APUA Highlights: June 2012
Dr. Stuart Levy receives ASM Lifetime Achievement Award
Congratulations to Dr. Stuart B. Levy on his selection as the 2012 Abbott-ASM Lifetime Achievement Award Laureate! The award is the highest recognition by the American Society for Microbiology for sustained contributions to the microbiological sciences. The ASM acknowledged Dr. Levy’s co-founding of APUA in 1981, and his tireless efforts through the organization for the past 30 years.
Dr. Hiroshi Nikaido (University of California, Berkeley) nominated Dr. Levy for “not only elucidating the genetics and biochemistry of one of the most important mechanisms for drug resistance, but also striv[ing] to minimize the selection and spreading of resistant bacteria.” Longtime colleague Dr. Steve Lerner (Wayne State University) also lauds Dr. Levy for “bringing his studies and their implications beyond the laboratory to influence directions in infectious disease research and public health policy.” The award recognizes the catalytic impact of the Alliance for the Prudent Use of Antibiotics and its network of affiliated chapters in 19 countries worldwide.
APUA national stakeholder meeting on antimicrobial use in food animal production
With the generous support of The Pew Charitable Trusts, APUA held a national stakeholder meeting on “Improving Antimicrobial Use in Food Animal Production: Alternatives, Options, and Incentives” from May 6 to May 7 at the Omni Shoreham Hotel in Washington D.C. In light of the recent voluntary guidances released by the FDA, the purpose of the meeting was to establish a forum for open discussion and evaluation of feasible alternatives among major stakeholders in the food animal industry so that concrete approaches could be reached to promote the judicious use of antibiotics.
Co-chairs Dr. Stuart Levy (Tufts University School of Medicine) and Dr. Joann Lindenmayer (Tufts University School of Veterinary Medicine) opened with keynote remarks, followed by discussions concerning the current U.S. regulatory framework, perspectives from individual sectors of the food industry, and possible alternative strategies. Represented groups included the animal health pharmaceutical industry, the livestock industry, trade and farming organizations, producers and retailers, veterinary associations, animal welfare associations, government, and academia.
Read APUA’s press release and find related information in the white paper from the 2012 Annual Conference of the National Institute for Animal Agriculture.
APUA and Pew campaign to strengthen FDA draft Guidance #213
The FDA recently released several guidance documents that may finally wean U.S. food producers off of using antibiotics for non-therapeutic purposes and growth promotion. Over three years, the guidances encourage drug companies to remove language promoting non-therapeutic use from their antibiotics. They will also promote veterinary oversight for all therapeutic antibiotic use in food animals. However, the current guidances may lose their efficacy by being recommendations rather than requirements. Help APUA and Pew strengthen these positive changes by commenting on draft Guidance #213 or by sending a letter to the FDA.
APUA joins Pew sign-on letter in support of NRDC lawsuit against FDA
In May 2011, the National Resources Defense Council and its co-litigants (the Center for Science in the Public Interest, the Food Animal Concerns Trust, the Union of Concerned Scientists, and Public Citizen) filed a lawsuit against the FDA to call for enforcement of its own 1977 ban on the use of penicillins and tetracyclines for growth promotion in food animal production.
This action was deemed necessary, since the FDA’s data from 2010 shows that 12.3 million pounds of tetracyclines and 1.9 million pounds of penicillins were still used for growth promotion, making them the #1 and #2 most-used antibiotics in food animal production. The FDA has not responded to petitions in 1999 and in 2005 demanding that they enforce the proposed ban.
On March 23, in a case presided over by Judge Theodore Katz, the court ordered that the FDA complete the proceedings to withdraw approval for penicillin and tetracycline use as feed additives for healthy animals unless the drug sponsors are able to prove in a public hearing that such uses are safe. On April 30, APUA signed on to a letter from the Pew Campaign on Human Health and Industrial Farming to Commissioner Margaret Hamburg, Deputy Commissioner Michael Taylor, and Director of the CVM Dr. Bernadette Dunham. The letter urges the FDA not to appeal the court’s decision, and points out that compliance with the order would encourage drug sponsors and food animal producers to participate in other programs that restrict off-label drug use (such as FDA final Guidance 209 and draft Guidance 213).
