3.2 Pneumonia, Tuberculosis & Respiratory Infections
Key Takeaways
- CURB-65 stratifies community-acquired pneumonia (CAP) 30-day mortality risk: scores 0–1 indicate low risk (<3%, home treatment), score 2 moderate risk (~9%, hospital admission), and scores 3–5 severe CAP (15–40%, urgent inpatient/ICU care).
- Pneumocystis jirovecii pneumonia (PJP) typically occurs in HIV patients with CD4 counts <200 cells/µL, presenting with exertional hypoxaemia out of proportion to chest radiography; treatment requires high-dose co-trimoxazole plus adjunctive corticosteroids if PaO2 is <8.0 kPa.
- Standard short-course therapy for drug-susceptible Mycobacterium tuberculosis consists of a 2-month intensive phase of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol (HRZE), followed by a 4-month continuation phase of Rifampicin and Isoniazid (HR).
- Ethambutol requires baseline visual acuity and color vision testing due to the risk of dose-dependent optic neuritis, whereas Isoniazid requires co-prescription of Pyridoxine (Vitamin B6 10–50 mg daily) to prevent peripheral neuropathy.
- Allergic Bronchopulmonary Aspergillosis (ABPA) occurs in patients with asthma or cystic fibrosis, characterized by total serum IgE >1000 IU/mL, Aspergillus-specific IgE/IgG positivity, peripheral eosinophilia (>500/µL), and central bronchiectasis on HRCT.
Community-Acquired Pneumonia (CAP): Pathogens & CURB-65 Stratification
Community-Acquired Pneumonia (CAP) is acute parenchymal lung infection acquired outside hospital or healthcare settings. Prompt identification of atypical pathogens and severity risk-stratification are essential for selecting appropriate empirical antimicrobial therapy.
Microbiology of CAP
- Streptococcus pneumoniae: Most common organism overall (50%). Classic features include abrupt high fever, pleuritic chest pain, rust-colored sputum, and herpes labialis reactivation.
- Haemophilus influenzae: Common in patients with underlying COPD or structural lung disease.
- Moraxella catarrhalis: Frequently seen in elderly COPD patients.
- Staphylococcus aureus: Causes necrotizing pneumonia with cavitary lesions and pneumatoceles, classically secondary to influenza infection.
- Mycoplasma pneumoniae: Atypical pathogen in young adults. Features include insidious onset, dry cough, erythema multiforme, bullous myringitis, and autoimmune cold-agglutinin haemolytic anaemia (IgM).
- Legionella pneumophila: Colonizes water systems (air conditioning, showers). Causes severe pneumonia with high fever, relative bradycardia, hyponatremia (due to SIADH), diarrhea, and elevated liver enzymes. Diagnosed via urinary antigen test (detects serogroup 1).
- Chlamydia psittaci: Psittacosis transmitted via contact with psittacine birds (parrots, pigeons). Features fever, splenomegaly, and severe headache.
- Coxiella burnetii: Q fever linked to contact with parturient livestock (cattle, sheep). Associated with hepatitis and culture-negative endocarditis.
CURB-65 Severity Stratification Score
The British Thoracic Society (BTS) CURB-65 score assigns 1 point for each of the following criteria:
- Confusion (Abbreviated Mental Test Score ≤8 or new disorientation)
- Urea >7.0 mmol/L
- Respiratory Rate ≥30 breaths/minute
- Blood Pressure (Systolic BP <90 mmHg OR Diastolic BP ≤60 mmHg)
- Age ≥65 years
| CURB-65 Score | 30-Day Mortality | Recommended Treatment Setting | Empirical Antibiotic Regimen (BTS Guidelines) |
|---|---|---|---|
| 0–1 | Low (<3%) | Home / Outpatient | Amoxicillin 500 mg PO TDS for 5 days (Alternative: Doxycycline 200 mg stat then 100 mg OD, or Clarithromycin 500 mg BD) |
| 2 | Moderate (~9%) | Hospital admission / Short-stay ward | Amoxicillin 500 mg–1 g PO/IV TDS + Clarithromycin 500 mg PO/IV BD for 7 days |
| 3–5 | High (15–40%) | Severe CAP; urgent hospital admission (consider ITU/HDU if score 4–5) | Co-amoxiclav 1.2 g IV TDS + Clarithromycin 500 mg IV BD (or Levofloxacin 500 mg IV BD) |
Hospital-Acquired Pneumonia (HAP) & Opportunistic Infections
Hospital-Acquired Pneumonia (HAP)
HAP is defined as pneumonia developing >48 hours after hospital admission. Key pathogens include Gram-negative bacilli (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter) and Staphylococcus aureus (including MRSA).
