What is the treatment guideline for a patient with abdominal tuberculosis (Koch's abdomen), considering factors such as impaired renal function, hepatic function, and potential drug interactions?

Treatment of Abdominal Tuberculosis (Koch's Abdomen)

Treat abdominal tuberculosis with the standard 6-month short-course chemotherapy regimen: 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (intensive phase), followed by 4 months of isoniazid and rifampin (continuation phase), which has been proven equally effective as 12-month regimens for all forms of abdominal TB. 1

Standard Treatment Regimen

• The preferred regimen consists of 2 months of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB), followed by 4 months of INH and RIF 2, 3, 4
• This 6-month short-course regimen achieved 99% clinical normalization in abdominal TB patients with no relapses during 5-year follow-up, matching the efficacy of 12-month standard therapy 1
• Ethambutol should be included in the initial regimen until drug susceptibility results are available, unless primary isoniazid resistance is documented to be less than 4% in the community 5
• All medications should be given daily during both phases for optimal outcomes 3

Critical Pre-Treatment Assessments

Before initiating therapy, obtain baseline liver function tests, renal function tests, visual acuity testing (Snellen chart), and screen for hepatitis B/C in high-risk patients 2, 6

• Check baseline ALT, AST, and bilirubin in all patients before starting hepatotoxic drugs 2
• Assess renal function (creatinine clearance) before using ethambutol or streptomycin 2
• Perform baseline visual acuity and color discrimination testing before ethambutol use 2
• Screen patients born in Asia/Africa, with injection drug use history, or HIV infection for hepatitis B and C 2, 6

Management with Impaired Hepatic Function

For patients with pre-existing liver disease but normal baseline liver enzymes, use the standard 4-drug regimen with intensive monitoring: check liver function tests weekly for 2 weeks, then every 2 weeks for the first 2 months 2

When to Stop Hepatotoxic Drugs

• Stop rifampin, isoniazid, and pyrazinamide immediately if ALT/AST rises ≥5 times upper limit of normal (ULN) without symptoms, or ≥3 times ULN with hepatitis symptoms (fever, malaise, vomiting, jaundice) 2, 6, 7
• If the patient is acutely ill or has infectious TB, continue treatment with non-hepatotoxic drugs: ethambutol plus streptomycin (with appropriate monitoring) or a fluoroquinolone 2, 7

Sequential Drug Reintroduction Protocol

Once liver function normalizes to <2 times ULN, reintroduce drugs sequentially with daily clinical and biochemical monitoring 2, 7

• Start isoniazid at 50 mg/day, increase to 300 mg/day after 2-3 days if no reaction occurs 2, 7
• After 2-3 additional days without reaction, add rifampin at 75 mg/day, increase to 300 mg after 2-3 days, then to 450 mg (<50 kg) or 600 mg (>50 kg) after another 2-3 days 2
• Finally add pyrazinamide at 250 mg/day, increase to 1.0 g after 2-3 days, then to 1.5 g (<50 kg) or 2.0 g (>50 kg) 2
• Never reintroduce pyrazinamide if it caused severe hepatotoxicity, as recurrence carries a poor prognosis 6, 7

Alternative Regimens for Severe Hepatic Disease

For patients with advanced liver disease or unstable hepatic function, retain rifampin and isoniazid if at all possible due to their crucial efficacy 2, 6

• Option 1 (pyrazinamide omitted): INH, RIF, and EMB for 2 months, followed by 7 months of INH and RIF (total 9 months) 2, 6, 7
• Option 2 (isoniazid and pyrazinamide omitted): RIF and EMB with a fluoroquinolone, injectable agent, or cycloserine for 12-18 months depending on disease extent 2, 6, 7
• Option 3 (minimal hepatotoxicity): EMB combined with a fluoroquinolone, cycloserine, and injectable agent for 18-24 months for patients with severe, unstable liver disease 2

Management with Impaired Renal Function

Isoniazid, rifampin, and pyrazinamide require no dose adjustment for renal insufficiency as they are predominantly metabolized by the liver 6, 8

Ethambutol Dose Adjustments

• Creatinine clearance 50-100 mL/min: 25 mg/kg body weight daily 8
• Creatinine clearance 30-50 mL/min: 25 mg/kg twice weekly 8
• Creatinine clearance 10-30 mL/min: 15 mg/kg every 36-48 hours 8
• Monitor serum drug concentrations to prevent toxicity 2, 8

Streptomycin in Renal Impairment

• Reduce dosing frequency to 12-15 mg/kg per dose two or three times weekly (maintain the milligram dose per administration) 6, 8
• Administer all anti-TB medications after hemodialysis sessions to prevent premature drug removal 8
• Monitor serum drug concentrations and perform baseline audiogram and vestibular testing 8

Monitoring During Treatment

Obtain sputum for smear and culture at baseline, then monthly until 2 consecutive specimens are negative (for pulmonary involvement); monitor weight monthly and adjust medication doses accordingly 2

• Assess adherence and monitor for TB symptom improvement (fever, night sweats, malaise) and medication adverse effects at each visit 2
• For patients on ethambutol: perform monthly inquiry about visual disturbances and monthly color discrimination tests 2
• Liver function tests are only required at baseline unless abnormalities exist, symptoms of hepatotoxicity develop, or the patient has chronic alcohol use, viral hepatitis, HIV, or takes other hepatotoxic medications 2
• Repeat drug susceptibility testing if the patient remains culture positive after completing 3 months of treatment 2

Critical Pitfalls to Avoid

• Do not use ethambutol in young children whose visual acuity cannot be monitored 2, 5
• Avoid streptomycin and ethambutol in renal failure if possible; if used, monitor serum drug concentrations and give substantially reduced dosages unless dialysis is used 2
• Educate patients and general practitioners about possible side effects and indications for stopping medication immediately (jaundice, dark urine, fever, malaise, vomiting, visual changes) 2, 7
• Consider directly observed therapy (DOT) for all patients to ensure adherence and prevent development of drug resistance 3, 5
• Surgery is reserved only for patients with suspected intestinal obstruction or perforation 1