Co-signers on the letter include the Institute for Agriculture and Trade Policy, the Johns Hopkins Center for a Livable Future, and many other groups.
APUA article in The Scientist
Dr. Stuart Levy (APUA President) and Bonnie Marshall (APUA International Program Director) published their article “Antibiotics in the animals we eat” in the “Critic at Large” section of the April 2012 issue of The Scientist as follow-up to their recent paper, “Food animals and antimicrobials: impacts on human health.” Dr. Levy compares the continued subtherapeutic antibiotic use in U.S. food animal production with the EU’s “precautionary principle,” which includes their ban on antibiotics as growth promoters. These measures have effectively controlled, and in some cases reversed, emergence and spread of resistant bacteria.
Dr. Levy elaborates on the “promiscuous nature of bacteria” and their ability to transfer resistance genes among vastly different strains. While the article acknowledges that resistant bacterial strains found in hospitalized patients and those found in livestock are dissimilar, tracking evolution of bacterial resistance has successfully shown passing of resistant bacterial strains such as MRSA between humans and animals.
In closing, Dr. Levy applauds the 2005 FDA ban on fluroquinolone use and the recent 2012 ban on off-label use of cephalosporins in livestock, but emphasizes the need for stricter measures for antibiotic use and warns against continued use of penicillins and tetracyclines as growth promoters.
APUA Clinical Newsletter Vol.30 No.1 available for download
The most recent issue of the APUA Clinical Newsletter has been sent to our mailing list and is available for download. The issue was themed "Confronting Today's Crisis in Antibiotic Development." It featured some of our most extensive coverage yet on this vital topic, showcasing the opinions of experts from academia, health law, professional organizations, and the pharmaceutical industry. Join our mailing list to have future Newsletters delivered to your inbox three times a year.
Call for nominations: 2012 APUA Leadership Award for Young Professionals
Nominations are now open for the 2012 APUA Leadership Award for Young Professionals, which will be presented to an outstanding young or mid-career professional who has demonstrated exceptional leadership in promoting the prudent use of antibiotics in an effort to contain antibiotic resistance. Consideration will be given to individuals in the fields of basic science, public policy, and clinical practice, with an emphasis on innovation. To nominate a young professional for this award, visit the APUA Leadership Award pageand download the nomination form.
Center for a Livable Future study finds residues of banned antibiotics in poultry feathers
A joint study by scientists at the Center for a Livable Future (Johns Hopkins School of Public Health) and the Biodesign Institute (Arizona State University) published on April 5 looked for antibiotics and other residues in feather meal, a poultry byproduct commonly used to supplement fertilizers and food animal feeds. Like human fingernails, feathers accumulate a record of the chemicals and drugs to which the animal has been exposed. The study made use of this characteristic to investigate what drugs are actually being fed to chickens.
Nachman et al. found significant amounts of fluoroquinolones in the feathers. Fluoroquinolones are classified as a “critically important” class of drugs by the WHO and have been banned in poultry production by the FDA since 2005. The ban was enacted at the time primarily because of a sharp increase in the rate of fluoroquinolone resistance inCampylobacter bacteria. Since then, rates of resistance to fluoroquinolones have slowed, but have not dropped. This failure to improve might be attributable to these indications that the poultry industry never actually stopped feeding fluoroquinolones to chickens.
As well as fluoroquinolone traces, all twelve tested samples of feather meal contained residues of anywhere from two to ten other types of antibiotics. They also tested positive for caffeine, and for the active ingredients from drugs like Tylenol, Benadryl, and Prozac. When Love et al. exposed strains of E. coli to the same antibiotics found in the feather meal, the concentrations present in feather meal were sufficient to select for resistant bacteria.
The Center for a Livable Future and the Biodesign Institute published their findings in two journals, Science for the Total Environment and Environmental Science and Technology. This research raises concerns that if the poultry industry cannot even be relied on to follow the law, they may not see any reason to comply with the FDA’s recently released voluntary guidances.
