This page covers the major respiratory pathogens in the community and hospital setting, the clinical syndromes they cause, the diagnostic approach for each, the relevant treatment, and the antibiotic stewardship principles that apply specifically to respiratory infection management.
Upper Respiratory Tract Infections: Mostly Viral, Rarely Bacterial
The common cold is caused by rhinoviruses (over 160 serotypes, most common cause of upper respiratory infection in adults and children), coronaviruses (including the four common coronaviruses causing mild cold-like illness, distinct from SARS-CoV-2), influenza A and B viruses (causing characteristic sudden-onset systemic illness with fever, myalgia, headache, and respiratory symptoms), parainfluenza viruses (causing croup in children), respiratory syncytial virus (RSV, major cause of bronchiolitis in infants and of severe pneumonia in elderly and immunocompromised), adenoviruses, and human metapneumovirus.
Bacterial causes of pharyngitis requiring treatment: Streptococcus pyogenes (Group A Streptococcus) causes acute streptococcal pharyngitis/tonsillitis, characterised by sore throat, tonsillar exudate, tender cervical lymphadenopathy, and fever without cough. The Centor criteria (and modified McIsaac score) are validated clinical decision rules that estimate the probability of GAS pharyngitis and guide antibiotic prescribing. Penicillin or amoxicillin for 10 days is the treatment of choice. Untreated GAS pharyngitis can lead to peritonsillar abscess and, in genetically susceptible individuals, acute rheumatic fever (ARF) with cardiac valve damage.
Epiglottitis: Haemophilus influenzae type b (Hib) was the classical cause, now rare in vaccinated populations. S. pyogenes, S. aureus, and other organisms can also cause epiglottitis. It is a life-threatening emergency requiring urgent airway management.
Community-Acquired Pneumonia: The Classic Bacterial Presentation
Community-acquired pneumonia (CAP) is the most common life-threatening infectious disease in high-income countries, with a 30-day mortality of 5 to 10 per cent overall but 20 to 50 per cent in elderly or severely ill patients. The CURB-65 score (Confusion, Urea above 7 mmol/L, Respiratory rate above 30, Blood pressure below 90/60, age 65 or above) stratifies severity and guides site of care (outpatient vs hospital vs ICU admission).
Streptococcus pneumoniae (the pneumococcus) is the most common bacterial cause of CAP in all age groups. It causes lobar pneumonia: fever, productive cough, pleuritic chest pain, and consolidation of a single lobe on chest X-ray. Bacteraemia occurs in approximately 25 per cent of pneumococcal CAP. Penicillin and amoxicillin remain effective for penicillin-susceptible strains. PCV13 and PCV15/20 vaccines substantially reduce pneumococcal disease incidence.
Haemophilus influenzae (non-typable): causes CAP particularly in patients with chronic obstructive pulmonary disease (COPD) and other underlying pulmonary conditions. Usually amoxicillin-susceptible, but beta-lactamase-positive strains (30 to 40 per cent in many countries) require co-amoxiclav or a cephalosporin.
Moraxella catarrhalis: causes acute exacerbations of COPD and less commonly CAP. Nearly always beta-lactamase-positive. Co-amoxiclav effective.
Mycoplasma pneumoniae: atypical pneumonia, particularly in young adults and school-age children in 3 to 5 year epidemic cycles. Presents with gradual onset, non-productive cough, relatively mild systemic symptoms relative to radiographic appearance, and negative standard culture (requires PCR or serology for diagnosis). Treatment: macrolide, tetracycline, or fluoroquinolone.
Chlamydophila pneumoniae: common cause of mild CAP. Similar clinical presentation to Mycoplasma. Diagnosed by PCR or paired serology.
Legionella pneumophila: causes Legionnaires' disease, a severe atypical pneumonia with prominent extrapulmonary features (hyponatraemia, elevated liver enzymes, gastrointestinal symptoms, neurological changes). Risk factors: exposure to contaminated aerosols (cooling towers, hot tub, hotel plumbing). Diagnosed by urinary antigen test (detects serogroup 1, responsible for 80 per cent of cases) within hours. Treatment: fluoroquinolone or azithromycin for at least 10 to 14 days.
Hospital-Acquired and Ventilator-Associated Pneumonia
Hospital-acquired pneumonia (HAP) and VAP are caused by a broader range of organisms than CAP, with significantly higher rates of antibiotic-resistant organisms due to prior antibiotic exposure and healthcare-related acquisition.
Early HAP/VAP (less than 5 days after admission/intubation): S. pneumoniae, Haemophilus influenzae, MSSA. Similar to CAP pathogens, generally more antibiotic-susceptible.
Late HAP/VAP (5 days or more after admission/intubation): Pseudomonas aeruginosa, MRSA, Acinetobacter baumannii, ESBL-producing Klebsiella, Enterobacter, Serratia. Much higher rates of MDR organisms, requiring broad-spectrum empiric therapy pending culture results.
Diagnosis of VAP is challenging: the clinical criteria (fever, purulent tracheal secretions, new pulmonary infiltrate, and increasing respiratory support) are non-specific. Quantitative culture of BAL or protected specimen brush (PSB) samples (greater than 10^4 CFU/mL for BAL, greater than 10^3 CFU/mL for PSB) improves diagnostic specificity over qualitative endotracheal aspirate culture.
Respiratory Virus Diagnostics: The Multiplex Revolution
The advent of multiplex respiratory PCR panels (such as BioFire FilmArray Respiratory Panel, Luminex NxTAG RPP) capable of simultaneously detecting 15 to 20 respiratory viruses and atypical bacterial pathogens from a single nasopharyngeal swab in 1 to 4 hours has transformed respiratory infection diagnostics.
