Stopping Infectious Diseases

LINDA HARDER   PHOTOGRAPHY TRACEY BROWN

 

Testing Baby Boomers, Decreasing Antibiotic Use are Key

Despite our ability to nearly eradicate measles and even to effectively treat HIV, a number of potentially deadly infectious conditions are on the rise. Our medical experts suggest the best approaches to stop or treat them.

Hepatitis C: Test all Baby Boomers

What is the most common infectious disease in the U.S. today? Perhaps surprisingly, it’s not HIV. Instead, it’s Hepatitis C, a disease that is estimated to affect about five million people in the U.S., many of whom are baby boomers born between 1945 and 1965. Compare that to about one million Americans suffering with HIV and 1.5 million with Hepatitis B.

“The first thing the average physician needs to know is that our diagnosis rates for Hepatitis C are miserable – about 39%,” observes Anurag Maheshwari, M.D., clinical assistant professor of medicine, University of Maryland School of Medicine, Institute for Digestive Health and Liver Disease at Mercy Medical Center. “That’s in stark contrast to HIV, where the rate is about 90%.”

The overall prevalence rates for Hepatitis C are 1.6%, but in baby boomers, the prevalence climbs to 4 or 5%; among inner city baby boomer African American males it may be as high as 8%.

“The highest transmission rate peaked in the 1960s,” Dr. Maheshwari notes. “That’s largely attributable to needle sharing among recreational injection drug use and unsafe medical practices, including blood transfusions and unsafe tattooing. Unprotected sex may also contribute, although the rate of sexual transmission of Hepatitis C is much lower than that for HIV. Unfortunately, some 20 to 35% of those infected don’t have identifiable risk factors.”

Hepatitis C Testing

That’s why, in 2012, the Centers for Disease Control and Prevention (CDC) recommended that all baby boomers get tested for Hepatitis C at least once in their lifetime, even when they have no identifiable risk factors. Physicians can order a simple blood test, the enzyme-linked immunosorbent assay (ELISA), with 94 to 98% accuracy.

Dr. Maheshwari urges primary care physicians to make this assay a routine part of an annual physical for baby boomers who have not yet had the test. “Testing for Hepatitis C should be like getting a colonoscopy for those over age 50,” he advises.

If Hepatitis C is detected by the ELISA test, the next step is determining the quantity and type of the virus. Unfortunately, abnormal liver function tests are not a reliable way to test for this virus. “Patients can have significant liver disease even when their liver function test is normal, so that test doesn’t necessarily indicate that all is well,” Dr. Maheshwari cautions.

Changing Treatment Implications

 A liver biopsy will reveal the presence of cirrhosis and/or the stage of liver disease. In the past, those with Stage 0 or Stage 1 liver disease were recommended deferring treatment, because interferon treatment has significant side effects that can include fatigue, anemia, rashes, nausea, mood swings and even severe depression. Instead, interferon treatment was reserved for those with Stage 2 or higher.

However, with newer treatments that don’t involve interferon, the conventional wisdom for patients at Stage 0 or 1 is changing.

“Patients worry about being able to keep working when they take interferon, which is injected subcutaneously,” Dr. Maheshwari says “But thanks to new options, that’s changing. Interferon treatment used to be 48 weeks in length. In the next six months, we will reduce that to three months of therapy. And in the next 24 months, we should be able to completely eliminate interferon and use pills only. Then we can argue that every patient with this virus should be treated.”

A recent Phase II trial conducted by the National Institute of Allergy and Infectious Diseases and the NIH Clinical Center, published August 28, 2013, in the Journal of the American Medical Association, found that patients — including those in difficult-to-treat populations — can achieve viral control through all-oral treatment regimens. Patients who were given a 24-week regimen of sofosbuvir along with weight-based ribavirin had a sustained virologic response to treatment of 68%. Another preliminary publication funded by Abbot Pharmaceuticals of a combination of three oral anti-viral medications demonstrated cure rates between 93-95% of patients in a small study published in the New England Journal (N Engl J Med 2013; 368:45-53).

“Some doctors and many patients mistakenly think there’s nothing that can be done to treat Hepatitis C,” warns Dr. Maheshwari. “That myth needs to be dispelled. It’s a curable, treatable condition, and failing to treat it can lead to cirrhosis or liver cancer, with possible liver failure and the need for a liver transplant as a consequence.”

No insurance company will provide life insurance if you have Hepatitis C, so why should we physicians leave it untreated? I personally believe that all patients with Hepatitis C should receive treatment, but we need options that are palatable. Thankfully, they’re around the corner.”

He concludes, “My dream is to eradicate this virus in the next 10 years. Physicians need to ensure that their baby boomer patients get tested, even those lacking evident risk factors. It takes five to seven years to progress from one stage to the next, but treatment depends on the patient’s personal preference and co-morbid conditions. A young, healthy 50 year old, for example, should take care of their infection now.”

