APUA Webinar on Antimicrobial Stewardship

Get Smart About Antibiotics Week

November 12-18, 2012

APUA is proud to have been a national partner of the CDC's Get Smart About Antibiotics Week since 2010. Get Smart About Antibiotics Week is an annual effort to coordinate the work of CDC’s Get Smart: Know When Antibiotics Work campaign, state-based appropriate antibiotic use campaigns, non-profit partners, and for-profit partners during a one week observance of antibiotic resistance and the importance of appropriate antibiotic use.

This year, for Get Smart About Antibiotics Week APUA produced a webinar about Antibiotic Stewardship.

Containing Healthcare Associated Infections Through Antibiotic Stewardship Live event: Wednesday, November 14, 2012  1:00 PM EST PACE® credit available until May 13, 2013 There is no charge to view this webinar.
Presenters:
Stuart Levy, M.D. Professor of Medicine Tufts University School of Medicine President, APUA	Shira Doron, M.D., M.S. Assistant Professor of Medicine Tufts University School of Medicine

A recent APUA study found that antibiotic-resistant infections can add nearly 13 hospital days per patient, and up to $26 billion in annual US healthcare costs*. The number of hospitalizations associated with C. difficile infections has tripled to 335,000 annually, while the number of deaths has quadrupled in the past decade.

New ESBLs have evolved dramatically in the recent decades, such that few treatment options remain for infections caused by these exceptionally resistant pathogens. And of the estimated 478,000 US hospitalizations with S. aureus infection, approximately 58% were related to MRSA. Antimicrobial Stewardship Programs (ASPs) are recommended by the CDC and IDSA as essential in controlling these most problematic infections. This webinar will describe the nature of antimicrobial resistance, identify trends of major resistant infections, and delineate the important components of successful antimicrobial stewardship.

This webinar will:
• Describe trends of major HAIs including MRSA, ESBLs and C. difficile
• Review the causes and mechanisms driving antibiotic resistance problems
• Explain the link between antibiotic overuse and the emergence of resistant infections
• Review effective ASP practices and the importance of diagnostics in improving antibiotic treatment and minimizing resistance
• Illustrate specific examples to enhance hospital-based antimicrobial stewardship

* (CIDOct 2009)

This webinar is produced by the Alliance for the Prudent Use of Antibiotics in conjunction with the Tufts Medical Center and is funded by an unrestricted grant from Alere.

To learn more about Antimicrobial Stewardship please see our recent APUA Clinical Newsletters:

Volume 29 No. 3
December 16, 2011
"Enhancing Infection Control with Antibiotic Stewardship" (PDF)

Volume 29 No.1
June 14, 2011
"Anitbiotic Stewardship Gaining Traction: Recommended Models and Resources" (PDF)

About the CDC Campaign
How to Become a CDC Get Smart Partner
CDC Daily Fact Sheets
APUA Fact Sheets
CDC Brochures
CDC Podcasts

Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry

Dr. Lance Price is a Senior Scientist, Office of Wellness and Healthy Communities, at the Interdisciplinary Health Policy Institute as well as a Senior Science Advisor at the Pew Charitable Trusts. He is a molecular microbiologist and public health researcher. Lance is also the director of the Center for Metagenomics and Human Health at the Translational Genomics Research Institute (TGen). 

A couple weeks ago we published the first US-based, multi-state study of antibiotic resistant Staphylococcus aureus in retail meat and poultry. We revealed that 47% of the samples were contaminated with S. aureus and that more than half of the isolates were multidrug resistant (i.e., resistant to three or more classes of antibiotics).

I’ve done countless media interviews since the paper appeared online, and the most frequent question that I hear is “What can we do to protect ourselves?” Unfortunately, there’s no straightforward answer to this simple question. We found S. aureus strains with MLST sequence types identical to those of strains that colonize and infect people, but we don’t know if they’re the exact same strains. Even if they were the same strains, we don’t know if meat is a good vehicle for S. aureus infection—anyone who says “it is” or “it is not” is not making their statement based on robust science, because we don’t have good data on this subject yet. Industry groups and the media have largely focused on the risk from ingestion, but we should also be concerned about skin infections from handling the contaminated products. Does having a cut on your hand increase your risk? Maybe. We need to answer this.

I have also read a few statements from people saying that if this were really a problem, we would have seen outbreaks of foodborne infections from contaminated products. I disagree. With such high prevalence rates, we would not expect outbreaks, but rather routine sporadic infections. Campylobacter spp. is a good example of this type of observation. More than 40% of fresh chicken products in the US are contaminated with Campylobacter spp. and a couple million Americans are sporadically infected each year. It’s entirely possible that some of the hundreds of thousands of S. aureus infections that occur in the US each year are from foodborne exposure. So, with all these knowledge gaps, I answer the question, “What can we do to protect ourselves?” by saying what every good public health person would say: “wash your hands repeatedly when handling raw meat and poultry; wash your cutting boards and other equipment; separate meats from vegetables that will be eaten raw; and, definitely cook your food properly.” I also add that people should treat their meat and poultry as potential biohazards and never let children handle these products when helping out in the kitchen.

