A 39-year-old man with a history of opioid use disorder and post-traumatic stress disorder (PTSD) presented to a psychiatric hospital with a chief complaint of suicidal ideation.
The patient complained of sudden onset of generalized malaise, nausea, and myalgia that began 12 hours earlier. He had experienced similar symptoms in the past when he reduced or stopped using opioids. The patient was admitted to the inpatient psychiatric facility because of his increasing depression related to drug use with a plan to overdose. The patient denied any significant past medical history. His surgical history included incision and drainage under local anesthesia for cutaneous limb abscess 2 years earlier. He said he used nearly a bundle (10 bags) of IV heroin daily, with last use 1 day ago, and a 50-pack-year tobacco history. He denied taking any prescription medications and other illicit drugs. During the review of systems, the patient said that his whole body hurt, and reported additional symptoms of fatigue, chills, diaphoresis, and nervousness.
The patient appeared toxic, emaciated, and lethargic, falling in and out of consciousness throughout the examination. His vital signs were BP, 138/89 mm Hg; heart rate, 108 beats/minute; respirations, 20; temperature, 39° C (102.2° F) orally; and SpO2, 96% on room air. He had visible track marks on all limbs. Cardiac examination revealed tachycardia without murmurs, rubs, or gallops. His lungs were clear to auscultation. He had diffuse muscle tenderness through his limbs and thorax. He was alert and oriented to person, place, and time once verbally aroused but was too lethargic to complete a full mental status and neurologic examination.
Because of the patient's high level of acuity and declining mental status, he was transferred to a tertiary medical facility for immediate diagnostic testing. Tests performed at the tertiary medical facility included a urinalysis, which was unremarkable. A urine drug screen was positive for opioids. ECG revealed sinus tachycardia. Bloodwork demonstrated a leukocytosis of 22,600 cells/mm3 (normal range, 3,800 to 10,800 cells/mm3) with 95% neutrophils and a left shift, and hemoglobin of 8.7 g/dL (normal range, 13.5 to 16.5 g/dL), indicating normocytic anemia. C-reactive protein was mildly elevated at 55 mg/L (normal range, less than 10 mg/L). Blood cultures were positive for methicillin-sensitive Staphylococcus aureus. A transthoracic echocardiogram (TTE) showed multiple small (less than 5 mm) vegetations attached to the tricuspid valve leaflets and an 11-mm vegetation on the chordae of the anterior tricuspid leaflet.
The patient was admitted to the ICU with the diagnosis of infectious endocarditis. He was treated by a multidisciplinary team and placed on empiric antibiotic therapy pending blood cultures. After blood cultures were positive for methicillin-sensitive Staphylococcus aureus, he was started on IV oxacillin. After 1 week of antibiotic therapy, the patient was clinically stable with negative blood cultures. After a 4-week antibiotic course, a repeat TTE showed right ventricular dysfunction and persistence of vegetation with severe tricuspid regurgitation. A culture of the valve showed methicillin-sensitive S. aureus. The patient underwent a tricuspid valve replacement using a bioprosthetic valve because of underlying heart failure. He was placed on anticoagulation therapy (warfarin bridged with low-molecular-weight heparin [enoxaparin]) for 3 months following the valve replacement, with recommended close follow-up. He was given antipyretics for fever and myalgia, and antiemetics for nausea.
The presence of withdrawal symptoms in a patient known to use IV drugs masked the presentation of infective endocarditis because of the concurrent symptoms. Infective endocarditis is an acute inflammation of the endocardium and heart valves typically secondary to a bacterial infection. The annual incidence is 3 to 9 cases per 100,000 patients in developed countries.1 Cases in IV drug users nearly doubled between 2002 (48 cases per 10,000) and 2016 (79 cases per 10,000).2 Although rare, infective endocarditis was previously and most commonly attributed to rheumatic heart disease in patients in developing countries. Now clinicians are seeing a significant increase in cases associated with IV drug use.3 Between 8% and 37.8% of all cases of infective endocarditis are diagnosed in IV drug users, which is nearly 20-fold higher than in patients who do not use IV drugs.4
Endocarditis can be characterized as infectious or noninfectious depending on whether a pathogen is the cause of the inflammation. Noninfectious endocarditis is typically caused by mechanical stress or trauma, chemicals, immunologic diseases, or turbulent blood flow precipitating damage to the endocardium.5
In a patient with endocarditis, a nonbacterial thrombus forms on a cardiac valve, secondary to endothelial trauma, usually from an underlying congenital or acquired cardiac issue. When bacteria in the bloodstream adhere to the thrombotic material present on the heart valve, infectious endocarditis results (Figure 1). Clinical risk factors include both cardiac and noncardiac causes (Table 1). IV drug use is the most common noncardiac cause.1,3,6 In patients who use IV drugs and those who do not, the most common bacterial organism causing infective endocarditis is Staphylococcus, followed by Streptococcal spp.1,7
TABLE 1. -
Common clinical risk factors for infective endocarditis1,3,6
Noncardiac risk factors
Previous episode of endocarditis
Intracardiac devices and prostheses
Congenital or acquired cardiac disease
Rheumatic valve disease
Underlying cardiac pathology (bicuspid aortic valve, mitral valve prolapse)
Right-sided infective endocarditis may be associated with repetitive trauma caused by particulate pollution present in IV drugs.8 The first valves to encounter IV particulate pollution are located in the right side of the heart. The tricuspid valve faces the heaviest burden of pollution and thus bears the most endothelial injury.8 For this reason, the right side of the heart is the most common location of infective endocarditis in IV drug users, with tricuspid valve involvement accounting for 90% of cases.8,9 In contrast, the left side of the heart (typically the mitral or aortic valves) is most frequently affected in patients who do not use IV drugs, because of underlying cardiac pathology.9
According to the CDC, increasing rates of infective endocarditis in IV drug users are further correlated with the increase in heroin abuse.10-13 Opioid prescriptions surged in the late 1990s, leading to misuse and addiction for many patients.14,15 Significant contributing factors include race, sex, lack of economic opportunity, poor work environments, and lower socioeconomic status. In recent years, IV drug users have accounted for a growing percentage of the patients presenting with infective endocarditis; one study found that IV drug users at highest risk for infective endocarditis were young, poor White men with comorbidities such as hepatitis C, HIV, liver disease, or alcohol abuse.2
Symptoms of infective endocarditis often are nonspecific and can mimic other conditions. Fever is a classic symptom and is present in 80% of patients with infective endocarditis.1 Patients also may have diaphoresis, chills, myalgia, malaise, or tachycardia (Table 2). Similarly, opioid withdrawal can cause vague flu-like symptoms as seen in the case patient. The patient's overlapping symptoms associated with opioid withdraw and infective endocarditis delayed the medical workup and subsequent treatment. The time between the patient's initial presentation and the cultures being drawn was roughly 47 hours. An additional 38 hours passed before blood cultures showed bacteremia, with the provision of antibiotic susceptibility testing delaying organism-specific treatment.
TABLE 2. -
Characteristic physical examination findings in patients with infective endocarditis27,33,34
Osler nodes—painful violaceous nodules in the pulp of fingers and toes
Janeway lesions—small, painless, irregular hemorrhagic macules on palms and soles
Roth spots—white-centered retinal hemorrhage
This clinical scenario should alert clinicians to work up patients for infective endocarditis if they have fever and pertinent risk factors even without hallmark symptoms of infective endocarditis such as cardiac murmurs, Roth spots, Osler nodes, or splinter hemorrhages.16 The Duke criteria and modified Duke criteria can be used to establish the diagnosis of infective endocarditis regardless of drug use (Table 3).17 A common misconception is that patients with infective endocarditis present with a cardiac murmur. Surprisingly, patients with infective endocarditis affecting the tricuspid valve rarely have an audible murmur.16 Other hallmark physical manifestations (Roth spots, Osler nodes, and splinter hemorrhages) also are rare.18 Given this variability of rare hallmark physical manifestations, transesophageal echocardiography is necessary to confirm the diagnosis.19
TABLE 3. -
Modified Duke Criteria for the diagnosis of infective endocarditis
|Reprinted with permission from Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med. 1994;96(3):200-209.
