Due to the ongoing opioid crisis and the related increase in injection drug use, rates of drug use-associated infective endocarditis (DUA-IE) have significantly increased, especially among young adults. Recent study findings offer an updated view of current trends and patient characteristics pertaining to this issue.

In a retrospective study published in 2019 in the Annals of Internal Medicine, researchers at the University of North Carolina at Chapel Hill and Duke University School of Medicine investigated trends in hospitalizations for DUA-IE at hospitals in North Carolina between 2007 and 2017.According to records obtained from a statewide hospital discharge database, patients with DUA-IE comprised 11% of IE hospitalizations over the study period.¹

Annual rates of DUA-IE hospitalizations with and without aortic valve repair increased approximately 12-fold (from 0.92 to 10.95 per 100,000) and 13-fold (from 0.10 to 1.38 per 100,000), respectively, between 2007 and 2017. In the final year of the study, 42% of patients hospitalized with DUA-IE underwent aortic valve repair.¹

The results also shed light on differing patient characteristics between groups. In a comparison of patients with DUA-IE vs those with IE who underwent aortic valve repair, those with DUA-IE were more likely to be younger (median age, 33 vs 56), women (47% vs 33%), White (89% vs 63%), and primarily insured by Medicaid (38%) or uninsured (35%).

Among patients with DUA-IE vs those with IE, the researchers found that both the median length of hospitalization (27 days vs 17 days) and median healthcare-associated costs ($250,994 vs $198,764) were increased among patients with DUA-IE. Of note, 282 DUA-IE hospitalizations comprised healthcare-associated costs of more than $78 million.¹

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According to the researchers, “DUA-IE is a critical emerging public health issue that is affecting the lives of young persons, burdening health systems and public insurance payers, and fundamentally reshaping the epidemiology and management of endocarditis.” They concluded that “enhancing the multidisciplinary infrastructure to address treatment and prevention of DUA-IE should be an urgent priority, including improved provision of addiction care in the inpatient and outpatient setting.”¹

In a study published in 2020 in the Journal of the American Heart Association, researchers at Yale University School of Medicine conducted a similar study focused on nationwide data. Analysis of records obtained from the National (nationwide) Inpatient Sample between 2005 and 2014 showed that IE hospitalizations involving opioid use disorder (OUD) increased from 6.3% to 11.6% over the study period.²

In contrast to the North Carolina findings, the US data showed a similar proportion of aortic valve operations for IE between patients with OUD (11.4%) vs those without OUD (11.1%). In addition, the rate of operative mortality was decreased among patients with OUD compared with those without OUD (4.3% vs 9.4%, respectively; P <.001).²

In terms of patient characteristics, those with OUD were more likely to be younger than those without OUD (37.6 ± 0.21 years vs 60.9 ± 0.16 years). Various comorbidities were more common among patients without OUD, including myocardial infarction, heart failure, peripheral vascular disease, diabetes mellitus, and chronic kidney disease; however, liver disease (46.0% vs 10.8%), and immunosuppressed status (4.3% vs 2.1%) were more common among those with OUD (all P <.0001).²

The researchers noted the “increasing need to recognize the distinct phenotype in patients with endocarditis related to [OUD], and adjust [the] perception of the operative risk, as the short‐term outcome of patients with [OUD] is favorable” compared with traditional endocarditis patients.²

Results of a study published in 2021 in the Journal of the American College of Cardiology also indicated fewer comorbidities and more favorable outcomes among patients with DUA-IE compared with those with IE. Of note, IE cases caused by Staphylococcus aureus occurred in 65.9% patients who use injectable drugs vs 26.8% in those who do not use injectable drugs (P <.001).³

In regard to treatment implications, experts have emphasized the importance of close collaboration between cardiologists, cardiothoracic surgeons, and infectious disease physicians to optimize outcomes in patients with DUA-IE.^4,5

To glean further insights regarding this topic, we interviewed Asher Schranz, MD, MPH, assistant professor of medicine in the Division of Infectious Diseases at the University Of North Carolina’s School of Medicine and lead author of the 2019 study described above.¹

We’ve seen some of the statistics and other findings about patients with IE who inject drugs, but what are you personally seeing in practice?

Dr Schranz: We continue to see a substantial number of patients hospitalized with invasive drug-related infections. These primarily manifest as endocarditis, but endocarditis doesn’t capture all drug-related infections. Many patients don’t have endocarditis but instead have bone, joint, or spine infections or other severe non-endocarditis infections. These infections typically require long courses of intravenous antibiotics, and patients often remain in the hospital for long periods to receive those antibiotics.

Unfortunately, it is not uncommon to see patients with repeated infections such as endocarditis due to ongoing unsafe injection drug practices. These repeated infections are often increasingly complex and may involve less common pathogens, such as Gram-negative bacilli.

What are the current treatment strategies and barriers to treatment for these patients?

