Antibiotic Resistance Research at Penn

Monday, January 9, 2017


Antibiotic resistance


​​​​​​​The University of Pennsylvania's health schools are engaged in a wide variety of research on the global threat of antibiotic resistance, including antimicrobial stewardship, efforts to develop new antimicrobials and antibiotic use in pets and livestock. Follow along this week as each day we feature a different aspect of that work.

Find us on Twitter at ‪#‎PennOneHealth‬, and find Penn's experts on antibiotic resistance here.

***

ANTIBIOTIC STEWARDSHIP

Perelman School of Medicine

All drugs – from the greatest medical treatments of the modern era to those that help only a small fraction of patients who take them – have benefits and risks, and researchers have to study both sides to quantify them and map out the best, safest uses. This balancing act is part of a constant quest within the medical community. In a perfect scenario, a drug will benefit the largest possible number of patients without causing side effects that outweigh those benefits.

It’s a calculation that’s different for each drug and each disease. Chemotherapy drugs, for instance, can cause severe side effects for individual cancer patients, but they may offer the best chance at beating the disease.

Antibiotic use represents a special challenge, in which too much of a good thing can be dangerous to public health as a whole, and the overuse of antibiotics over the past few decades has led to resistant strains of bacteria. In other words, the bugs are getting stronger, and smarter, and the antibiotics we have can potentially stop working if we’re not careful about how we use them.

The fight against a common, costly, hospital-acquired infection known as Clostridium difficile, or C. diff offers an illuminating case study in the area of so-called antibiotic stewardship. C. diff causes diarrhea and can lead to severe inflammation of the bowel and other complications. Patients with compromised immune systems – including those who undergo stem cell or bone marrow transplants to treat their cancers – are especially at risk. Even with a course of antibiotics, C. diff can lead to longer hospital stays and increased treatment cost. A study published in 2015 in the American Journal of Gastroenterology found the average cost of C. diff ranges from $8,911 to $30,049 per patient.  

Read the full story at the Penn Medicine News Blog.

***

PETS AND ANTIMICROBIAL RESISTANCE

School of Veterinary Medicine

Infection caused by antimicrobial-resistant bacteria is a growing problem in both human and veterinary medicine. Dogs, cats, and many other pets can carry and become infected by drug resistant bacteria just like their owners. The exchange of microbes between people and animals is complex and multifaceted. 

Antimicrobial resistance can make infections difficult to treat, and veterinarians are committed to the judicious use of antibiotics. This means prescribing the right antibiotic for the right organism in the right way. Pet owners can help prevent antimicrobial resistance from developing during treatment of an infection by:

• Adhering strictly to the dosing instructions for antibiotics as prescribed by their veterinarian and always completing full courses of antimicrobials.

• Supporting their veterinarian’s decision to perform bacterial culture and sensitivity. This test can help determine the best antibiotic to treat a pet’s infection. • Choosing to not feed bone- and raw food-based diets.

• Understanding that a veterinarian may choose not to treat a pet with an antibiotic because an infection may be self-limiting (clears on its own) or be caused by a virus (which does not respond to antibiotics).

Together, veterinarians and pet owners can work to combat the emergence of antibiotic resistance in our pets. These efforts can ultimately lead to healthier pets, families, and homes.

Read the full white paper on Penn Vet's website.

***

NEMATODE MOVEMENT

School of Engineering and Applied Science

The round worm Caenorhabditis elegans, a nematode, is a puzzling creature.

previous study at the University of Pennsylvania established that, in some cases, these nematodes are actually counter-current and swim upstream rather than with the flow of liquid as a result of hydrodynamic forces. Another study indicated that they tend to accumulate next to surfaces.

Now, a new study published in the Journal of the Royal Society Interface finds that, rather than settling to the bottom of a pool of water as one would expect for an animal heavier than water, the nematodes seem to “swim happily” through the liquid.

Using two microscopes, one that observed from above and the other from the side, the researchers found that, despite their slow pace and inability to develop lift, the nematodes manage to remain essentially suspended above the bottom of the vessel through constant collisions with it. By continuously bouncing against the bottom, they can maintain their swimming gait.

This could have applications in identifying drug resistance. The nematodes that are more susceptible to drugs are weaker and less able to climb. By collecting the drug-resistant ones, researchers can subject them to genetic analysis to try to identify which genes instill the drug resistance.

Read the full story on the Penn News site.

