Like it or not, infectious disease providers are at the crossroads of the opioid epidemic. They are now confronting the realization that to fully treat infections related to injection drug use (IDU), they also have to address their patients’ underlying comorbidity—the drug addiction. This places them on the front line of the opioid epidemic, and it’s not a place they necessarily want to be.
In a survey of 1,273 ID providers with 53% (672) responding, more than two-thirds said they treat people who inject drugs (PWID), yet only 46% thought they should actively manage the substance use disorder (SUD) (Open Forum Infect Dis 2018;5[7]:ofy132. doi:10.1093/ofid/ofy132).
Experts who spoke with Infectious Disease Special Edition said ID providers should consider SUD management in their care for these patients. At a minimum, they should ask about IDU and counsel patients to consider treatment. Some might even consider prescribing concurrent medications for SUD, according to Alysse G. Wurcel, MD, MS, an infectious disease physician, at Tufts Medical Center, in Boston.
Others might feel more comfortable with an SUD consult.
Anthony Fauci, MD, the director of the National Institute of Allergy and Infectious Diseases, suggested that ID providers and those treating SUD work together (J Infect Dis 2019 Apr 3. [Epub ahead of print]). “It should be a give-and-take of two subspecialties, and that is the reason why we thought it would be a good idea to talk about the fact that we have a converging public health crisis with infections and opioid abuse. We should get the specialists in both of these public health areas to be aware of each other,” Dr. Fauci said.
“With a lot of patients, we worry about compliance. We worry about psychosocial issues, and so, we have to address them. We have to have multidisciplinary teams,” Thomas M. File Jr., MD, MSc, MACP, the chair of the Infectious Disease Division at Summa Health System and a professor of internal medicine at Northeast Ohio Medical University in Akron, explained at the 2019 annual MAD-ID (Making a Difference in Infectious Diseases) meeting in Orlando, Fla. “This is what you really need to evaluate and try to do an intervention on these patients.”
Where They Intersect
There is growing evidence that PWID have a higher risk for a multitude of infections, not only from the risks presented by unsafe injection and sex practices but also due to opioid-induced immunosuppression.
“The evidence for opioid use and the risk for infection is more than just anecdotal reporting from health care providers,” said Andrew Wiese, MPH, PhD, an assistant professor in the Division of Pharmacoepidemiology, Department of Health Policy, at Vanderbilt University Medical Center, in Nashville, Tenn.
“It has been established that the injection of opioids is linked to a higher risk of infection among injection drug users due to high-risk injection practices, other concurrent high-risk behaviors, and the likely contamination of drugs, needles and injection sites.
“However, it is also important to recognize the evidence for opioid-induced immunosuppression among those using prescribed opioids. Certain opioids, including morphine and fentanyl, have been shown to disrupt lymphocyte and phagocyte proliferation, reduce innate immune cell activity, and inhibit cytokine and antibody expression in experimental studies,” Dr. Wiese explained (Br J Pharmacol 2018;175[14]:2717-2725; Future Microbiol 2018;13(8):849-852). “Recent evidence from epidemiological studies among humans has also consistently shown that those using prescription opioids have a higher risk of serious infections, and that the risk varies based on the opioid type and dose.”
Although heroin and fentanyl are both highly addictive opioids that are frequently injected, they are not the only ones, Dr. Wurcel reminded, and each has a different effect on the body. People also inject cocaine, methamphetamine, ecstasy (3,4-methylenedioxymethamphetamine), ketamine, angel dust (phencyclidine, or PCP) and prescription drugs such as hydrocodone bitartrate-acetaminophen (Vicodin, AbbVie) and dextroamphetamine-amphetamine.
“When we think about injecting drugs, we have to think about them individually,” she said. “As the pharmacists readers will know, cocaine and opioids, for example, act so differently on the body. When you inject cocaine, it is a vasoconstrictor. If there was an infection around the area you injected, the vasoconstriction properties of cocaine prevent your blood and your immune system from getting to the part of the body to address the infection.
