4.2 Viral Respiratory Pathogens & Tuberculosis
Key Takeaways
- Tuberculosis is enumerated under lower respiratory tract infections in both the Infectious Disease and Pulmonary Disease blueprint categories.
- Active tuberculosis must be excluded before treating latent infection, because monotherapy in active disease generates resistance.
- Isoniazid causes hepatotoxicity and pyridoxine-responsive peripheral neuropathy; ethambutol causes optic neuritis with loss of color discrimination.
- Pyrazinamide causes hyperuricemia and hepatotoxicity, and rifampin causes orange discoloration of body fluids with extensive cytochrome P450 induction.
- Antiviral therapy for influenza provides greatest benefit when started within 48 hours, but is still indicated for hospitalized or high-risk patients presenting later.
Last updated: August 2026
1. Viral Respiratory Pathogens: Influenza & COVID-19
Influenza (Influenza A & B)
- Clinical Presentation: Abrupt onset of high fever, rigors, myalgias, headache, non-productive cough, and prostration.
- Diagnostics: Reverse-transcriptase PCR (RT-PCR) of nasopharyngeal swab (rapid molecular test of choice).
- Antiviral Therapy:
- Oseltamivir (Tamiflu): Neuraminidase inhibitor (75 mg PO BID for 5 days). Indicated for all hospitalized patients, individuals with severe/progressive illness, or high-risk outpatients (age >=65, pregnant/postpartum <2 weeks, chronic pulmonary/cardiac/renal/hepatic disease, immunosuppressed, BMI >=40) regardless of symptom duration. In healthy outpatients with uncomplicated influenza, treatment provides maximum benefit when started within <=48 hours of symptom onset.
- Baloxavir marboxil (Xofluza): Cap-dependent endonuclease inhibitor administered as a single weight-based oral dose (40 mg for 40–79 kg; 80 mg for >=80 kg); effective alternative for outpatients within 48 hours.
- Complications: Secondary bacterial pneumonia classically caused by Staphylococcus aureus (including MRSA) and Streptococcus pneumoniae; suspect when a patient develops recrudescent fever, productive purulent sputum, and new pulmonary consolidation following initial influenza recovery.
COVID-19 (SARS-CoV-2)
| Clinical Severity | Definition & Clinical Criteria | Recommended Pharmacotherapy |
|---|---|---|
| Mild-to-Moderate (Outpatient High Risk) | SpO2 >=94% on room air, no dyspnea, but high risk for progression (age >=65, obesity, DM, CKD, immunosuppression) | • First-Line: Nirmatrelvir-ritonavir (Paxlovid) 300/100 mg PO BID x 5 days initiated within 5 days of symptom onset. (Adjust dose to 150/100 mg BID for eGFR 30–59 mL/min; contraindicated if eGFR <30 mL/min).<br/>Critical Check: Review CYP3A4 drug-drug interactions (contraindicated with simvastatin, amiodarone, rivaroxaban, tacrolimus, carbamazepine).<br/>• Second-Line: IV Remdesivir (200 mg IV day 1, 100 mg IV days 2–3) initiated within 7 days of symptom onset. |
| Hospitalized Requiring Supplemental Oxygen | SpO2 <94% on room air requiring low-flow nasal cannula O2 | • Dexamethasone 6 mg IV/PO daily for up to 10 days (or until discharge) PLUS<br/>• Remdesivir 200 mg IV day 1, then 100 mg IV daily for 5 days (extend to 10 days if intubated). |
| Hospitalized on High-Flow Oxygen / NIV / Mechanical Ventilation | High-flow nasal cannula (HFNC), non-invasive ventilation (NIV), or invasive mechanical ventilation with systemic inflammation (CRP >=75 mg/L) | • Dexamethasone 6 mg IV daily PLUS<br/>• Tocilizumab (IL-6 receptor antagonist; 8 mg/kg IV single dose, max 800 mg) OR Baricitinib (oral JAK-1/2 inhibitor; 4 mg PO daily for 14 days). |
2. Tuberculosis (Mycobacterium tuberculosis)
Latent Tuberculosis Infection (LTBI) Screening & Diagnosis
- Diagnostic Modalities:
- Interferon-Gamma Release Assay (IGRA - QuantiFERON-TB Gold, T-SPOT.TB): Measures in vitro IFN-gamma release by sensitized T-cells exposed to M. tuberculosis-specific antigens (ESAT-6, CFP-10). Preferred in individuals with prior BCG (Bacille Calmette-Guérin) vaccination (eliminates false-positive cross-reactivity) and in patients unlikely to return for TST reading.
