8.4 Respiratory Infections & Bronchiectasis
Key Takeaways
- Streptococcus pneumoniae remains the most frequent bacterial cause of CAP, typically presenting with high rigors, rust-coloured sputum, and lobar consolidation; atypical organisms display signature clinical clues such as Legionella (hyponatraemia, diarrhoea, cooling towers) and Mycoplasma (cold haemolytic anaemia, erythema multiforme).
- Pneumocystis jirovecii pneumonia (PJP) affects immunocompromised patients (HIV CD4 < 200 cells/mcL), presenting with exertional desaturation, clear chest auscultation, high LDH, and requiring high-dose co-trimoxazole plus adjunctive steroids if PaO2 < 9.3 kPa.
- The CURB-65 score stratifies 30-day CAP mortality: Confusion (AMTS <= 8), Urea > 7.0 mmol/L, Respiratory rate >= 30/min, Blood pressure (SBP < 90 or DBP <= 60 mmHg), and Age >= 65; scores of 3-5 demand urgent inpatient admission and IV co-amoxiclav plus IV clarithromycin.
- Bronchiectasis diagnosis is established by high-resolution CT demonstrating the 'signet ring' sign (bronchoarterial diameter ratio > 1.0) and lack of peripheral bronchial tapering; aetiologies include cystic fibrosis (upper lobe), Kartagener syndrome (lower lobe with dextrocardia), and ABPA.
- First isolation of Pseudomonas aeruginosa in bronchiectasis mandates an immediate, aggressive eradication attempt with oral ciprofloxacin or IV antipseudomonal beta-lactam combined with nebulised colistimethate, alongside twice-daily chest physiotherapy.
Lower respiratory tract infections and chronic suppurative airway diseases feature heavily across both papers of the MRCP(UK) Part 1 examination. Candidates must master the distinct pathogen-specific clinical phenotypes of community-acquired pneumonia (CAP), risk stratification using the validated CURB-65 prognostic tool, the diagnosis and emergency management of opportunistic Pneumocystis jirovecii pneumonia, and the aetiological investigation and multidisciplinary management of bronchiectasis.
1. Community-Acquired Pneumonia: Pathogen-Specific Signatures
Correct antimicrobial selection hinges on recognizing distinguishing epidemiological, extrapulmonary, and laboratory clues pointing to specific microbial culprits.
1. Typical Bacterial Pathogens
- Streptococcus pneumoniae (Pneumococcus): Gram-positive lancet-shaped diplococci. The most frequent causative pathogen ($50\text{–}60%$ of CAP cases). Classic presentation: sudden onset of high fever, shaking rigors, pleuritic chest pain, tachypnoea, rust-coloured sputum (mixture of lysed erythrocytes, neutrophils, and fibrin), herpes labialis, and dense lobar consolidation on chest radiography. Rapid urinary antigen detection has a sensitivity of $70\text{–}80%$ and persists despite prior antibiotic initiation.
- Staphylococcus aureus: Gram-positive cocci in clusters. Infrequent in primary CAP but classically complicates post-influenza viral pneumonia. Produces an aggressive, necrotizing pneumonia with rapid cavitation, pneumatoceles (thin-walled cystic spaces), spontaneous pneumothorax, and empyema. If Methicillin-Resistant S. aureus (MRSA) is suspected, linezolid or vancomycin must be added.
- Klebsiella pneumoniae: Encapsulated Gram-negative bacillus. Classically affects individuals with chronic alcohol misuse, severe malnutrition, or diabetes mellitus. Characterized by severe necrotizing pneumonia predominantly involving the right upper lobe, producing cavitation, bulging of the interlobar fissure on CXR, and thick, viscous "redcurrant jelly" sputum.
- Pseudomonas aeruginosa: Non-fermenting Gram-negative bacillus. Common in patients with structural lung disease (severe bronchiectasis, cystic fibrosis, advanced COPD with frequent steroid/antibiotic courses). Requires antipseudomonal $\beta$-lactams (piperacillin-tazobactam, ceftazidime, meropenem) plus an aminoglycoside or fluoroquinolone.
