Antimicrobial use in livestock can hurt humans

All IPs know that bacterial resistance to antimicrobials is increasing, but the problem isn’t just poor stewardship in humans – animal use is a culprit, too. The FDA recently released a draft guidance titled “The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals,” which is intended to develop policy on animal antimicrobial use as it affects bacterial resistance and human health.

The guidance summarizes 15 key scientific reports going back to 1969 and then issues FDA’s non-binding recommendations. The reports study evidence that antimicrobial use in food-producing animals develops resistant bacteria, as well as evidence that bacteria is transmitted from the animals to humans. Almost every report concludes that using antimicrobials in food-producing animals poses a public health risk due to the development of bacterial resistance (the reports that do not reach the same conclusion say simply that there wasn’t enough evidence at the time to reach any conclusion at all).

Not all antimicrobial use in livestock is problematic – FDA does make the point that using antimicrobials is beneficial when it ensures animal health. However, sometimes antimicrobials are not used to prevent, treat, or control any disease, but to increase rate of weight gain or improve feed efficiency. Further, some of these antimicrobials are medically important for use in humans. As it is critically important that we maintain the effectiveness of antimicrobials for humans, FDA now calls non-therapeutic animal use “injudicious.” FDA recommends that non-therapeutic use of antimicrobials in animals be discontinued, and that all use should be overseen by veterinarians.

The guidance notes that FDA’s suggestions are non-binding, and requests comments from all interested parties.

You can read the guidance itself here: http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM216936.pdf

FAQ on the guidance here: http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm216939.htm

Daily oral chlorhexidine to help prevent VAP

The Institute for Healthcare Improvement (IHI) recently recommended that adult critical care patients be treated daily with oral chlorhexidine. IHI cites a 2007 meta-study which found that treatment of mechanically-ventilated adults with oral chlorhexidine was associated with a lower risk of ventilator-associated pneumonia (VAP). After continued review of the literature, and after using chlorhexidine in the IHI Ventilator Bundle in Scotland for over a year, the IHI recommends a 0.12% chlorhexidine solution. The recommendation states that “There is little if any evidence of other oral care processes having an effect on the development of VAP, but it makes sense that good oral hygiene and the use of antiseptic oral decontamination reduces the bacteria on the oral mucosa and the potential for bacterial colonization in the respiratory tract.”

Read the full recommendation here: http://www.ihi.org/IHI/Topics/CriticalCare/IntensiveCare/Changes/IndividualChanges/DailyOralCarewithChlorhexidine.htm

New Approaches for Syndromic Surveillance

The interest in syndromic surveillance in Ontario hospitals is understandably high given their experience with SARS in early 2003. The adoption of syndromic surveillance in hospital settings worldwide has been gradual, with mostly public health agencies and defense agencies taking an interest in this surveillance method. Since syndromic surveillance is dependent on early patient contact, and care delivery models are drastically changing, new opportunities for syndromic surveillance emerge.

There’s been plenty of talk on Google Flu Trends since it launched in early 2009 in the midst of H1N1. Twitter and other Web 2.0 platforms are similarly being used to track syndromic trends to detect early outbreaks. CDC has even suggested that as retail health clinics like RediClinic and MinuteClinic, with their modern IT infrastructure and national presence, serve as early detectors of syndromic trends.

As personal health records gain in adoption, these could also provide opportunities for de-identified surveillance for targeted syndromes.

Playing chess with MRSA

Researchers from Duke University Medical Center developed a protein design algorithm that is capable of predicting potential drug resistance mutations in MRSA. The algorithm turns predicting mutations into a game of chess where the computer is like a chess player that tries to anticipate an opponent's moves.

The researchers built the algorithm to look for mutations in a specific MRSA enzyme called dihydrofolate reductase (DHFR). DHFR is necessary for MRSA to replicate itself and is also a key source of drug-resistant mutation. The algorithm looks for mutations in DHFR with two key characteristics. First is a positive design mutation which is a mutation that still allows the enzyme to function. The second is a negative design mutation which is a mutation that blocks the function of the drug.

