- 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
- Suspect endocarditis in any IDU with fever without an otherwise identifiable source.
- Pathogens: S. aureus- 60%, Streptococcal species- 20%, P. aeruginosa- 10%, Candida - 5%, S. epidermidis- 2%.
- Valve involved: tricuspid - 60%.
- 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
- 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 above criteria
- Echocardiographic valve abnormality but not diagnostic for vegetation
- S. aureus (MSSA, preferred):
- Standard course: oxacillin or nafcillin 2gm IV q4h x 6wks + gentamicin 1mg/kg IV q8h x 3-5d.
- Alternative: cefazolin 2gm IV q6h IV x 6 wks +/- gentamicin 1mg/kg IV q8h x 3-5d.
- Note: though gentamicin part of 2005 guidelines, many no longer use for planned 4-6 wk treatment regimens due to toxicity issues and lack of demonstrable benefit.
- S. aureus (MRSA or pen allergy, preferred):
- Vancomycin 15mg/kg q 12h x 6 wks; goal trough >15-20mcg/ml
- Streptococcus viridans
- PCN sensitive, MIC < 0.12:
- Penicillin G12-18 mil Units by continuous infusion or divided into 4-6 daily doses x 4wks
- Ceftriaxone 2gm IV q24h x 4wks
- PCN G or ceftriaxone (above doses) + gentamicin1mg/kg IV q8h x 2wks
- Beta-lactam allergy:
- Vancomycin 15mg/kg IV q12h x 4wks
- Short course:
- PCN MIC >0.12ug/ml-≤0.5µg/ml:
- PCN MIC > 0.5µg/ml (also including Abiotrophia defectiva and Granulicatella species, Gemella species): use enterococcal regimen.
- PCN sensitive, MIC < 0.12:
- Ampicillin 2g IV q4h or aqueous pen G 18-20 mil U/d IV continuous or divided into 4-6 doses x 4-6 wks plus gentamicin* 1 mg/kg q8h IV or IM x 4-6 wks
- Vancomycin 15 mg/kg q 12 h IV plus gentamicin* 1 mg/kg q8h IV or IM x 4-6 wks.
- HACEK organisms:
- P. aeruginosa (use in vitro data to guide, preferred):
- Piperacillin 4gm IV q4h or ceftazidime 2gm IV q8h + tobramycin 2.5mg/kg IV q8h IV (high dose, peak goal 15-20 mcg/ml) +x 4-6wks
- Alternatives: combination therapy
- Candida (preferred):
- Culture negative:
- Indications: severe heart failure, uncontrolled infection, persistent bacteremia despite abx, fungal endocarditis, unstable prosthetic valve, periannular extension.
- Tricuspid valve: may consider valvectomy or vegetectomy + valvuloplasty.
- Aortic or mitral-valve: usually requires replacement.
- Issues: some cardiac surgeons are reluctant to operate on addicts for IE, some require assurance there will be drug rehabilitation.
- 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 mortality rate when CD4 counts < 200.
Basis for recommendation
- Baddour LM et al: Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 111:e394, 2005 [PMID:15956145]
Comment: Latest set of AHA recommendations used for this module.
- Chambers HF, Korzeniowski OM, Sande MA: Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts. Medicine (Baltimore) 62:170, 1983 [PMID:6843356]
Comment: Major differences are: 1) the better prognosis in the addict population; 2) the high rate of tricuspid valve involvement and 3) the high frequency of pulmonary complications. Finding supporting tricuspid valve endocarditis were: pleurisy 30%, pulmonary infiltrates (presumably septic embolic) 80%, signs of tricuspid valve insufficiency (gallop, large V wave, pulsatile liver) 30%.
- Shrestha NK et al: Injection Drug Use and Outcomes After Surgical Intervention for Infective Endocarditis. Ann Thorac Surg Jun 19 [PMID:26095108]
Comment: 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 followup after 6 mos shows a much smaller risk.
- Fernández Guerrero ML et al: Endocarditis caused by Staphylococcus aureus: A reappraisal of the epidemiologic, clinical, and pathologic manifestations with analysis of factors determining outcome. Medicine (Baltimore) 88:1, 2009 [PMID:19352296]
Comment: Review of S. aureus endocarditis in 133 patients including 53 IDU's. Mortality of right sided endocarditis in IDUs was 3.7% vs. 82% in cases associated with IV lines.