Unfortunately, almost everyone has focused on the consumer end of the food chain, when the problem clearly starts with the food animal producer. The prevalence of antibiotic-resistant S. aureus antibiotic use in food animal production. on meat and poultry is most likely a result of largely unregulated

While doctors are told to use antibiotics sparingly for their patients, millions of pounds of antibiotics—many of which are important for clinical medicine—are used as common production tools to improve feed efficiency, stimulate growth, and prevent diseases in food animals. I was once told “antibiotics is a crutch for poor animal husbandry” by the owner of a major US poultry production company. I am not a veterinarian, but I can say with confidence that any animal production system that requires the routine input of antibiotics to keep animals from becoming sick is a broken system. There is no justification for this flagrant antibiotic abuse while doctors and scientists are working frantically to preserve the utility of these drugs to treat sick people.

So what’s next? Now that we know that multidrug resistant S. aureus is common in our food supply, we need to define the risk to consumers. Occupational studies are probably the most powerful place to start. Studying food animal workers will tell us about the infectious potential of the strains that we’re finding on our food. Looking at prep cooks and butchers will move us even closer to the risk posed by handling meat and poultry. But, we’ll eventually have to bring these studies to the consumer’s kitchen to see how and how often consumers are exposed to S. aureus from food.

All that said, our future research shouldn’t follow the lead of the media and focus exclusively on the consumer end of the food chain. We also need to better understand the situation in the CAFO and slaughterhouse. How can we decrease antibiotic-resistant S. aureus colonization among food animals in CAFOs? How can we reduce meat contamination in the slaughter facilities? And one urgent question in my mind is: What is the relationship between ceftiofur use and MRSA colonization among food animals? Ceftiofur is a third generation cephalosporin and has been shown to kill off other S. aureus and select directly for MRSA in the laboratory. Are the new MRSA strains—such as ST398—that we are seeing in food animals a direct result of ceftiofur use? We need to answer all of these questions, but we’ll need cooperation by the food animal industry to do so.

Anyway, there are lots of import questions to answer here, and I’d be interested in hearing your thoughts…

Lance

Evidence-Based Strategies for the Containment of Antibiotic Resistance

Professor Sabiha Essack (B. Pharm., M. Pharm., PhD), Dean of the Faculty of Health Sciences and Professor in the School of Pharmacy and Pharmacology at the University of KwaZulu-Natal is a Welcome Trust Research Fellow who completed research towards her PhD in Pharmaceutical Microbiology at St Bartholomew’s and the Royal London School of Medicine and Dentistry in the United Kingdom. She is also the president of APUA-South Africa.

Antimicrobial resistance is currently the greatest challenge to the effective treatment of infections globally. Resistance adversely affects both clinical and financial therapeutic outcomes with effects ranging from the failure of an individual patient to respond to therapy and the need for expensive and/or toxic alternative drugs to the social costs of higher morbidity and mortality rates, longer durations of hospitalisation, increased health care costs and the need for changes in empirical therapy. Resistance may emerge by selection pressure (overuse/indiscriminate antimicrobial use in developed vs under-use/misuse in developing countries) but is perpetuated by diverse risk factors and maintained within environments as a result of poor infection control. Population-specific drug pharmacokinetics and pharmacodynamics also play a role. The WHO, US, UK and EU have initiated strategies for the containment of resistance, with surveillance critical to all.

Surveillance in South Africa should be disease-based, establishing sensitivity profiles of common causative organisms to inform the development of or amendment to standard treatment guidelines and essential drugs lists adopted within national drug policies in developing countries globally. The manner of antimicrobial use (overuse, underuse, inadequate dosing) associated with resistance must be established for appropriate intervention in terms of rational drug use, a reduction in use and dosing regimens based on population-specific pharmacokinetics and pharmacodynamics. Risk factors unique to South African communities (poverty, HIV) and hospitals (duration of hospitalisation, location within the hospital, intensive care unit stay, surgery, wounds, previous and current antimicrobial therapy, mechanical ventilation, urinary catherterisation, nasogastric intubation, central venous and peripheral catheters, previous hospitalisation and transfer from another unit or hospital) must be determined and due vigilance exercised in patients exhibiting classical risk factors for the acquisition of or colonisation with resistant pathogens.

 

Hygiene and sanitation (in communities) and infection control (in hospitals) status must be determined and interventions initiated to prevent the spread of resistance. Pharmacokinetics and pharmacodynamics specific to diverse populations must be devised to optimise antimicrobial therapy. Evidence-based treatment of infections guided by local susceptibility/resistance would ensure productive, economically viable individuals capable of fulfilling their social roles. Efficacious treatment would assure sustainable livelihoods in all populations (healthy and otherwise) as infections are the most frequently encountered health problem even in the absence of HIV/AIDS. While one infection will ultimately be fatal, the efficacious use of antibiotics will successfully treat several infections in the lifetime of the AIDS patient even in the presence of a compromised immune system sustaining the economic viability of the country and preventing the economic collapse portended by the World Bank. South Africa has unique needs in the antimicrobial resistance arena, needs to be addressed in the context of severe financial, human resources and technological challenges.

