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Respiratory infection—bacterial 

Respiratory infection—bacterial
Respiratory infection—bacterial

Stephen Chapman

, Grace Robinson

, John Stradling

, Sophie West

, and John Wrightson

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date: 29 June 2022

Community-acquired pneumonia (CAP)

CAP is a common disease, associated with significant morbidity and mortality.


A syndrome of infection that is usually bacterial, with symptoms and signs of consolidation of part(s) of the lung parenchyma. This is different to bronchitis (see Respiratory infection—bacterial p. [link]).


  • CAP is the commonest infectious cause of death and the 6th leading cause of death in the UK and USA (with age-adjusted death rates of between 1 and 24/100, 000)

  • Up to 42% of UK adults with CAP require hospital admission. Hospital mortality varies between 5% and 12%

  • A BTS multicentre UK study showed that 5–10% of patients with CAP require ICU admission

  • Mortality is up to 50% in those admitted to ICU

  • CAP managed in the community has a mortality of <1%.


The lung and tracheobronchial tree are usually sterile below the level of the larynx, so an infecting agent must reach this site via a breach in host defences. This may be by micro-aspiration (which occurs in around 45% of healthy individuals overnight), haematogenous spread, direct spread from an adjacent structure, inhalation, or activation of previously dormant infection.


See Box 40.1. Broadly similar pathogens are seen in patients managed in the community and in hospital. A single pathogen is identified in 85% of cases. The proportion of cases with >1 pathogen is unknown.

Risk factors for CAP

  • Aspiration Typically caused by anaerobes and Gram-negative organisms

  • Alcoholism and diabetes Typically associated with bacteraemic pneumococcal pneumonia. Anaerobes and mixed infections are more common in alcoholics

  • Oral steroids/immunosuppression Legionella infection may be more common

  • Cigarette smoking is the strongest independent risk factor for invasive pneumococcal disease in immunocompetent patients

  • COPD Haemophilus influenzae and Moraxella catarrhalis are more common, and COPD is more common in those with bacterial pneumonia

  • Nursing home residents have an increased frequency of CAP, with aspiration, Gram-negative organisms, and anaerobes more common than in age-matched elderly people. Haemophilus influenzae is the most common causative organism. Mycoplasma pneumoniae and Legionella are less common.

CAP: clinical features

  • Fever

  • Cough

  • Sputum

  • SOB

  • Pleuritic chest pain

  • Non-specific features in the elderly. May present ‘off legs’ or with confusion, in the absence of fever.


  • Raised RR (may be the only sign in the elderly)

  • Tachycardia

  • Localizing signs on chest examination. Reduced chest expansion on the affected side, with signs consistent with consolidation (reduced air entry, with bronchial breathing, reduced percussion note, increased vocal resonance) and crackles. A normal chest examination makes the diagnosis unlikely.


of CAP is made on the basis of:

  • Symptoms and signs of an acute lower respiratory tract infection

  • New focal chest signs

  • New radiographic shadowing, for which there is no other explanation

  • At least one systemic feature (e.g. sweating, fevers, aches, and pains)

  • No other explanation for the illness.

Most helpful in diagnosis

  • Fever, pleuritic pain, dyspnoea, and tachypnoea

  • Signs on chest examination.

Specific clinical features of pathogens

The aetiological agent cannot be accurately predicted from the clinical features alone, although some features are more statistically likely with one pathogen than another. The exception to this is the presence of chest pain or fever (>39°C) in those admitted to ICU, which predicts a higher likelihood of streptococcal pneumonia.

  • Streptococcus pneumoniae Increasing age, comorbidity (especially cardiovascular), acute onset, high fever, and pleuritic chest pain

  • Bacteraemic Streptococcus pneumoniae Alcohol, diabetes, COPD, dry or no cough, ♀

  • Legionella Younger patients, smokers, absence of comorbidity, more severe infection, neurological symptoms, evidence of multi-system disease (e.g. abnormal liver enzymes and raised CK)

  • Mycoplasma pneumoniae Younger patients, prior antibiotics, less multi-system involvement but extrapulmonary involvement, including haemolysis, cold agglutinins, hepatitis, skin and joint problems

  • Staphylococcus aureus Recent influenza-like illness

  • Chlamydophila psittaci Longer duration of symptoms prior to admission, headache

  • Coxiella burnetii (Q fever) Dry cough, high fever, headache, ♂, animal exposure, e.g. sheep and goats

  • Klebsiella pneumoniae Low platelet count and leucopenia, ♂.

Rare causes

  • Acinetobacter Older patients, history of alcoholism, high mortality

  • Streptococcus ‘milleri’ group Dental or abdominal source of infection

  • Streptococcus viridans Aspiration is a risk factor.

CAP: severity assessment

  • CAP has a wide range of severity. An assessment of severity enables the most appropriate care to be delivered in the most appropriate clinical setting

  • Early identification of patients at high risk of death allows early decisions about hospital admission and possible need for assisted ventilation to be made

  • Assessment of disease severity depends on the experience of the clinician; a number of predictive assessment models have been trialled. These severity models should be regarded as adjuncts to clinical assessment, and regular reassessment of the disease is needed.

Poor prognostic factors

Those with two or more adverse prognostic factors are at high risk of death and should be managed as for severe CAP.

  • Age ≥65

  • Coexisting disease Including cardiac disease, diabetes, COPD, stroke

  • RR ≥30/min—this is one of the most reliable predictors of disease severity

  • Confusion Abbreviated mental test score (AMTS) ≤8

  • BP Systolic ≤90mmHg and/or diastolic ