Heart devices, infections and treatments
Volume 8, Issue 3
Heart valve infections are one of the complications of implanted cardiac devices. Mayo Clinic's infectious disease experts are leaders in finding solutions to this problem, and their research has already changed medical practice and helped heart patients everywhere.
M. Rizwan Sohail, M.D.
James M. Steckelberg, M.D.
When M. Rizwan Sohail, M.D., entered his fellowship in infectious disease at Mayo Clinic in Rochester, Minn., nearly a decade ago, an important trend was under way. The number of patients with newly implanted pacemakers, replacement valves and other heart devices was on the rise, and the technology was saving lives. But there was a down side, too, he quickly learned.
"We were seeing many cases of device infections," Dr. Sohail recalls. And because the devices were so new, no protocols existed to treat the infections.
But the infections were oddly familiar. They followed a pattern similar to that of an uncommon disease that had been a medical mystery for more than a century — endocarditis, an infection of the inner lining of the heart (endocardium) that can damage or destroy heart valves.
The patients Dr. Sohail studied tested positive for bacteria that existed in clusters on the heart valves. The bacteria were encased in high concentrations within a protective layer called biofilm. They had low metabolic activity and grew slowly. Because most antibiotics work best when bacteria are rapidly reproducing, this cardiac infection was hard to treat.
A legacy of expertise and discovery
Concern about his patients with lifesaving implants piqued Dr. Sohail's research curiosity. He steered his work to study device infections, to find out how common they are, and to determine how best to treat them.
He happened to be in the right place. For more than 60 years, researchers at Mayo Clinic have maintained special interest in endocarditis, and their work has had an impact on treatment worldwide.
"It's part of the legacy of our division," Dr. Sohail says, referring to the Division of Infectious Diseases, which is part of Mayo Clinic's Department of Internal Medicine. That particular niche — a cardiovascular infection focus group that consults with a wide range of specialties — continues to address endocarditis and is now looking to improve the future for patients with implanted devices.
Medical intrigue about endocarditis dates back more than a century.
"Historically there's always been a real fascination and intellectual interest in this rather uncommon infection," says infectious disease specialist James M. Steckelberg, M.D., of Mayo Clinic in Rochester, Minn., who has been studying endocarditis for two decades.
As far back as the late 1800s, doctors were aware of a connection between the signs and symptoms — fever, malaise, muscle wasting and abnormal heart rhythms — and post-mortem findings of destroyed heart valves. Endocarditis tended to occur in patients who'd had rheumatic fever, or in those with congenital problems.
But for decades, physicians had nothing to offer in the way of treatment. Every patient died, usually of heart failure, within months.
Mayo Clinic discovers new treatments
Biofilm on the surface of an implanted device.
That changed at Mayo Clinic in the early 1940s. Mayo Clinic internist Wallace Herrell, M.D., became the first to test the new drug penicillin on a patient with endocarditis. Although Alexander Fleming had predicted that the antibiotic he discovered would be ineffective for this particular disease, Dr. Herrell found otherwise.
In fact, penicillin could cure two types of endocarditis, one caused by streptococcus — a bacterial strain that exists in the mouth and gut — and one caused by staphylococcus — a strain that exists on the skin. Taking the treatment further during the 1950s, infectious disease specialist Joseph Geraci, M.D., of Mayo Clinic in Rochester, Minn., tested a combination of penicillin and streptomycin, and found it effective in patients. Dr. Geraci went on to write a landmark series of papers about bacterial endocarditis, defining types of patients who became ill and the efficacy of combinations of penicillin with other antibiotics.
The trouble was that endocarditis is highly varied, and even now, it continues to evolve.
As Walter R. Wilson, M.D., recalls, by the time he arrived at Mayo Clinic for residency in 1971 some strains of bacteria were already resistant to penicillin. Dr. Wilson had harbored personal interest in endocarditis since starting medical school when he read a Harvard medical student's case study from 1931 of his own bout with endocarditis, written up to two days before death. "It broke my heart to read the article," Dr. Wilson recalls. "I never forgot it."
Joining Dr. Geraci, Dr. Wilson added another component to the growing body of research by establishing the Infectious Diseases Laboratory in 1981 — it's now run by Robin Patel, M.D., a professor of medicine and microbiology in the Mayo Clinic College of Medicine — and developing animal models of endocarditis.
"As we looked in the rats, we were able to see things that would have taken generations if we were only observing humans," he says.
