What is the recommended approach for testing and treating brucellosis?

Testing for Brucellosis

The diagnosis of brucellosis should be established through blood cultures (2 sets) combined with serological testing, with bone marrow culture reserved for cases where blood cultures are negative despite high clinical suspicion. 1, 2

Diagnostic Approach

Initial Laboratory Testing

• Blood cultures (2 sets) are essential and should be obtained in all suspected cases, with sensitivity ranging from 15-70% depending on laboratory practices and requiring prolonged incubation up to 4 weeks 1, 2
• Serological testing using standard tube agglutination (STA) is the most widely used confirmatory test, with titers ≥1:160 considered diagnostic when combined with compatible clinical presentation 1, 3
• Baseline inflammatory markers including ESR and CRP should be obtained, as mild transaminitis and pancytopenia are commonly observed 1

When to Consider Brucellosis

• Patients presenting with fever and epidemiologic risk factors: consumption of unpasteurized dairy products, occupational exposure (farmers, veterinarians, abattoir workers), or residence in endemic areas 1
• Subacute presentations with low-grade relapsing fever, lymphadenopathy, hepatosplenomegaly, or osteoarticular complications (sacroiliitis, spondylitis affecting lumbar spine) 1
• Returned travelers from endemic regions presenting with fever of unknown origin 1

Advanced Diagnostic Testing

Bone marrow culture has the highest sensitivity and is considered the investigation of choice when blood cultures are negative, as the high concentration of Brucella in the reticuloendothelial system enables better organism detection 1, 3

Serological test interpretation:

• In endemic settings with suspected vertebral osteomyelitis, strongly positive Brucella serology (≥1:160) combined with compatible imaging obviates the need for image-guided biopsy 1
• False-negative serology may occur early in infection, with blocking antibodies, or due to prozone phenomenon 3
• Coombs test should be performed to detect incomplete antibodies in subacute or chronic cases 3

Special Considerations for Complicated Disease

For suspected brucellar vertebral osteomyelitis:

• Obtain blood cultures and Brucella serology in all patients with subacute vertebral osteomyelitis residing in endemic areas 1
• MRI of the spine is the imaging modality of choice (97% sensitivity, 93% specificity) 1
• Avoid image-guided biopsy if blood cultures are positive for Brucella or if serology is strongly positive (≥1:160) in endemic settings 1

Laboratory Safety Precautions

Critical safety note: Blood culture requests should be discussed with the laboratory beforehand, as initial processing requires special biosafety level 3 precautions due to risk of aerosolized transmission to laboratory workers 1

Molecular Testing

• PCR assays offer high sensitivity (100% in pre-treatment samples) and specificity with rapid turnaround, but long-term persistence of positive results after treatment has unclear clinical significance 4, 2
• PCR should be considered complementary to traditional methods rather than a replacement, particularly for asymptomatic exposed individuals 4
• Lack of validated commercial tests and interlaboratory reproducibility issues currently limit widespread PCR adoption 2

Treatment Recommendations

First-line treatment for uncomplicated brucellosis is doxycycline 100 mg twice daily for 6 weeks combined with either streptomycin 15 mg/kg daily IM for 2-3 weeks OR gentamicin 5 mg/kg daily IV for 7 days. 5

Standard Treatment Regimens

• Doxycycline + Streptomycin: Doxycycline 100 mg PO twice daily for 6 weeks PLUS streptomycin 15 mg/kg IM daily for 2-3 weeks (lowest relapse rate) 5
• Doxycycline + Gentamicin: Doxycycline 100 mg PO twice daily for 6 weeks PLUS gentamicin 5 mg/kg IV daily as single dose for 7 days (WHO-recommended, comparable efficacy with wider availability) 5
• Doxycycline + Rifampicin: Doxycycline 100 mg PO twice daily for 6 weeks PLUS rifampicin 600-900 mg PO daily for 6 weeks (alternative when aminoglycosides contraindicated) 5

Alternative Regimens

• Trimethoprim-sulfamethoxazole (TMP-SMX) 800+160 mg twice daily for 6 weeks may be used as a cost-effective alternative in resource-limited settings or as a third agent in complicated cases 1, 5
• Fluoroquinolone-containing regimens (ofloxacin or ciprofloxacin) should be reserved as second or third agents due to higher cost and risk of promoting antimicrobial resistance 1, 5

Treatment Duration and Monitoring

• Standard treatment duration is 6 weeks for most regimens 5
• Relapse rates range from 5-15% even with appropriate treatment, but relapses are usually mild and respond to the same regimens 5
• In regions where brucellosis and tuberculosis coexist, consider public health implications of rifampicin use, as this may contribute to mycobacterial resistance 5, 6

Complicated Disease Treatment

For neurobrucellosis or brucellar spondylitis:

• Aminoglycoside-containing regimens may be superior to rifampicin-containing ones for brucellar spondylitis 6
• MRI should be performed when spinal involvement is suspected 6
• Immobilization is crucial for cervical involvement to prevent devastating neurological complications 6