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, weight loss, night sweats.
  • Endocarditis, particularly due to MRSA, appears to be rising, commensurate with the U.S. opioid epidemic[11].
  • 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.
  • 2023 Duke Clinical Criteria for Definitive IE: 2 Major OR 1 Major + 3 Minor OR 5 Minor.
    • Major (microbiology):
      • Typical organisms x 2 blood cultures
      • Non-typical organisms x 3/3 or 3/4 positive blood cultures
    • Major (imaging):
      • Echocardiography or cardiac CT w/ vegetation, valvular/leaflet perf/abscess, aneurysm, intracardiac fistula
      • New valve regurgitation
      • New partial dehiscence of prosthetic valve as compared with previous imaging
      • Abnormal metabolic activity involving a native or prosthetic valve, ascending aortic graft (with concomitant evidence of valve involvement), intracardiac device leads or other prosthetic material on [18F]FDG PET/CT imaging
    • Major (surgical):
      • Evidence of IE documented by direct inspection during heart surgery, neither Major Imaging Criteria nor subsequent histologic or microbiologic confirmation
    • Minor:
      • Predisposing cardiac condition (h/o IE, h/o valve repair, prosthetic valve, congenital heart disease, > mild regurgitation or stenosis, CIED, hypertrophic obstructive CM) 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 or positive PCR or other nucleic acid-based test (amplicon or shotgun sequencing, in situ hybridization) for an organism consistent with IEr from a sterile body site other than cardiac tissue, cardiac prosthesis, or arterial embolus; or a single finding of a skin bacterium by PCR on a valve or wire without additional clinical or microbiological supporting evidence.
      • Abnormal metabolic activity as detected by [18F]FDG PET/CT within 3 mo of implantation of prosthetic valve, ascending aortic graft (with concomitant evidence of valve involvement), intracardiac device leads or other prosthetic material
      • New valvular regurgitation identified on auscultation if echocardiography is not available
  • 2023 Duke Pathological Criteria for Definitive IE:
    • Microorganisms identified in the context of clinical signs of active endocarditis in vegetation, from cardiac tissue, from an explanted prosthetic valve or sewing ring, from an ascending aortic graft (with concomitant evidence of valve involvement); from an endovascular intracardiac implantable electronic device (CIED); or an arterial embolus OR active endocarditis (vegetations, leaflet destruction, or adjacent tissue of native or prosthetic valves showing variable degrees of inflammatory cell infiltrates and healing) identified in or on a vegetation; from cardiac tissue; from an explanted prosthetic valve or sewing ring; from an ascending aortic graft (with concomitant evidence of valve involvement); from a CIED; or an arterial embolus
  • "Typical" organisms include Staphylococcus aureus; Staphylococcus lugdunensis; Enterococcus faecalis; all streptococcal species (except for Streptococcus pneumoniae and Streptococcus pyogenes), Granulicatella and Abiotrophia spp., Gemella spp., HACEK group microorganisms (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae)
  • In the setting of intracardiac prosthetic material, the following additional organisms should be considered "Typical": coagulase-negative staphylococci, Corynebacterium striatum and Corynebacterium jeikeium, Serratia marcescens, Pseudomonas aeruginosa, Cutibacterium acnes, nontuberculous mycobacteria (especially M. chimaerae), and Candida spp.



  • Patients with active substance use often are frequently challenging, whether cared for in 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 weeks) 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[3][10].
    • 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[10].

Antibiotics: empiric

Pathogen-specific recommendations

  • See the specific pathogen module for additional information.
  • S. aureus (MSSA, preferred):
    • Short course: 2-week course only for tricuspid valve (not MV or AoV) if vegetation < 2cm, no emboli besides lung, negative blood cultures by day 4.
  • S. aureus (MRSA or severe PCN allergy):
  • 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[9].