The algorithm could be incorporated into better drug design to beat MRSA's drug-resistant mutations. For example, scientists would be able to design drugs that can pre-emptively deal with possible resistance in the future.

More on this topic

Transplanting what?

For some patients with persistent, recurring colonic infections, doctors have turned to fecal bacteriotherapy – transplanting a stool sample from a healthy donor into the patient’s colon.  Pediatrics recently reported the successful use of this technique to cure a 2-year-old girl suffering from a many-months-long infection of Clostridium difficile, using her father as the donor.  After the transplant, the girl’s symptoms resolved within 36 hours.

Clinicians have hypothesized that bacteriotherapy works by reestablishing the normal population of microflora in a patient’s colon, but have previously been unable to test this due to limits in microbiology. Now, The New York Times has reported another successful bacteriotherapy treatment – this time with a new development. 

A woman had lost 60 pounds over the course of an 8-month-long C. difficile infection, and her clinician, Dr. Khoruts, turned to bacteriotherapy as a last resort.  The procedure was again successful, resolving the patient’s diarrhea within one day.  However, Dr. Khoruts did something different from the other cases – he took genetic snapshots of the patient’s colonic microflora before and after the fecal transplant.  He found that before the transplant, the population was severely deficient in Firmicutes and Bacteroidetes bacteria, but 14 days after the transplant, the colonic microflora was dominated by Bacteroides species strains – just like the healthy donor’s.

Dr. Khoruts’s results strongly support the idea that fecal bacteriotherapy normalizes the bacterial population in the colon, resulting in restoration of normal bowel function.  Because he focused on which bacteria were present before and after transplantation, his work opens up the possibility of refining this therapy to use specific microbes grown within a controlled environment.  Not only would that kind of scientific advance make the therapy more widely available, but it would eliminate the risks associated with human donor specimens. 

Researchers are just beginning to understand the millions of bacterial species that live in and on humans, and their role in keeping us healthy. This field of research may present many more opportunities to develop novel therapies, and the mounting evidence of successful fecal bacteriotherapy points the way to future clinical studies.

Pediatrics article: http://www.pediatricsupersite.com/view.aspx?rid=65701
New York Times article: http://www.nytimes.com/2010/07/13/science/13micro.html
Dr. Khoruts's Journal of Clinical Gastroenterology abstract: http://journals.lww.com/jcge/Abstract/2010/05000/Changes_in_the_Composition_of_the_Human_Fecal.10.aspx

Conversations on hand hygiene

I had the opportunity to speak with a number of IPs at APIC. One of the topics that routinely came up was hand hygiene. During the poster session, I spoke with Brenda Grant from Stamford Hospital, who was presenting on the hand hygiene initiative at her hospital. By using a multi-faceted approach that included patient and health worker education and independent monitors, Stamford was able to achieve a higher hand hygiene compliance rate than when compliance was enforced by infection control staff alone. However, a challenge she and many other IPs face is to correlate compliance to reduction in HAIs.

I also had a lively discussion with Paula Ghazarian from Via Christi Hospital-Wichita on a different aspect of the issue. One of Paula's concerns is the definition of "hand hygiene opportunity." It's catchy to say "foam in, foam out," which implies that hand hygiene should be done every time someone enters and exits a patient room. Everyone thought this approach would improve compliance, but healthcare workers who are going from room to room replenishing supplies or delivering meals are challenged to comply with it. For example, healthcare workers who are taking contaminated equipment from the patient's room to the soiled utility room (while still wearing their soiled gloves) point out that they cannot complete hand hygiene until they have dropped off the equipment. As a result, people start to make exceptions - which are logical, but which have the effect of undermining the message.

What's the hand hygiene challenge at your hospital?

How much extra revenue is infection control making for a hospital?

One of the challenges infection preventionists face is convincing hospital executives the value of their work, in terms of dollars saved for the hospital. In almost every hospital, infection control is considered a cost center. This perception makes it difficult for IPs to obtain new resources and during times of economic hardship, infection control budgets are often ones that get cut first.