Clinically important pathogens on current multiplex panels: influenza A and B, RSV A and B, SARS-CoV-2, parainfluenza 1-4, human metapneumovirus, adenovirus, rhinovirus/enterovirus, coronavirus (non-SARS), bocavirus, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordetella pertussis.
The clinical impact of rapid multiplex results: a positive influenza result allows targeted antiviral therapy (oseltamivir) while avoiding unnecessary antibiotics. A positive RSV result allows appropriate isolation and precautions. A positive SARS-CoV-2 result triggers specific pathways for isolation, notification, and management. Negative results for all common viruses in a seriously ill patient support consideration of unusual or difficult-to-detect pathogens including Pneumocystis jirovecii (PCP), Aspergillus, and other fungi.
Frequently Asked Questions
What are the most common causes of community-acquired pneumonia?
The most common bacterial causes of CAP are Streptococcus pneumoniae (most common), Haemophilus influenzae, and atypical organisms including Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. In practice, many cases of mild to moderate CAP are viral and do not require antibiotic therapy.
What is Legionnaires' disease?
Legionnaires' disease is a severe form of pneumonia caused by Legionella pneumophila (most commonly serogroup 1), acquired by inhaling contaminated aerosols from water sources (cooling towers, showerheads, fountains). It typically presents with high fever, non-productive cough, extrapulmonary features (hyponatraemia, confusion, diarrhoea), and does not respond to penicillin or amoxicillin. Urinary antigen testing provides rapid diagnosis.
What is CURB-65?
CURB-65 is a validated clinical severity score for CAP, assigning 1 point each for: Confusion (new), Urea above 7 mmol/L, Respiratory rate above 30/min, Blood pressure below 90 mmHg systolic or below 60 mmHg diastolic, age 65 or above. Score 0 to 1: low severity, consider outpatient treatment. Score 2: moderate, consider hospitalisation. Score 3 or above: severe, consider ICU admission.
What is atypical pneumonia?
Atypical pneumonia is a clinical presentation characterised by gradual onset, non-productive cough, headache and malaise, relatively mild physical examination findings, and multilobar or interstitial infiltrates on chest X-ray, without the classical lobar consolidation of pneumococcal pneumonia. It is caused by organisms that cannot be grown on standard culture media: Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, Coxiella burnetii (Q fever).
What is Pneumocystis jirovecii pneumonia (PCP)?
PCP is a life-threatening opportunistic infection caused by the fungus Pneumocystis jirovecii (previously classified as a protozoan, P. carinii) in immunocompromised patients, particularly those with HIV infection and CD4 count below 200 cells/microlitre, patients on immunosuppressive therapy, and haematological malignancy patients. It presents with subacute progressive exertional dyspnoea, dry cough, and bilateral interstitial infiltrates on CT. Diagnosed by BAL PCR or microscopy with specific stains (Grocott methenamine silver, calcofluor white). Treatment: high-dose co-trimoxazole.
What is RSV and why is it important?
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection in infants (bronchiolitis) and a major cause of severe respiratory disease in elderly and immunocompromised adults. In healthy adults, RSV causes a cold-like illness. There are no broadly available effective specific therapies (inhaled ribavirin is used in some immunocompromised patients). Two RSV vaccines for adults (Arexvy and mRESVIA) received regulatory approval in 2023.
What is the value of respiratory multiplex PCR?
Respiratory multiplex PCR panels simultaneously detect 15 to 20 pathogens from a single swab in 1 to 4 hours, providing rapid aetiological diagnosis. This allows targeted antiviral treatment (oseltamivir for influenza), appropriate infection control precautions, avoidance of unnecessary antibiotics for viral illness, and detection of co-infections (where two or more pathogens are present simultaneously).
What organisms cause pneumonia in immunocompromised patients?
Immunocompromised patients are susceptible to all the pathogens that cause pneumonia in immunocompetent patients plus: Pneumocystis jirovecii (PCP, especially HIV and transplant patients), Aspergillus fumigatus (invasive pulmonary aspergillosis, especially haematological malignancy and solid organ transplant), CMV (in transplant recipients), Cryptococcus neoformans (HIV patients), Nocardia, and endemic fungi (Histoplasma, Coccidioides, Blastomyces in endemic regions).
What is Bordetella pertussis and how is it diagnosed?
Bordetella pertussis causes whooping cough (pertussis): characterised by paroxysmal coughing spells followed by an inspiratory whoop, particularly severe in unvaccinated infants where it can cause life-threatening respiratory failure. Diagnosis is by nasopharyngeal PCR (most sensitive during the catarrhal and early paroxysmal phase) or serology (ELISA for IgG anti-pertussis toxin, useful later in disease course). Treatment is a macrolide (azithromycin or clarithromycin) primarily to reduce transmission; clinical benefit is greatest if started in the catarrhal phase.
When should antibiotic therapy be withheld in respiratory infection?
Antibiotic therapy should be withheld in: clear viral respiratory infections (common cold, uncomplicated influenza without bacterial co-infection, viral bronchitis), mild sore throat without features of GAS infection (no tonsillar exudate, no lymphadenopathy, cough present suggesting viral aetiology), and acute exacerbations of COPD without evidence of bacterial infection (no change in sputum colour or purulence, no systemic features). Procalcitonin-guided protocols assist antibiotic withholding decisions in respiratory infection with good evidence of safety.