- Jain V et al: Infective endocarditis in an urban medical center: association of individual drugs with valvular involvement. J Infect 57:132, 2008 [PMID:18597851]
Comment: Review of 247 cases of endocarditis in San Francisco, 74% were IDUs, most heroin users. OR for IDUs vs. others: S. aureus 5.5, E. faecalis 0.2. tricuspid valve 4.4, mitral valve 0.4.
- Wang A et al: Contemporary clinical profile and outcome of prosthetic valve endocarditis. JAMA 297:1354, 2007 [PMID:17392239]
Comment: IDU's accounted for 167/1797 (9.2%) in global collaborative study.
- Haque NZ et al: Infective endocarditis caused by USA300 methicillin-resistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents 30:72, 2007 [PMID:17428640]
Comment: Seven cases of S. aureus(USA 300) reported in IDU patients. Five were tricuspid valve. One patient had CHF and died.
- Gebo KA 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 43:426, 2006 [PMID:17099314]
Comment: 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. Most common pathogen - S. aureus - 69% including MRSA in 28%. At one year 52% were dead and 16% had a recurrence.
- Fowler VG et al: Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 355:653, 2006 [PMID:16914701]
Comment: Prospective trial of S. aureusendocarditis showed daptomycin (6mg/kg/day) was "not interior" to vancomycin therapy.
- Bassetti S, Battegay M: Staphylococcus aureus infections in injection drug users: risk factors and prevention strategies. Infection 32:163, 2004 [PMID:15188077]
Comment: Author note the epidemic spread of MRSA in injection drug users across Europe and N. America. Nasal carriage is a risk for infection and IDU's have high risks of colonization.
- Moreillon P, Que YA: Infective endocarditis. Lancet 363:139, 2004 [PMID:14726169]
Comment: Review of endocarditis including cases associated with IDU. Major pathogens with IDU risk: S. aureus 69%, Streptococcus 7%, Enterococcus 2%, fungus 2%, culture negative 5%. References for publications for 1993-2003: http://image.thelancet.com/extras/02art12165webappendix.pdf
- Miró JM, del Río A, Mestres CA: Infective endocarditis and cardiac surgery in intravenous drug abusers and HIV-1 infected patients. Cardiol Clin 21:167, 2003 [PMID:12874891]
Comment: Review from Barcelona, Spain-IE accounts for 5-10% of deaths in IDUs, prevalence is 30-70% in developed countries. Tricuspid valve accounts for 60-70%. Mortality is similar with and without HIV unless CD4 < 200. Their experience with surgery for IE in patients with HIV the 1 year survival rate is 65% and the 5-10 actuarial rate is 35%. Overall risk of infection in IDUs is estimated at 2-5% per year.
- Wilson LE et al: Prospective study of infective endocarditis among injection drug users. J Infect Dis 185:1761, 2002 [PMID:12085322]
Comment: Prospective study of 2,529 injection drug users x 10 yrs showed 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%.
- Petrosillo N et al: Endocarditis caused by Aspergillus species in injection drug users. Clin Infect Dis 33:e97, 2001 [PMID:11565094]
Comment: Author presents 3 cases including two with HIV.
- Fortún 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 33:120, 2001 [PMID:11389505]
Comment: The authors report a prospective study of cloxacillin vs vancomycin x 14d for S. aureusendocarditis in IDUs. All patients also received aminoglycosides. Cloxacillin proved superior to vancomycin with cure rates of 100% & 60%, respectively.
- Frontera JA, Gradon JD: Right-side endocarditis in injection drug users: review of proposed mechanisms of pathogenesis. Clin Infect Dis 30:374, 2000 [PMID:10671344]
Comment: The authors conclude that there is no unifying hypothesis to explain this clearly established association.
- Heldman AW et al: Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med 101:68, 1996 [PMID:8686718]
Comment: This is one of the few published prospective controlled trials of treatment of endocarditis. The attempt was to find an adequate oral agent for IDU with S. aureusendocarditis. The authors showed cipro + rifampin x 4wks was as good as nafcillin + gent x 4wks; the side effects clearly 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.
