According to the Philippine TB guidelines, what are the recommended diagnostic tests and treatment regimens (including drug doses, duration, and special modifications) for a newly diagnosed drug‑susceptible pulmonary TB patient, for extrapulmonary TB, TB meningitis/bone/joint disease, previously treated TB (Category II), multidrug‑resistant TB, and TB/HIV co‑infection?

Philippine TB Guidelines: Diagnostic and Treatment Recommendations

Newly Diagnosed Drug-Susceptible Pulmonary TB

All newly diagnosed drug-susceptible pulmonary TB patients in the Philippines should receive a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) daily for 2 months, followed by isoniazid and rifampin (HR) for 4 months. 1, 2

Initial Diagnostic Workup

• Obtain at least 3 sputum specimens on different days for acid-fast bacilli (AFB) smear microscopy and mycobacterial culture before initiating treatment 1, 2
• At least one baseline specimen should be tested using GeneXpert MTB/RIF (rapid molecular test) 2, 3
• Drug susceptibility testing for isoniazid, rifampin, ethambutol, and pyrazinamide must be performed on all initial isolates 2
• Chest radiograph should be obtained at baseline 1

Drug Dosing for Adults (Daily Therapy)

• Isoniazid: 5 mg/kg (maximum 300 mg) 1
• Rifampin: 10 mg/kg (maximum 600 mg) 1
• Pyrazinamide: 15-30 mg/kg (maximum 2.0 g) 1
• Ethambutol: 15-20 mg/kg (maximum 2.5 g) 1

Critical Treatment Modifications

• Patients with cavitation on initial chest radiograph AND positive cultures at 2 months: Extend continuation phase to 7 months (total 9 months of treatment) 1
• HIV-negative patients with negative sputum smears at 2 months AND no cavitation: May use 4-month regimen, though 6 months is preferred 1
• Ethambutol can be discontinued once susceptibility to isoniazid, rifampin, and pyrazinamide is confirmed 1

Monitoring During Treatment

• Monthly sputum smear and culture until 2 consecutive specimens are negative 2
• Patients who remain smear-positive at 3 months require immediate reevaluation for nonadherence or drug-resistant TB 1
• Baseline and monthly monitoring of liver enzymes (AST, ALT, bilirubin, alkaline phosphatase), serum creatinine, and platelet count 1

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Extrapulmonary TB

Extrapulmonary TB (excluding TB meningitis, bone/joint disease) should be treated with the same 6-month HRZE regimen as pulmonary TB. 1, 4

Diagnostic Approach

• Microscopic examination and culture of infected body fluids and/or tissue are necessary for definitive diagnosis 4
• Chest radiograph should still be obtained, as it will often show signs of old or active pulmonary TB in 46% of extrapulmonary cases 5, 4
• Tuberculin skin testing should be performed, but a negative result does not exclude diagnosis 4

Treatment Duration

• Standard 6-month therapy is adequate for most extrapulmonary sites 4
• Exception: TB meningitis, bone/joint TB, and miliary TB require longer treatment (see below) 4

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TB Meningitis and Bone/Joint TB

TB meningitis requires 9-12 months of treatment with HRZE for 2 months followed by HR for 7-10 months. 6, 5

TB Meningitis Specific Considerations

• Antiretroviral therapy and antituberculosis treatment should be initiated simultaneously, regardless of CD4 cell counts 5
• Adjunctive corticosteroids may be beneficial, though evidence in HIV-infected patients is uncertain 5
• Higher mortality rates occur in HIV co-infected patients and those with multidrug-resistant TB meningitis 5
• Monitor for paradoxical TB-associated immune reconstitution inflammatory syndrome (IRIS) 5

Bone/Joint TB

• Treatment duration: 9-12 months minimum 4
• Same initial 4-drug regimen (HRZE) for 2 months, followed by HR for 7-10 months 1, 4

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Previously Treated TB (Category II/Retreatment Cases)

Previously treated TB patients require GeneXpert testing and culture with drug susceptibility testing before initiating retreatment, as they are at high risk for drug resistance. 1, 3

Diagnostic Priority

• GeneXpert MTB/RIF assay should replace sputum microscopy as initial test 1
• Sputum mycobacterial cultures and drug susceptibility testing are mandatory 1
• Chest radiograph should be performed 1
• Higher rates of resistance to isoniazid and streptomycin occur in previously treated patients 1

Initial Empiric Regimen (While Awaiting Susceptibility Results)

• If drug resistance is suspected: Start with at least 4 drugs to which organisms are presumed susceptible 2
• Never add a single drug to a failing regimen, as this rapidly creates drug resistance 7, 8

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Multidrug-Resistant TB (MDR-TB)

For MDR/RR-TB (resistance to at least isoniazid and rifampin), the preferred regimen is the 6-month BPaLM regimen: bedaquiline, pretomanid, linezolid (600 mg daily), and moxifloxacin. 1