Nachman KE, et al. (2012) Arsenic species in poultry feather meal. Sci Total Environ 417-418:183-188.
Love DC, et al. (2012) Feather meal: a previously unrecognized route for reentry into the food supply of multiple pharmaceuticals and personal care products (PPCPs). Environ Sci Technol 46(7):3795-3802.
CDC tracks initiatives in three states that show progress in combating C. difficile
In March, the U.S. CDC responded to alarming nationwide highs in C. difficile infection rates in hospitals by launching a Vital Signs campaign on "Making Healthcare Safer: Stopping C. difficile Infections," with the help of APUA and other strategic partners. Following the successful public awareness campaign, the CDC published three new Public Health Practice Stories from the Field from Illinois, Massachusetts, and New York to highlight the states’ success in reducing infection rates. In Illinois, where CDI incidence had more than doubled between 1999 and 2009, 20 hospitals established multidisciplinary prevention teams and emphasized prevention strategies like hand hygiene, contact precautions, lab alerts, and staff/patient education. Their campaign also highlighted the vital role of environmental service workers through the video “Not Just a Maid Service.” The Illinois Campaign to Eliminate C. difficile saw a 15-26% decrease in CDI over one year.
A similar prevention campaign in 27 Massachusetts hospitals utilized the same types of multidisciplinary teams and prevention strategies, but also introduced an antibiotic stewardship component. The hospitals organized regional workshops and three statewide learning and sharing workshops, including “Building Stewardship: A Team Approach” co-sponsored by APUA. In post-program surveys many hospitals noted that it was helpful to plan for a two-year program, as implementing strategies took time and participants were at various stages of readiness.
The largest of the three, the New York C. difficile Collaborative, recruited 47 hospitals to implement “prevention bundles” that emphasized contact precaution at symptom onset, patient cohorting, and rigorous environmental cleaning (using a checklist of 48 elements for daily and terminal inspection). The program resulted in a 20% reduction in hospital-acquired CDI, saving hospitals anywhere from $2.7 million to $6.8 million.
"Antibiotic resistance in foodborne pathogens"
According to the Center for Science in the Public Interest’s white paper, “Antibiotic Resistance in Foodborne Pathogens: Evidence of the Need for a Risk Management Strategy,” rampant use of antibiotics in animal agriculture (accounting for 80% of all antimicrobials used, 65% being similar or identical to those used in human medicine) increases the likelihood that foodborne illnesses will be longer, more serious, and harder to treat. The paper cites antibiotic use in growth promotion practices and low doses in animal feed to prevent diseases caused by overcrowding or unsanitary conditions as major contributors to antibiotic resistance. CSPI’s review of antibiotic-resistant foodborne illness outbreaks shows that outbreaks were most common in dairy products, with 12 such outbreaks since 1973, and ground beef, with 10 outbreaks. Four outbreaks were linked to poultry, with ground turkey appearing for the first time as a source of antibiotic-resistant bacteria during the two 2011 outbreaks linked to Jennie-O and Cargill products.
"Metagenomic epidemiology and antibiotic resistance"
“Metagenomic epidemiology: a public health need for the control of antimicrobial resistance” by Dr. Fernando Baquero of APUA’s Scientific Advisory Board (published in the July 2012 Supplement of Clinical Microbiology and Infection) highlights the utility of metagenomics, which applies genomic analysis to entire communities of microbes, to explore the presence of antibiotic resistance genes in various biological units. He applies this to the intestinal microbiome, which is exposed to environmental accumulation of resistance genes, intestinal organisms from other hosts, and microbiome-damaging agents such as antibiotics. Metagenomics provides the possibility of exploring the flow of resistance genes and identifying possible “high risk associations,” which could then be used to predict and design interventions to limit antibiotic resistance. Dr. Baquero's publication complements the important findings of the Human Microbiome Project Consortium, which in the June issue of Nature published the most extensive study conducted so far on genomes of the microbiome - identifying over 5 million genes from the bacteria found in 242 healthy subjects. The Consortium emphasizes the importance of maintaining the balance of a healthy bacterial ecosystem rather than killing off the microbiome indiscriminately through the irresponsible use of antibiotics.
