Lucan · Conditions

Empiric antibiotics: severity-stratified CAP

Australian guidance: eTG Antibiotic — CAP

1. Definition and epidemiology

Community-acquired pneumonia (CAP) is an acute infection of the lung parenchyma occurring outside hospital or within 48 hours of admission. Selecting the correct empiric antibiotic regimen requires first stratifying severity, because the causative pathogen spectrum and mortality risk shift substantially between mild outpatient disease and severe inpatient illness. In Australia, CAP accounts for approximately 77,000 hospitalisations annually; 30-day mortality is below 1% in community-managed patients but rises to 10 to 12% among those admitted to hospital.

2. Pathophysiology

The pathogen spectrum that drives empiric antibiotic selection in CAP is shaped by the mechanism of infection and host vulnerability. Streptococcus pneumoniae, the dominant typical pathogen, reaches alveoli via microaspiration of oropharyngeal secretions. Once established, it triggers an acute exudative inflammatory response: alveolar capillary permeability increases, neutrophils flood the alveolar space, and consolidation follows the classic Robbins sequence of congestion, red hepatisation, grey hepatisation, and resolution (Robbins Ch 15). Atypical organisms (Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae) replicate intracellularly and cause interstitial rather than lobar inflammation; they lack a cell wall and are intrinsically resistant to beta-lactam antibiotics, mandating the addition of a macrolide or tetracycline regardless of severity tier. In severe CAP, systemic cytokine release drives sepsis-type physiology, and the risk of Legionella and Gram-negative organisms (including Pseudomonas aeruginosa in structurally damaged lungs) rises, justifying broader empiric cover.

3. Clinical presentation and diagnostic criteria

Typical CAP presents with acute onset fever, rigors, productive cough, pleuritic chest pain, and dyspnoea. Localised consolidation on examination (dullness to percussion, bronchial breath sounds, increased tactile vocal fremitus) strongly supports the diagnosis. Atypical CAP produces a more insidious onset with dry cough, myalgia, headache, and extrapulmonary features such as diarrhoea (Legionella) or a maculopapular rash (Mycoplasma). Severity scoring governs antibiotic tier selection: the CORB score (Confusion, Oxyhaemoglobin saturation below 90%, Respiratory rate 25 or above per minute, Blood pressure systolic below 90 mmHg or diastolic 60 mmHg or below) assigns 1 point per criterion and is used at triage to stratify into community or hospital treatment. The SMART-COP score is used in the inpatient setting to predict need for intensive respiratory or vasopressor support; a score of 5 or above identifies high-risk patients who require ICU review.

4. Investigations and AU-specific cutoffs

Severity scoring precedes all other investigation decisions and directly determines antibiotic tier.

CORB 0 to 1 supports community management with oral antibiotics. CORB 2 indicates hospital admission. CORB 3 to 4 mandates urgent senior review and ICU consideration.

Chest radiograph is mandatory for all patients being admitted to hospital. It confirms the diagnosis, quantifies lobar vs multilobar involvement, identifies pleural effusion or cavitation, and provides a baseline for monitoring treatment response.

Blood cultures (two sets) and sputum culture should be collected before antibiotic administration in all hospitalised patients. Legionella urinary antigen is indicated for moderate to severe CAP and has high specificity for serogroup 1. Pneumococcal urinary antigen (sensitivity 70 to 80% in AU) is particularly useful after prior antibiotic exposure when culture yield is low. Nasopharyngeal PCR for influenza is recommended in season.

Blood tests should include a full blood count, urea and electrolytes, creatinine, liver function tests, and C-reactive protein. CRP above 100 mg/L supports a bacterial cause. Lactate is indicated in moderate to severe disease to screen for occult hypoperfusion. SpO2 on room air is obtained in all patients; arterial blood gas is added when SpO2 falls below 94% or in any patient with moderate to severe disease.

5. Management

Empiric antibiotic selection is stratified into three tiers based on CORB severity at presentation.

Tier 1 — Mild CAP (CORB 0 to 1, community management)

First-line therapy is amoxicillin 1 g orally three times daily plus doxycycline 100 mg orally twice daily (loading dose 200 mg on day 1), continued for 5 days. Amoxicillin covers typical organisms including S. pneumoniae; doxycycline adds atypical cover. In younger patients without comorbidities where atypical infection is clinically unlikely, amoxicillin monotherapy is acceptable. Doxycycline monotherapy is an alternative when typical bacterial CAP is less likely (e.g. atypical features predominate in a young adult with no comorbidities).

Tier 2 — Moderate CAP (CORB 2, hospital admission)

Intravenous benzylpenicillin 1.2 g four to six hourly plus doxycycline 100 mg orally or intravenously twice daily is the standard combination. Where oral medication is not tolerated, azithromycin 500 mg intravenously once daily may replace doxycycline. This combination targets S. pneumoniae (benzylpenicillin) alongside atypical organisms (doxycycline or azithromycin). Adding a macrolide or tetracycline to the beta-lactam backbone is associated with a survival benefit compared with beta-lactam monotherapy in hospitalised CAP.