SHEA published a guideline on making a business case for infection control that listed concrete steps to help IPs evaluate resource options using economic analysis, which in turn can be presented to hospital executives who are making budget decisions. Dr. Eli Perencevich, who helped write the document, talked about the core concepts at this year's APIC conference.

The idea that I like the best is calculating the additional number of bed-days that become available as a result of good infection prevention. hospitals make money by bringing in new patients. The number of patients a hospital can accomodate is limited by the number of beds available. In addition to calculating cost saved, IPs can also show the revenue generated by reducing infection rates.

SHEA Guideline

APIC Update

There are so many interesting talks at APIC that there is not enough time to digest it all. A couple topics that I want to expand on in later posts (but want to mention in this post) are 1) How IPs can reposition their roles and their department as revenue centers as opposed to cost centers and, 2) Controversies on hand hygiene compliance, and 3) NOLA cuisine.

I will write more about each of these topics in the next few days.

In the mean time, the Vecna team is having a wonderful time. Ron did a celebrity photo shoot with Dr. Peter Pronovost, the author of Safe Patients, Smart Hospitals. The Wheel of Infection at our booth was a big hit with IPs.

Atul Gawande Keynote at APIC this morning

Sat in Atul Gawande's keynote at APIC this morning. His focus was on the role of infection control, and he of course discussed in-depth the checklist movement and how it can be applied even beyond infection control. Presented his experience as he followed Brigham and Women's IP Debbie Yokoe around to see the hospital through the eyes of an infection preventionist. Some highlights from the keynote:

1. The role of an infection preventionist shouldn't be an "infection control cop". Contrasted against the Semmelweis approach of berating clinicians and providing constant reminders.

2. The people who are most careful in the operating room are often those who are the least careful outside the operating room - cited his own experience when his own patient picked up MRSA.

3. Because primary care and life expectancy is improving globally, more surgical procedures will occur, and there will be more opportunities for surgical site infections.

4. Described the checklist creation process. It is an involved process that can require up to 50 iterations before a usable checklist is developed. Goals are to create a checklist that can be executed quickly and is simple to understand. Implementing a checklist is "more than dropping a sheet of paper in the operating room."

5. Only 25% of hospitals in the US are currently using the checklist (I'm assuming he's talking about the surgery checklist). Washington state implemented it statewide and achieved reduction of infections by 25%.

Just-in-Time Healthcare

Yesterday's New York Times had an article on the application of Kaizen, or Continuous Performance Improvement (CPI) principles at hospitals to reduce cost and increase efficiency. As a Six Sigma enthusiast, I was excited to see that the same concepts that have been used in manufacturing is making its way into healthcare and hospitals are reaping benefits from CPI practices. Hopefully more hospitals will adopt these principles and that one day we will achieve Just-in-Time Healthcare.

NY Times Article

Finally, I am at the APIC Conference this week and so are many of my fellow bloggers. Come to booth #1107 to meet the bloggers!

Vecna Medical Team at APIC - Booth 1107

The Vecna Medical team has arrived at APIC in New Orleans! We braved the rain and the thunderstorm to set up the booth, and we're ready to attend and participate tomorrow.

We're looking forward to Dr. Pronovost's keynote tomorrow as well as Dr. Perencevich's talk on "Economics and Clinical Consequence of your Decision Making." We've already been catching up with IPs and other attendees on our way to the trip. Looking forward to hear what's on your mind.

We'll be periodically posting during the conference, so visit the blog often over the next few days. Drop by our booth 1107 if you'd like to connect with us.

Class I Recall of Cepheid’s Xpert MRSA/SA Blood Culture Assay products for use with GeneXpert Dx System

As reported on fda.gov, “The firm received increasing numbers of complaints for false negative MRSA results when compared to MRSA positive results received from culture methods. All Cepheid MRSA/SA Blood Culture Assay products have a potential of generating infrequent rates of false negative MRSA results, which could result in incorrect treatment or delay of care for patients with MRSA infection.”

