A Therapeutic Challenge: Quadruple-Valve Endocarditis Resulting From Injection Drug Use

Final Diagnosis

Quadruple-valve infective endocarditis with methicillin-resistant Staphylococcus aureus (MRSA) in a patient with a patent foramen ovale (PFO) who injects drugs.

History of Present Illness

A 35-year-old man with a medical history of intravenous polysubstance use disorder, PFO, and tricuspid regurgitation due to prior episodes of tricuspid valve infective endocarditis (IE) was transferred to a tertiary care center from a community hospital, where he presented with shortness of breath and was found to be in shock.

Medical History

The patient’s history was notable for severe polysubstance use disorder, with intravenous drug use (IVDU) for at least 5 years prior to admission. He also had a chronic hepatitis C virus infection, history of skull fracture with plate placement, seizure disorder after a traumatic brain injury, and below-the-knee amputation after a necrotizing infection.

His infectious history was notable for tricuspid valve IE with methicillin-sensitive S aureus 3 years prior to this presentation. At that time, transthoracic echocardiogram (TTE) results revealed a vegetation of 22 × 37 mm on the tricuspid valve with moderate tricuspid regurgitation. Findings from a bubble study revealed a PFO. Results from a CT scan of his chest showed numerous bilateral septic pulmonary emboli and occlusion of the right lower lobe pulmonary artery, believed to be mixed thrombus and infection. He was deemed to be a poor surgical candidate due to his drug use and underwent catheter-directed debulking of the vegetation via vacuum thrombectomy. He completed the appropriate antibiotic treatment. His TTE results after this procedure demonstrated severe tricuspid regurgitation with flail of the posterior leaflet and dilation of the right ventricle. A cardiothoracic surgeon recommended tricuspid valve repair and pulmonary embolectomy, but the patient declined. Five months prior to presentation, he developed tricuspid valve IE with MRSA with innumerable septic pulmonary emboli as well as systemic emboli to the brain. He again completed the recommended antibiotic course. Following this, he had multiple hospital admissions related to decompensated heart failure, during which he again declined surgery. He had blood cultures collected with no growth during these admissions.

Three weeks prior to presentation, he was admitted with right-hand cellulitis and MRSA bacteremia. His MRSA isolate had a vancomycin minimum inhibitory concentration (MIC) of 2. TTE results revealed a small (12 x 8 mm) tricuspid valve vegetation. His aortic and mitral valves had no significant abnormalities, and his pulmonic valve was not visualized. He left the hospital after 3 days and did not complete his course of antibiotics.

Key Medications

He was taking no medications at the time of admission. He had previously taken buprenorphine-naloxone (Suboxone) and methadone. In the hospital, long- and short-acting opioids were initiated to manage opioid withdrawal, with a plan to transition back to buprenorphine-naloxone.

Epidemiological History

The patient was injecting 1 bundle (approximately 14 bags) of fentanyl and xylazine daily at the time of hospital admission. He had a history of benzodiazepine, cocaine, and methamphetamine use. He lived with a family member.

Physical Examination

The patient had initial afebrility and tachycardia, with normal blood pressure. He had tachypnea and required 40 liters per minute of high-flow oxygen with 90% fraction of inhaled oxygen. He appeared to have illness and cachexia. He was lethargic but had no neurologic deficits. He had a grade 2 out of 6 holosystolic murmur. He had a stage 2 decubitus wound on his left hip. He had a prior left leg amputation and had edema of the right leg.

Studies

Significant laboratory values included a white blood cell count elevated at 25 × 103/μL (normal range, 4.0-11.0 × 103/μL), hemoglobin level of 8.6 g/dL with a baseline of 10 g/dL, and platelet count of 88 × 103/μL (normal range, 150-450 × 103/μL). His creatinine level was 2.6 mg/dL with a baseline of 0.9 mg/dL, and his blood urea nitrogen level was 71 mg/dL (normal range, 6-20 mg/dL). The patient’s lactic acid level was 3.0 mmol/L (normal range, 0.4-2.0 mmol/L), and the high-sensitivity troponin level was 7739 ng/L (normal range, 12-76 ng/L). Results from blood cultures were positive for MRSA in all 4 bottles collected. Vancomycin MIC eventually resulted in 1. Results from a chest x-ray showed pulmonary vascular congestion and a small right pleural effusion. TTE results (FIGURE) showed an ejection fraction of 55% to 60% and a severely dilated right ventricle. All 4 valves had vegetations and impaired function. The aortic valve had moderate thickening, mild regurgitation, and a vegetation of 13 × 5 mm. The mitral valve had mild thickening, mild regurgitation, and severe stenosis due to obstruction from multiple vegetations, with the largest measuring 28 × 17 mm. The pulmonic valve had severe thickening, moderate regurgitation, and a vegetation of 9 × 10 mm. The tricuspid valve had thickening and partial destruction of all 3 leaflets, resulting in noncoaptation and torrential regurgitation. There were multiple tricuspid vegetations, with the largest measuring 33 × 22 mm. A large mass of 35 × 9 mm was also seen originating from the right superior pulmonary vein, extending into the left atrium.

