What is the protocol for tuberculosis (TB) culture and treatment?

TB Culture and Treatment Protocol

For tuberculosis diagnosis, obtain three sputum specimens (preferably early morning samples on separate days) for AFB microscopy, culture, and drug susceptibility testing before initiating treatment, then start empiric four-drug therapy with isoniazid, rifampin, pyrazinamide, and ethambutol while awaiting culture results. 1

Diagnostic Testing Protocol

Specimen Collection

• Collect three sputum specimens on separate days, ideally early morning samples 1
• 90% of adults with suspected TB should have three cultures obtained before starting antituberculosis therapy (50% benchmark for children 0-12 years due to difficulty obtaining expectorated sputum) 2
• Perform collection in an airborne infection isolation (AII) room or sputum induction booth to prevent transmission 1
• For patients unable to produce sputum spontaneously, use sputum induction with hypertonic saline or bronchoscopy under appropriate infection control measures 1
• Specimens with >5 ml volume yield sputum smear positivity greater than 90% 3

Laboratory Processing Timeline

• AFB microscopy must be completed within 24 hours of specimen collection 1
• Nucleic acid amplification (NAA) testing should be completed within 48 hours to rapidly identify M. tuberculosis complex 1
• Mycobacterial culture using both solid and liquid media should provide results within 14 days 1
• Culture detects 10-100 viable mycobacteria per ml and is 81% sensitive and 98.5% specific in active disease 3

Drug Susceptibility Testing

• Drug susceptibility testing is mandatory on all initial isolates to guide therapy 2, 4
• Isoniazid and rifampin resistance can be reliably measured; pyrazinamide, ethambutol, and streptomycin resistance testing has technical limitations 3

Treatment Protocol for Drug-Susceptible TB

Initial Empiric Therapy

Start treatment immediately with the four-drug regimen while awaiting culture results: 1, 4

• Isoniazid (INH)
• Rifampin (RIF)
• Pyrazinamide (PZA)
• Ethambutol (EMB)

This four-drug regimen is mandatory in geographic areas where ≥4% of TB isolates are resistant to isoniazid 2

Treatment Phases

Intensive Phase (2 months): 1, 4

• All four drugs (INH, RIF, PZA, EMB) given daily for 8 weeks (56 doses)
• Pyrazinamide dosing: 25 mg/kg (20-30 mg/kg) daily 4

Continuation Phase (4 months): 1, 4

• Isoniazid and rifampin only for 18 weeks (126 doses)
• Total treatment duration: 6 months for drug-susceptible disease 4, 5

Treatment Duration Extensions

Extend continuation phase to 7 months (total 9 months) if: 4

• Cavitary pulmonary TB with positive cultures after 2 months of therapy
• TB meningitis (extend to 9-12 months total) 4

Monitoring During Treatment

Sputum Monitoring

• Collect monthly sputum specimens until two consecutive specimens are culture-negative 1
• 90-95% of patients will be culture-negative after 3 months of appropriate therapy 4
• If sputum remains smear-positive at 3 months, perform culture and susceptibility testing within 1 month 2
• Evaluate persistently positive cultures for nonadherence, unrecognized drug resistance, malabsorption, and diabetes mellitus 4

Clinical Monitoring

• Perform monthly clinical evaluations to identify adverse effects and assess adherence 1
• Monitor liver function tests, especially in patients with pre-existing liver disease 3

Infection Control and Isolation

Respiratory Isolation Requirements

• Maintain respiratory isolation for all patients with suspected or confirmed smear-positive pulmonary or laryngeal TB 2, 1
• 90% of smear-positive TB patients should remain in respiratory isolation until smear converts to negative 2

Criteria for Discontinuing Isolation

A patient is considered non-infectious when all three criteria are met: 1

• Receiving effective therapy
• Showing clinical improvement
• Three consecutive negative sputum AFB smears collected on different days

Treatment Failure and Drug Resistance

Definition of Treatment Failure

• Continuously or recurrently positive cultures after 4 months of appropriate therapy 4

Management of Treatment Failure

• Add at least two, preferably three, new drugs to which susceptibility can be inferred 2, 4
• Never add a single drug to a failing regimen 4
• Consider adding a fluoroquinolone, an injectable agent, and an additional oral agent 4
• 100% of patients with suspected treatment failure must be prescribed >2 new antituberculosis agents 2

Drug-Resistant TB

• Consult a TB expert for suspected or confirmed drug-resistant TB 6
• For MDR-TB (resistant to isoniazid and rifampin), refer to specialized units with quality-controlled drug susceptibility testing 3

Case Management and Adherence

Patient-Centered Approach

• Assign a public health case manager to assess needs and barriers to treatment adherence 2
• Develop an individualized case management plan with the patient's active input 2
• Provide education about tuberculosis, treatment expectations, possible adverse effects, and infection control measures 2

Directly Observed Therapy (DOT)

• Use DOT as standard practice, where patients swallow medications under direct observation of a healthcare worker 2
• Implement patient reminders, follow-up systems for missed appointments, incentives/enablers, and field/home visits 2

Common Pitfalls

• Avoid intermittent therapy with rifampin >600 mg once or twice weekly—this causes higher incidence of "flu syndrome," hematopoietic reactions, and renal failure 7
• Rifampin induces metabolism of many drugs including oral contraceptives, requiring alternative contraceptive measures 7
• Take rifampin 1 hour before or 2 hours after meals with a full glass of water 7
• Warn patients about discoloration (yellow, orange, red, brown) of teeth, urine, sweat, sputum, and tears; soft contact lenses may be permanently stained 7

Reporting Requirements

• Report 100% of active TB cases to the local public health department within 1 week of diagnosis 2
• Perform HIV testing on 80% of all TB patients within 2 months of diagnosis 2