  • 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.
    • Valvectomy is an option for tricuspid valve endocarditis.
  • Concurrent HIV infection increases the mortality rate when CD4 counts < 200.
  • A transesophageal echocardiogram (TEE) is recommended for patients with an initial negative transthoracic echocardiogram (TTE) if sufficient clinical suspicion remains that would inform a treatment decision, those with inadequate TTE views or those with intracardiac complications on TTE.

Basis for recommendation

  1. Fowler VG, Durack DT, Selton-Suty C, et al. The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria. Clin Infect Dis. 2023;77(4):518-526.  [PMID:37138445]

    Comment: The 2023 Duke-ISCVID IE Criteria propose new microbiology diagnostics (enzyme immunoassay for Bartonella species, polymerase chain reaction, amplicon/metagenomic sequencing, in situ hybridization), imaging (positron emission computed tomography with 18F-fluorodeoxyglucose, cardiac computed tomography), and inclusion of intraoperative inspection as a new Major Clinical Criterion. Additionally, the list of "typical" microorganisms causing IE was expanded (e.g., it now includes E. faecalis and all strep spp except pneumoniae and pyogenes) and provides for pathogens to be considered as typical only in the presence of intracardiac prostheses (e.g., Corynebacterium striatum and jeikeium, C. acnes, Pseudomonas aeruginosa). The requirements for timing and separate venipunctures for blood cultures were removed. Last, additional predisposing conditions (transcatheter valve implants, endovascular cardiac implantable electronic devices, prior IE) were clarified.

  2. 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).

  3. 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: A review of the literature focuses on oral step-down therapy for treating IE.

  4. 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. Goehringer F, Lalloué B, Selton-Suty C, et al. Compared Performance of the 2023 Duke-International Society for Cardiovascular Infectious Diseases, 2000 Modified Duke, and 2015 European Society of Cardiology Criteria for the Diagnosis of Infective Endocarditis in a French Multicenter Prospective Cohort. Clin Infect Dis. 2024;78(4):937-948.  [PMID:38330171]

    Comment: The 2023 criteria were compared to 2000 modified Duke and 2015 European Society of Cardiology (ESC) criteria among 1,194 patients treated for IE 2017-2022 (35% with PVE and 24% with a cardiac implanted electronic device). 2023 criteria had a 97.6% Se and 46% Sp. In patients without CIED, Se was 94.8% and Se was 53.8%.
    Rating: Important

  2. Papadimitriou-Olivgeris M, Monney P, Frank M, et al. Evaluation of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria in a Multicenter Cohort of Patients With Suspected Infective Endocarditis. Clin Infect Dis. 2024;78(4):949-955.  [PMID:38330243]

    Comment: The 2023 criteria were compared to 2000 modified Duke and 2015 European Society of Cardiology (ESC) criteria among 2,132 patients at two Swiss hospitals treated for IE 2014-2022. 2023 criteria showed a higher sensitivity (84%) than previous versions (70%). However, the specificity of the new clinical criteria was lower (60%) compared to earlier versions (74%).
    Rating: Important

  3. Baddour LM, Weimer MB, Wurcel AG, et al. Management of Infective Endocarditis in People Who Inject Drugs: A Scientific Statement From the American Heart Association. Circulation. 2022;146(14):e187-e201.  [PMID:36043414]

    Comment: Nicely done review of IE in PWID, which has complicating factors of addiction medicine and psychosocial factors. Reviewing the literature, ~41% undergo valve surgery with reinfection common if not in substance use therapy. However, there is little uniform approach as centers vary in conservative to more aggressive surgical therapy of endocarditis.

  4. 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

  5. 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 between the two groups in 30-day post-surgical mortality or in-hospital mortality.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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 it was still not sufficiently powered. Other smaller studies offer varying quality and outcomes.

  13. 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: In a 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

  14. 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: This is a retrospective study of patients with 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

  15. 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

  16. 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%.

  17. 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

  18. 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.

  19. 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: At the time, this was 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.

  20. 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).

  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: May 10, 2024