Infection Prevention + Optimal Antibiotic Use = Zero Infections

Julia Moody, MS SM (ASCP), Clinical Director, Infection Prevention, Clinical Services Group, HCA, Inc, APIC Antimicrobial Stewardship Task Force

Antibiotics are the second most common medication prescribed in the US. Although the discovery of antibiotics advanced the treatment of infections, excessive use frequently occurs. Bacteria easily adapt to become resistant, often at an alarming rate, posing a threat to public health safety, because new, more powerful antibiotic development is limited. This threat to public health safety was recognized on World Health Day, April 7, 2011, and endorsed by Centers for Disease Control and Prevention (CDC) and healthcare professional organizations in the U.S. To address the threat, antimicrobial stewardship programs are instituted to optimize antibiotic use and improve patient outcomes, while decreasing the development of resistance.

Antibiotic exposure is the single most important risk factor in C. difficile infection, a cause of severe diarrhea, serious intestinal complications and death. In some parts of the U.S., C. difficile is more common than MRSA. New cases of C. difficile infection occurring during a hospital stay are an indicator of adverse drug events as there is growing evidence that the risk for infection drops with antimicrobial stewardship.

What is the science of infection prevention and the value for hospitalized patients? Hospitals are where the most vulnerable patients in intensive care units, those with chronic health conditions and whose immune systems are unable to fight infection, rely totally on antibiotics to treat life-threatening infections. Resistant bacteria can leave these patients without an effective antibiotic for their infections.

How does the role of infection preventionists decrease the risk of infections and slow the pace of antibiotic resistance in healthcare settings? Infection prevention uses scientifically proven concepts to (1) identify trends and occurrences of drug resistant bacteria [MDROs], like MRSA, and new, emerging resistance in gram negative bacteria; (2) apply practices to prevent transmission of these MDROs to other patients, using bundles of hand hygiene before and after patient contact, isolation precautions placing patients in private rooms, where caregivers wear gowns and gloves, and environmental cleaning to ensure that surfaces and equipment are completely cleaned to reduce the presence of bacteria in the environment; (3) implement care bundles – like checklists – that when consistently performed, reduce the risk of getting an infection from use of catheters or after undergoing a surgical procedure; and (4) share findings of MDRO-related infections with the antimicrobial stewardship team members to identify successes and improvement opportunities.

What have been the outcomes? In the past 10 years, healthcare epidemiologists and infection preventionists – in collaboration with their direct care co-workers – have documented dramatic reductions in the frequency of infections, especially among patients in ICUs, as reported into the CDC’s National Healthcare Safety Network (NHSN) database.

What can you do today to prevent infections and save antibiotics for their intended use? Practice good hand hygiene with alcohol based hand rubs or soap and water, know what common infections do not respond to antibiotics, like the common cold, viral sore throats and influenza, take the full dose of antibiotics when prescribed for true infections, and keep current on vaccinations.

Why Urgent Action is Needed to Safeguard Drug Treatments for Future Generations

Dr Mario Raviglione is Director of the WHO Stop TB Department. He is leading preparations for World Health Day 2011.

The World Health Organization (WHO) is marking World Health Day – April 7 - this year with a call to Combat Drug Resistance and protect vital antimicrobial drugs the effectiveness of which is increasingly under threat. We believe that concerted action under the stewardship of governments, and engaging health professionals such as prescribers and pharmacists. Civil society and the pharmaceutical industry is needed to slow down the impact of drug resistance and preserve medical advances for future generations.

Every year, WHO uses the anniversary of its founding to draw the world’s attention to an urgent health problem. Clearly, drug resistance fits the definition. It’s not a new problem, but it still needs urgent action across the health sector and beyond it.

In her message to governments around the world, the WHO Director-General, Dr Margaret Chan, spelled out the problem: "The message on this World Health Day is loud and clear. The world is on the brink of losing these miracle cures." In the absence of urgent corrective and protective actions, the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated.

On Thursday, WHO will publish a policy package that spells out the measures governments and their national partners need to take to safeguard these vital medicines.

We know that the discovery and use of antimicrobial drugs to treat diseases such as leprosy, tuberculosis, malaria, gonorrhea, syphilis, pneumonias and other killer diseases has changed the course of our history as a species. We must act now to prevent those discoveries from being put at risk.

Tuberculosis, malaria and HIV all face severe constraints due to rising levels of resistance, and resistant strains of gonorrhea and shigella are limiting treatment options. Serious infections acquired in hospitals are now often fatal because they are so difficult to treat and drug-resistant strains of microorganism are spread overnight from one geographical location to another in today's interconnected and globalized world. Resistance is also emerging to the antiretroviral medicines used to treat people living with HIV.