“So, we know injection of cocaine causes worse abscesses, etc.,” she explained.
Infections are among the leading reasons why PWID visit the emergency department (ED). In a 2012 study by Fairbairn et al, skin and soft tissue infections (ssSIs) were the leading reason for an emergency department visit by PWID, followed by medication refills and aftercare (typically for wounds); respiratory infections; wounds and lacerations; miscellaneous bacterial or viral infections; cardiac and circulatory disease (often endocarditis); and neurologic disorders and seizures (J Emerg Med 2012;43[2]:236-243).
This adds a significant burden to the overall cost of health care. Tookes et al looked at the infections in a cohort of PWID who came to Jackson Memorial Hospital, in Miami, over a year, and found that the total cost of treatment for IDU-related infections during that period was $11.4 million (PLoS One 2015;10[6]:eo129360. doi:10.1371/journal.pone.0129360).
That is $11.4 million in one hospital in one year.
If you doubt that number, remember the sheer number of the cohort—an estimated 11.8 million people in the United States—misuse opioids, with almost 1 million injecting heroin. Their infections tend to be more expensive to treat because they suffer repeat infections that become resistant or require surgical intervention for debridement or amputation, or they require IV antibiotics and are admitted for extended periods.
“Back when I was directly involved in patient care, there were two big things I always worried about with the injection drug users that I didn’t think about with non-injection drug users,” said Steven N. Leonard, RPh, PharmD, BCIDP, an associate professor, Department of Pharmacy Practice, Rudolph H. Raabe College of Pharmacy, Ohio Northern University, in Ada.
“The first was the risk of them leaving the hospital against medical advice before they could be treated, likely due to withdrawal or desire to continue to use. The second was the thought of how we might finish a potentially long course of IV therapy for something like endocarditis. A typical, non–drug-abusing patient might get sent home with a PICC [peripherally inserted central catheter] to finish the course of therapy, but for reasons that I think are obvious, that was never really a viable option in an injection drug–using patient,” Dr. Leonard said.
Whether PWID can be discharged on outpatient parenteral antimicrobial therapy (OPAT) is a major concern. In the survey discussed above, 79% of the ID providers said their patients frequently required more than two weeks of IV antibiotics, and 76% admitted them to provide these antibiotics.
“Most felt—76%—that the management particularly for IV antibiotics, that the total course be administered within the facility because they were concerned about compliance and the effect of ability and safety of OPAT in these types of patients,” said Dr. File, Dr. File, who is the president-elect of the Infectious Diseases Society of America. “This is something that is of great concern.
“I can tell you there are new data suggesting that if you have a collaborative effort of an addiction medicine team and an OPAT team together, you can successfully administer long-term antibiotics IV for endocarditis, for example, in these patients, but it requires a very significant, labor-intensive process with an addiction medicine team overseeing these patients.
“You just can’t go ahead and do it without that type of input,” added Dr. File, who is also a member of the Infectious Disease Special Edition editorial advisory board.
Each institution handles this issue differently, Dr. Wurcel explained. “The way we do it in my institution, if you use injection drugs and you need six weeks of antibiotics, we have the addiction medicine person see you. We have a small percentage of people who have a social support system that maybe we would see as OK to send home. But the vast majority of people, it is felt that they cannot go home.”
However, a lot of patients won’t consent to admission or check themselves out against medical advice to continue to inject drugs, and there are few other options.
For some, a long-acting injectable like dalbavancin (Dalvance, Allergan), especially for an ssSI, might be helpful if it can be covered by insurance. In that case, PWID would come into the infusion center once a week for treatment. Dr. Wurcel admitted that was not optimal, but it could be an alternative to six weeks of inpatient IV therapy.
Two recent studies in The New England Journal of Medicine showed that an initial treatment of IV antibiotics followed by oral therapy might someday be an option, even for serious infection. “This would present a great solution for what has been a problem in the past,” Dr. Leonard said.
