What is the treatment regimen for intestinal tuberculosis (TB)?

Intestinal Tuberculosis: Comprehensive Overview

Treatment Regimen

Intestinal tuberculosis should be treated with a standard 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months, followed by isoniazid and rifampin for 4 months. 1, 2

Initial Phase (First 2 Months)

• Four-drug regimen: Isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) administered daily 1, 2
• Dosing for adults: INH 5 mg/kg (max 300 mg), RIF 10 mg/kg (max 600 mg), PZA 25 mg/kg (max 2000 mg), EMB 15-25 mg/kg 3, 4
• Dosing for children: INH 10-15 mg/kg (max 300 mg), RIF 10-20 mg/kg (max 600 mg), PZA 30-40 mg/kg, EMB 15-25 mg/kg 3
• Ethambutol should be included unless primary isoniazid resistance is documented to be less than 4% in the community 1, 2

Continuation Phase (Months 3-6)

• Two-drug regimen: Isoniazid and rifampin only 1, 2
• Can be administered daily or 2-3 times weekly under directly observed therapy (DOT) 2
• Daily dosing is strongly recommended over intermittent regimens to prevent drug resistance 5

Alternative Dosing Schedules

• Option 1: Daily therapy for 8 weeks, then daily or 2-3 times weekly for 16 weeks 3
• Option 2: Daily for 2 weeks, then twice weekly for 6 weeks, then twice weekly for 16 weeks 3
• Option 3: Three times weekly for entire 6 months (must use DOT) 3
• All intermittent regimens (twice or thrice weekly) must be administered as directly observed therapy 2

Epidemiology and Clinical Presentation

Prevalence and Risk Factors

• Intestinal TB comprises 11-16% of extrapulmonary tuberculosis cases 6
• Only 20% of intestinal TB patients have concurrent active pulmonary TB 7
• HIV co-infection significantly increases risk and may require extended treatment duration 3, 8
• Chronic hepatitis B co-infection can complicate management 8

Anatomical Distribution

• Most commonly affected sites: Ileocecal region and jejunoileum (>75% of gastrointestinal TB) 7, 9
• Can involve any part of GI tract from oral cavity to perianal area 9
• May also affect peritoneum, mesentery, and associated viscera 6, 9

Clinical Manifestations

• Nonspecific symptoms: Abdominal pain, fever, weight loss, diarrhea or constipation 7, 10, 6
• Physical findings: Abdominal tenderness, palpable mass, ascites 6, 9
• Complications: Intestinal obstruction, perforation, hemorrhage, fistula formation, adhesions 7, 6, 9
• Symptoms often mimic Crohn's disease or malignancy, leading to diagnostic delays 7, 8, 10

Diagnostic Approach

Initial Evaluation

• High index of suspicion is critical, especially in endemic areas or immigrant populations 10, 9
• Obtain detailed epidemiological history including country of origin, TB exposure, HIV status 8, 10
• Use medical translators when language barriers exist to ensure accurate history 8

Imaging Studies

• CT scan: Shows bowel wall thickening (particularly terminal ileum), lymphadenopathy, ascites 8, 6
• Ultrasound: Useful for detecting ascites, bowel wall thickening, mesenteric lymph nodes 6
• MRI: Can provide detailed soft tissue characterization 6
• Barium studies: May show strictures, ulcerations, or fistulas 6

Endoscopic Evaluation

• Colonoscopy with ileoscopy is the diagnostic procedure of choice 7, 6
• Multiple biopsies must be taken from ulcer margins (not just ulcer base) 7, 6
• Tissue should be sent for: routine histology, acid-fast bacilli (AFB) smear, mycobacterial culture, and molecular testing 7, 6
• Endoscopic findings include transverse ulcers, nodules, strictures, and pseudopolyps 6, 9

Microbiological and Histological Diagnosis

• Sensitivity limitations: AFB smear, culture, and PCR have lower sensitivity due to paucibacillary nature 6, 9
• Histology: Look for caseating granulomas with Langhans giant cells 7, 6
• Culture: Gold standard but takes 4-8 weeks; provides drug susceptibility testing 6, 9
• Molecular tests: GeneXpert MTB/RIF can provide rapid diagnosis and rifampin resistance detection 6
• Blood cultures may be positive in disseminated disease 8

