Ninety-one Americans die every day from opioid overdose, estimates the Centers for Disease Control and Prevention, but that statistic leaves out the devastation inflicted by diseases that often travel with injecting drug use—HIV/AIDS, hepatitis B and C, and infective endocarditis. Identifying the first three in the emergency department requires little more than a blood test, but infective endocarditis requires a sharp eye, knowledge of its signs, and the wherewithal to undertake the clinical activities needed for a diagnosis, said experts who have studied the problem.

“It is often missed on initial presentation,” said David Carr, MD, an emergency physician at University Health Network in Toronto, Ontario, Canada, and an associate professor of emergency medicine and the assistant director of risk management and faculty development in the network. “However, with a growing opioid epidemic with more intravenous drug use, rates of endocarditis rise.”

IV drug use is not the only risk factor, but include the usual suspects such as patients who have had a mechanical heart valve replacement, said Dr. Carr, who had everyone at the Social Media and Critical Care conference buzzing about the topic when he spoke there this past June in Berlin. More unusual cases are associated with chemotherapy with anti-cancer drugs and the autoimmune disorder lupus.

Among the common symptoms of endocarditis when patients show up in the emergency department are fever, which affects 95 percent of patients, heart murmur, vague aches and pains, and weight loss. “Pull out your stethoscope,” he said. “Heart murmur is one indication for auscultation. You won't find it on an ultrasound machine.”

Often, the endocarditis is not acute and is missed, said Dr. Carr. Blood cultures won't speed up the diagnosis, he said, but he still recommends that emergency and primary care physicians get them for patients who say they feel bad and have a fever and other nonspecific symptoms. The samples should be taken an hour apart from three different sites. “Five to 10 percent of patients with endocarditis are blood culture-negative,” he said. “Often, patients are on antibiotics before they come to the emergency department.”

Physicians sometimes have to send patients home until the culture comes back, but they don't necessarily have to start antibiotics right away, he said. The physician should alert the patient to the possibility of endocarditis, however, if an unusual result comes back.

Drug users, who have morphed from pill takers to shooters, often of heroin, and whose rates of endocarditis are five percent per year, can be infected with bacteria other than the usual Staphylococcus aureus. The risks of overdose and endocarditis increase as opioid users shift from prescription drugs such as oxycodone and oxymorphone to heroin, which may be cut with even more dangerous drugs such as fentanyl. Crushing the pills increases the risk of contamination with particulates that lead to endocarditis, as can other unsterile techniques such as licking the needles and sharing drug paraphernalia.

As the epidemic escalates, Dr. Carr said, the patient may need a team that includes a cardiologist, a cardiovascular surgeon, and an infectious disease specialist as the quarterback leading care.

Perhaps those teams should start in the areas of the country hardest hit by the opioid epidemic. Recent information from the CDC indicates the highest rates of drug overdose death between 2014 and 2015 occurred in Connecticut, Florida, Illinois, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Jersey, New York, North Carolina, Ohio, Pennsylvania, Rhode Island, Tennessee, Washington, and West Virginia.

Complications

A study comparing endocarditis patients who did and did not use intravenous drugs found that the IV drug users stayed in the hospital longer, underwent heart surgery at higher rates, and died at greater rates even though they were younger than the non-IV drug users. (Am J Med Sci 2016;352[6]:603.)

Length of stay for the 48 injection drug users with infective endocarditis was 26 days vs. 12 days for the 79 infective endocarditis patients who did not inject drugs, according to the study. The drug-using group was also younger, 32 vs. 54 for those who did not use drugs. Infective endocarditis cases in drug users increased from 14 percent of hospitalization in 2009 to 56 percent in 2014. Hospital mortality did not differ between the groups: 10.4 percent for IV drug users vs. 8.9 percent for non-drug users (p=0.77).

Daniel Clark Files, MD, an assistant professor of pulmonary, critical care, allergy, and immunologic medicine at Wake Forest School of Medicine in Winston-Salem, NC, who led the study, noted that the areas of North Carolina from which these patients were drawn seemed to have a greater use of oxymorphone than other areas in the United States battered by the epidemic. “We think that there are things in the compounding of this material that cause patients to have a higher incidence of endocarditis,” he said. “In many other areas of the country hard hit by opioid abuse, users switch to heroin as the pills become harder to obtain.”

Often, Dr. Files said, emergency physicians see patients with less severe complications such as abscesses. “I say they should be thinking about endocarditis and high risk. Make sure you get blood cultures on those patients with abscesses reporting injection drug use.”

The epidemic is clearly growing. The incidence of hospital discharge for drug dependence with endocarditis in North Carolina between 2010 and 2015 increased twelvefold—0.2 to 2.7 per 100,000 people per year, according to the CDC's Morbidity and Mortality Weekly Report. (2017;66[22]:1.) Aaron T. Fleischauer, PhD, the career epidemiology field officer for the CDC's Office of Public Health Preparedness and Response, North Carolina Division of Public Health, led the team that analyzed hospitalization for endocarditis among people with diagnosed drug dependence, and found that as heroin-related overdose deaths quadrupled between 2002 and 2014, concomitant infectious complications of such drug use also increased.

“Endocarditis can be a surrogate marker for drug abuse,” said Dr. Fleischauer. “It is one of the more important indicators because it is a serious health complication with exorbitant health care costs in a population that is less likely to have health insurance.”

Attacking the epidemic will require reducing the availability of the drugs while ensuring that patients get drug rehabilitation. “Right now, I would say the substance abuse community has the capability to handle only a fraction of the drug users. Without substance abuse treatment facilities, I think we can anticipate the numbers to stay the same,” Dr. Fleischauer said. “I think another answer is harm reduction. North Carolina has passed some laws allowing safe syringe exchange,” he said.

Yet another study found increases in endocarditis and hepatitis C. That retrospective study at the University of Cincinnati Medical Center from Jan. 1, 1999, to Dec. 31, 2009, found a twofold increase in infective endocarditis, a sixfold increase in opiate toxicology screens, and a threefold increase in antibodies for hepatitis C, said the lead author, Susana Keeshin, MD, who is now at the University of Utah. (Am J Med Sci 2016;352[6]:609.)

“Some of the reasons people use drugs are economic,” she said. “A lot of patients become addicted after having legitimate medical reasons for taking the drugs. They lost their jobs, or their insurance is not as good as it had been. It just became cheaper to use heroin.”

It is a difficult and complicated problem, she said, noting that focus groups revealed that some of the younger patients just started with injecting drugs. Identifying a drug epidemic relies on overdoses, Dr. Keeshin said. “All these infections we are seeing, we could use them as a marker to understand there's an epidemic.”

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