“On July 1, 2010, the company issued a press release and sent its customers a revised Corrective Action Notice letter instructing them not to report the MRSA negative result when a MRSA negative/SA positive result is generated on the Cepheid MRSA/SA Blood Culture Assay. Instead, customers were instructed to conduct further antimicrobial susceptibility testing to determine the MRSA result. The MRSA positive/SA positive results generated on the Cepheid MRSA/SA Blood Culture Assay can still be reported. The new instructions will be incorporated in future product labeling. “

The FDA goes on to note that Class I recalls are the most serious type of recall, and that if the products are used, there is a reasonable probability that they will cause serious adverse health consequences, or death.

More information, including model and lot numbers, can be found on the FDA’s website at: http://www.fda.gov/MedicalDevices/Safety/RecallsCorrectionsRemovals/ListofRecalls/ucm218002.htm.

Bigger Brains by Busting Bugs

Reducing and preventing infectious disease leads not only to healthier populations, but also to smarter ones, says a paper recently published in Proceedings of the Royal Society. It’s been previously shown that there is a global variation in intelligence, and that richer, more developed countries have higher average IQs. The paper analyzes several possible factors in this variation, and comes to the conclusion that prevalence of infectious disease is the best predictor of average national IQ.

Their theory, which the authors call the parasite-stress hypothesis, states that infectious disease adversely affects the developing brain because it diverts energy from the brain’s growth to dealing with the parasites. If the growing brain doesn’t get the nutrients and energy it needs, then it will not develop as well as a sufficiently nourished brain, which therefore leads to lower intelligence. The authors do note that parasite stress is likely not the only cause of the global variation in intelligence, but is most probably one of a number of contributing elements.

Interestingly, previous studies have shown that the frequency of asthma and allergies correlates with both higher intelligence and reduced exposure to pathogens. This leads the paper’s authors to hypothesize that the relationship between intelligence and autoimmune diseases might be dependent on exposure to infectious diseases. If a developing child is exposed to fewer infectious diseases, the brain can develop better; however, the body then doesn’t have as many infections to fight, and perhaps it turns on itself as a result.

The study certainly raises a number of issues, including the validity of IQ tests as a measure of intelligence, and issues about how to combat vicious circles (countries are poor because they are sick, and are sick because they are poor). However, setting those aside, the findings seem to underscore the importance of preventing infection to keep us both healthy and smart.

The link to the full text of the paper is here: http://rspb.royalsocietypublishing.org/content/early/2010/06/29/rspb.2010.0973.full

MDROs in agriculture

Humans aren't the only ones battling multi-drug resistant organisms (MDROs), wheat, as it turns out, is also susceptible to fast evolving infectious superbugs. A story on the wheat rust in last week's Economist reminded me of our ongoing battle with MDROs.

Wheat rust is a type of fungal infection that attacks the wheat plant's stem by forming red pustules on the plant and eventually causes the crops to die. The disease is highly infectious - responsible for killing one fifth of America's wheat harvest in the first half of the 20th century.

The discovery of a wheat rust resistant gene in the 1940s led to genetically modified wheat seeds that were resistant to the fungus and seemingly eliminated the disease for the next 40 years.

Scientists have now found that the fungus is making a comback and in a more virulent form. The first case was discovered in 1998 in Uganda. The fungus has evolved to overcome the resistant gene in the wheat plant and has become more lethal to the crop. The new variant, called Ug99, quickly spread to Kenya and Ethiopia and then to the Middle East, evolving into new forms as it spreads. Scientists fear that it will make its way to Southeast Asia and the Far East where 3/5 of world's wheat is grown.

In order to combat the fungus, scientists have developed over 60 experimental varieties of wheat with multiple resistant genes. However, whether or not any of them would work remains to be seens. An even bigger challenge is figuring out how to distribute the new seeds to all of world's wheat growing regions.

http://www.economist.com/node/16481593?story_id=16481593
http://en.wikipedia.org/wiki/Wheat_leaf_rust