Laparoscopy/Laparotomy

• Indications: Diagnostic uncertainty, suspected malignancy, or when less invasive methods fail 7, 6
• Allows direct visualization and biopsy of peritoneum, mesenteric nodes, and bowel serosa 6, 9
• Also indicated for surgical complications (perforation, obstruction, hemorrhage) 7, 6

Special Populations and Situations

HIV Co-infection

• Extended treatment duration: At least 9 months and for at least 6 months beyond documented culture conversion 1
• Monitor for malabsorption which may affect drug levels 3
• Drug level monitoring may be necessary in advanced HIV disease to prevent multidrug-resistant TB 3
• Consider drug interactions between antiretroviral therapy and rifampin 2, 3

Pregnancy

• Avoid streptomycin: Causes congenital deafness due to ototoxicity 3
• Pyrazinamide use controversial: Not routinely recommended due to inadequate teratogenicity data, though WHO now supports its use 3
• Recommended regimen: INH, RIF, and EMB for initial phase if pyrazinamide avoided 3
• Treatment duration should be extended to 9 months if pyrazinamide not used 5, 3

Drug-Resistant Tuberculosis

• Isoniazid-resistant TB: Treat with 6 months of RIF, EMB, and PZA 2
• Rifampin-resistant TB: Requires longer regimen (18-24 months) and expert consultation 2
• Multidrug-resistant TB (MDR-TB): Resistance to both INH and RIF requires individualized regimen based on susceptibility testing 2, 1
• WHO recommendations for MDR/RR-TB: 9-month all-oral regimen for fluoroquinolone-susceptible cases, or 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) 1
• Never add a single new drug to a failing regimen 5

Culture-Negative Disease

• Empiric treatment warranted if clinical and radiographic findings strongly suggest intestinal TB, despite negative histology, smear, and culture 2, 7
• At least three specimens should be obtained before declaring culture-negative 2
• Consider bronchoscopy or other diagnostic procedures if pulmonary involvement suspected 2
• Continue full 6-month treatment course even if cultures remain negative 2

Monitoring and Follow-up

Clinical Assessment

• Regular evaluation for symptom improvement: resolution of abdominal pain, fever, weight gain 1, 5
• Monitor for treatment adherence, especially in patients at high risk for nonadherence 2
• Assess for drug-related adverse effects at each visit 5

Laboratory Monitoring

• Baseline tests: Complete blood count, liver function tests, renal function, HIV testing 2
• Liver function tests: Monitor every 2-4 weeks during treatment due to hepatotoxicity risk with INH and RIF 5
• Visual acuity testing: Baseline and monthly if using ethambutol, especially in children 3
• Drug susceptibility testing: Perform on all initial isolates and repeat if cultures remain positive at 3 months 2

Radiological Follow-up

• Imaging surveillance: May be necessary to monitor response in peritoneal or intestinal TB 1
• Repeat imaging if clinical response inadequate or complications suspected 5

Treatment Response Evaluation

• Expected response: Clinical improvement within 2-4 weeks, radiological improvement by 2-3 months 6, 9
• Smear-positive at 3 months: Reevaluate for nonadherence or drug-resistant bacilli 2
• Culture-positive at 3 months: Repeat drug susceptibility testing and consider treatment failure 2

Directly Observed Therapy (DOT)

Rationale and Implementation

• Nonadherence is the main cause of treatment failure and drug-resistant TB 2
• Universal DOT recommended for all TB patients because clinicians cannot predict adherence 2
• DOT involves a healthcare provider or designated person observing medication ingestion 2
• Mandatory for: All intermittent regimens (twice or thrice weekly), drug-resistant TB, high-risk patients (injection drug users, alcoholics, homeless) 2

DOT Settings and Personnel

• Can be administered in: TB clinics, community health centers, homeless shelters, prisons, nursing homes, schools, drug treatment centers 2
• Personnel may include: nurses, health aides, correctional staff, community workers, social workers, reliable volunteers 2
• Incentives and enablers: Transportation vouchers, food, housing assistance may improve adherence 2

Performance Indicators

• Target: 90% of patients should complete treatment within 12 months 2
• If completion rate <90%, expand DOT program 2
• Communities using DOT have decreased rates of drug-resistant TB and relapse 2

Surgical Management

General Principles

• Medical therapy is primary treatment; surgery is generally not required for uncomplicated intestinal TB 2, 1, 7
• All patients should receive full course of anti-TB chemotherapy regardless of surgical intervention 7