His group tested combinations of antibiotics — like penicillin and gentamicin — and determined optimal dosages and regimens for certain strains of bacteria. In clinical studies, they defined parameters for gentamicin use and means to control toxicity of the drug. They changed treatment protocols for certain infections like enterococcal endocarditis, which arises from the urinary tract. They found that those who were sick longer needed protracted medication, but those ill for less than three months could complete treatment within a month.
Population studies impact diagnosis
Larry M. Baddour, M.D., is the HH Sheikh Khalifa Bin Zayed Al-Nahyan Professor of Infectious Diseases Honoring Walter R. Wilson, M.D.
Walter R. Wilson, M.D., is the Edward C. Rosenow, III, M.D., Professor of The Art of Medicine.
By the 1990s, outcomes for patients treated with these regimens were markedly improving. Dr. Steckelberg, who joined Dr. Wilson's lab as a fellow and had previous graduate training in computer science, started a registry of endocarditis patients at Mayo Clinic. The registry enabled comparisons of bacterial cultures, diagnoses, treatments and outcomes, and provided the basis for new clinical studies.
Dr. Steckelberg also became interested in the epidemiology of the disease, delving into the Rochester Epidemiology Project, a longstanding, comprehensive trove of patient records from all of Olmsted County in Minnesota. His studies showed that endocarditis is more prevalent in men, and that it increases in incidence with age.
He also linked endocarditis to a range of valve-damaging diseases. A significant finding was that stroke, long associated with endocarditis, decreased with antimicrobial therapy.
"So we learned early diagnosis can be important," Dr. Steckelberg says.
But the epidemiology also verified what doctors around the world were seeing: The incidence of endocarditis was pronounced among patients with prosthetic heart devices. When Larry M. Baddour, M.D., now chair of the Division of Infectious Diseases, arrived at Mayo Clinic in 2005, it became clear that a new set of challenges lay ahead.
For one, the bacteria that were causing infections in implant patients were slightly different from those associated with infective endocarditis. There were early-onset infections after the implant surgery, and also later ones. Further, blood cultures couldn't always reveal whether the device itself was also infected and needed to be removed.
"We sat down to talk about what was next," Dr. Wilson says. "It appeared we had the same window of opportunity that I had a number of years ago to define the natural history of the disease with these devices, the clinical risk factors and the optimal treatment."
Authoring national treatment guidelines
Biofilm forms on implants when bacteria stick to their surfaces. They multiply into colonies and form a protective slime that allows them to move and collect nutrients while staying safe from antibiotic treatment.
And that's just what they've done. All the work at Mayo Clinic has led to several recommendations that are now espoused by the American Heart Association (AHA).
The guidelines, authored over the last decade by Drs. Wilson and Baddour, have developed treatment protocols and prevention guidelines for infective endocarditis. They changed a decades-old protocol, finding it unnecessary to give antibiotics prophylactically before dental procedures, except for the highest risk patients. They presented the first guidelines for treatment of patients with infected implanted cardiac devices.
"The 2010 document was the first of its kind," Dr. Baddour says. "The AHA had never had a document like that before."
As the use of implanted cardiac devices continues to grow — more than 10,000 have been implanted at Mayo Clinic in the last five years — there's no doubt that the work on device-related infection will be of the utmost significance. Dr. Baddour emphasizes that treatment of these complex patients remains a multidisciplinary undertaking.
"Interest in this condition has come out of infectious disease," he says, "but management is a collaboration involving cardiovascular surgery, cardiology, electrophysiology and others."
The research will build on its broad-based legacy as it faces new bacterial challenges, such as the hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) and long-lasting implants like ventricular-assist devices.
The Rochester-based researchers recently joined forces with Mayo Clinic infectious disease researchers in Florida and Arizona, an endeavor that will bring new information to the registry and provide more information about effective patient management.
One of Dr. Sohail's interests is in improving the diagnosis of device infections, in particular to prevent unnecessary surgeries to replace pacemakers. He's exploring the use of ultrasonic waves to break up the biofilm on devices so that the clustered bacteria can be more easily cultured and analyzed.
The goal of these diverse studies continues to be "finding the best ways to make a difference for patients, whether it's through prevention strategies, early diagnostic techniques, quick diagnosis or the identification of risk factors," Dr. Sohail says. "Ultimately we hope the wide range of our work will identify the best protocols for care."