Dr Schranz: Treatment is 2-fold and includes both treatment of endocarditis and addressing the substance use disorder (SUD). Antibiotic treatment for DUA-IE is no different than for endocarditis that is unrelated to injection drug use. In addition to antibiotics, the treatment may include surgical operations under certain indications. The decision to pursue an operation should not be limited by a patient’s SUD status. Overall, the available data suggest that postoperative outcomes in the short term are no worse among patients with DUA-IE compared with those with IE unrelated to drug use.⁶

That said, it is critical that treatment for endocarditis be coupled with meaningful, patient-centered care for those with a SUD. For patients with OUD, this should include treatment with medications such as buprenorphine or methadone. All patients should be given naloxone at hospital discharge, as well as information on infection and overdose prevention strategies, such as safer injection techniques, decreasing the risk for overdose by not using drugs alone, and referral to available syringe exchange programs.

What would you recommend to clinicians in terms of treating these patients as well as advocating for better SUD treatment and harm reduction?

Dr Schranz: Optimal treatment involves addressing both the infectious disease care as well as SUD treatment and harm reduction.⁶Harm reduction is a broad term but generally refers to the concept of meeting patients “where they are” in terms of preferred behaviors. For patients who continue to use injectable drugs, this would include having discussions on strategies to decrease both the risk for overdose and future infections.

Additional strategies for clinicians to consider in their day-to-day practices include ensuring all patients are screened appropriately for hepatitis B virus (HBV), hepatitis C virus, and HIV infection; providing guideline-concordant immunization for hepatitis A virus, HBV, and tetanus, given that injection drug use is a risk factor for these conditions; offering a pneumococcal polysaccharide vaccine (PPSV23) if indicated; and considering HIV pre-exposure prophylaxis for patients who inject drugs.

Clinicians may consider outpatient parenteral antibiotic therapy (OPAT) for select patients with DUA-IE. At many institutions, patients with injection drug-related infections are not considered to be appropriate candidates for OPAT and often are hospitalized for several weeks until they receive antibiotics.⁷ However, patients who receive optimal SUD care may complete their antibiotic course at home once stabilized. Experiences among clinicians at numerous institutions including our own, as well as findings from a small trial, support this recommendation.⁸

Not every patient is an appropriate candidate for OPAT. For example, lack of stable housing may hinder a patient’s ability to engage in appropriate at-home health care. Infectious disease physicians who treat patients with injection drug-related infections may consider developing their own internal criteria to evaluate whether patients would successfully complete OPAT.

What are other remaining needs in this area in terms of policy, research, or education?

Dr Schranz: Many patients who inject drugs are negatively impacted by various social determinants of health, such as a lack of stable housing, transportation, telephone service, or insurance coverage. Advocacy to improve these conditions for patients may improve their outpatient care following hospital discharge. Policies that improve insurance coverage, such as Medicaid expansion under the Affordable Care Act, can help remove barriers toward effective outpatient SUD treatment.

Patients with injection drug-related infections have significantly increased rates of premature hospital discharge, including discharges against medical advice. To prevent hospital readmission, clinicians should develop methods to increase patients’ adherence to outpatient care following discharge.

Future research should also focus on the role of long-acting glycopeptide antibiotics, such as dalbavancin and oritavancin, which have been used as second-line therapy for patients who are prematurely discharged from the hospital. Currently, the available data is insufficient to assess whether these antibiotics are truly effective therapies.

Disclosure: Some author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.

References

Schranz AJ, Fleischauer A, Chu VH, Wu LT, Rosen DL. Trends in drug use-associated infective endocarditis and heart valve surgery, 2007 to 2017: a study of statewide discharge data. Ann Intern Med. 2019;170(1):31-40. doi:10.7326/M18-2124
Mori M, Brown KJ, Bin Mahmood SU, Geirsson A, Mangi AA. Trends in infective endocarditis hospitalizations, characteristics, and valve operations in patients with opioid use disorders in the United States: 2005-2014. J Am Heart Assoc. 2020;9(6):e012465. doi:10.1161/JAHA.119.012465
Pericàs JM, Llopis J, Athan E, et al; International Collaboration on Endocarditis (ICE) Investigators. Prospective cohort study of infective endocarditis in people who inject drugs. J Am Coll Cardiol. 2021;77(5):544-555. doi:10.1016/j.jacc.2020.11.062
MU Health Care. Physician engages colleagues to help patients with heart valve infection. Accessed online November 8, 2021.
Vasudevan A, Vyas K, Chen LC, Terhune J, Whitt S, Regunath H. 1910. Developing a multi-disciplinary team for infective endocarditis: a quality improvement project. Open Forum Infect Dis. 2018;5(Suppl 1):S549. doi:10.1093/ofid/ofy210.1566
Schranz A, Barocas JA. Infective endocarditis in persons who use drugs: epidemiology, current management, and emerging treatments. Infect Dis Clin North Am. 2020;34(3):479-493. doi:10.1016/j.idc.2020.06.004
Ceniceros AG, Shridhar N, Fazzari M, Felsen U, Fox AD. Low use of outpatient parenteral antimicrobial therapy for drug use-associated infective endocarditis in an urban hospital system. Open Forum Infect Dis. 2021;8(3):ofab083. doi:10.1093/ofid/ofab083
Fanucchi LC, Walsh SL, Thornton AC, Nuzzo PA, Lofwall MR. Outpatient parenteral antimicrobial therapy plus buprenorphine for opioid use disorder and severe injection-related infections. Clin Infect Dis. 2020;70(6):1226-1229. doi:10.1093/cid/ciz654

This article originally appeared on Infectious Disease Advisor

Addressing Drug Use-Associated Infective Endocarditis