2. Atypical & Opportunistic Pathogens
- Legionella pneumophila: Fastidious aerobic Gram-negative rod that thrives intracellularly within alveolar macrophages. Transmitted via inhalation of contaminated aerosols from colonized man-made water systems (hotel air conditioning cooling towers, spa pools, hospital showers). Classic clinical triad: High spiking fevers with relative bradycardia (Faget's sign), gastrointestinal symptoms (profuse watery diarrhoea, severe abdominal cramps), and neurological abnormalities (confusion, encephalopathy, ataxia). Laboratory clues: Marked hyponatraemia (secondary to SIADH and renal tubulopathy), hypophosphataemia, elevated transaminases, lymphopenia, and microscopic haematuria. Diagnosis: Urinary antigen test (detects L. pneumophila serogroup 1, accounting for $> 80%$ of clinical cases). Treatment: IV fluoroquinolones (levofloxacin) or macrolides (clarithromycin).
- Mycoplasma pneumoniae: Extracellular organism lacking a peptidoglycan cell wall (intrinsically resistant to all $\beta$-lactam antibiotics!). Common in children, university students, and military recruits. Insidious onset of headache, sore throat, dry cough, and low-grade fever. Extrapulmonary manifestations: Cold autoimmune haemolytic anaemia (AIHA) mediated by IgM autoantibodies directed against the erythrocyte I antigen (cold agglutinins causing acrocyanosis and Coombs-positive haemolysis), erythema multiforme (targetoid iris lesions), Stevens-Johnson syndrome, myocarditis, Guillain-Barré syndrome, and transverse myelitis. Diagnosis: PCR on throat swab. Treatment: Macrolides, doxycycline, or respiratory fluoroquinolones.
- Chlamydia (Chlamydophila) psittaci: Transmitted by psittacine birds (parrots, parakeets, pigeons). Presents with high fever, dry cough, severe headache, hepatosplenomegaly, and macular rash (Horder's spots). Treatment: Doxycycline.
- Coxiella burnetii (Q Fever): Zoonosis acquired from cattle, sheep, and goats (contact with placenta/amniotic fluid during unpasteurized milk ingestion or calving). Characterized by high fevers, severe headache, abnormal liver function tests, and culture-negative endocarditis. Treatment: Doxycycline.
- Pneumocystis jirovecii (PJP / PCP): Atypical unicellular fungus. Classically affects immunocompromised hosts, notably HIV-infected patients with $\text{CD}_4 \text{ count} < 200\text{ cells/}\mu\text{L}$, or those on potent immunosuppressants. Clinical presentation: Subacute progressive exertional breathlessness, dry cough, and fever. Physical examination may reveal completely normal lung auscultation despite severe, life-threatening exertional oxygen desaturation. Investigations: CXR shows bilateral perihilar ground-glass infiltrates with sparing of lung apices and costophrenic angles. Markedly elevated serum lactate dehydrogenase (LDH). Definitive diagnosis: Sputum induction or bronchoalveolar lavage stained with Grocott's methenamine silver (GMS) stain revealing cup-shaped cysts, or quantitative PCR. Therapy: High-dose oral or IV co-trimoxazole (trimethoprim-sulfamethoxazole $15\text{–}20\text{ mg/kg/day}$ of trimethoprim component) for 21 days. Adjunctive systemic corticosteroids (oral prednisolone or IV methylprednisolone) MUST be initiated concurrently if room air $\text{PaO}_2 < 9.3\text{ kPa}$ ($< 70\text{ mmHg}$) or alveolar-arterial ($A\text{-}a$) oxygen gradient $\ge 35\text{ mmHg}$ to prevent fatal respiratory deterioration caused by the acute lysis of fungal organisms.
2. CURB-65 Prognostic Score & Antimicrobial Risk Stratification
The British Thoracic Society (BTS) and NICE endorse the validated CURB-65 scoring system to stratify 30-day mortality risk and guide admission and antibiotic decisions.