- Empirical Regimen: Piperacillin-tazobactam 4.5 g IV TDS, Ceftazidime 2 g IV TDS, or Meropenem 1 g IV TDS. Add Vancomycin or Teicoplanin if MRSA risk factors are present.
Pneumocystis jirovecii Pneumonia (PJP / PCP)
PJP is an opportunistic fungal infection occurring in immunocompromised patients, classically in HIV-infected individuals with a CD4 count <200 cells/µL, or non-HIV patients receiving high-dose immunosuppression (e.g., organ transplants, high-dose steroids, anti-TNF agents).
- Clinical Presentation: Insidious onset of progressive exertional dyspnoea, dry non-productive cough, and fever. Physical examination often demonstrates profound exercise-induced arterial desaturation out of proportion to chest radiograph findings.
- Diagnostics: Chest radiograph typically reveals bilateral perihilar interstitial infiltrates ("bat-wing" pattern). Serum Lactate Dehydrogenase (LDH) is markedly elevated. Diagnostic confirmation requires immunofluorescence staining or PCR of induced sputum or Bronchoalveolar Lavage (BAL) fluid.
- Antimicrobial Treatment: First-line regimen is high-dose Co-trimoxazole (Trimethoprim 15–20 mg/kg/day + Sulfamethoxazole 75–100 mg/kg/day IV or PO divided q6h) for 21 days.
- Adjunctive Corticosteroid Indications: Systemic corticosteroids (oral Prednisolone 40 mg BD for 5 days, then 40 mg OD for 5 days, then 20 mg OD to day 21) MUST be initiated within 72 hours if arterial blood gas demonstrates:
- PaO2 <8.0 kPa on room air, or
- Alveolar-arterial (A-a) oxygen gradient ≥35 mmHg (≥4.7 kPa). Rationale: Steroids attenuate the severe pulmonary inflammatory response triggered by organism lysis during co-trimoxazole initiation.
Pulmonary Tuberculosis: Pathophysiology, Diagnostics & RIPE Regimen
Tuberculosis (TB) is caused by Mycobacterium tuberculosis, an acid-fast, aerobic bacillus transmitted via airborne droplet nuclei.
Pathophysiology & Clinical Manifestations
- Primary TB: Inhaled bacilli multiply in alveolar macrophages, forming a subpleural parenchymal lesion (Ghon focus) combined with ipsilateral hilar lymphadenopathy, termed the Ranke complex. Most primary infections undergo cell-mediated containment resulting in Latent TB Infection (LTBI).
- Reactivation TB: Occurs primarily in the apical and posterior segments of the upper lobes due to high regional oxygen tension (PaO2). Symptoms include fever, night sweats, weight loss, anorexia, chronic productive cough, and haemoptysis.
Diagnostic Modalities
- Sputum Smear: Acid-fast bacilli (AFB) identified via Ziehl-Neelsen (red rods on blue background) or Auramine-rhodamine fluorescent staining. Requires ≥3 morning sputum samples.
- Nucleic Acid Amplification (GeneXpert MTB/RIF): Rapid automated PCR detecting M. tuberculosis DNA and rifampicin resistance mutations (rpoB gene) within 2 hours.
- Mycobacterial Culture: Liquid culture (MGIT) remains the gold standard for definitive diagnosis and drug susceptibility testing (takes 1–4 weeks).
- Latent TB Screening: Interferon-Gamma Release Assay (IGRA e.g., T-SPOT.TB, QuantiFERON-TB Gold) or Tuberculin Skin Test (TST / Mantoux test).
