection be quantitative, comprehensive, ongoing and unbiased, and suggests some new approaches to accomplish these goals.
Since its premiere in NYC in May 2014, Resistance has screened across North America, Europe, Australia and Africa and received thousands of viewings on Netflix, iTunes, Amazon and many other delivery platforms. It has partnered with 10 national NGOs and 30 regional and local groups to reach at least six million individuals. The film won Best International Feature award at Toronto’s Planet in Focus Film Festival, and has been viewed by U.S. Capitol Hill staff and recognized on the floor of Congress. Its message of highlighting the dangers of the overuse of antibiotics in factory farming has driven the passage of 50 local resolutions by U.S. city and municipal governments to act on the misuse of antibiotics in animal agriculture. Resistance is now available on DVDs and downloads at resistancethefilm.com.
ANTIBIOTIC RESISTANCE IN THE NEWSSerious infections continue to plague professional sports
The problem of community-acquired MRSA (methicillin-resistant Staphylococcus aureus) has received nationwide attention recently with the report of a serious foot infection that threatens the career of a New Giants linebacker. The report highlights the severity of MRSA infections that have plagued contact sports for a number of years and the need for emphasis on strict locker room hygiene practices—involving drastic renovations, ultraviolet lights and other sanitizing measures, including formalized consulting relationships with professional infection control specialists—in order to contain the highly transmissible pathogen. See the CDC webpage on MRSA for routes of transmission and a list of preventive tips.
Novel treatment regimen found
While contact sports managers scramble to control MRSA infection and lawyers dispute whether the infections were community or hospital-acquired, scientists at Washington University School of Medicine have uncovered a trio of drugs that may prove effective against the multi-drug-resistant pathogen. While typically ineffective as single agents, a beta-lactam combo of meropenem, piperacillin and tazobactam has been found to act synergistically, producing bactericidal activity in vitro against 73 MRSA variants and also in vivo in mice. The combo was found to be as effective as linezolid, a highly potent, but more expensive monotherapy.
Bacteriophages exploited for prevention and treatment
Meanwhile, scientists at Brigham Young University have been investigating bacteriophages as a means to combat MRSA. In a PLoS ONE report, Jensen et al describe a significant reduction in MRSA from contaminated glass and fabrics. The findings support the idea of utilizing bacteriophages as a disinfection tool for both hard and soft surfaces.
On the commercial front, AmpliPhi, a leader in the development of bacteriophage therapy, has announced the results of its in vivo tests using a bacteriophage cocktail against Staphylococcus aureus. In lung-infected mice, the intranasal injection of the bacterial cocktail performed as well as the “last-resort” antibiotic, vancomycin, showing a 3-log reduction in pathogen. The results provide additional validation for bacteriophage therapy as a potential treatment for antibiotic- resistant infections.
See the recent APUA feature article on the current status of bacteriophage therapy here.
Scotland ramps up MRSA control efforts
In a multi-faceted plan (Putting your money where your mouth is: Scotland’s attack on MRSA pays off) that utilizes antimicrobial stewardship, infection prevention and control—and importantly, is backed by government funding—Scotland achieved an abrupt (within 4 months) and permanent reduction in targeted antibiotic hospital use, followed by a gradual decline in community use. Indirectly, this led to a 32% reduction in community-based MRSA infection. The hospital utilized a 2-step intervention: first, a persuasive approach, followed by selective antibiotic removal coupled with prescription authorization by an infectious diseases expert. Additionally, a national hand hygiene campaign was launched, accompanied by MRSA screening upon hospital admission. The stewardship intervention package is estimated to have prevented >3000 community MRSA cases and is viewed as an important model for other countries that are developing a national strategy.
ANTIBIOTIC STEWARDSHIP NEWSChain Reaction: How top restaurants rate on reducing use of antibiotics in their meat supply. To evaluate the commitment of major chain restaurants in their attitudes towards antibiotics, the authors viewed the public statements of the top 25 restaurants and created a scorecard intended to be published annually. Most top U.S. restaurants have no public policy concerning antibiotic use. Five chains – Chipotle Mexican Grill, Panera Bread, Chick-Fil-A, Dunkin’ Donuts and McDonald’s are working meaningfully to limit routine antibiotic use. The report contains survey questions and methodology used; an in-depth evaluation of its findings, including a scorecard for the top 25; a compendium of company profiles and their antibiotic use policies; and current trends in chicken production that indicate a response to consumer pressure for antibiotic-free meat.