| Variable | Clinical Diagnostic Criterion | Assigned Score |
|---|---|---|
| C — Confusion | New mental confusion: Abbreviated Mental Test Score (AMTS) $\le 8$, or new disorientation in person, place, or time | 1 |
| U — Urea | Serum urea $> 7.0\text{ mmol/L}$ (reflects dehydration, catabolism, or sepsis-induced AKI) | 1 |
| R — Respiratory Rate | Tachypnoea with respiratory rate $\ge 30\text{ breaths/min}$ | 1 |
| B — Blood Pressure | Systolic blood pressure $\text{SBP} < 90\text{ mmHg}$ OR Diastolic blood pressure $\text{DBP} \le 60\text{ mmHg}$ | 1 |
| 65 — Age | Patient age $\ge 65\text{ years}$ | 1 |
Risk Stratification & Recommended Antibiotic Regimens
| CURB-65 Score | 30-Day Mortality | Recommended Care Setting | First-Line Antimicrobial Regimens (NICE Guidelines) |
|---|---|---|---|
| 0 – 1 | $< 3%$ | Suitable for outpatient / community management | Oral amoxicillin $500\text{ mg}$ three times daily for 5 days.<br>(Penicillin allergy: oral doxycycline $200\text{ mg}$ loading then $100\text{ mg}$ od, or oral clarithromycin $500\text{ mg}$ bd) |
| 2 | $\approx 9%$ | Inpatient general medical ward admission (or closely supervised outpatient care) | Dual therapy with oral/IV amoxicillin $500\text{ mg}$ tds PLUS a macrolide (oral/IV clarithromycin $500\text{ mg}$ bd).<br>(Penicillin allergy: oral/IV levofloxacin $500\text{ mg}$ od) |
| 3 – 5 | $15\text{–}40%$ | Urgent inpatient admission; immediately assess for HDU / ICU admission | Intravenous co-amoxiclav $1.2\text{ g}$ three times daily PLUS intravenous clarithromycin $500\text{ mg}$ twice daily.<br>(Alternative: IV cefuroxime/ceftriaxone PLUS IV clarithromycin; Penicillin allergy: IV levofloxacin $500\text{ mg}$ bd) |
3. Bronchiectasis: Aetiology & Pathophysiological Workup
Bronchiectasis is a chronic, irreversible abnormal dilation and distortion of the bronchi resulting from a self-perpetuating vicious cycle of impaired mucociliary clearance, chronic bacterial colonization, persistent transmural neutrophilic inflammation, and progressive destruction of the bronchial muscular and elastic structural components (Cole's vicious cycle hypothesis).
Underlying Aetiologies
- Post-Infective (~30%): Severe necrotizing childhood infections (measles, pertussis, adenovirus, pulmonary tuberculosis, or severe childhood pneumonia).
- Cystic Fibrosis (CF): Autosomal recessive mutation in the CFTR gene (chromosome 7, $\Delta\text{F508}$ most common), causing defective cyclic AMP-dependent chloride transport across epithelial surfaces, dehydrated viscous mucus, recurrent infections (S. aureus, P. aeruginosa), pancreatic exocrine insufficiency, and predominantly upper lobe bronchiectasis.
- Primary Ciliary Dyskinesia (PCD) / Kartagener Syndrome: Autosomal recessive mutations in ciliary ultrastructural proteins (outer or inner dynein arms). Kartagener syndrome features the classic clinical triad of:
- Bronchiectasis (predominantly affecting the middle and lower lobes).
- Situs inversus / Dextrocardia (caused by absent embryonic nodal ciliary rotation).
- Chronic pansinusitis and nasal polyposis, accompanied by male infertility (immotile sperm flagella) and subfertility in females.
- Allergic Bronchopulmonary Aspergillosis (ABPA): Hypersensitivity reaction to colonized Aspergillus fumigatus in patients with underlying asthma or cystic fibrosis. Key features: Fleeting pulmonary infiltrates, central/proximal bronchiectasis with normal peripheral bronchi, expectoration of thick brown mucus plugs containing fungal hyphae, peripheral blood eosinophilia ($> 0.5 \times 10^9/\text{L}$), markedly elevated total serum $\text{IgE} > 1000\text{ IU/mL}$, and positive specific IgE/IgG to Aspergillus. Treatment: Oral prednisolone combined with oral itraconazole.
- Immunodeficiency Syndromes: Primary hypogammaglobulinaemia (Common Variable Immunodeficiency [CVID], X-linked agammaglobulinaemia [Bruton's], selective IgA deficiency, IgG subclass deficiency) and secondary immunodeficiency (HIV, post-chemotherapy).
- Connective Tissue Diseases: Rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus.
- Alpha-1-Antitrypsin (AAT) Deficiency: Associated with basal panacinar emphysema and bronchiectasis.
Clinical Presentation & Diagnostic Investigations
- Symptoms: Chronic daily cough productive of copious, purulent sputum (often layered into three distinct zones upon standing: frothy top layer, turbid liquid middle layer, and thick purulent sediment), recurrent febrile chest infections, dyspnoea, and intermittent haemoptysis (arising from hypertrophied, friable bronchial arteries).
- Physical Signs: Coarse, pan-inspiratory or 'popping' crackles auscultated over the affected lung bases; coarse expiratory rhonchi; and digital clubbing (present in up to $30%$).
- High-Resolution CT (HRCT) of the Chest: Gold Standard:
- The "Signet Ring" Sign: Internal lumen diameter of a bronchus exceeds the diameter of its accompanying pulmonary artery branch (bronchoarterial ratio $> 1.0$).