***

PREVENTIVE ANTIBIOTICS AND DENTAL TREATMENT

School of Dental Medicine

Every year, more than 1 million Americans have surgery to replace a joint, such as a hip or knee. One of the biggest risks of these procedures is infection.

According to a review conducted in 2015 for the American Dental Association (ADA), led by Thomas Sollecito, chair and professor of the Department of Oral Medicine in the School of Dental Medicine, that doesn’t mean it’s always necessary for people with joint replacements to receive antibiotics before dental treatment to prevent prosthetic joint infection.

This practice arose in the 1990s and early 2000s, after a few studies showed indirect evidence that bacteria from the mouth could enter the bloodstream following dental treatment. The concern was that these bacteria could theoretically lead to prosthetic joint infections. But many experts questioned the significance of these findings. So in 2012, the ADA, along with the American Association of Orthopedic Surgeons, conducted a systematic review and published a guideline about the practice that read, “The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.”

The guideline, however, remained confusing for many practitioners.

 “That ‘might consider discontinuing’ language left dentists in a real quandary as to what to do,” Sollecito says.

 The 2015 review, published in the January 2015 issue of the  Journal of the American Dental Association, picked up where the 2012 study left off. Sollecito and colleagues re-examined the scientific studies that had been reviewed in 2012 and also considered a few additional papers that the earlier report had not considered, that did not demonstrate direct evidence that dental procedures led to prosthetic joint infections.

In fact, none of the studies they looked at showed a clinically significant association that a dental procedure causes prosthetic joint infection.

Read the full Penn Current story here.

***

FEED DIRECTIVE

School of Veterinary Medicine

The Veterinary Feed Directive (VFD) final rule, which went into effect on January 1, 2017, impacts producers and owners of food-producing animals and the veterinarians who care for them. The directive applies not only to large flocks and herds, but also to small groups (“backyard flocks”) of animals.

The U.S. Food and Drug Administration (FDA) implemented the final rule of the VFD to address concerns about antimicrobial resistance, judicious use of antimicrobials, and veterinary oversight of the use of “medically important” antimicrobials in feed and water for food-producing animals.

As a result, some antibiotics previously available for purchase over-the-counter will require a VFD/prescription from a licensed veterinarian who has an established relationship with the animal owner/producer purchasing the medications. Use of some antibiotics will have new restrictions.

Penn Vet's Sherrill Davison authored a white paper explaining the rule change, and Penn Vet has assembled a resource kit about antibiotic resistance and veterinary medicine.

For more information, visit www.vet.upenn.edu/antibiotic-resistance.  

***

UNITED NATIONS DECLARATION

Perelman School of Medicine

Since Alexander Fleming first discovered penicillin nearly 100 years ago in 1928, antibiotics have been used to help treat infections and save millions of lives around the world. But recently, overuse of antibiotics in everything from prescriptions to livestock to agricultural products has taken what was once seen as a lifesaving cure and created a looming global health crisis—antimicrobial resistant infections. The micro-organisms that cause infections such as pneumonia, tuberculosis, HIV, and post-operative infections are becoming increasingly difficult to predict. Over time, these organisms have mutated and evolved to outsmart the very medications that were designed to treat them—becoming what’s commonly known as a superbug.

Each year, 700,000 people die from superbug infections and a new study estimates that that number could rise to 10 million by 2050—making superbug infections one of the biggest known threats to humanity today—and unless urgent action is taken, that threat will only continue to grow.

 “Antibiotic resistance threatens our ability to treat even simple bacterial infections,” said Ebbing Lautenbach, chief of the division of Infectious Diseases in the Perelman School of Medicine at the University of Pennsylvania. “Superbugs are quickly becoming one of the biggest threats to modern medicine.”

That’s why the United Nations and its 193 member states are looking to make big strides in the coming years to stomp out these superbug infections. Last week, during the United Nations General Assembly in New York, the UN made history by signing a global declaration to combat these infections.  To date, the UN has only agreed on three other global health interventions: HIV in 2001, non-communicable diseases in 2011, and Ebola in 2013—putting superbugs in an elite but urgent group of public health challenges that impact people around the world.

Lautenbach was one of many experts who attended the global forum in New York last week, urging UN countries to take the pledge.

“The acknowledgment from the UN is long overdue,” Lautenbach said. “Superbugs used to be thought of as local or regional challenges, but we are now seeing that these organisms can spread rapidly from country to country, meaning the response to antimicrobial resistance must be a global one.”

Read the full article on the Penn Medicine News Blog here.