Fecal Transplants for C. Diff Become Accepted

As the number of U.S. cases of clostridium difficile (C. diff) climbs from roughly 150,000/year in 2000 to about 500,000/year today, and as 15,000 Americans now die from the infection each year, finding effective treatments for refractive cases has become more urgent. The overuse of antibiotics has clearly helped fuel the rise of this disease.

Those over 65 and in long-term-care facilities are at highest risk, while a growing number of pregnant women and children suffer from C. diff. In children, those most at risk have inflammatory bowel disease (IBD), are immuno-suppressed due to transplantation or oncological diseases, or are in chronic-care facilities.

The CDC recently reported that 75% of patients with C. diff actually were already colonized with the disease when they were admitted to a hospital or nursing home. That flew in the face of accepted wisdom that most patients contracted the disease as a result of their stay in such facilities, and suggested that efforts should focus on avoiding contamination from newly admitted patients.

Preventing C. Diff

Maria Oliva-Hemker, M.D., professor of pediatrics and director of pediatric gastroenterology and nutrition at the Johns Hopkins Children’s Center, comments, “The problem with antibiotics is that they kill the good bacteria as well as the bad. In an uncompromised host, there’s some evidence that using probiotics helps. Probiotics can be useful, but they only restore several species of the thousands that populate our gut. And most yogurt in the U.S. has a low concentration of probiotics – if any. As physicians, we need to make sure patients are getting only the antibiotics they need, and getting the right ones, though it’s challenging in an era where patients are conditioned to ask for them.”

New Treatments

Vancomycin and metronidazole have been the go-to treatments for years. In 2011, the FDA approved fidaxomicin (Dificid, Dificlir) as an alternative treatment to vancomycin or metronidazolefor treating this condition. Vancomycin is effective in preventing relapse in about 75% of cases. A recent study demonstrated that fidaxomicin’s relapse rate is only 15%, but it is expensive and far from a panacea.

Diverting loop ileostomy with colonic vancomycin lavage is being tested to replace colectomies in some patients.

Gaining acceptance as another treatment approach is stool (fecal) transplantation. The concept dates back to ancient Chinese in the early first century, and to Western usage in the 1950s. However, only recently has it gained real traction, as studies demonstrate its value. While only about 500 published cases of the procedure exist worldwide today, the success rates with stool transplants have been sufficiently impressive to launch its reconsideration.

A randomly-controlled trial published in the New England Journal of Medicine (NEJM) on Jan. 17, 2013, found that the infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin, at least in an adult population. The trial was stopped early as a result of the far greater efficacy of fecal transplantation (81% resolved after one infusion vs. 31% receiving vancomycin alone).

Fecal transplants are now being tried as a treatment approach in children. “Some 20% of children with C. diff will have recurrence of their diarrhea following vancomycin treatment, and 40 to 60% of these will have a second episode. Fecal transplant should be considered for children who don’t respond to two standard courses of antibiotics,” Dr. Oliva-Hemker states.

Fecal Transplants Extend to Children

While several area hospitals have performed the procedure in adults, the Johns Hopkins Children Center is one of a handful of pediatric hospitals in the country to offer this therapy. Early results are promising, though Dr. Oliva-Hemker expects a relatively small number of cases in the pediatric C. diff population.

Dr. Oliva-Hemker notes, “The procedure has no published short-term side effects, but we don’t know about the long term. Could the transplant of donor stool lead to obesity, for example? So caution is still the rule. However, the truly exciting aspect of this treatment is that, in the future, it may be useful for treating ulcerative colitis, Crohn’s disease and other digestive diseases.”

“The more we know about the microbiome, the more we respect it,”she concludes. “It’s integral to our immune system.

The Procedure

The procedure involves identifying a suitable donor, often the parent. After extensive screening (similar to that undertaken for a blood donor) and stool analysis determines that the donor is a low infection risk, the child is scheduled for the procedure. Within 12 hours of the procedure, the donor provides a stool sample. It can be introduced in the patient’s digestive tract through a nasal-gastric tube, a colonoscopy, or an enema.

According to Dr. Suchi Hourigan, a pediatric gastroenterology fellow involved in the Hopkins protocol, “We use a colonoscopic approach exclusively, which has the advantage of allowing us to view the colon at the same time.”

A number of companies are seeking to replace donor stool with cultured organisms. RePOOPulate is one such product. “The science is not there yet, but when we know what part of the microbiome works, this could be a viable approach. It would allow the procedure to be more standardized,” concludes Dr. Hourigan, who is investigating the microbiome changes that occur in fecal transplantation.

MRSA: A Baltimore Epidemic?

When examining MRSA (Methicillin-resistant Staphylococcus aureus) trends, you have to be careful how you look at the numbers. While the organism — caused by a strain of staph bacteria that’s become resistant to the beta-lactam antibiotics such as methicillin, oxacillin, penicillin and amoxicillin — is becoming more prevalent, the rate of MRSA infections is on the decline.