Over the last decade, WHO has established many initiatives to understand and address drug resistance - particularly in relation to some of the world's most deadly infectious diseases. Those measures must now be further strengthened and implemented. New collaborations, led by governments working alongside civil society, health professionals and the private sector are essential if we are to halt the public health threat of drug resistance.

APUA has been a leader in promoting rational use of drugs and prevention and containment of antimicrobial resistance for many years. WHO looks forward to an intensified collaboration with APUA and all its chapters.

The Overuse of Antibiotics in Food Animal Production Needs to Be Addressed

The Food and Drug Administration (FDA) issued guidelines to curb the non-therapeutic use of antibiotics in food-producing animals last June. The hope is that food producers will reserve these vital antibiotics for disease treatment and prevention.  According to the FDA, in 2009 nearly 29 million pounds of antibacterial drugs (includes 3.7 million kilograms of Ionophores) were sold for animal use, almost four times the amount sold for human use that year. Data released later last year revealed that of all the antibiotics used in the United States, 80% is used in animals and the use is not to treat or prevent disease, but to make the animals gain weight faster and to compensate for the crowded conditions often found in such enormous facilities.

APUA believes that more action needs to be taken on this issue and that these guidelines will have little impact in fighting the growing threat of antibiotic resistance to public health unless the agency halts the practice and establishes a system to monitor compliance.

High-volume use of antibiotics at food animal production sites is a major contributor to the selection and transfer of resistance genes that can end up in human pathogens.

What are your thoughts on the use of antibiotics in food animal production?

For more information please contact Carol Cogliani

Resistant Salmonella Concord from Ethiopia

APUA chapter advisor for sub-Saharan Africa, Dr. Iruka Okeke, Ph.D. and current assistant professor of biology at Haverford College offers her insights on drug-resistant Salmonella Concord infections in Ethiopian adoptees.


There have been a number of worrisome reports in the recent medical literature about drug-resistant Salmonella Concord infections in Ethiopian adoptees.  The reports come from the USA, France, Norway and Denmark, plus a case report from Spain.  Based on global epidemiology of Salmonella, which includes very little information from every country in Africa combined, Salm. Concord is unusual.  The reports about what seems to be an epidemic come from less than two hundred individuals in all over a period of about seven years.  Thus, in a sense, they represent an archetypical example of what University of Virginia’s Richard Guerrant and his co-workers referred to as the ‘eyes of the hippopotamus’  – a mere scratch on the surface of what could be a deeper problem of unimaginable girth. 

 Unfortunately, too much of what we know about pathogens and drug resistance in resource-limited areas still comes from studies performed very distant from those places -  on isolates from returning travelers, or as in the Salmonella Concord case, recent immigrants.  Is it true, as some have suggested, that selection of resistant Salmonella Concord occurs in orphanages that overuse or abuse antibiotics in order to speed up adoption and empty out needed spaces?  Could we nip the problem in the bud by restricting antibiotic use in a few institutions and prescreening international adoptees?  Or is the average Ethiopian child at equal risk of a Salmonella Concord infection, with a significantly lower chance of having it detected and treated appropriately?  And are other, less susceptible individuals transporting Salmonella genomes packed with mobile resistance genes from endemic areas with an efficiency that is analogous to human transport via concord only a decade before?  Should we be developing a Salm. Concord vaccine to deal with the last two possibilities?  Or will the current apparent outbreak burn itself out before we get started?

 Getenet Beyene and co-workers have finally performed a small, but much-needed study to address these vital questions and they’ve done so where it is needed – in Addis Ababa and rural South-West Ethiopia.  The results, published in the January 2011 issue of the Journal of Infections in Developing Countries, are clarifying, if troubling.  Working at Tikur Anbessa Hospital in Addis Ababa and Jimma University Hospital, the researchers looked for Salmonella and other pathogens in the blood of patients with fever and in stool specimens from individuals with diarrhea.  Non-typhoidal Salmonella were isolated from the blood of 26 patients and from the stool of 59 more individuals.  Salmonella enterica serovariety Concord was the most common Salmonella serovar detected, being four times as common as all other Salmonella combined, and it was more invasive than other serovarieties.   The lack of evidence of clonality among the isolates suggests that this is no new epidemic and data from a smaller study published 25 years ago report Salm. Concord from Ethiopia, strongly suggesting that this pathogen has lurked undetected for at least a quarter of a century (Ashenafi and Gedebou, 1985, Trans R Soc Trop Med Hyg 79: 719-721).  Since 1985, Salm. Concord isolates from Ethiopia appear to have become more prevalent, and resistant to more antibiotics.  The isolates in the recent report were resistant to most affordable antibacterial options in Ethiopia.