BPaLM Regimen Indications

• MDR/RR-TB with fluoroquinolone susceptibility 1
• Can be used in people living with HIV 1
• Contraindications: Age <14 years, pregnancy/breastfeeding, prior exposure to any component drug for ≥30 days 1

Pre-Extensively Drug-Resistant TB (Fluoroquinolone Resistance)

• Use BPaL regimen (without moxifloxacin) 1
• If sputum cultures remain positive between months 4-6, extend to 9 months total 1

Extensively Drug-Resistant TB

• Requires individualized 18-month longer regimen 1
• At least 4 drugs to which organisms are known or presumed susceptible 2
• Specialized consultation required 1

Alternative Regimens When BPaLM Cannot Be Used

• 9-month all-oral regimen (for MDR-TB without fluoroquinolone resistance) 1
• 18-month individualized longer regimen 1

Monitoring Considerations

• Close monitoring required for patients with cardiac disease, QTc prolongation, BMI <17, hemoglobin <7 g/dL, or platelet count <75,000/mm³ 1
• Linezolid-sparing regimens suggested for pre-existing peripheral neuropathy grade III-IV 1

Critical Finding from Philippines

• Rifampicin resistance detected in 19.3% of GeneXpert-positive cases in Manila tertiary hospital, with 53% increase in yield from universal testing 3

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TB/HIV Co-Infection

For TB/HIV co-infected patients, initiate TB treatment first with the standard 4-drug regimen (HRZE), then start antiretroviral therapy (ART) within 2-8 weeks based on CD4 count. 7, 2, 6

TB Treatment Regimen

• Initial phase: 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (daily therapy required for all HIV co-infected patients) 1, 6
• Continuation phase: Isoniazid and rifampin for minimum 7 months (total 9 months minimum) 1
• Vitamin B6 supplementation should be given to all co-infected patients receiving isoniazid to reduce peripheral neuropathy 6

Timing of ART Initiation

• CD4 <50 cells/mm³: Initiate ART within 2 weeks of starting TB treatment 2, 6
• CD4 ≥50 cells/mm³: Initiate ART within 8-12 weeks of starting TB treatment 2, 6
• For TB meningitis: Initiate ART and TB treatment simultaneously regardless of CD4 count 5

Managing Drug Interactions

• Rifampin interacts with protease inhibitors and non-nucleoside reverse transcriptase inhibitors 7, 6
• If ART regimen contains ritonavir or cobicistat: Substitute rifabutin 150 mg daily for rifampin 7, 6

HIV-Specific Monitoring

• HIV testing and counseling should be offered to all TB patients 1
• CD4+ lymphocyte count should be obtained in all HIV-infected TB patients 1
• Liver function tests require more frequent monitoring due to increased hepatotoxicity risk 7
• Higher rates of extrapulmonary and disseminated disease occur with progressive HIV 6, 4

Immune Reconstitution Inflammatory Syndrome (IRIS)

• May present as apparent worsening of TB symptoms after ART initiation 7, 5
• Most patients can be treated symptomatically with NSAIDs 6
• Minority benefit from corticosteroids 6
• Generally do not require cessation of therapy unless space-occupying lesions present 6

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Universal Implementation Requirements

Directly Observed Therapy (DOT)

• All TB treatment should be directly observed where a treatment supporter watches medication ingestion 7, 2
• Particularly critical for patients with social risk factors 7
• Five-day-a-week administration is acceptable when using DOT 1

Case Reporting

• All new and retreatment TB cases must be reported to local public health authorities within 1 week of diagnosis 1, 2

Respiratory Isolation

• All persons with suspected or confirmed smear-positive pulmonary or laryngeal TB must be placed in respiratory isolation 1
• Patients considered noninfectious after: receiving effective therapy, clinical improvement, and 3 consecutive negative sputum smears collected on different days 1
• 90% of smear-positive patients should remain in isolation until smear converts to negative 1

Treatment Interruptions

• Interruption <14 days: Continue treatment to complete planned total doses (if all doses completed within 3 months) 2
• Interruption ≥14 days: Restart treatment from the beginning 2

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Critical Pitfalls to Avoid

• Never assume negative GeneXpert equals no TB – culture remains gold standard, particularly in paucibacillary disease 8, 3
• Never initiate single-drug treatment for suspected active TB, as this rapidly creates drug resistance 7, 8
• Never add a single drug to a failing regimen – always add at least 2 new drugs 1, 7
• Do not delay sputum collection while observing – this loses diagnostic time and risks progression 8
• Do not use tuberculin skin tests or IGRAs to diagnose active TB disease, as these are often negative with active disease 6
• In the Philippines, health-seeking behavior is often inappropriate (43% take no action, 31.6% self-medicate) – health education and public-private DOTS collaboration are essential 9