What is the treatment for recurrent pulmonary tuberculosis (PTB)?

Treatment for Recurrent Pulmonary Tuberculosis (PTB)

For patients with recurrent pulmonary tuberculosis, treatment should be based on the prior treatment history, with standard intensive phase regimen for those previously treated with DOT for drug-susceptible TB, and an expanded empiric regimen for those with irregular treatment history or suspected drug resistance. 1

Initial Approach to Recurrent PTB

Diagnostic Confirmation

• Vigorous efforts should be made to establish a microbiological diagnosis and obtain cultures for drug susceptibility testing to guide appropriate therapy 1
• Rapid molecular and phenotypic diagnostics should be used whenever feasible to detect drug resistance and inform regimen selection 1
• Caution should be exercised when interpreting molecular test results at the time of recurrence, as false positives for M. tuberculosis DNA and rifampin resistance have been reported 1

Treatment Based on Prior Treatment History

For Patients Previously Treated with DOT for Drug-Susceptible TB:

• Retreatment using the standard intensive phase regimen (daily INH, RIF, PZA, and EMB) until susceptibility test results are available 1
• Most relapses with drug-susceptible organisms occur within the first 6-12 months after completion of therapy 1
• In the majority of patients treated with DOT and rifamycin-containing regimens, relapses occur with susceptible organisms 1

For Patients with Irregular Treatment or No DOT:

• Higher risk of acquired drug resistance should be inferred 1
• An expanded empiric regimen should be initiated, especially in patients with: 1
  • Impaired immunity
  • Limited respiratory reserve
  • CNS involvement
  • Other life-threatening circumstances

Expanded Empiric Regimen Components

The expanded empiric regimen for suspected drug resistance typically includes: 1, 2

• Standard intensive phase regimen:
  • Isoniazid (INH): 5 mg/kg up to 300 mg daily 3
  • Rifampin (RIF): According to weight-based dosing 4
  • Pyrazinamide (PZA): 25 mg/kg (20-30 mg/kg) daily 5
  • Ethambutol (EMB): According to weight-based dosing 1

Plus additional drugs:

• A later-generation fluoroquinolone 1, 2
• An injectable agent (amikacin, kanamycin, or capreomycin) 1, 2
• Depending on severity of disease or anticipated resistance, an additional second-line drug 1

Important Considerations

Causes of Recurrent TB

• True relapse: Endogenous recrudescence of the original infection due to failure of chemotherapy to sterilize host tissues 1
• Exogenous reinfection: Infection with a new strain of M. tuberculosis, more common in high-incidence settings or where infection control is poor 1

Risk Factors for Relapse

• Extensive disease at baseline 1
• Sputum cultures remaining positive after completion of intensive phase treatment 1
• Irregular treatment or poor adherence to previous regimen 1

Drug Resistance Considerations

• Risk of acquired drug resistance is substantial in patients who relapse after: 1
  • Self-administered therapy (SAT)
  • Highly intermittent regimen in HIV infection
  • Non-rifamycin-containing regimen
  • Second-course of first-line regimen reinforced by streptomycin

Administration and Monitoring

• All drugs should be administered using directly observed therapy (DOT) 1, 2
• After 3 months of appropriate therapy for drug-susceptible TB, 90-95% of patients should have negative cultures and show clinical improvement 1, 5
• Patients with persistently positive cultures after 4 months should be considered treatment failures and evaluated for drug resistance 5, 2

Special Situations

When Exogenous Reinfection is Suspected

• Treatment regimen should be influenced by the drug susceptibility pattern of the presumed source case 1
• If the source case has drug-resistant organisms, an expanded empiric regimen based on the resistance profile of the source case may be suitable 1

Multiple Drug-Resistant TB (MDR-TB)

• Treatment must be individualized based on susceptibility studies 1
• Consultation with an expert in tuberculosis treatment is strongly recommended 1, 2
• Never add a single drug to a failing regimen to prevent further acquired resistance 6, 2

Common Pitfalls

• Failure to obtain drug susceptibility testing before initiating therapy 1
• Adding a single new drug to a failing regimen, which can lead to further drug resistance 1, 2
• Inadequate initial regimen in patients with suspected drug resistance 1
• Not considering the possibility of exogenous reinfection in high-incidence settings 1, 7
• Overlooking potential causes of poor treatment response such as malabsorption, diabetes mellitus, or nonadherence 1