 Oddly, the literature suggests that this serovar has a narrow geographic range.  However, our perceptions can only be as broad as our vision. There are reasonably good data from Kenya, which suggest that Salm. Typhimurium and Typhi are more important there, but with next to no data from other nearby locations, we cannot be sure that the problem is not extensive. While the endemicity, invasiveness and resistance of Salm. Concord in Ethiopia all give cause for concern, as Beyene et al emphasize in their discussion, the now global problem of multidrug-resistant Salmonella Concord must be addressed from endemic areas.  The very first step is determining where these are, and what exactly are the risk factors for infection.  Everyone is at risk when any part of the world lacks the diagnostic capacity to identify, track and control resistant pathogens. Microbes made the resistance problem a global one decades ago.  To deter them, we need local surveillance worldwide. 

 Iruka N Okeke

Haverford College

The International Society of Chemotherapy's African Network

APUA expert panel member and Secretary General of the International Society of Chemotherapy, Dr. Ian Gould, discusses launching of the ISC African Network.

Recently in South Africa, as Secretary General of the International Society of Chemotherapy, I was very pleased to be able to launch a new initiative- the ISC African network. The network will work in close conjunction with the ISC working group on Antibiotic Stewardship (AS) which is co-chaired by Gabriel Levy Hara (Argentina) and Jim Hutchison (Canada). It will be a working group of the Infection Prevention Control African Network (IPCAN) jointly with ISC.

The aims are to create a worldwide web-based compilation of antimicrobial stewardship efforts and activities, the people involved with them, their products and accomplishments. The website will display the collected information and promote sharing. It will be used as a platform for further Antimicrobial Stewardship Working Group initiatives. We believe that this could really help colleagues of different specialities (physicians, pharmacists, microbiologists and health care managers) in formulating and enacting AS initiatives.

Other aims of the ISC AS working group include:

1. Performing international studies of antimicrobial consumption in all five continents.
2. Distance learning courses to address specific and locally prevalent problems (e.g., rational management of URI, principles and experiences with antimicrobial stewardship programs, frequent problems regarding antimicrobial use in the elderly, etc).
3. To work with pharmacists of the different countries in common aspects (regulation, educational programs) regarding use and misuse of antimicrobials.
4. To advocate for the regulation of sales and distribution of antimicrobials worldwide.
5. To hold meetings to highlight stewardship issues.

We are also in discussion about a first position statement to include critical tips in prescribing. ISC is in regular contact with other groups active in this area such as WHO, APUA, CDDEP and CGD as we need to join forces as much as is possible in this critical area.


I M Gould

The APUA African Chapter Network Initiative Uncovers New Data to Guide Improved Antibiotic Therapy

In 2001, APUA set out to develop a chapter network in Sub-Saharan Africa to supplement the limited resources available there to fight high rates of infectious disease. A major focus has been reduction of preventable or easily treatable bacterial diseases such as pneumonia and diarrheal diseases which are prevalent in the general population and often co-infect HIV patients.

Since 2001, APUA has established chapters in Ethiopia, Gambia, Kenya, Mozambique, Namibia, Nigeria, Senegal, South Africa, Tanzania, Uganda, and Zambia, with several more under development. APUA chapters in Zambia and Uganda facilitated introduction of APUA’s recent situation analysis funded by the Bill and Melinda Gates Foundation. With the chapters’ assistance, APUA staff, Dr. Susan Foster and Dr. Aníbal Sosa coordinated in-country research teams of over 100 workers, compiling over 10,000 records from rural and urban sites. At the end of the two year study, country stakeholders were convened to consider implications and recommend interventions.

Key findings from the APUA situation analysis in Zambia and Uganda include:

1. Health staff are still commonly prescribing the antibiotic cotrimoxazole for acute respiratory infection due to S. pneumoniae — even though resistance levels to this drug are very high and the standard for treatment has been changed to amoxicillin.
2. Febrile children even with respiratory distress are almost as likely to get a drug meant to treat malaria as they are to get an antibiotic.
3. In both countries, laboratories need to be upgraded with the proper equipment to collect data on drug resistance rates to various antibiotics and treatment guidelines need to be updated more frequently.

The APUA global chapter network in over 65 countries seeks to improve diagnosis and treatment of infections through improving regulatory policies and clinical practices. The APUA works in close collaboration with other organizations including the WHO, CGD, and the CDC. For more information on the APUA Global Chapter Network see the APUA Chapter Network page on our Web site or to learn more about the Gates Foundation Project in Zambia and Uganda visit our Current Projects page.

Beating resistance? Yes it can be done!

Dr. Steven J. Projan is the Senior Vice President of Research and Development and Innovative Medicines Head of Infectious Diseases and Vaccines at MedImmune.