Indications for Surgery

• Diagnostic uncertainty: When malignancy cannot be excluded 1, 7, 6
• Acute complications: Intestinal perforation, complete obstruction, massive hemorrhage 1, 7, 6
• Chronic complications: Strictures causing recurrent obstruction, fistula formation 7, 9
• Treatment failure: Lack of response to medical therapy after adequate trial 5
• Large abscess formation requiring drainage 5

Surgical Procedures

• Exploratory laparotomy: For diagnosis or management of complications 7
• Resection: For strictures, perforations, or localized disease 6, 9
• Bypass procedures: For obstructing lesions when resection not feasible 9
• Drainage: For abscesses or loculated ascites 6

Adjunctive Therapies

Corticosteroids

• Not routinely recommended for abdominal TB due to limited evidence 1
• Small study showed trend toward fewer fibrotic complications but not statistically significant 2
• May be considered in severe cases with specialist consultation 2
• Contraindication: Should not be given if intestinal TB misdiagnosed as inflammatory bowel disease, as steroids can worsen infection 8

Supportive Care

• Nutritional support: Essential, especially for malnourished patients 5
• Symptom management: Analgesics for pain, antiemetics for nausea 9
• Monitoring for malabsorption: May require parenteral nutrition or drug level monitoring 3

Screening and Prevention

Latent TB Screening

• Before anti-TNF therapy: Screen with patient history, chest X-ray, tuberculin skin test (TST), and interferon-gamma release assays (IGRA) 2
• TST interpretation: ≥5 mm induration considered positive for latent TB 2
• IGRA preferred: In BCG-vaccinated individuals due to better specificity 2
• False negatives: Can occur with corticosteroids >1 month, immunomodulators >3 months, or active IBD 2
• Booster TST: May be appropriate 1-2 weeks after initial negative test in immunosuppressed patients 2

Latent TB Treatment Before Immunosuppression

• Complete therapeutic regimen for latent TB before starting anti-TNF therapy 2
• Delay anti-TNF: At least 3 weeks after starting latent TB chemotherapy, except in urgent clinical situations 2
• Chemotherapy regimens vary by geographic area and epidemiological background 2

Public Health Measures

• Report all cases promptly to local public health department 2
• Allows contact tracing, source case investigation, and monitoring of treatment adherence 2
• Report suspected cases before culture confirmation to enable timely public health response 2

Common Pitfalls and Caveats

Diagnostic Pitfalls

• Mimicry of Crohn's disease: Intestinal TB can be misdiagnosed as inflammatory bowel disease, leading to inappropriate steroid therapy that worsens infection 7, 8, 10
• Low sensitivity of microbiological tests: Negative AFB smear, culture, or PCR does not exclude diagnosis due to paucibacillary nature 6, 9
• Inadequate biopsy sampling: Must take multiple biopsies from ulcer margins, not just ulcer base 7
• Language barriers: Use medical translators to obtain accurate epidemiological history 8

Treatment Pitfalls

• Incomplete treatment course: Adherence to full 6-month regimen is critical to prevent relapse and drug resistance 1, 5
• Premature discontinuation: Even if symptoms improve early, complete entire treatment course 2
• Inadequate initial regimen: Four-drug regimen necessary in areas with >4% isoniazid resistance 2, 1
• Adding single drug to failing regimen: Never add just one new drug; causes further acquired resistance 5
• Drug interactions: Rifampin interacts with many medications including antiretrovirals, requiring regimen adjustments 2, 3

Monitoring Pitfalls

• Inadequate hepatotoxicity monitoring: Liver function tests must be checked every 2-4 weeks 5
• Missing visual changes with ethambutol: Baseline and monthly visual acuity testing required 3
• Failure to assess adherence: Clinicians are poor at predicting which patients will adhere; use DOT liberally 2
• Not repeating susceptibility testing: If cultures positive at 3 months, repeat testing to detect acquired resistance 2

Special Population Pitfalls

• HIV co-infection: May require longer treatment (9 months) and drug level monitoring 1, 3
• Pregnancy: Avoid streptomycin (ototoxicity) and consider avoiding pyrazinamide (extend to 9 months) 3
• Elderly patients: Reduce streptomycin dose due to increased toxicity risk 11
• Renal insufficiency: Dose adjustments needed for renally cleared drugs 11