Clinical Course

The infectious diseases team recommended dual MRSA therapy with daptomycin and ceftaroline because of the patient’s recent MRSA isolate with vancomycin MIC of 2, which has been associated with higher rates of vancomycin failure. The cardiothoracic surgery team was consulted and considered surgical intervention, which would have included aortic valve replacement and repair of the mitral and tricuspid valves. Because of the extent of infection involving both right- and left-sided valves, catheter-directed thrombectomy was not considered. The patient had clinical deterioration and required cardioversion for supraventricular tachycardia. He had increasing oxygen requirements and developed worsening lactic acidosis with renal and hepatic derangements. On the second day of hospitalization, the patient experienced cardiac arrest and died.

Discussion

We present a case of quadruple-valve endocarditis in a 35-year-old man with a history of injection drug use, which ended in the patient’s death. Major risk factors for quadruple-valve endocarditis include structural heart defects and injection drug use,¹ both of which were present in this case. Unlike previous case reports, which primarily document patients with multiple-valve involvement at presentation, our patient had a long history of endocarditis, with multiple hospitalizations and antibiotic courses before ultimately seeding all 4 valves. He had right-sided heart failure as a result of tricuspid regurgitation from prior episodes of endocarditis; the elevated right-sided pressure may have caused right-to-left shunting across his PFO, allowing blood and bacteria to bypass the pulmonary circulation and more easily cause left-sided infections. This right-to-left shunting and the prolonged MRSA bacteremia with incomplete treatment were the mechanisms leading to involvement of all 4 valves. In the past 2 decades, there has been a dramatic increase in the number of cases of IE in people who inject drugs (PWID) driven by the opioid epidemic. Between 2010 and 2015, the proportion of IE cases related to IVDU increased from 15% to 29%.² These cases are increasingly affecting young people. From 1999 to 2016, IE deaths among PWID increased 3-fold compared with a 1.5-fold increase in IE deaths in people who do not inject drugs; among PWID who died of IE, the proportion of people younger than 35 years tripled in this period.³ Despite this increase in IE in PWID, quadruple-valve endocarditis remains a rare occurrence. Up to 86% of IE cases among IVDU involve the right side of the heart, most commonly the tricuspid valve.⁴ A 2019 review of quadruple-valve endocarditis identified only 22 cases.¹ Since the publication of that review, 5 additional case reports have been identified.^5-9 Endocarditis affecting all 4 valves has high morbidity and mortality; the reported mortality rate is approximately 50%.¹

Retrospective studies indicate that early valve surgery is critical in preventing mortality in these patients.^1,5,8,9 This does not necessarily require 4-valve replacement, as valve debridement and repair have also been successful.¹⁰ Similar to this case, many of the patients in the published case reports¹ did not undergo surgical intervention despite heart failure and large vegetations.

The reason is not always clear, but often, patients are too ill to be operated on by the time they are diagnosed. For patients with major risk factors, especially structural heart defects and a history of IVDU, the index of suspicion for multivalve involvement should be high. Transesophageal echocardiography is more sensitive than TTE for the visualization and ultimate diagnosis of multivalve endocarditis.¹⁰ Early recognition and early surgical consultation are critical to prevent mortality. As highlighted by this case, addressing underlying substance use disorders is essential.

References

1. Zheng S, Soh JXJ, Shafi H. Quadruple valve infective endocarditis presenting with suspected Austrian syndrome: a case report and a case series of quadruple valve infective endocarditis. Diagn Microbiol Infect Dis. 2019;94(1):60-65. doi:10.1016/j.diagmicrobio.2018.11.023

2. Rudasill SE, Sanaiha Y, Mardock AL, et al. Clinical outcomes of infective endocarditis in injection drug users. J Am Coll Cardiol. 2019;73(5):559-570. doi:10.1016/j.jacc.2018.10.082

3. Njoroge LW, Al-Kindi SG, Koromia GA, ElAmm CA, Oliveira GH. Changes in the association of rising infective endocarditis with mortality in people who inject drugs. JAMA Cardiol. 2018;3(8):779-780. doi:10.1001/jamacardio.2018.1602

4. Shmueli H, Thomas F, Flint N, Setia G, Janjic A, Siegel RJ. Right‐sided infective endocarditis 2020: challenges and updates in diagnosis and treatment. J Am Heart Assoc. 2020;9(15):e017293. doi:10.1161/JAHA.120.017293

5. Starobin B, Hillstrom JL. Grand slam: a case of quadruple valve infective endocarditis. J Am Coll Cardiol. 2022;79(suppl 9):2285. doi:10.1016/S0735-1097(22)03276-4

6. Noor A, Butcher B. Quadruple valve endocarditis. Chest. 2017;152(suppl 4):A39. doi:10.1016/j.chest.2017.08.070

7. Kan JA, Bach CR, Stephenson CR. A case of quadruple-valve endocarditis. Mayo Clin Proc. 2025;100(1):17-18. doi:10.1016/j.mayocp.2024.09.013

8. Milicic M, Milacic P, Vukovic P, Nesic I, Tabakovic Z, Zivkovic I. Surgical treatment of quadruple valve endocarditis in a patient with heart failure. Kardiochir Torakochirurgia Pol. 2023;20(3):202-204. doi:10.5114/kitp.2023.131950

9. Planinc M, Kutlesa M, Barsic B, Rudez I. Quadruple-valve infective endocarditis caused by Abiotrophia defectiva. Interact Cardiovasc Thorac Surg. 2017;25(6):998-999. doi:10.1093/icvts/ivx200

10. Yao F, Han L, Xu ZY. Surgical treatment of multivalvular endocarditis: twenty-one-year single center experience. J Thorac Cardiovasc Surg. 2009;137(6):1475-1480. doi:10.1016/j.jtcvs.2008.11.046