The question posed is: In an ideal world, what would be your approach to accelerating drug development and strengthening antibiotic stewardship? First and foremost we need to do a better job of encouraging basic research in microbiology because it is from a profound understanding of the underlying biology that all drug discovery comes. The good news is that funding in this area has improved (although given the recent political events this may be a transitory phenomenon) and technology marches on allowing new insights on the microbial ecology of the human being. And when those novel discoveries are made we need a far more sophisticated approach to both drug development and regulatory processes such as basing decisions on “Real World Evidence” rather than the artificiality of Phase III clinical trials. But in terms of stewardship it is becoming increasingly clear that the best way to deal with infections due to resistant bacteria is to prevent them in the first place. As such an increased emphasis on prophylaxis is the best approach from a public health point of view. The success of the pneumococcal conjugate vaccine in reducing the use of antibiotics has been well documented; however another important way to curtail the use of antibacterial drugs is to prevent viral respiratory infections, especially lower respiratory infections (it should be noted that 1/3rd to 2/3rd of the mortality in H1N1 influenza patients was due to secondary bacterial pneumonias and other respiratory viruses such RSV or human rhinovirus type C are likely to play role here as well). Therefore vaccines and immunoprophylactics for both viral and bacterial infections should play an increasing role in both public health practices and industrial research. To further focus our industrial efforts (and stimulate additional research) I support the Infectious Disease Society of America’s call for longer periods of market exclusivity for novel infectious disease products.

Discovery & Stewardship of Narrow Spectrum Antibiotics

APUA board member, Philip Walson, M.D., who is the Editor-in-Chief of Clinical Therapeutics, provided his comments on the recent article, "Optimer Seeks Quick Green Light From FDA for Antibiotic Against Deadly Bug"

It is too early to be sure what the future holds for this new antibiotic, especially compared to much cheaper generic drugs like metronidazole. However, the development of any new antibiotic is welcome and development and commercialization of any so called ``narrow spectrum´´ antibiotics is especially encouraging. The company will now have to convince physicians to adopt a totally new strategy to treating infections; one that includes first making a clear, specific diagnosis and then using a drug designed to treat only the one diagnosed infection and not selecting a ``shotgun´´ approach to all possible infectious agents. If they are successful this should both increase the use of this antibiotic and help to combat excessive, non-specific antibiotic use by training physicians to think differently about the use of antibiotics. This includes considering the development of resistance as a major outcome variable in antibiotic selection. Such thinking can only be welcomed given the rapidly developing rates of multidrug antibiotic resistance which is due at least in part to the overuse of broad spectrum antibiotics.

What does the general public actually know about antibiotics and their activity?

In observance of the ECDC's Antibiotic Awareness Day today, November 18, we asked Dr. Cliodna McNulty, Medical Microbiologist and head of the Health Protection Agency's PCU, to share her thoughts on what the British public knows about antibiotics.

I have been involved in three large household surveys in Britain finding out what the general public think about antibiotics and resistance. The public's attitudes have changed little over the last 7 years. Reassuringly, most of the general public agree that overuse of antibiotics increases resistance, and that antibiotic resistance is increasing. Respondents also know the principles of prudent antibiotic use, as very few disagreed with the statement, "A course of antibiotics should always be completed" and the same percentage didn't agree that "Antibiotics should not be taken unnecessarily."

However, despite many public campaigns the use of antibiotics hasn't changed. A similar number in 2009 to that of 2003 reported having an antibiotic in the past year. Respondents were less knowledgeable about whether antibiotics were active against coughs and colds, viruses, bacterial and our normal flora. A third think that "Antibiotics work on most coughs and colds" and more think that "Antibiotics can kill viruses." This indicates that there are a substantial group of the British public who believe that antibiotics will be of value when they have a cough or cold and are therefore still likely to request antibiotics from clinicians when they have these conditions.

In future antibiotic educational campaigns, it may be better to discuss the need for antibiotics in relation to the severity of infection or syndrome, rather than the type of microbes (be they bacteria or viruses) responsible.

What are your thoughts and ideas?

It's Time to Get Smart About Antibiotics

This guest blog was written by Jean Patel , PhD, D(ABMM), Deputy Director, Office of Antimicrobial Resistance for Centers for Disease Control and Prevention

When I began my career in antimicrobial resistance at the Centers for Disease Control and Prevention (CDC), cephalosporin-resistant Enterobacteriaceae and methicillin-resistant Staphylococcus aureus were the focus of attention . In a few short years, bacterial pathogens have continued to outwit us by changing their genetic make-up enough to survive nearly all antibiotics that might be considered for treatment.

In the past 10 years, carbapenems have been the “drugs of last resort” for Enterobacteriaceae. However, today we have identified carbapenem-resistant Enterobacteriaceae (CRE), which carry an enzyme called the Klebsiella pneumoniae carbapenemase (KPC), in at least 35 states and globally. Most recently, CRE with new mechanisms of resistance (called NDM-1 and VIM) were also identified in the United States.

Now is the time for action. Antibiotics are a shared resource – and becoming a scarce resource. Appropriate use of existing antibiotics can limit the spread of antibiotic resistance, preserving antibiotics for the future.

On November 15-18, 2010, CDC and our partners will observe Get Smart About Antibiotics Week, in an effort to focus attention on improving antibiotic use as a key effort to reduce antibiotic resistance. The U.S. observance will coincide with the European and Canadian antibiotic awareness days, November 18, 2010. In conjunction with Get Smart Week 2010, CDC will unveil its new Get Smart for Healthcare campaign focused on improving antibiotic use in hospitals and long-term care facilities. Improving antibiotic use in in-patient settings can improve cure rates and reduce Clostridium difficile.