In the POET (Partial Oral Treatment of Endocarditis) trial, 400 Dutch patients with endocarditis from the most common bacterial causes, who were receiving IV antibiotics, continued their IV treatment or were switched to oral antibiotics. There was no significant difference in outcomes between the two regimens (N Engl J Med 2019;380[5]:415-424). (Of note, people who were less likely to be compliant were ineligible for study entry.)
In the OVIVA (Oral Versus Intravenous Antibiotics for Bone and Joint Infection) trial, more than 1,000 patients with bone and joint infections from 26 U.K. hospitals were assigned randomly into an IV therapy or oral antibiotic group. Again, the response to treatment was similar between the groups (N Engl J Med 2019;380[5]:425-436).
However, Helen Boucher, MD, from Tufts, wrote in an accompanying editorial that it was premature to give up on IV therapy for these infections because more research is needed. The studies were open-label trials, included few patients with resistant organisms, and used treatments that were not available in the United States (N Engl J Med 2019;380[5]:487-489).
It Takes a Village
Regardless of whether the patient has HIV, cellulitis or endocarditis, the underlying SUD cannot be ignored, according to Dr. Wurcel, even if people are not ready for treatment to overcome their addiction. “Some people are not ready to stop using drugs. At least you can teach them how to potentially avoid an infection by using different needles and washing their hands.”
Medications, such as buprenorphine-naloxone (Suboxone, Indivior), also can be prescribed along with their antibiotics, said Dr. Wurcel, although she admitted she has so many SUD patients that she might be more comfortable prescribing these medications than others might be. “Not all infectious disease doctors think that this is their task,” she said.
“Who should prescribe them is a tricky question,” she said. “I feel comfortable prescribing, and then the patients follow up with me afterward.”
The first step is to ask about drug use, especially whether they inject drugs. “There needs to be screening at all health care settings,” Dr. File said. “We ask about smoking. We ask about cholesterol. We have to ask about their use of opioids in a general medical evaluation.”
Dr. Wurcel said it was important to ask the question in a nonjudgmental way and to explain to patients that the health care provider needs the information to manage the infection.
Dr. File agreed. Any health care provider who thinks the addiction is the patient’s fault needs to “get over it. It’s a medical illness.”
However, he added, that does not preclude the patients from having some responsibility to manage their own medical illness, which is why an addiction medicine professional should be consulted and part of the treatment team. “They have to be counseled that they are responsible to manage their own medical illness,” he said.
Dr. Fauci concurred. “Given the predominance of opioids and opioid morbidity and mortality leading to 47,600 deaths in 2017 alone, we now have people who are experts in opioid abuse disorder, and then you have the classic ID people.
“As we get deep into the opioid epidemic, you realize that there is this association between infection and opioid use,” he said. “They need to work together, so that they don’t miss an opportunity to help these patients. Given the problem we have, be aware and get people under the proper care.”
Unfortunately, some health care systems still do not provide comprehensive care for SUD. In the ID provider survey, only one-third said their institution provided comprehensive care for addiction, so it might take some effort to convince the C-suite of the need for this team approach.
In addition, better guidelines are needed, and health care providers must be compensated for their care of these patients, Dr. File said.
Another issue is to make sure that PWID are tested regularly for HIV, HCV and sexually transmitted diseases, Dr. Wurcel suggested. “We know we are missing opportunities because we are not asking people each and every time they come in. You screen for HIV whenever there is a risk. If someone is injecting weekly, they have a risk every week, so we need to be treating them. People look at HIV or hep C as an annual test, but it’s not a PAP smear or a mammogram.”
Because most people with opioid use disorder began the walk down that path with an opioid prescription, Dr. Wiese warned, “all providers, not just infectious disease providers, should exercise caution when prescribing opioid analgesics. The relationship between opioids and infections is not limited to the IDU population.” He added that infectious disease providers should consider opioid use as a risk factor for infection when making pain management decisions.
“It’s not just an opioid epidemic. It’s not just a hep C epidemic. It’s not just an HIV epidemic,” Dr. Wurcel said. “They are intertwined, and the sum of them is greater than the individual epidemics in themselves.”
The sources reported no relevant financial relationships.