Endocarditis in persons who inject drugs

Valeria Fabre, M.D.


Common organisms among people who inject drugs (PWID)


  • Fever, malaise, chest/back pain, cough, dyspnea, arthralgia/myalgia, neurologic sx, wt loss, night sweats.
    • Back pain could represent vertebral osteomyelitis, discitis and/or epidural abscess
  • Endocarditis, particularly due to MRSA, appears to be rising, commensurate with the U.S. opioid epidemic[7].
  • Suspect endocarditis in any PWID with fever without an otherwise identifiable source.
  • Pathogens: S. aureus- 60%, Streptococcal species- 20%, P. aeruginosa- 10%, Candida - 5%, S. epidermidis- 2%.
  • Right-sided endocarditis is more common than left-sided, with the tricuspid valve involved in 90%.


  • See the endocarditis module for additional diagnostic details.
  • Duke Clinical Criteria: 2 Major OR 1 Major + 3 Minor OR 5 Minor.
    • Major (microbiology):
    • Major (valve):
      • Echocardiography w/ vegetation definitive/oscillating mass
      • New valve regurgitation
    • Minor:
      • Predisposing cardiac condition or IDU
      • Fever ≥ 38°C (100.4°F)
      • Vascular phenomenon (arterial emboli, mycotic aneurysm, intracerebral bleed, conjunctival hemorrhages, Janeway lesions)
      • Immune phenomenon (glomerulonephritis, Osler nodes, Roth spots, positive rheumatoid factor)
      • Positive blood cultures not meeting the above criteria
      • Echocardiographic valve abnormality but not diagnostic for vegetation



  • Patients with active substance use often are frequently challenging to remain in care at hospitals or nursing facilities to receive IV-based treatment.
    • Working with substance use counselors and entertaining combined medication-assisted treatment for opioids may lead to more durable success.
  • Short-course therapy (2 wks) with IV abx may be possible for some patients with uncomplicated TV endocarditis (see below).
  • Oral therapy can be considered in some instances as step-down therapy[2][6].
    • Oral options based on susceptibility testing and after discussion with ID. Antibiotics used in published studies included linezolid, amoxicillin, and trimethoprim-sulfamethoxazole, among others.
      • The largest oral step-down trial (POET) did not have MRSA cases in their population, so this population is not as well studied[6].

Antibiotics: empiric

Pathogen-specific recommendations

  • See the specific pathogen module for additional information.
  • S. aureus (MSSA, preferred):
    • Short course: 2 wk course only for tricuspid valve (not MV or AoV) if vegetation < 2cm, no emboli besides lung, negative blood cultures by day 4.
  • For other pathogens on native valves, see the endocarditis module.
  • See PROSTHETIC VALVE endocarditis for PVIE regimens.


  • Indications: severe heart failure, uncontrolled infection, persistent bacteremia (> 5 days) despite abx, fungal endocarditis, unstable prosthetic valve, periannular extension, large persistent vegetation.
    • Tricuspid valve: may consider valvectomy or vegetectomy + valvuloplasty.
    • Aortic or mitral valve: usually requires replacement.
  • The reported proportion of patients with right-sided IE requiring surgery is 5%-40%.
  • Issues: some cardiac surgeons are reluctant to operate for IE, requiring assurance there will be drug rehabilitation or refusing second or third valve replacement.
    • Available literature does not suggest a mortality difference between IDU and non-IDU patients with endocarditis[5].


  • Usual presentation: fever, chest x-ray with septic emboli, blood culture yields S. aureus, echocardiogram - tricuspid valve vegetations.
  • Surgery: prognosis for prosthetic valve without drug rehabilitation is poor.
    • For tricuspid valve endocarditis - valvectomy is an option.
  • Concurrent HIV infection increases the mortality rate when CD4 counts < 200.
  • Trans-esophageal echocardiogram (TEE) is recommended for patients with an initial negative trans-thoracic echocardiogram (TTE) if sufficient clinical suspicion remains that would inform treatment decision, those with inadequate TTE view or intracardiac complication on TTE.

Basis for recommendation

  1. Dahl A, Fowler VG, Miro JM, et al. Sign of the Times: Updating Infective Endocarditis Diagnostic Criteria to Recognize Enterococcus faecalis as a Typical Endocarditis Bacterium. Clin Infect Dis. 2022;75(6):1097-1102.  [PMID:35262664]

    Comment: Using data from a prospective study of 344 patients with E. faecalis bacteremia evaluated with echocardiography, the authors demonstrated that designating E. faecalis as a "typical" endocarditis pathogen, regardless of the place of acquisition or the portal of entry improved the sensitivity to correctly identify definite endocarditis from 70% (modified Duke criteria) to 96% (enterococcal adjusted Duke criteria).