Baquero F. (2012) Metagenomic epidemiology: a public health need for the control of antimicrobial resistance. Clin Microbiol Infec 18 (Suppl. 4): 67-73.
The Human Microbiome Project Consortium. (2012) A framework for human microbiome research. Nature 486:215-221.
"Antibiotic stewardship and early discharge from hospital"
A UK study “Antibiotic stewardship and early discharge from hospital: impact of a structured approach to antimicrobial management” by Dryden et al. (published in the May 2012 issue of Journal for Antimicrobial Therapy) assessed the impact of having an infection team review patients receiving antibiotics in six hospitals across the UK and establish the patients’ suitability for continued care in the community. The study found that using infection team review had significant impact on antimicrobial use, facilitating the IV to oral switch, reducing the volume of antibiotics used and the risk of HAIs, and saving up to 481 bed-days.
Dryden M, et al. (2012) Antibiotic stewardship and early discharge from hospital: impact of a structured approach to antimicrobial management [published online ahead of print May 23 2012]. J Antimicrob Chemotherhttp://m.jac.oxfordjournals.org/content/early/2012/05/23/jac.dks193.full. Accessed June 14, 2012.
APUA Reports from the Field
In response to our call for international perspectives on the antibiotic development crisis, Dr. Emma Keuleyan (Medical Institute of the Ministry of the Interior) provided a thoughtful analysis of the state of antibiotic stewardship in Bulgaria. Bulgaria has implemented many praiseworthy stewardship practices in the past decade, including strengthening the Bulgarian Drug Agency’s control over OTC sales of antibiotics, implementing biannual quality control checks for laboratories, and standardizing antimicrobial susceptibility testing. Multidisciplinary antibiotic stewardship teams led by microbiologists are also in place at almost every hospital.
However, the Bulgarian market is not considered lucrative enough by pharmaceutical companies, causing a scarcity of some important classes of antibiotics – including antibiotics against Gram-negative and panresistant bacteria, such as nitrofurantoin and colistin. Antibiotics sold domestically have also been found to be priced higher than in other countries. Dr. Keuleyan warns that these considerations, and the termination of a Program for Antimicrobial Resistance Surveillance and Rational Antibiotic Policy due to lack of funding, are serious obstacles in “one of the countries with the lowest GDP in Europe, [where] the funds for healthcare are respectively smaller.” Dr. Keuleyan’s detailed analysis will be featured in the upcoming issue of the APUA Clinical Newsletter in August.
APUA-Cuba continues to grow, with more than 1400 members in over 60 medical specialties at the latest count. Since April, Dr. Moisés Morejón (Manual Fajardo Hospital) and his colleagues have held multiple symposia on antimicrobial resistance and need for new antibiotics, including the meeting of the Committee on Antimicrobial Resistance at the 21st meeting of the Pan-American Association of Infectology (API). One of their recent conferences discussed the applicability of modern diagnostic technology in detecting HAI pathogens and identifying resistant phenotypes in immunocompromised patients.
APUA-Cuba has proposed national guidelines citing APUA recommendations for correct antibiotic use in critical-care patients in the face of rising rates of HAIs and infection from multidrug-resistant Acinetobacter baumannii. Other proposed guidelines include those for antibiotic use in surgical prophylaxis, and established parameters for sequential antibiotic therapies that will hopefully evolve into sophisticated antibiotic stewardship programs. Pneumonia is another growing concern in Cuba, especially in children, and has stimulated discussions on the importance of correct diagnosis and provided an incentive for pneumococcal vaccine development. APUA-Cuba has evaluated international guidelines for community-acquired pneumonia, citing guidelines from IDSA/ATS and the South American working groups ConsenSur and SEPAR as being the most useful.
This year Dr. Morejón published his book Enfermedades Tropicales Mayores: Enfermedades Olvidadas o Desatendidas (Forgotten Tropical Infectious Diseases). Dr. Morejón echoes WHO’s statement on the realm of infectious disease: “The developing world is paying the price for the industrial world’s negligence.”