What is the initial workup for a patient suspected of having brucellosis?

Initial Workup for Suspected Brucellosis

Obtain two sets of blood cultures with prolonged incubation (up to 4 weeks), baseline inflammatory markers (ESR and CRP), and serological testing using standard tube agglutination (STA) with titers ≥1:160 considered diagnostic when combined with compatible clinical presentation. 1

Clinical Assessment

Key Historical Features to Elicit

• Epidemiologic risk factors: consumption of unpasteurized dairy products, occupational exposure to livestock (veterinarians, farmers, slaughterhouse workers), or residence in/travel from endemic areas 1, 2
• Symptom pattern: fever (acute or subacute low-grade relapsing pattern), sweats, headaches, back pain, physical weakness 3, 1
• Osteoarticular symptoms: new or worsening back/neck pain suggesting possible vertebral osteomyelitis 3
• Systemic manifestations: lymphadenopathy, hepatosplenomegaly 1

Physical Examination Priorities

• Perform pertinent motor/sensory neurologic examination, particularly in patients with back or neck pain 3
• Assess for hepatosplenomegaly and lymphadenopathy 1
• Evaluate for focal neurologic deficits that may indicate spinal involvement 3

Laboratory Workup

Essential Initial Tests

• Blood cultures (2 sets): Must be obtained in all suspected cases, though sensitivity ranges only 15-70% depending on laboratory practices 1, 4

  • Critical caveat: Notify the laboratory beforehand as initial processing requires biosafety level 3 precautions due to aerosolized transmission risk to laboratory workers 1
  • Requires prolonged incubation up to 4 weeks, though modern automated systems may detect acute cases within 5-7 days 1, 4

• Serological testing: Standard tube agglutination (STA) is the most widely used confirmatory test 1, 5

  • Titers ≥1:160 are considered diagnostic when combined with compatible clinical presentation 3, 1
  • In endemic settings, false-negative serologic tests are unusual in patients with brucellar vertebral osteomyelitis—all patients in one study had titers ≥1:160 3
  • Important limitation: In non-endemic areas (like the United States), false-positive tests are more likely, and additional confirmation may be warranted 3

• Baseline inflammatory markers: ESR and CRP should be obtained 3, 1

  • Mild transaminitis and pancytopenia are commonly observed 1

When Blood Cultures Are Negative

• Bone marrow culture: Has the highest sensitivity and is the investigation of choice when blood cultures are negative despite high clinical suspicion 1, 6

Imaging for Suspected Vertebral Involvement

When to Image

• Obtain spine MRI in patients with suspected vertebral osteomyelitis (new or worsening back/neck pain with fever, elevated ESR/CRP, or bloodstream infection) 3, 1
• MRI is the imaging modality of choice with 97% sensitivity and 93% specificity 1

Biopsy Decision Algorithm

In endemic settings with suspected brucellar vertebral osteomyelitis:

• Do NOT perform image-guided biopsy if:
  • Blood cultures are positive for Brucella 3
  • Serology is strongly positive (≥1:160) 3, 1
• DO perform image-guided biopsy if:
  • Blood cultures and serology are negative but clinical suspicion remains high 3
  • In non-endemic areas where false-positive serology is more likely 3

In non-endemic settings:

• Consider image-guided biopsy even with positive serology due to higher false-positive rates 3
• Evaluation by infectious disease specialist and spine surgeon is advised 3

Special Considerations

Geographic Context Matters

• In endemic countries (Greece, Middle East, Mediterranean), Brucella is a very common cause of vertebral osteomyelitis 3, 6
• In low-endemicity countries (United States), ELISA screening is performed initially, followed by confirmatory agglutination test 3

Laboratory Safety

• Blood culture requests must be discussed with the laboratory beforehand due to biosafety requirements 1
• Brucellosis is the most frequent laboratory-acquired bacterial infection 7

Pitfalls to Avoid

• Do not delay blood cultures: Modern automated systems can detect acute cases within routine 5-7 day protocols, though longer incubation may be needed for protracted cases 4
• Do not rely on single titer: While most patients with active brucellosis have titers ≥160, no single titer is always diagnostic—follow-up sera and clinical context are essential 5
• Do not perform unnecessary biopsies: In endemic settings with strongly positive serology (≥1:160) and compatible imaging, biopsy adds no value and carries procedural risks 3