What medications should I add to a patient's regimen?

Medication Management for Treatment-Resistant Tuberculosis

When treating tuberculosis with persistent positive smears or cultures at 3 months, you must add at least two new drugs to which the organism is likely to be susceptible to prevent further drug resistance development. 1

Assessment of Treatment Failure

When a TB patient shows continued positive smears and cultures at or after 3 months of treatment, this indicates potential treatment failure that requires immediate intervention. The two most common causes are:

1. Nonadherence to therapy
2. Infection with drug-resistant bacilli 1

Diagnostic Approach

• Obtain specimens for culture and drug susceptibility testing
• Do not wait for complete susceptibility results (which can take up to 6 weeks) before modifying treatment

Medication Addition Algorithm

Step 1: Never add a single drug to a failing regimen

Adding only one medication to a failing regimen creates de facto monotherapy, which leads to resistance to the new drug. This is considered unacceptable practice. 1

Step 2: Add multiple effective medications

• Add at least 2 drugs to which the organism is likely susceptible 1
• If drug-resistant TB is confirmed or strongly suspected, add at least 3 drugs 1
• When susceptibility is unknown, include several drugs with different mechanisms of action to maximize the chance of effectiveness

Step 3: Drug selection considerations

For drug-resistant TB requiring second-line agents:

• Include an injectable agent (capreomycin, amikacin, or kanamycin) 1
• Add a fluoroquinolone such as ofloxacin 1
• Consider ethionamide, p-aminosalicylic acid, or cycloserine 1

Critical Warnings

• NEVER add a single drug to a failing regimen - this creates resistance and worsens outcomes 1
• NEVER continue the same regimen when treatment failure is evident
• The treatment regimen must always include at least 2 drugs to which the organism is susceptible 1

Special Considerations

For MDR-TB (Multi-Drug Resistant TB):

• Regimens employing 4-6 medications appear to be associated with better outcomes 1
• Directly Observed Therapy (DOT) is mandatory
• Avoid intermittent therapy; daily administration is required 1

For Monitoring:

• Continue to assess clinical symptoms
• Monitor sputum smears and cultures
• Consult with a TB expert for complex cases of drug resistance 1

Conclusion

Treatment failure in tuberculosis represents a potential therapeutic disaster if not managed correctly. The cardinal rule is to never add a single drug to a failing regimen. Instead, add at least two (preferably three) new drugs to which the organism is likely susceptible, based on susceptibility testing or epidemiological data. This approach minimizes the risk of creating further drug resistance and improves patient outcomes.