Standard Anti-Tuberculous Pharmacotherapy (2HRZE / 4HR)
Treatment of drug-susceptible active pulmonary TB comprises a 2-month intensive phase followed by a 4-month continuation phase:
| Drug | Primary Adverse Effects | Clinical Monitoring & Prevention |
|---|---|---|
| Rifampicin (R) | Hepatic transaminitis, orange-red discoloration of body fluids (tears, urine, sweat), potent inducer of cytochrome P450 enzymes (lowers levels of oral contraceptives, warfarin, antiretrovirals) | Baseline and monthly LFTs; counsel regarding contact lens staining and drug interactions |
| Isoniazid (H) | Peripheral neuropathy (due to pyridoxine depletion), hepatotoxicity, drug-induced lupus erythematosus | Co-prescribe Pyridoxine (Vitamin B6 10–50 mg daily); baseline LFTs |
| Pyrazinamide (Z) | Hyperuricaemia (can precipitate acute gout), severe hepatotoxicity, arthralgias | Serum uric acid, LFTs |
| Ethambutol (E) | Optic neuritis (decreased visual acuity, red-green color blindness, central scotoma) | Baseline Snellen visual acuity and Ishihara color vision testing; discontinue immediately if visual symptoms occur |
Pulmonary Aspergillosis Spectrum
Aspergillus fumigatus causes a spectrum of lung diseases depending on host immune status and underlying lung architecture:
- Aspergilloma ("Fungal Ball"): Colonization of a pre-existing tuberculous cavity or bulla. Chest radiograph/CT shows a solid mass with a crescent of surrounding air (Monod sign), which moves when the patient changes position. Can cause catastrophic haemoptysis requiring bronchial artery embolisation or surgical resection.
- Allergic Bronchopulmonary Aspergillosis (ABPA): Hypersensitivity reaction (Types I and III) to Aspergillus colonizing airways in patients with asthma or cystic fibrosis.
- Diagnostic Criteria:
- History of asthma or CF,
- Total serum IgE >1000 IU/mL,
- Positive Aspergillus skin prick test or specific IgE,
- Elevated Aspergillus IgG precipitins,
- Peripheral blood eosinophilia (>500 cells/µL),
- HRCT showing central/proximal bronchiectasis.
- Treatment: Oral Prednisolone (0.5 mg/kg/day tapered over 3 months) combined with oral Itraconazole 200 mg BD to reduce fungal burden.
- Diagnostic Criteria:
- Invasive Aspergillosis: Rapidly progressive necrotizing pneumonia in severely immunocompromised hosts (profound neutropenia <500/µL, allogeneic stem cell transplant). HRCT shows nodules with surrounding ground-glass attenuation (halo sign) or cavitating lesions (air-crescent sign). Serum galactomannan antigen is positive. First-line therapy is IV Voriconazole or Isavuconazole.
A 72-year-old man presents to the emergency department with a 3-day history of fever, right-sided pleuritic chest pain, and productive cough with rust-colored sputum. On examination, he is confused (Abbreviated Mental Test Score 6/10). Temperature is 38.9°C, blood pressure is 84/52 mmHg, pulse rate is 110 beats/minute, and respiratory rate is 32 breaths/minute. Laboratory investigation reveals a blood urea of 9.4 mmol/L and white cell count of 18.5 x 10^9/L. Chest radiograph confirms right lower lobe consolidation. What is his CURB-65 score and the most appropriate initial management setting?
A 38-year-old man with HIV (CD4 count 110 cells/µL) not currently receiving antiretroviral therapy presents with a 2-week history of progressive exertional shortness of breath, fever, and non-productive cough. On examination, respiratory rate is 26 breaths/minute and resting oxygen saturation on air is 89%. Chest radiograph shows faint bilateral perihilar interstitial opacities. Arterial blood gas on air demonstrates pH 7.44, PaO2 7.1 kPa, PaCO2 4.2 kPa. High-dose IV co-trimoxazole is initiated. Which of the following adjunctive therapies should be commenced immediately?
A 44-year-old woman is commenced on standard four-drug anti-tuberculous therapy (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) for culture-confirmed pulmonary tuberculosis. Before starting treatment, she is prescribed Pyridoxine (Vitamin B6 10 mg daily) alongside her regimen. Which specific adverse drug effect is Pyridoxine prescribed to prevent?