What is the treatment for osteomyelitis due to tuberculosis?

Osteomyelitis due to Tuberculosis

Definition and Anatomy

Tuberculous osteomyelitis is a chronic bone infection caused by Mycobacterium tuberculosis that accounts for 3-5% of all extrapulmonary TB cases and represents the most common cause of spinal infections worldwide. 1, 2

• The infection most commonly affects the vertebral column (Pott disease), followed by long bones, particularly the metaphyseal regions of the distal femur, proximal tibia, and distal tibia in children 1, 3
• In children, lesions frequently cross the growth plate (physis) to involve the epiphysis, unlike typical bacterial osteomyelitis 3
• The proximal humerus, ribs, and other long bones can also be affected 2, 4

Etiology and Pathophysiology

• Tuberculous osteomyelitis results from hematogenous spread of M. tuberculosis from a primary pulmonary focus, though pulmonary symptoms may be absent in up to 50% of cases 2, 4
• The infection is more common in endemic regions and in patients from areas of high TB prevalence 1
• In developed countries with low TB incidence, it predominantly affects older adults (>40 years), while in high-incidence countries it more commonly affects children 1
• The pathophysiology involves granulomatous inflammation with caseous necrosis, leading to progressive bone destruction without significant periosteal reaction 4, 3

Clinical Manifestations

The presentation is typically insidious, with chronic bone pain lasting 2-39 months that fails to respond to non-steroidal anti-inflammatory drugs, often without systemic or pulmonary symptoms. 2, 4

• Patients may present with a palpable bone mass, localized swelling, or chronic limb pain without fever or constitutional symptoms 2, 3
• Vertebral TB characteristically involves destruction of two or more contiguous vertebrae with spread along the anterior longitudinal ligament 1
• Paravertebral or epidural abscesses may develop, potentially causing neurologic compromise 1
• The absence of systemic symptoms often leads to delayed diagnosis, with patients initially treated for musculoskeletal pain 4

Diagnosis

MRI is the imaging modality of choice for early detection, while biopsy with microbiological and histopathological confirmation is mandatory for definitive diagnosis. 1, 4

Imaging Findings

• Plain radiographs in early stages may be normal; advanced lesions show osteolytic, round to oval lesions with marginal sclerosis and minimal periosteal reaction 4, 3
• MRI demonstrates characteristic features: on T1-weighted sequences, loss of distinction between disc space and adjacent vertebral marrow; on T2-weighted sequences, increased signal intensity from disc and involved marrow 1
• Radiographic clues suggesting TB include: destruction of ≥2 contiguous vertebrae, spread along anterior longitudinal ligament, disc infection with or without paraspinal mass, or spondylitis without disc involvement 1
• CT or MRI should be obtained when plain radiographs are normal but clinical suspicion remains high 4

Microbiological Diagnosis

• Image-guided aspiration biopsy should be performed in all suspected cases to obtain specimens for culture and histopathology 1
• Specimens should be sent for mycobacterial cultures in addition to routine bacterial cultures when epidemiologic factors or characteristic radiologic features suggest TB 1
• Holding antibiotics for 1-2 weeks prior to biopsy is reasonable when feasible to increase microbiological yield, except in patients with neurologic compromise or hemodynamic instability 1
• Interferon-gamma release assays (IGRA) and tuberculin skin testing (PPD) have higher sensitivity than PPD alone, particularly in immunocompromised patients 1, 5
• Polymerase chain reaction (PCR) testing can provide rapid confirmation when positive 2
• Pathologic examination reveals caseous necrosis and granulomatous inflammation 2, 4

Treatment

Tuberculous osteomyelitis requires a minimum of 6-9 months of multidrug antituberculous chemotherapy, with surgical debridement reserved for specific indications. 1, 6, 7

Medical Management

• The standard regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months (intensive phase), followed by isoniazid and rifampin for 4-7 months (continuation phase), totaling 6-9 months of therapy 1, 5
• Bone and joint TB requires longer therapy than pulmonary TB; most guidelines recommend extending treatment to 9 months minimum 1
• Directly observed therapy (DOT) is strongly recommended for all TB patients, as nonadherence is the main cause of treatment failure and drug resistance 1, 5
• For isoniazid-resistant TB, treat with 6 months of rifampin, ethambutol, and pyrazinamide 1
• Rifampin-resistant or multidrug-resistant TB requires 18-24 months of therapy and expert consultation 1, 5
• HIV co-infected patients should receive at least 9 months of treatment 5

Surgical Management

• Surgical debridement is beneficial for both diagnosis and treatment, particularly when extensive curettage can eradicate infection 6, 3
• Indications for surgery include: drainage of large abscesses, neurologic compromise, spinal instability, progressive deformity, or failure of medical therapy 1, 6
• In vertebral TB with neurologic compromise or hemodynamic instability, immediate surgical intervention is required 1
• For long bone lesions with transphyseal involvement in children, careful surgical debridement through the physis is safe and does not cause permanent physeal damage 3
• Immobilization is not necessary and does not improve outcomes 6

Monitoring Response

• Clinical symptoms typically improve within 4-6 weeks of initiating therapy 3
• Bone lesions decrease in size within 3-6 months on imaging 3
• Sputum smears and cultures (when applicable) should become negative by 3 months; persistent positivity warrants reevaluation for nonadherence or drug resistance 1
• Follow-up imaging should continue for several years, as complete remodeling of skeletal lesions occurs gradually 3
• A favorable response to chemotherapy is obtained in 92% of cases with appropriate treatment 6

Critical Pitfalls to Avoid

• Do not delay biopsy in patients with chronic bone pain unresponsive to analgesics, as TB should be considered even without systemic symptoms 2, 4
• Do not treat with antibiotics alone without confirming the diagnosis, as this mimics chronic pyogenic osteomyelitis, tumors, or other granulomatous lesions 4
• Do not use shorter treatment durations (<6 months) for bone and joint TB, as this increases relapse risk 1
• Do not withhold surgical debridement when indicated, particularly for large abscesses or neurologic compromise 1, 6
• Do not assume pulmonary symptoms must be present; up to 50% of patients with tuberculous osteomyelitis have no pulmonary manifestations 2, 4
• Recognize that super-added pyogenic infection can occur in 8% of cases with persistent sinus after chemotherapy 6