- Tuberculin Skin Test (TST / PPD): Measures delayed-type hypersensitivity induration (measured in mm across the forearm at 48–72 hours).
| TST Induration Cutoff | Target Populations Considered Positive |
|---|---|
| >= 5 mm | • HIV-infected individuals<br/>• Recent close contacts of persons with active infectious tuberculosis<br/>• Fibrotic/cavitary changes on chest radiograph consistent with prior inactive TB<br/>• Solid organ transplant recipients and immunosuppressed patients (receiving >=15 mg/day prednisone equivalent for >=1 month or anti-TNF-alpha biologics) |
| >= 10 mm | • Recent immigrants (<5 years) from high-prevalence countries (Asia, Africa, Latin America, Eastern Europe)<br/>• Injection drug users<br/>• Residents and employees of high-risk congregate settings (prisons, nursing homes, homeless shelters, healthcare facilities)<br/>• Mycobacteriology laboratory personnel<br/>• High-risk clinical conditions: Diabetes mellitus, chronic renal failure/hemodialysis, silicosis, gastrectomy, leukemia/lymphoma, head/neck cancer, body weight <90% ideal |
| >= 15 mm | • All persons with no known risk factors for tuberculosis (general population) |
Treatment of Latent Tuberculosis Infection (LTBI)
Rule out active pulmonary/extrapulmonary TB with symptom review and chest radiograph prior to initiating LTBI therapy. Preferred short-course rifamycin-based regimens are superior due to higher completion rates and lower hepatotoxicity:
- 3HP Regimen (Preferred): Once-weekly Isoniazid (900 mg) + Rifapentine (900 mg) for 3 months (12 doses total).
- 4R Regimen (Preferred): Daily Rifampin (600 mg daily) for 4 months.
- 3HR Regimen: Daily Isoniazid (300 mg) + Rifampin (600 mg) for 3 months.
- 6H / 9H Monotherapy (Alternative): Daily Isoniazid (300 mg daily) for 6 to 9 months plus Pyridoxine (Vitamin B6 25–50 mg daily).
Treatment of Active Tuberculosis
Active disease is treated with a two-phase regimen consisting of an initial 2-month Intensive Phase (RIPE) followed by a 4-month Continuation Phase (RI) (total 6 months).
Active TB Regimen:
Intensive Phase (Months 1–2): Rifampin + Isoniazid (with Pyridoxine) + Pyrazinamide + Ethambutol
Continuation Phase (Months 3–6): Rifampin + Isoniazid (with Pyridoxine)
| Drug | Mechanism of Action | Classic Adverse Effects | Monitoring & Clinical Pearls |
|---|---|---|---|
| Rifampin (RIF) | Inhibits DNA-dependent RNA polymerase | • Orange-red discoloration of urine, sweat, tears, and contact lenses<br/>• Potent CYP450 (CYP3A4) inducer (lowers levels of OCPs, warfarin, DOACs, methadone, protease inhibitors)<br/>• Hepatotoxicity, cholestasis, thrombocytopenia | Baseline LFTs and CBC; counsel patient regarding harmless orange secretions and need for barrier contraception. |
| Isoniazid (INH) | Inhibits mycolic acid synthesis | • Peripheral neuropathy (due to pyridoxine deficiency)<br/>• Hepatotoxicity (toxic metabolite acetylhydrazine)<br/>• Drug-induced lupus (anti-histone antibodies) | Co-prescribe Pyridoxine (Vitamin B6 25–50 mg daily) in all patients at risk for neuropathy (DM, pregnancy, alcoholism, renal failure, malnutrition). Discontinue INH if AST/ALT >3x ULN with symptoms, or >5x ULN without symptoms. |
| Pyrazinamide (PZA) | Disrupts plasma membrane and energy metabolism | • Hyperuricemia (causes non-gouty arthralgias and acute gout attacks)<br/>• Hepatotoxicity (most potent hepatotoxin among RIPE drugs) | Avoid in severe liver disease; monitor uric acid if symptomatic gout develops. Can be omitted in pregnant women (extend continuation phase). |
| Ethambutol (EMB) | Inhibits arabinosyl transferase (disrupts arabinogalactan cell wall) | • Retrobulbar Optic Neuritis (decreased visual acuity, central scotoma, loss of red-green color discrimination) | Baseline and monthly testing of visual acuity (Snellen chart) and color discrimination (Ishihara plates); discontinue immediately if visual changes occur. Adjust dose in renal failure. |
Test Your Knowledge
A 44-year-old woman is undergoing evaluation for pulmonary tuberculosis after presenting with chronic cough, night sweats, hemoptysis, and apical cavitary infiltrates on chest imaging. Sputum acid-fast bacilli (AFB) smear and PCR confirm Mycobacterium tuberculosis susceptible to all first-line agents. She is started on the standard 4-drug intensive regimen consisting of Rifampin, Isoniazid with Pyridoxine, Pyrazinamide, and Ethambutol. Which of the following baseline and ongoing monitoring evaluations is specifically required due to the toxicities of this regimen?
A
B
C
D