View APUA’s press release announcing its 2015 Honor Roll of antibiotic-sparing companies here. study of U.S. outpatient prescribing patterns from a nationally representative database, Suda and colleagues reported 1.56 billion antibiotic prescriptions dispensed as follows between 2005 and 2010: physicians - 80.4%, dentists -10.4%, nurse practitioners- 4.4% and physician assistants- 4.9%. Penicillins were prescribed mostly frequently. While prescribing rates decreased among doctors and dentists, they doubled among nurse practitioners and physician assistants. Prescriptions for broad-spectrum antibiotics, such as macrolides and quinolones, also increased within these two groups. The authors urge a focus on reversing prescribing trends among mid-level providers and suggest further research on the prescribing habits of dentists.
Utilizing a personality profiling tool that distinguishes 16 different personality qualities, Australian researchers Lindsay Grayson and colleagues surveyed over 1000 health care workers and developed customized intervention strategies to better promote hand hygiene, antimicrobial stewardship, and isolation procedure awareness. Certain qualities such as individualism, uncertainty avoidance, and cynicism regarding advertising messages varied between doctors, nurses and support staff, and also between senior, visiting and junior hospital medical officers. The plan was based on the concept that different personality types will respond to different infection prevention/control (IPC) message strategies and achieve better compliance. study which compared outcomes from standard monotherapy with dual therapy, i.e., vancomycin plus a beta-lactam, researchers Branch-Elliman and colleagues found a reduction of up to 63% in SSI. The strongest association was found for cardiac procedure. The authors noted that this success still needs to be weighed against the risks of potential C. difficile infection, antimicrobial resistance, and kidney toxicity. PNAS, can perforate bacterial cell membranes. The rigid spirals are packaged into positively charged exterior shells that attract them to the negatively charged gram-positive and gram-negative bacteria. The polypeptides are less attracted to the more weakly charged human cells. The perforated bacterial cell membranes can also permit a second targeted drug to by-pass cellular resistance mechanisms, making dual therapy more effective than either alone. Subsequent work will focus on specifically targeting pathogenic bacteria. development of “conformal” biosensors, consisting of silk-based inks amended with a variety of compounds that can be ink-jet printed on selected surfaces. Among multiple other applications, the technology can be utilized to create germ-detecting surgical gloves that display the word ‘contaminated’ and alert health care workers to the presence of harmful bacteria. The versatile silk-based technology enables printing sensors on arbitrary surfaces and could someday potentially be impregnated with drugs to deliver antibiotics and other growth factors to targeted areas of the body, such as wounds.
NATIONAL and INTERNATIONAL DEVELOPMENTSGlobal Antibiotic Awareness Week is set for Nov 16-22 and the theme will be “Antibiotics: handle with care.” A variety of resources (infographics, fact sheets, posters and multi-media materials) are available so that Member States and health partners can assist the campaign in its mission to encourage best antibiotic practices and avoid further resistance spread.
At the recent UN Sustainable Development Summit held Sept 25-27 in New York, 193 of the world’s leaders committed to 17 broad-based, global goals for achievement in the next 15 years. The issue of antimicrobial resistance appeared for the first time on the Sustainable Development Agenda, which is a global plan of action for people, planet and prosperity. The document states: “…We will equally accelerate the pace of progress made in fighting malaria, HIV/AIDS, tuberculosis, hepatitis, Ebola and other communicable diseases and epidemics, including by addressing growing anti-microbial resistance and the problem of unattended diseases affecting developing countries.”
In the U.S., The Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (CARB) held its inaugural public meeting on September 29. The task force, consisting of appointed academic and private-sector experts, is chaired by Dr. Martin Blaser (read interview here) and is expected to “provide advice, information, and recommendations…to preserve the effectiveness of antibiotics by optimizing their use; advance research to develop improved methods for combating antibiotic resistance and conducting antibiotic stewardship; strengthen surveillance of antibiotic-resistant bacterial infections; prevent the transmission of antibiotic-resistant bacterial infections; advance the development of rapid point-of-care and agricultural diagnostics; further research on new treatments for bacterial infections; develop alternatives to antibiotics for agricultural purposes; maximize the dissemination of up-to-date information on the appropriate and proper use of antibiotics to the general public and human and animal healthcare providers; and improve international coordination of efforts to combat antibiotic resistance.” The meeting agenda can be found here. View the archived webcast here. SB 27(Livestock: Use of Antimicrobial Drugs), a landmark legislation that sets the strictest standards in the U.S. for the use of medically important human antibiotics in food animals. The bill was strongly supported by Louise Slaughter, author of PAMTA in Congress, who wrote, “…we have faced opposition at every turn from industries more concerned with protecting their bottom line than protecting the health of Americans. It seems that the best chance for change will come from the states and I am so proud that California has taken up this fight.” The bill, which goes into effect on Jan 1, 2018, will stop over- the-counter sales of antibiotics and will ban the routine feeding of antibiotics to chickens, cattle and pigs. Veterinary approval is required for administration to animals that are sick or confronted with an elevated risk. Will Historic White House Actions Scant the Role of Farms?).