Together, we can address this global resistance threat. By leveraging our collective resources towards preserving these vital therapies for the future, we can protect patients and save lives.

Welcome to APUA's new blog, "Superbugs and Drugs"®!

Antibiotics were long considered “miracle drugs,” capable of saving lives from bacterial infections once considered fatal. However, decades of misuse and overuse have led to the emergence of antibiotic-resistant strains of bacteria invulnerable to many of the drugs we have available today. Since 1981, APUA has promoted improved antimicrobial access and more appropriate use with the goal of “preserving the power of antibiotics”®. We accomplish our mission by conducting antimicrobial resistance research, education, and advocacy at the grassroots, national and global levels.

By extending into the blogosphere, APUA experts intend to serve as a global platform to provide insights and provoke your responses on the impact of antibiotic resistance and strategies for improving antibiotic access and use. We will feature entries from the APUA Staff and our Expert Panel, which consists of selected members of our Scientific Advisory Board, APUA chapter leaders, and other experts in this field. We encourage you to join in the discussion.

Thank you,

Kathleen Young, Executive Director and Stuart B. Levy, MD, President

Agricultural, Environmental, and Community Sources of Resistance

A new study from the Johns Hopkins Bloomberg School of Public Health gives further evidence that antibiotic resistance is only just the result of antibiotic use and abuse in human medicine, but that a reservoir of resistance, from farm animals and environmental contamination, is a significant contributor as well. A team of scientists led by Henry D. Kalter examined E. coli samples in more than 500 young Peruvian children, then compared resistance levels to a range of factors in the children's households and communities. The results are published in this month's issue of the American Journal of Tropical Medicine and Hygiene.As would be expected, the children's own use of antibiotics, as well as family member use, was a significant risk factor for their carriage of drug-resistant bacteria. Applying an antibiotic to a population of bacteria selects for the resistant ones to survive, and though these bacteria might not immediately cause disease, they may pass these genes to other species of bacteria, for example through conjugation.

But the authors also found evidence for a transfer of resistant bacteria between food animals and humans - specifically, through market chicken raised with antibiotics. Living in a community with more families raising chickens, as opposed to buying their chicken at a market, was a significant protective factor against children's carriage of resistant bacteria. Market chickens were also significanlty more likely to carry antibiotic-resistant bacteria than home-raised chickens, and presumably transferred this resistance to humans in the community though the food chain or direct contact. Dr. Edward T. Ryan, president of the American Society of Tropical Medicine and Hygiene, explained the study's importance in this respect:

"[The study] improves our understanding of the growing global public health threat of antibiotic resistant organisms, and underscores the critical role that antibiotic use in animals plays in contributing to this threat. The vast majority of the tons and tons of antibiotics ingested each year on this planet are administered to livestock and animals. This study clearly shows that such use comes with a very real cost to human health."

The study also identified a link between environmental contamination with antibiotic-resistant bacteria and increased carriage of resistant E. coli. In fact, as the authors write,

"In these poor communities in a developing country, with inadequate protection of excreta and water, contamination of the environment with antibiotic-resistant bacteria appeared to play at least as great a role in children's carriage of resistant E. coli as did the children's own antibiotic use."

These results corroborate the need for a big-picture approach to addressing antibiotic resistance in both developing and developed nations. The authors cite the intensive use of antibiotics on chickens raised in Peru as a factor contributing to resistance in humans there, but this is hardly an isolated issue - millions of pounds of antibiotics are administered to farm animals every year in the United States, and the presence of an environmental and agricultural reservoir of resistance genes is a threat to the success of antibiotic treatment everywhere.

VRSA in Philadelphia

The first U.S. case of vancomycin-resistant Staphylococcus aureus (VRSA) since 2007 has been identified in a University of Pennsylvania hospital, according to a Philadelphia Inquirer article published today. VRSA is an even more formidable but rare cousin of MRSA, an infection that kills over 19,000 people in the U.S. every year.

The most recent case is a woman on kidney dialysis who was infected both with MRSA and with vancomycin-resistant enterococci (VRE). Vancomycin is used to prevent infection in kidney patients, exposing them to resistance risks. In this case, MRSA bacteria acquired resistance to vancomycin, the drug commonly used to treat MRSA, through genetic transfer from VRE bacteria.

VRSA infections are worrisome because vancomycin is often used as a drug of last resort when other antibiotics fail. Although VRSA is still susceptible to a limited number of antibiotics, these treatments are more costly and invasive than vancomycin and can have serious side effects. Like MRSA, VRSA can be transferred between individuals directly or through objects that have come into contact with infected patients, making it a potentially dangerous force in healthcare settings.