  2. Spellberg B, Chambers HF, Musher DM, et al. Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis: A Narrative Review. JAMA Intern Med. 2020;180(5):769-777.  [PMID:32227127]

    Comment: Updated review of the literature on oral step-down therapy for the treatment of IE.

  3. Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation. 2015;132(15):1435-86.  [PMID:26373316]

    Comment: Current IE management guidelines by the American Heart Association


  1. Shmueli H, Thomas F, Flint N, et al. Right-Sided Infective Endocarditis 2020: Challenges and Updates in Diagnosis and Treatment. J Am Heart Assoc. 2020;9(15):e017293.  [PMID:32700630]

    Comment: Updated review of the management of right-sided IE. Right-sided IE accounts for 5% to 10% of all IE cases. Compared with left-sided IE, it is more often associated with intravenous drug use, intracardiac devices, and central venous catheters.
    Rating: Important

  2. Hall R, Shaughnessy M, Boll G, et al. Drug Use and Postoperative Mortality Following Valve Surgery for Infective Endocarditis: A Systematic Review and Meta-analysis. Clin Infect Dis. 2019;69(7):1120-1129.  [PMID:30590480]

    Comment: This study examined 13 studies, including 1593 patients, of which 341 were IDU-IE in the meta-analysis. IDU-IE patients more frequently had tricuspid valve infection, Staphylococcus infection, and heart failure before surgery. Meta-analysis revealed no statistically significant difference in 30-day post-surgical mortality or in-hospital mortality between the two groups.

  3. Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019;380(5):415-424.  [PMID:30152252]

    Comment: In patients with endocarditis on the left side of the heart (including cases due to streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci) who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment.
    Rating: Important

  4. Jackson KA, Bohm MK, Brooks JT, et al. Invasive Methicillin-Resistant Staphylococcus aureus Infections Among Persons Who Inject Drugs - Six Sites, 2005-2016. MMWR Morb Mortal Wkly Rep. 2018;67(22):625-628.  [PMID:29879096]

    Comment: Persons who inject drugs have 16.3x more invasive MRSA infections than others. MRSA infections increased dramatically from 4.1% in 2011 to 9.2% in 2016. Infection types were frequently associated with nonsterile injection drug use causing invasive MRSA infections, including endocarditis, osteomyelitis, and skin and soft tissue infections.

  5. Huang G, Barnes EW, Peacock JE. Repeat Infective Endocarditis in Persons Who Inject Drugs: "Take Another Little Piece of my Heart". Open Forum Infect Dis. 2018;5(12):ofy304.  [PMID:30555849]

    Comment: One-year mortality for patients who injected drugs and had a second bout of endocarditis was 36.3%. Staphylococcus aureus was the most common offending pathogen but occurred less commonly than in the patient’s first bout of IE.

  6. Wang A, Gaca JG, Chu VH. Injection Drug Use-Associated Infective Endocarditis-Reply. JAMA. 2018;320(18):1939-1940.  [PMID:30422192]

    Comment: Infective endocarditis from intravenous drug use increased from 7% to 12% of hospitalizations between 2000 and 2013 in the US (much higher rates reported by single-center studies).
    Rating: Important

  7. Thiagaraj AK, Malviya M, Htun WW, et al. A novel approach in the management of right-sided endocarditis: percutaneous vegectomy using the AngioVac cannula. Future Cardiol. 2017;13(3):211-217.  [PMID:28326804]

    Comment: A minimally invasive approach may hold some promise with further study in assisting infection control in patients with TV disease.

  8. Shrestha NK, Jue J, Hussain ST, et al. Injection Drug Use and Outcomes After Surgical Intervention for Infective Endocarditis. Ann Thorac Surg. 2015;100(3):875-82.  [PMID:26095108]

    Comment: A study from Cleveland Clinic found a 10x risk of death or reoperation in the 3-6 month period after cardiac surgery in those who use injection drugs. Available follow-up after 6 mos shows a much smaller risk.

  9. Al-Omari A, Cameron DW, Lee C, et al. Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review. BMC Infect Dis. 2014;14:140.  [PMID:24624933]

    Comment: The authors review seven trials examining oral therapy for bacterial endocarditis. The most extensive study used ciprofloxacin and rifampin for right-sided disease with equivalent results to traditional IV therapy (Heldman 1996) but still was not sufficiently powered. Other smaller studies offer varying quality and outcomes.

