This state-of-the-art review outlines aspects of diagnosis and management of drug use-associated infective endocarditis (DUA-IE). The following are key points to remember:

Background:

1. The global prevalence of intravenous (IV) drug use has increased significantly over the past decade, together with concomitant opioid and methamphetamine use disorders. The estimated number of deaths related to drug overdose in the United States in 2021 exceeded 100,000.
2. Utilization of acute health services for DUA-IE has increased dramatically as well, estimated to have increased by >400% from 2005–2016, and the proportion of admissions for DUA-IE has nearly doubled (6.9%–12.1%).
3. Clinical research typically has excluded patients who inject drugs, and as such, there is very limited prospective observational or experimental data on how to guide treatment.
4. A multidisciplinary approach to the care of these complex and vulnerable patients is essential, including a holistic attitude toward their longitudinal care with the incorporation of harm reduction.

Epidemiology:

1. Individuals with DUA-IE are typically younger, more likely to have HIV and chronic liver disease, and prior endocarditis. The native tricuspid valve is more often involved together with septic emboli. Cardiac devices, and resultant device-related infections, are not common in this young patient population. More recent studies, however, are finding that >40% of cases involve left-sided valves.
2. The most common organism is Staphylococcus aureus, followed by viridans group streptococci, enterococci, coagulase-negative staph, and fungal organisms.
3. Risk factors for in-hospital mortality in right-sided DUA-IE include vegetations >2 cm, or fungal etiology, while risk factors for 6-month mortality include prior infective endocarditis (IE), left-sided IE, polymicrobial etiology, presence of paravalvular abscess or fistula, and stroke.
4. Readmission after index hospitalization has been reported to range from 22%–49% with about one third of patients using injection drugs again. Some smaller studies report up to 70% of patients continuing drug use after a first operation and 44% after a second operation.

Diagnostics:

1. The Modified Duke criteria classify patients into definite, possible, or rejected cases of IE. The risk that drug injection confers is equal to that of one of the minor Duke Criteria: “predisposing heart condition” such as bicuspid aortic valve or prosthetic valve.
2. Transthoracic echocardiography (TTE) is the standard initial imaging modality with guidelines recommending TEE for those meeting Duke clinical criteria for possible IE, those with prosthetic valve(s), and when there is concern for complicated IE. Sensitivity of TTE for identifying IE is ~70% for native valves and ~50% for prosthetic valves, both of which improve to ~90% with TEE. Assessment should include: all valves and degree of their dysfunction, subvalvular apparatus, intracardiac hardware, abscess formation, and intracardiac shunt or fistulae.
3. Initial electrocardiography (ECG) and subsequent ECG monitoring should be done to evaluate conduction disturbances due to periannular extension of the infection, especially in aortic valve endocarditis.
4. Advanced imaging modalities include: A) multi-detector computed tomography (CT) angiography, which has improved visualization of perivalvular abscess and pseudoaneurysm, but less accurate visualization of vegetations. Additionally, it may identify extracardiac sites of infection such as septic emboli. B) Fluorodeoxyglucose (FDG)/positron emission tomography (PET) and leukocyte scintigraphy add diagnostic value for prosthetic valves and cardiac device-related infections, though they perform less well for native-valve endocarditis. FDG-PET/CT has also been shown to have prognostic value in both prosthetic and native valve endocarditis.
5. It is crucial to examine the patient’s substance use disorder (SUD), ideally by a team of addiction experts, who can provide a holistic narrative of the patient, comprehensive trauma-informed assessment of the addiction, mental health history, and assessment of patient’s readiness to engage in SUD treatment.
6. A 9-point scale of clinical and psychosocial risk factors (cravings; unstable home environment; dual psychiatric diagnosis; history of drug overdose; history of multiple relapses; polysubstance abuse; family history of addiction; history of trauma; limited willingness to change) was designed by the University of Alabama-Birmingham to stratify persons who inject drugs as low risk (<3 points), and who could be discharged for antibiotic completion duration versus high risk (>4 points) and who should remain hospitalized for treatment.