- Lack of bronchial tapering: Bronchi fail to taper progressively towards the lung periphery (bronchial walls visible within $1\text{ cm}$ of the costal pleura).
- Bronchial wall thickening and mucus plugging (producing a "tree-in-bud" appearance reflecting active bronchiolitis).
Multidisciplinary Management & Pseudomonas aeruginosa Colonization
- Airway Clearance Techniques (Physiotherapy): The non-pharmacological cornerstone of therapy. Daily or twice-daily chest physiotherapy incorporating the Active Cycle of Breathing Techniques (ACBT), postural drainage, and oscillatory positive expiratory pressure (OPEP / Flutter / Acapella devices) to dislodge secretions.
- Mucoactive Agents: Inhaled nebulised hypertonic saline ($6\text{–}7%$) or carbocisteine to reduce sputum viscosity.
- Prophylactic Long-Term Antibiotics: In patients suffering $\ge 3$ acute exacerbations per year, long-term prophylactic macrolide therapy (oral azithromycin $250\text{ mg}$ three times weekly) significantly reduces exacerbation rates through anti-inflammatory and immunomodulatory mechanisms. (Mandatory baseline ECG to exclude prolonged QTc, and sputum mycobacterial culture to exclude occult non-tuberculous mycobacteria [NTM], which would develop macrolide resistance).
- Management of Pseudomonas aeruginosa Colonization:
- Colonization by P. aeruginosa accelerates lung function decline, triples hospitalization risk, and doubles mortality.
- First Isolation Eradication Protocol: Immediate, aggressive attempt at eradication is mandatory upon the very first isolate. Regimens combine high-dose oral ciprofloxacin ($750\text{ mg}$ twice daily for 14 days) or IV antipseudomonal $\beta$-lactams (piperacillin-tazobactam or ceftazidime) with nebulised colistimethate sodium or tobramycin for up to 3 months.
- Chronic Colonization: Maintenance long-term inhaled nebulised colistimethate or tobramycin to suppress bacterial load.
A 54-year-old businessman is admitted to hospital with a 4-day history of high spiking fevers, dry cough, pleuritic chest discomfort, and profuse watery diarrhoea. He recently returned from a business convention staying at a newly refurbished hotel. On examination, he is confused (Abbreviated Mental Test Score 6/10), febrile at 39.6 C, heart rate 72 beats/min regular (relative bradycardia), blood pressure 104/62 mmHg, and respiratory rate 28 breaths/min. Auscultation reveals bronchial breathing and coarse crackles over the right mid- and lower lung zones. Laboratory investigations reveal: haemoglobin 134 g/L, white cell count 14.8 x 10^9/L, neutrophils 13.1 x 10^9/L, lymphocytes 0.6 x 10^9/L, serum sodium 124 mmol/L, serum potassium 3.8 mmol/L, urea 8.4 mmol/L, creatinine 112 micromol/L, ALT 94 IU/L, and AST 88 IU/L. Chest radiograph demonstrates dense right middle and lower lobe consolidation. What is the most likely causative pathogen and guideline-directed antimicrobial therapy?
An 82-year-old woman is brought to the emergency department from a residential care home with acute confusion, productive cough with purulent sputum, and breathlessness. On physical examination, her Abbreviated Mental Test Score (AMTS) is 5/10 (previously 10/10). Her temperature is 38.8 C, respiratory rate is 34 breaths/min, blood pressure is 84/52 mmHg, and oxygen saturation is 89% on ambient air. Auscultation reveals dense bronchial breathing and coarse crackles over the left lower zone. Laboratory results show: white blood cell count 18.2 x 10^9/L, serum urea 11.4 mmol/L, and serum creatinine 138 micromol/L. A portable chest radiograph confirms left lower lobe consolidation. What is her CURB-65 score, and what is the most appropriate initial management strategy?
A 38-year-old woman presents to the chest clinic with a long-standing history of chronic cough productive of copious, daily, foul-smelling purulent sputum (approximately 60 mL daily) and recurrent episodes of lower respiratory tract infections requiring multiple antibiotic courses each year. She has never smoked. Examination reveals coarse pan-inspiratory crackles over both lung bases that persist after coughing, and mild bilateral digital clubbing. High-resolution CT (HRCT) of the chest reveals dilated, non-tapering bronchi with an internal bronchoarterial diameter ratio of 1.6 ('signet ring' sign) and mucosal thickening in the lower lobes bilaterally. Sputum microscopy and culture yield a heavy growth of Pseudomonas aeruginosa for the first time. What is the most appropriate management plan?