  10. Jain V, Yang MH, Kovacicova-Lezcano G, et al. Infective endocarditis in an urban medical center: association of individual drugs with valvular involvement. J Infect. 2008;57(2):132-8.  [PMID:18597851]

    Comment: Review of 247 cases of endocarditis in San Francisco, 74% were injection drug users, most heroin users. OR for IDUs vs. others: S. aureus 5.5, E. faecalis 0.2. tricuspid valve 4.4, mitral valve 0.4.
    Rating: Important

  11. Lodise TP, McKinnon PS, Levine DP, et al. Impact of empirical-therapy selection on outcomes of intravenous drug users with infective endocarditis caused by methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother. 2007;51(10):3731-3.  [PMID:17664322]

    Comment: Retrospective study of IE due to MSSA who received empiric vancomycin versus beta-lactam or beta-lactam + vanc. Vancomycin patients switched to beta-lactam therapy once susceptibility results became available and had outcomes inferior to those treated with beta-lactam from the initiation of therapy. Based on the observed results, empirical therapy with beta-lactam and an anti-methicillin-resistant S. aureus agent should be considered for serious S. aureus infections.
    Rating: Important

  12. Wang A, Athan E, Pappas PA, et al. Contemporary clinical profile and outcome of prosthetic valve endocarditis. JAMA. 2007;297(12):1354-61.  [PMID:17392239]

    Comment: PWID accounted for 167/1797 (9.2%) in a global collaborative study.
    Rating: Important

  13. Gebo KA, Burkey MD, Lucas GM, et al. Incidence of, risk factors for, clinical presentation, and 1-year outcomes of infective endocarditis in an urban HIV cohort. J Acquir Immune Defic Syndr. 2006;43(4):426-32.  [PMID:17099314]

    Comment: The incidence of endocarditis with HIV and IDU risk decreased from 20.5/1000 person-years in the pre-HAART era to 6.6/1000 person-years in the HAART era. The most common pathogen - is S. aureus - at 69%, including MRSA 28%. At one year, 52% died, and 16% had a recurrence.

  14. Fowler VG, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355(7):653-65.  [PMID:16914701]

    Comment: A prospective trial of S. aureus endocarditis showed daptomycin (6mg/kg/day) was "not interior" to vancomycin therapy.
    Rating: Important

  15. Wilson LE, Thomas DL, Astemborski J, et al. Prospective study of infective endocarditis among injection drug users. J Infect Dis. 2002;185(12):1761-6.  [PMID:12085322]

    Comment: A prospective study of 2,529 injection drug users x 10 yrs showed the incidence of endocarditis was 7/1000 pt yrs which is about 100-fold higher than for non-ID users. Major pathogen - S. aureus in 76%, Strep 13% & Staph unspecified 7%.

  16. Fortún J, Navas E, Martínez-Beltrán J, et al. Short-course therapy for right-side endocarditis due to Staphylococcus aureus in drug abusers: cloxacillin versus glycopeptides in combination with gentamicin. Clin Infect Dis. 2001;33(1):120-5.  [PMID:11389505]

    Comment: The authors report a prospective study of cloxacillin vs. vancomycin x 14d for S. aureus endocarditis in injection drug users. All patients also received aminoglycosides. Cloxacillin proved superior to vancomycin, with cure rates of 100% & 60%, respectively.
    Rating: Important

  17. Frontera JA, Gradon JD. Right-side endocarditis in injection drug users: review of proposed mechanisms of pathogenesis. Clin Infect Dis. 2000;30(2):374-9.  [PMID:10671344]

    Comment: The authors conclude that no unifying hypothesis exists to explain this established association.

  18. Heldman AW, Hartert TV, Ray SC, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med. 1996;101(1):68-76.  [PMID:8686718]

    Comment: This is one of the few published prospective controlled trials of the treatment of endocarditis. The attempt was to find an adequate oral agent for IDU with S. aureus endocarditis. The authors showed cipro + rifampin x 4 weeks was as good as nafcillin + gent x 4 weeks; the side effects favored the oral regimen. The practical use of this oral regimen has been confounded by the increasing resistance of S. aureus to fluoroquinolones and the issue of reliability/compliance of this population to an oral regimen.

  19. Pulvirenti JJ, Kerns E, Benson C, et al. Infective endocarditis in injection drug users: importance of human immunodeficiency virus serostatus and degree of immunosuppression. Clin Infect Dis. 1996;22(1):40-5.  [PMID:8824964]

    Comment: The authors review 144 cases of IE in injection drug users, including 45 with HIV S. aureus accounted for 65% of cases. Mortality was higher with a CD4 count < 200 (but this is from the pre-HAART era).

  20. 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):200-9.  [PMID:8154507]

    Comment: Duke criteria as basis for diagnosis of endocarditis.
    Rating: Important

  21. Straumann E, Stulz P, Jenzer HR. Tricuspid valve endocarditis in the drug addict: a reconstructive approach ("vegetectomy"). Thorac Cardiovasc Surg. 1990;38(5):291-4.  [PMID:2264037]

    Comment: The authors present an alternative to tricuspid valve removal for refractory endocarditis in addicts. Vegetectomy with valvuloplasty is now frequently preferred.

Last updated: February 5, 2023