With regard to progress made in the one year since the President’s release of CARB (Combating Antibiotic Resistant Bacteria) the multi-organization coalition, Keep Antibiotics Working, has issued a report card which assigns mediocre to failing grades on six of CARB’s objectives. Of particular concern, after one year, the Obama Administration has still failed to gain the funding necessary for implementation of the plan. The State of the World’s Antibiotics, 2015, updating the global status of antibiotic resistance, antibiotic consumption by humans and animals, and the global antibiotic pipeline. It concludes with 6 directives for country-level action, which includes the reduction and eventual phase-out of sub-therapeutic antibiotics in food animals.
In a multi-year effort to fill in missing drug resistance and consumption data from developing countries, the CDDEP has updated its interactive Resistance Map from 39 countries to a total of 69—and now includes India—a country that lacks a national data reporting system.
PUBLICATIONS AND EVENTS OF INTERESTWorld Antibiotic Awareness Week Antibiotics: Handle with care. Nov 16-22
CDC “Get Smart about Antibiotics Week” This annual one-week observance will occur Nov 16-22 and coincides with WHO’s first Global Antibiotic Awareness Week, both of which aim to raise awareness of the threat of antibiotic resistance and the importance of appropriate antibiotic prescribing and use.
A World Without Antibiotics: Conclusions from the Uppsala Health Summit held June 2-3, 2015 This 38-page post-conference report contains the conclusions and recommendations from six workshops that covered topics of antimicrobial access; research and innovation for new economic models addressing resistance; new therapies and improved diagnostics; and antibiotics in animal production and environmental impacts.
The State of the World’s Antibiotics 2015 by Hellen Gelband et al., CDDEP. A comprehensive report on the status of antibiotic use and resistance around the world—and an expanded, updated and redesigned version of CDDEP’s Resistance Map.
Tackling antimicrobial resistance at global and local scales by Hellen Gelband and Ramanan Laxminarayan. Trends in Microbiology, Sept 2016, 23:524-6
Abstr: Antibiotic resistance, similar to climate change is a shared global problem, but unlike climate change, national and local action produces localized benefits in addition to improving the global situation
Antimicrobial Stewardship: Managing Antibiotic Resistance—a free, 6-week, online course sponsored by FutureLearn. Course content relates to a hospital drama in order to guide the student towards a fuller understanding of the importance of antimicrobial stewardship.
Nonmedical Uses of Antibiotics: Time to Restrict Their Use? By RW Meek and LJ Piddock, PLOS Biology, Oct 2015. Examines the potential impacts of non-medical uses of antibiotics in animal husbandry, bee keeping, aquaculture, ethanol production, horticulture, antifouling paints, food preservation and domestic hygiene and provides a list of recommendations to reduce these uses.
Antibiotic Resistance: myths and misunderstandings—a blog post by Tara C. Smith, PhD, (Kent State University), ScienceBlogs –Aetiology. Posted Sept. 10, 2015. Presents a Q & A “overview” of the antibiotic resistance problem that attempts to clarify a very complex problem for the lay reader.
From “An enzyme able to destroy penicillin” to carbapenemases: 70 years of beta-lactamase misbehavior. by J.M. Frere, E. Sauvage and F. Kerff. Curr Drug Targets, Oct. 2015. An historical overview tracing the development of resistance to the beta-lactam antibiotics.
Current Issues in and Approaches to Antimicrobial Resistance: An overview of the current clinical challenges and approaches to management by Paul Cook MD. Infectious Disease Special Edition. Oct 2015:19. Reviews current CDC resistance threats, resistance mechanisms, beta-lactamase challenges, treatment of MDR agents, and resistance prevention.