Two separate positive blood cultures showing S. aureus, viridans streptococci, Streptococcus gallolyticus, HACEK group (Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans Cardiobacterium hominis, Eikenella corrodens, Kingella kingae)
Persistently positive blood culture
Typical bacterial causes of infective endocarditis: At least two positive blood cultures drawn more than 12 hours apart
Typical bacterial skin contaminants: Three or a majority of four or more separate blood cultures (with first and last drawn at least 1 hour apart)
Echocardiographic evidence: Vegetation, abscess, new partial dehiscence of prosthetic valve, new valvular regurgitation
Predisposition: IV drug use or presence of a predisposing heart condition
Temperature of 38° C (100.4° F) or greater
Vascular phenomena: Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, or Janeway lesions
Immunologic phenomena: Glomerulonephritis, Osler nodes, Roth spots, or rheumatoid factor
Microbiologic evidence: Positive blood cultures not meeting major criteria OR serologic evidence of bacteria consistent with infective endocarditis
Early diagnosis and treatment is key to preventing complications. Common and serious complications include valvular dysfunction, heart failure, systemic emboli, sepsis, and death.20 Several studies have found that patients who use IV drugs have worse outcomes, including higher mortality after valve replacement and increased frequency of repeat endocarditis infections, than patients who do not use IV drugs.21,22
Each year, about 34,000 patients seek treatment for infective endocarditis, and mortality is 10% to 30%.2 According to the 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease, organism-specific antimicrobial therapy and a holistic multidisciplinary team approach is essential to treat bacterial endocarditis in patients who use IV drugs, and should include clinicians from cardiology, infectious disease, cardiac surgery, neurology, nephrology, addiction specialists, case management, and nursing. Empiric antimicrobial therapy may only be necessary in patients with sepsis and those with high-risk presentations.23 Successful treatment requires antibiotic therapy.24,25 The most appropriate antibiotic is based on identification of the infectious organism, its susceptibility, and whether the patient has a nonnative valve. For patients who use IV drugs, vancomycin with or without nafcillin or oxacillin is the recommended empiric therapy.26 Duration of therapy depends on the infection site and pathogen. Four to 6 weeks of antimicrobial treatment is needed for patients with native valves and 6 weeks for those with prosthetic valves. Shorter durations may be reasonable in certain patient populations, such as those with right-sided pathology and those affected by Haemophilus aphrophilius, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae (HACEK) species, and viridans streptococci organisms.27
Treatment challenges in IV drug users include opposition to prolonged hospital stays and poor compliance with in-home antimicrobial therapy. A short course of antimicrobial therapy has been studied and may be considered in these patients.27,28 A 2-week inpatient parenteral antibiotic regimen has been proposed with close follow-up for patients with uncomplicated tricuspid valve endocarditis.22
Patients are considered to have complicated presentations and may require valve replacement surgery if they have coexisting heart failure, cerebrovascular complications, perivalvular abscess, cardiac fistulas, infective endocarditis in a prosthetic valve, systemic embolism, persistent sepsis, or difficult to treat or resistant organisms.22,29,30
Patients who continue IV drug use are most likely to have poor outcomes and repeat infections, especially if they required surgical management.20 Most relapses occur within 1 to 2 months of completing antibiotic therapy, so patient education and close follow-up to ensure adherence to addiction treatment (psychotherapy and MAT) and medical treatment plans are vital.31
The opioid epidemic has greatly contributed to the annual rise of infectious endocarditis among IV drug users.2 Clinicians must be able to identify the clinical presentations of opioid withdrawal and infective endocarditis in patients who use IV drugs because these conditions can occur concurrently. Consider infective endocarditis in a febrile patient who uses IV drugs. Prompt diagnosis and treatment of infective endocarditis improves outcomes and prevents complications and recurrences.20 Also include treatment for the underlying opioid addiction. Including MAT therapy in addition to antibiotics and surgery when treating infective endocarditis in patients who use IV drugs addresses the heart of the opioid epidemic.32
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