Long-Term Consequences of Antibiotic Treatment

One week of antibiotic treatment can impact commensal bacteria populations and genetic resistance for years, according to a new study published in the Public Library of Science journal, PLoS ONE. A team of researchers led by Hedvig E. Jakobsson of the Swedish Institute for Infectious Disease Control observed the changes brought on by antibiotics prescribed for gastric and duodenal ulcers and found that the balance of commensal bacteria, particularly in the gut, was still disturbed four years following treatment.

The authors followed three patients with ulcers caused by the bacterium Helicobacter pylori and three controls. The case patients were treated twice a day for seven days with the standard course of antibiotics: metronidazole, clarithromycin, and omeprazole. In case patients, bacterial diversity in fecal samples decreased immediately following treatment, with a particular decline in Actinobacteria. In addition, the initially low abundance of erm(B) genes that code for antibiotic resistance increased by 3-5 orders of magnitude in case patients following treatment.

One year after treatment, erm(B) genes were still present at 1,000 times their pre-treatment level, and continued to be elevated four years post-treatment. According to the authors, this increase in resistance could be a result of horizontal gene transfer between bacteria or multiplication of existing drug-resistant bacteria following changes in commensal populations.

There were also changes in the throat microbiota of patients receiving antibiotic treatment, but this population showed more stability than gut bacteria.

Commensal intestinal bacteria are essential to the human immune system, and disruption of this population has potentially dangerous and long-lasting consequences. While calling for larger studies to back up their findings, the researchers emphasized the importance of limited and prudent antibiotic use to prevent the spread of potentially pathogenic antibiotic-resistant bacteria.

Tracing the Roots of MRSA

A study published earlier this year used genomic analysis to trace one of the most common strains of MRSA, ST239, back to the introduction of widespread antibiotic usage in 1960's Europe. The genomic data also gave researchers insight into the transmission of MRSA on both local and global levels.

Led by Dr. Simon Harris of the Wellcome Trust Sanger Institute, the authors analyzed 63 ST239 isolates, 43 of those from different locations around the globe over a period from 1982-2003. By determining the presence single nucleotide polymorphisms (SNPs), small variable regions in an organism's genome, in each isolate, they were able to create a phylogeny that maps out the likely origin of each strain (see image).


The completed puzzle told the researchers that the isolates clustered by location, as would be expected, but that some isolates seemed to have been transmitted between two locations, perhaps by a single individual. For example, isolates from a MRSA outbreak in a London hospital were part of the same genetic cluster that belonged to Thai isolates, indicating the likelihood of a "single intercontinental transmission event."

The phylogeny was created to limit the number of common SNPs that would have come about by convergent evolution - when a mutation develops multiple times in different branches of a genetic tree. Of the SNPs that did indicate convergent evolution, over 25 percent of these were genes involved with resistance to currently-used antibiotics, showing that clinical practice of drug use is a major driver of evolution towards resistant bacteria.

Finally, the analysis allowed the researchers to calculate the rate of mutation of ST239 bacteria at one core SNP every six weeks. Using this figure, they were able to trace a common ancestor for all of the isolates to one strain originating in Europe in the mid-to-late 1960's. This coincides with the beginning of the popular use of antibiotics in Europe, and with the first identified MRSA cases there.

This study may be most useful for the technique it uses to trace resistant isolates through time and location. Combined with improved global surveillance of MRSA, these methods may be used to detect introduction of new strains and target the needed forms of diagnostics and interventions, the authors write.

Coauthor Dr. Sharon Peacock told The Telegraph:

"We are now able to discriminate between one strain and another, even where they are very closely related. Our research should inform global surveillance strategies to track the spread of MRSA.

"The implications for public health are clear: this technology represents the potential to trace transmission pathways of MRSA more definitively so that interventions or treatments can be targeted with precision and according to need."

Bedside Reading

Maryn McKenna is the author of a new book released yesterday, "Superbug: The Fatal Menace of MRSA," on the hospital, community, and environmental dangers of methicillin-resistant Staphylococcus aureus. McKenna, a science and medical journalist with the University of Minnesota's Center for Infectious Disease Research and Policy, discussed the book yesterday on NPR's Fresh Air with Terry Gross. You can listen to the interview here or read the transcript online.

In the interview, McKenna discusses the increased complication in treating MRSA infections due to crossover between what were originally separate healthcare-associated and community-associated MRSA strains. Now, she says, strains that were typically isolated to the hospital or to community settings (prisons and locker rooms, for example) are showing up in unexpected places and behaving in unexpected ways. As a result, doctors are not sure what the drug-resistance pattern of a given infection is -- and as a result, rely on prescribing the most intense drugs available. She also explains the dangers of low-dose antibiotics in farm animals, and the possibility of MRSA being transferred from animals to humans. Although she acknowledges that preventing the spread of MRSA and the development of resistance in general is difficult given the overprescription and overuse of antibiotics, as well as MRSA's resilience as an organism, McKenna does recommend a few things people can do to protect themselves: wash your hands, make sure your kids shower after sports, and use antibiotics appropriately.

Image courtesy of www.npr.org