Treatment of DUA-IE:

Antimicrobial therapy:

1. Empiric coverage for gram-positive organisms should include coverage for Methicillin Resistant Staph Aureus (vancomycin), while gram-negative organism coverage should include Pseudomonas (cefepime). Once full microbiological data returns, regimens should be more narrowly tailored.
2. Whereas standard treatment for IE is often 6 weeks of antimicrobial therapy, guidelines support abbreviated treatment duration for certain right-sided IE, with the benefit of less indwelling catheter time and less exposure to antimicrobials.
3. Oral antibiotics may be the agent of choice in certain circumstances, but the gold standard therapy typically is still parenteral antibiotics. Long-acting lipoglycopeptide antibiotics are not yet approved by the Food and Drug Administration (FDA) for IE, often too costly, and logistics of access too complicated.
4. Interactions between antibiotics and psychiatric medications can occur. A few common examples include: rifampin (a potent CYP3A4 inducer) and buprenorphine/methadone; linezolid (MAO-inhibitor), which may increase risk of serotonin syndrome; and QTc prolongation with fluoroquinolones and azoles together with methadone and several psychiatric drugs.

Surgical therapy:

1. Decisions to proceed with surgery are complicated by concerns of recurrent drug use and subsequent reinfection of a prosthetic valve.
2. Surgery is technically complex because of extensive tissue destruction. A recent meta-analysis showed persons who inject drugs had 47% greater risk of death and more than twice the risk of a reoperation, with 40% mortality at 5 years. Other studies have shown similar 5-year survival and operative mortality for those with and without DUA-IE.
3. The creation of a STOP (Stratification Risk Analysis in Operative Management) score predicts operative morbidity and mortality based on the presence of nine criteria: active endocarditis, emergency intervention, dialysis, liver disease, enterococcal infections, lung disease, prosthetic valve endocarditis, aortic valve disease, multivalve disease.
4. Current ACC/AHA guidelines provide limited recommendations and suggest avoiding surgery given subsequent risk of prosthetic infection. For right-sided infections, surgery is typically recommended only after failed medical therapy, septic pulmonary embolism, and large vegetations. Tricuspid regurgitation alone is not an indication for surgery unless there is recurrent right-sided heart failure.
5. Valve repair remains preferable over replacement and is associated with lower risk of reinfection. When valve replacement is indicated, mechanical valves are typically used given the patients’ younger age, which then is associated with additional challenges of compliance with anticoagulation.
6. Percutaneous mechanical aspiration has been evaluated in recent years as a safe alternative to surgery. It is a continuous suctioning circuit that can debulk right-sided vegetations (with decreases in size up to 14 mm). Residual vegetations are common, tricuspid regurgitation can worsen, and abscess or leaflet destruction cannot be addressed.

Treatment of Addiction:

1. Addiction consultation teams are critical in providing patient-centered care, support, ensuring adequate symptom management, and long-term help with abstinence. Many hospitals do not have such teams and there is a growing need for trained providers to manage SUD.
2. Initiation of addiction treatment during the hospital stay improves post-discharge outcomes.
3. Medications for opiate use disorder include methadone and buprenorphine, which reduce all-cause mortality and overdose-related mortality up to 50% when compared to no treatment or psychosocial treatment alone. Extended-release naltrexone is a second-line agent that has lower rates of treatment retention and abstinence, though is still better than placebo or counseling alone.
4. For stimulant use disorder (methamphetamines and cocaine), there is no FDA-approved pharmacotherapy.
5. A critical component of all SUD treatments includes harm reduction, the nonjudgmental, noncoercive, person-centered approach to care that focuses on reducing negative. Harm reduction interventions, such as counseling regarding safe injection practices and providing access to clean syringe service programs, have shown to reduce the risk of bacterial infections.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Cardiovascular Care Team, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Implantable Devices, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Interventions and Imaging, Interventions and Structural Heart Disease, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Analgesics, Opioid, Anticoagulants, Bicuspid Aortic Valve Disease, Cardiac Surgical Procedures, Computed Tomography Angiography, Defibrillators, Implantable, Diagnostic Imaging, Drug Overdose, Echocardiography, Electrocardiography, Endocarditis, Bacterial, Heart Failure, Heart Valve Diseases, Heart Valve Prosthesis, HIV Infections, Liver Diseases, Lung Diseases, Methadone, Methamphetamine, Positron Emission Tomography Computed Tomography, Reinfection, Risk Factors, Staphylococcus aureus, Staphylococcal Infections, Stroke, Substance Abuse, Intravenous, Tricuspid Valve Insufficiency, Vancomycin

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