The CDC reports that the number of healthcare-associated (HA) MRSA cases climbed from 22% of staph infections in 1974 to 64% in 2004. A national prevalence survey in 2010 also documented that MRSA prevalence was higher in 2010 than in 2006.

However, compared with 2006, the rate of MRSA infection has decreased at the same time that the rate of MRSA colonization has increased. The most recent CDC data showed that over 62,000 severe MRSA infections occurred in 2011, and more than 11,000 people died. However, life-threatening HA-MRSA infections have been declining since 2005, especially for those with bloodstream infections.

Further, the proportion of HA-MRSA has decreased as CA-MRSA has increased. Perhaps nowhere is that more true than in Baltimore. Bruce Gilliam, M.D., medical director of the Institute of Human Virology clinic at the Midtown campus of the University of Maryland Medical Center, believes that Baltimore has one of the highest rates of CA-MRSA in the country. “About 60% of the University’s emergency department patients with a culture that grows Staph aureus have MRSA,” he says.

“Not everyone gets skin abscesses from MRSA. Those who do likely have the more virulent strains,” explains Dr. Gilliam We know there are different strains with different virulence factors. At the 2013 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this September, they found that having MRSA when admitted to the hospital was less of a problem than acquiring it in the hospital, because a sick person with multiple co-morbidities will do worse with a bad bug.

“If a hospital can identify that the patient has MRSA when they are admitted, they can better control it,” Dr. Gilliam concludes.

Rapid Testing Is Key

In place of the standard test for MRSA that involved sending a tissue sample or nasal swab to a lab and waiting 48 hours for results, a number of new rapid diagnostic tests are now available on the market, such as GeneXpert.

“However, these tests are expensive and not yet widely used,” Dr. Gilliam observes. “We have to figure out how to use them in a way that improves care. Getting people on a narrow-spectrum antibiotic as soon as possible, such as one that treats gram-positive bacteria only and not also gram negative. Current research has focused on how to identify people with resistant infections versus those whose infections are not resistant.”

Continued Need for Education

“Pediatricians and other physicians are slowly doing a better job of using the appropriate antibiotic only when needed, rather than giving patients who demand an antibiotic one even when it’s not appropriate,” continues Dr. Gilliam. But even physicians don’t always draw a link between giving a patient an antibiotic in the office today and the rise of superbugs – they’re more focused about having an individual patient do well.”

Infectious disease experts estimate that as much as half of the antibiotics currently prescribed are unnecessary. “The overuse and misuse of antibiotics is a large part of the problem,” Dr. Gilliam agrees. “Dutch studies involving children with otitis media found that they could reduce drug resistance if they used antibiotics only when needed.”

Newer Weapons, Similar Outcomes

Hospitals have been pursuing new ways to prevent MRSA. A study of 75,000 ICU patients published in the NEJM in May 2013 found that using daily chlorhexidine wipes and antimicrobial nasal ointment on all ICU patients reduced the presence of MRSA by 37%. This approach was more effective than isolating MRSA patients and treating them differently.

Since treating MRSA is expensive – estimated to cost $10,000 or more per case – preventing it is a key component of controlling healthcare costs as well as health.

 “In today’s hospitals, one factor in our favor is also likely the increase in private rooms,” Dr. Gilliam remarks. “However, most providers don’t identify or address MRSA in the clinic situation or the physician exam room. No one is looking at this – instead, the focus is on hospitals and long term care facilities.”

He adds, “Several new drugs have become available in the past seven to 10 years, including linezolid, daptomycin and ceftaroline fosamil. They can replace vancomycin when there’s toxicity but they may not be better at treating Staph aureus.”

Dr. Gilliam concludes, “Unfortunately, we don’t have the silver bullets for MRSA that it appears we’ll soon have for hepatitis C. We have lots of newer weapons, but not necessarily better outcomes. We need a medical system that recognizes that not getting the right care costs more. The Dutch were able to decrease antimicrobial resistance when they decreased usage of antibiotics. We need similar measures here in the U.S.”

____________________________________

Anurag Maheshwari, M.D., clinical assistant professor of medicine, University of Maryland School of Medicine, Institute for Digestive Health and Liver Disease at Mercy Medical Center.

Maria Oliva-Hemker, M.D., Stermer Family Professor of pediatric inflammatory bowel disease and professor of pediatrics, Johns Hopkins University School of Medicine; director of pediatric gastroenterology and nutrition at the Johns Hopkins Children’s Center.

Bruce Gilliam, M.D., associate professor of medicine and medical director of the Institute of Human Virology clinic at the Midtown campus of the University of Maryland Medical Center.


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One Comment

  1. Janice BristolNo Gravatar
    Posted April 28, 2014 at 9:06 pm | Permalink

    I have been having MRSA for several years. I have taken a lot of antibotics. I have also had the pip line in my arm. The Mrsa will go away and come back after a lot of months. I need a doctor that specializes in MRSA treatment. I go to a ENT doctor now. I would love to go a doctor that specializes in MRSA.
    Ms. Janice Bristol 443-902-5212 Thank You,

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