- Pulvirenti JJ et al: Infective endocarditis in injection drug users: importance of human immunodeficiency virus serostatus and degree of immunosuppression. Clin Infect Dis 22:40, 1996 [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 CD4 count <200 (but this is from the pre-HAART era).
- Durack DT, Lukes AS, Bright DK: New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 96:200, 1994 [PMID:8154507]
Comment: Duke criteria as basis for diagnosis of endocarditis.
- Torres-Tortosa M et al: Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis. Grupo de Estudio de Enfermedades Infecciosas de la Provincia de Cádiz. Eur J Clin Microbiol Infect Dis 13:559, 1994 [PMID:7805683]
Comment: Injection drug users with S. aureus tricuspid valve endocarditis were treated with cloxacillin 2gm q 4h IV + amikacin 7.5mg/kg q 12h x 2 wks. Among 72, 67 were cured, 4 needed longer course & 1 died in the hospital. This is the largest study of the 2 wk regimen.
- Arbulu A, Holmes RJ, Asfaw I: Surgical treatment of intractable right-sided infective endocarditis in drug addicts: 25 years experience. J Heart Valve Dis 2:129, 1993 [PMID:8261149]
Comment: The authors from Detroit with what appears to be the greatest experience with tricuspid valve surgery in IDUs with endocarditis review 61 cases. 1)Tricuspid valve replacement 100% mortality due to inability to control infection, reinfection due to IDU, or inability to comply with anticoagulation; 2) Tricuspid valvectomy (55 pts): acute mortality 11%; 9/10 who died 6mo-13 yrs later died from complications of injection drug use.
- Graves MK, Soto L: Left-sided endocarditis in parenteral drug abusers: recent experience at a large community hospital. South Med J 85:378, 1992 [PMID:1566138]
Comment: The distribution of valves in 67 addicts with endocarditis was tricuspid in only 27 (40%) - low than usually reported. Pathogens were S. aureus - 58% & strep species 25%.
- Levine DP, Fromm BS, Reddy BR: Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 115:674, 1991 [PMID:1929035]
Comment: Vancomycin is considered inferior to nafcillin/oxacillin for methicillin-sensitive S. aureus.
- Straumann E, Stulz P, Jenzer HR: Tricuspid valve endocarditis in the drug addict: a reconstructive approach ("vegetectomy"). Thorac Cardiovasc Surg 38:291, 1990 [PMID:2264037]
Comment: The authors present an alternative to tricuspid valve removal for refractory endocarditis in addicts. Vegetectomy with valvuloplasty is now frequently preferred.
- Korzeniowski O, Sande MA: Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts: A prospective study. Ann Intern Med 97:496, 1982 [PMID:6751182]
Comment: A famous prospective study that compared Nafcillin x 4wks + gent x 2 wks vs. nafcillin alone in non-addicts with S. aureusendocarditis. Combination treatment showed more rapid sterilization of blood cultures, but no difference in outcome by clinical parameters. The authors concluded gentamicin did not add significantly; nevertheless, most authorities (and the AHA Council on endocarditis) advocate 3-5days of an aminoglycoside.
- Arbulu A, Asfaw I: Tricuspid valvulectomy without prosthetic replacement. Ten years of clinical experience. J Thorac Cardiovasc Surg 82:684, 1981 [PMID:7300401]
Comment: The authors provide a follow-up of patients who underwent tricuspid valvectomy. Most tolerated the lack of a tricuspid valve in the early post-op period, but many eventually required valve replacement at a second procedure due to refractory right heart failure.
- Reyes MP, Lerner AM: Current problems in the treatment of infective endocarditis due to Pseudomonas aeruginosa. Rev Infect Dis 5:314, 1983 Mar-Apr [PMID:6405476]
Comment: The authors draw from their experience with P. aeruginosaendocarditis in addicts in Detroit. Their recommendations are provided here - high dose tobramycin (8mg/kg/d) to achieve peak levels of 15-20ug/ml combined with an anti-pseudomonal penicillin or ceftazidime.
- Reisberg BE: Infective endocarditis in the narcotic addict. Prog Cardiovasc Dis 22:193, 1979 Nov-Dec [PMID:116317]
Comment: The estimated rate of endocarditis in active injection drug users is estimated at 1.5-2/1000/year. (The estimate for the general population is 3.8/100,000/yr)
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