Tier 3 — Severe CAP (CORB 3 to 4 or SMART-COP 5 or above, ICU consideration)

Empiric cover is expanded to ensure Legionella is reliably treated. The recommended regimen is benzylpenicillin 1.2 g intravenously four to six hourly plus azithromycin 500 mg intravenously once daily. Azithromycin provides superior intracellular penetration for Legionella compared with doxycycline. Where structural lung disease, recent hospitalisation, or heavy immunosuppression raises the probability of Pseudomonas aeruginosa, benzylpenicillin is replaced by piperacillin-tazobactam 4.5 g intravenously six hourly.

Penicillin hypersensitivity

For non-severe immediate or delayed hypersensitivity, ceftriaxone 1 g intravenously once daily can replace benzylpenicillin. For confirmed severe immediate penicillin allergy (anaphylaxis), moxifloxacin 400 mg orally or intravenously once daily is recommended as monotherapy covering both typical and atypical organisms.

De-escalation and step-down

Intravenous to oral switch is appropriate after 48 to 72 hours when the patient is afebrile, haemodynamically stable, tolerating oral fluids, and SpO2 is adequate on low-flow oxygen. The antibiotic regimen should be narrowed once blood and sputum culture results are available, consistent with antimicrobial stewardship principles. Total duration is 5 days for mild to moderate CAP and 7 to 10 days for severe or Legionella CAP.

6. Pharmacology and AU PBS notes

Amoxicillin 500 mg capsules (generic; Amoxil, Cilamox). PBS listed without restriction for community respiratory infections. Preferred over amoxicillin-clavulanate in uncomplicated CAP as the broader spectrum of co-amoxiclav is unnecessary and increases adverse effects.

Doxycycline 100 mg tablets (generic; Doryx, Vibramycin-D dispersible tablets). PBS listed. Take with food and a full glass of water, and remain upright for at least 30 minutes to reduce the risk of oesophageal ulceration. Avoid in pregnancy and children under 12 years.

Azithromycin 500 mg tablets and 500 mg intravenous vials (generic; Zithromax). PBS listed for respiratory infections. Prolongs the QTc interval; use with caution in patients on other QTc-prolonging agents. Once-daily dosing supports early switch to outpatient therapy.

Benzylpenicillin (penicillin G) 600 mg and 1.2 g vials. Intravenous use only. No specific PBS inpatient restriction. Narrow spectrum preserves microbiome integrity and is preferred over ampicillin or broader beta-lactams for standard CAP in the absence of Gram-negative risk factors.

Ceftriaxone 1 g and 2 g vials. PBS listed for inpatient use. Once-daily dosing facilitates hospital-in-the-home (HITH) programmes used widely across Australian metropolitan health networks.

Piperacillin-tazobactam 4.5 g vials. Used only when Pseudomonas is a genuine risk. Authority required under some state formularies. Broader use should be avoided to preserve this agent for resistant organisms.

Moxifloxacin 400 mg tablets and 400 mg infusion. PBS authority required for CAP in patients with penicillin allergy. Should not be used as empirical first-line in fluoroquinolone-naive patients with no allergy, to preserve susceptibility. Contraindicated in patients with QTc prolongation, prior tendinopathy, or concurrent QTc-prolonging drug use.

7. Complications and monitoring

Failure to improve within 48 to 72 hours (persistent fever, worsening SpO2, haemodynamic deterioration) should trigger microbiological review, a repeat chest radiograph, and reconsideration of the diagnosis. Differential diagnoses to consider include parapneumonic pleural effusion or empyema (suspect if fever persists beyond 72 hours; investigate with thoracic ultrasound and diagnostic pleural tap if an effusion is present), lung abscess (cavitation on chest radiograph, failure to defervesce, anaerobic or S. aureus aetiology), bacteraemia progressing to septic shock, and respiratory failure requiring non-invasive or invasive ventilation.

Antibiotic-related monitoring includes renal function in patients receiving beta-lactams, liver function with azithromycin in hepatic impairment, and QTc surveillance when using azithromycin or moxifloxacin. Clostridium difficile infection risk is elevated with any antibiotic; new diarrhoea after 48 hours of therapy warrants stool testing.

At follow-up, a chest radiograph at 6 weeks post-discharge is recommended for patients aged 50 years or above, or those with a smoking history, to confirm radiological resolution and exclude an underlying endobronchial malignancy. Pneumococcal vaccination should be offered during the admission or at follow-up for all previously unvaccinated patients. Annual influenza vaccination should be reinforced.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.