Culture Negative Endocarditis 5/7/2019

We recently had a case of a middle age man with SLE on chronic prednisone, ESRD on PD, presenting with acute on chronic shoulder pain x 10 days. Presentation was initially concerning for septic arthritis, and joint washout revealed gross purulence from the shoulder joint. Cultures were sent but no additional fluid studies were obtained.

A subsequent TTE, and later a TEE, confirmed a mitral valve vegetation concerning for concurrent infective endocarditis. However, multiple sets of blood cultures, fungal cultures, synovial fluid culture from the initial I&D/wash out, and even 16S PCR of the synovial fluid were all negative. This is a rare case of culture negative endocarditis which is later thought to be more likely Libman Sacs!


Septic Arthritis

  • Epidemiology
    • Risk factors: Advanced age, pre-existing joint dz, recent surgery or injection, SSTI, IVD, indwelling catheter, immunosuppression.
    • Most cases arise from hematogenous seeding, hence bacteremia is common.
    • Direct inoculation: usually due to trauma, surgery/injections, or wounds.
  • Microbiology
    • Usually mono-microbial, and Staph aureus is the most common cause of septic arthritis in adults.
    • GNR can be seen in older adults or in immunocompromised patients
  • Presentation
    • Monoarthritis is most common
      • Edematous, painful, warmth, limited ROM
      • Older patients may not be febrile
    • 20% of cases can present as oligoarticular or polyarticular infection. Polyarticular septic arthritis is more likely to occur in pts with RA
    • Most common affected joint is the knee
    • Could be a manifestation of infective endocarditis, esp amongst IVDU
  • Diagnosis
    • Synovial fluid analysis and culture, should be obtained prior to abx
    • Positive gram stain or culture is gold standard and diagnostic
      • PCR only required in rare cases since most non-gonococcal cultures obtained prior to antibiotics return positive. Negative cultures can result due to recent abx or atypical organism.
    • In pts with purulent synovial fluid (WBC 50k-150k) but culture negative, a presumptive dx can be made.
      • Likelihood of septic arthritis inc with inc leukocyte count
    • Blood cultures should be obtained
    • Should also evaluate for endocarditis given most common organism is staph aureus
    • Imaging:
      • Always get a radiograph to evaluate for concurrent bone/joint involvement
      • CT/MRI can be useful if looking for an effusion
  • DDx
    • Infectious
      • Gonococcal arthritis
      • Lyme disease
      • TB arthritis
      • Viral (usually polyarticular), i.e. Zika, Dengue, chikungunya, parvo, rubella, adenovirus
    • Non-infectious
      • Crystal dz
      • Reactive arthritis
  • Management
    • Joint drainage, severe infectious may require repeated aspiration or even wash out.
    • Abx
      • Most cases are staph, MRSA cases on the rise
      • Suspect pseudomonas if pt is immunocompromised or has h/o IVDU
      • Intra-articular abx: typically not used
      • Duration:
        • Staph aureus with bacteremia: At least 4 weeks
        • Staph aureus without bacteremia: at least 14 days IV, followed by 1-2 weeks PO
        • Bone involvement: 4-6 weeks
        • Any organisms, any bone involvement: 4-6 weeks
        • Other organisms: Typically at least 4 weeks

Culture Negative Endocarditis

  • Definition: Endocarditis without an identified organism in at least 3 independent blood cultures with negative growth after 5 days
  • Epidemiology
    • 2-7% of IE cases
    • 3 most common causes:
      • Previous abx
      • Inadequate samples
      • Atypical organisms (fastidious bacteria i.e. zoonotic microbes, fungal)
  • Microbiology
    • Farm animal exposure: Brucella, Coxiella (Q-fever)
    • Homeless: Bartonella Quintana
    • Cat: Bartonella hensale
    • Ingestion of unpasteurized milk: Brucella, Coxiella
    • Immunocompromised: Fungi, Coxiella
    • HACEK: Most common agents of culture negative endocarditis
      • Haemophilis aphrophulus
      • Actinobacillus
      • Cardiobacterum hominis
      • Eikenella corrdens
      • Kingella
  • Diagnosis
    • PCR, histology, special cultures are helpful.
    • PCR
      • 16S Ribosomal DNA: Bacteria
      • 18S Ribosomal DNA: Fungi
  • Non-infectious DDx
    • APLS, associated with Q fever
    • Acute rheumatic fever
    • Atrial myxoma
    • Libman Sachs endocarditis (non-bacterial thrombotic endocarditis or NBTE)
      • Seen in:
        • SLE
        • Advanced cancer
        • Hypercoagulable state
    • Vasculitis
    • Mural thrombus

NBTE (Non-bacterial thrombotic endocarditis)

  • Epidemiology
    • Rare affected all age group with no sex preference, most commonly 40s – 80s
    • Most commonly associated with pts with concurrent SLE or advanced malignancy (lung cancer, pancreatic cancer, gastric cancer)
    • Other associated conditions: APLS, rheumatic heart disease, RA.
  • Pathophysiology
    • A form of non-infectious endocarditis characterized by deposition of thrombi on halve valves, most commonly mitral or aortic
  • Presentation
    • Usually asx but high risk of thromboembolic events
    • May present with acute stroke or coronary ischemia
  • Diagnosis
    • Exclusion: Demonstration of vegetations on echo in absence of systemic infection in patients with risk factors.
  • Management
    • Systemic anticoagulation
      • Clinical experience and retrospective studies had shown this is beneficial due to high rate of emboli in pts with NBTE
    • Treat underlying condition
    • Surgery
      • Surgical excision for NBTE vegetation, can be considered in only selective cases and generally avoided.

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