Treatment of Pulmonary Tuberculosis
The recommended treatment for drug-susceptible pulmonary tuberculosis is a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol given daily for 2 months (intensive phase), followed by isoniazid and rifampin daily for 4 months (continuation phase). 1, 2
Standard Treatment Regimen
Intensive Phase (First 2 Months)
Four-drug therapy is essential during the initial 8 weeks, with all medications administered together daily 1:
The intensive phase rapidly kills tubercle bacilli and renders patients non-infectious within weeks 1
Ethambutol can be omitted only if the local isoniazid resistance rate is documented to be ≤4%, but this is rarely the case in most settings 3
Continuation Phase (Months 3-6)
Isoniazid and rifampin daily for 4 additional months (total treatment duration: 6 months) for patients with non-cavitary disease who have negative sputum cultures at 2 months 1, 2
Extend the continuation phase to 7 months (total 9 months of treatment) if either of the following conditions exist 1, 2:
- Cavitary disease present on initial chest radiograph
- Sputum cultures remain positive at completion of 2 months of treatment
Critical Monitoring Requirements
Baseline Testing
Obtain medical history, physical examination, chest x-ray, tuberculin skin test, and at least three sputum specimens for acid-fast bacilli smear, culture, and drug susceptibility testing before initiating treatment 1
HIV antibody testing and counseling are recommended before treatment 1
Baseline liver function tests if the patient has risk factors for hepatotoxicity (chronic liver disease, alcohol use, concurrent hepatotoxic medications, pregnancy) 1
During Treatment
Monthly sputum cultures until two consecutive negatives are documented 1, 2
Patients should demonstrate sputum conversion (culture negativity) within 3 months of treatment initiation 2
If sputum remains smear-positive at 3 months, immediately evaluate for non-adherence, treatment failure, or drug resistance 2
Special Populations
HIV-Infected Patients
Use the same standard 6-month regimen as HIV-negative patients 1
Avoid once-weekly isoniazid-rifapentine in the continuation phase 1
Screen antimycobacterial drug levels in patients with advanced HIV disease to prevent malabsorption and emergence of resistance 2
Implement directly observed therapy for all HIV-positive patients 1
Pregnant Women
Initiate standard treatment whenever tuberculosis is suspected, using isoniazid, rifampin, pyrazinamide, and ethambutol safely 1
Avoid streptomycin due to its ototoxicity to the fetus 1
Breastfeeding is safe while on first-line antituberculosis medications 1
Counsel about reduced oral contraceptive effectiveness with rifampin 1
Culture-Negative, Smear-Negative Tuberculosis
A 4-month treatment regimen is adequate for HIV-uninfected adult patients with AFB smear- and culture-negative pulmonary tuberculosis 4
Operationally, treatment is initiated with the standard intensive phase of isoniazid, rifampin, pyrazinamide, and ethambutol daily for 2 months 4
If all cultures on adequate samples are negative and there is clinical or radiographic response after 2 months, the continuation phase with isoniazid and rifampin can be shortened to 2 months 4
If there is concern about the adequacy of workup or accuracy of microbiologic evaluations, a standard 6-month regimen remains preferred 4
Recurrent or Previously Treated Tuberculosis
Assume acquired drug resistance until proven otherwise 5
Start with at least 4-5 drugs that the patient has NOT received previously, including a fluoroquinolone if available 5
Obtain drug susceptibility testing immediately before initiating treatment, including testing for resistance to isoniazid, rifampin, pyrazinamide, and fluoroquinolones 5
Never add a single drug to a failing regimen—this will create further drug resistance 5
Implement directly observed therapy for all recurrent cases 5
Multidrug-Resistant TB (MDR-TB)
MDR-TB is defined as resistance to at least isoniazid AND rifampin 2
Use the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, and moxifloxacin) for eligible patients 2
Use at least 5 drugs in the intensive phase and at least 4 drugs in the continuation phase when using traditional longer MDR-TB regimens 2
Directly Observed Therapy (DOT)
Implement DOT for all intermittent regimens, HIV-positive patients, and recurrent cases, as it improves adherence and treatment success 1
DOT is the observation of the patient by a health care provider or other responsible person as the patient ingests anti-tuberculosis medications 3
Common Pitfalls to Avoid
Do not rely on clinical improvement alone—bacteriologic confirmation of cure is essential 2
Continuous treatment is critical, particularly in the initial phase—avoid treatment interruptions whenever possible 1
Monitor for hepatotoxicity with baseline and regular liver function tests, especially in patients with chronic liver disease 2
Adjust doses of oral hypoglycemics in diabetic patients, as rifampin reduces sulfonylurea efficacy 2
Do not use shortened 4-month fluoroquinolone-containing regimens for drug-susceptible TB, as they substantially increase relapse rates compared to standard 6-month regimens 6