What are the essential evaluations and considerations before starting anti-tuberculosis (TB) treatment in a patient with potential pre-existing conditions such as liver or kidney disease, Human Immunodeficiency Virus (HIV) infection, and previous TB treatment?

Pre-Treatment Checklist Before Starting Anti-Tuberculosis Treatment

Before initiating anti-TB treatment, you must obtain a comprehensive clinical history, baseline chest radiograph, sputum for smear and culture with drug susceptibility testing, baseline laboratory tests (particularly liver and renal function), HIV testing, and assess for pre-existing conditions that may require regimen modification.

Essential Clinical History and Examination

Document the following critical elements:

• Prior TB treatment history - verify adequacy of any previous treatment, as inadequate prior therapy significantly increases reactivation risk 1
• Risk factors for drug resistance - previous TB treatment, origin from high-resistance areas, known exposure to drug-resistant cases 1
• HIV status and CD4 count - HIV testing is mandatory for all TB patients, as coinfection fundamentally alters treatment approach and monitoring 1, 2
• Pre-existing liver disease - document history of hepatitis B or C, alcoholic hepatitis, cirrhosis, or chronic alcohol use 1
• Renal function status - baseline assessment needed as several drugs require dose adjustment in renal insufficiency 1
• Pregnancy status - streptomycin is contraindicated due to fetal ototoxicity; pyrazinamide data are limited 1, 3
• Current medications - identify potential drug interactions, particularly with rifampin which induces metabolism of many drugs including oral contraceptives and antiretrovirals 1
• Diabetes mellitus - requires strict glucose control and may necessitate increased oral hypoglycemic doses due to rifampin interaction 3

Mandatory Baseline Investigations

Obtain these tests before treatment initiation:

Microbiological Studies

• At least three sputum specimens for acid-fast bacilli (AFB) smear and mycobacterial culture - spot sample on day 1, overnight sample, and morning spot sample on day 2 1, 3
• Rapid molecular testing (e.g., GeneXpert) on at least one baseline specimen to detect rifampin resistance 1
• Drug susceptibility testing for isoniazid, rifampin, ethambutol, and pyrazinamide on all culture-positive specimens 1

Radiographic Studies

• Baseline chest radiograph for all patients to assess extent of disease and identify cavitation 1
• Additional imaging as needed for suspected extrapulmonary TB 1

Laboratory Tests

Baseline liver function tests (AST/ALT and bilirubin) are indicated for:

• Patients with HIV infection 1
• Pregnant women and those within 3 months postpartum 1
• History of liver disease (hepatitis B or C, alcoholic hepatitis, cirrhosis) 1
• Regular alcohol users 1
• Patients taking other potentially hepatotoxic medications 1

Note: Baseline liver testing is no longer routinely required for all patients over age 35, but should be considered individually for those on multiple medications 1

Additional baseline tests:

• Renal function (creatinine, creatinine clearance) - essential for dose adjustment of streptomycin, ethambutol, and isoniazid 1
• Complete blood count 1
• HIV testing - mandatory for all TB patients 1
• Hepatitis B and C screening for patients with risk factors (injection drug use, birth in Asia or Africa, HIV infection) 1
• Fasting glucose or HbA1c for patients with diabetes risk factors 1
• Visual acuity and color discrimination testing if ethambutol will be used 1

Special Populations Requiring Modified Approach

Patients with Pre-existing Liver Disease

If AST is more than three times normal before treatment:

• Option 1: Use rifampin, ethambutol, and pyrazinamide for 6 months, avoiding isoniazid 1
• Option 2: Use isoniazid and rifampin for 9 months supplemented by ethambutol until susceptibility confirmed, avoiding pyrazinamide 1
• Option 3: For severe liver disease, use rifampin plus ethambutol for 12 months, preferably with a fluoroquinolone for the first 2 months 1
• Frequent clinical and laboratory monitoring is mandatory to detect drug-induced hepatic injury 1

Patients with Renal Insufficiency

Specific dosing adjustments required for:

• Streptomycin, ethambutol, and isoniazid based on creatinine clearance 1
• For hemodialysis patients: administer all drugs after dialysis 1
• Monitor serum drug concentrations for cycloserine and ethambutol in renal failure 1

Pregnant Women

Use isoniazid, rifampin, and ethambutol as initial regimen 1, 3

• Avoid streptomycin - documented fetal ototoxicity 1
• Pyrazinamide can probably be used safely but data are limited; if not used, extend treatment to 9 months 1
• Provide pyridoxine 10 mg/day prophylactically 3

HIV-Infected Patients

Critical considerations:

• CD4 count at TB diagnosis - median is typically very low (61 cells/μL) in coinfected patients 2
• Screen for malabsorption - may require therapeutic drug monitoring in advanced HIV disease 4, 2
• Assess for drug interactions between rifampin and antiretrovirals, particularly protease inhibitors and NNRTIs 3, 5
• Higher index of suspicion needed as HIV-infected patients have lower rates of cavitary disease and higher rates of extrapulmonary/disseminated TB 5

Patient Education and Adherence Assessment

Before starting treatment, establish:

• Patient understanding of latent versus active TB, treatment duration, and importance of adherence 1
• Directly observed therapy (DOT) plan - recommended for all patients to ensure compliance 4, 6
• Education about adverse effects - unexplained anorexia, nausea, vomiting, dark urine, jaundice, rash, persistent paresthesias, visual changes 1
• Instructions for medication timing - can be taken with food if gastrointestinal symptoms occur 1
• Contraception counseling for women on rifampin and oral contraceptives - advise additional contraceptive method 1

Common Pitfalls to Avoid

• Do not start treatment without drug susceptibility testing - resistance can emerge rapidly, and empiric regimens may be inadequate 7, 6
• Do not use three-drug regimens unless INH resistance is documented to be <4% in the community and patient has no risk factors for resistance 6
• Do not delay HIV testing - coinfection fundamentally changes treatment approach and prognosis 1, 2
• Do not assume normal liver function in high-risk patients without baseline testing - hepatotoxicity risk is substantially elevated in certain populations 1
• Do not forget to assess for extrapulmonary disease - obtain sputum even if chest radiograph is negative in HIV-positive patients 5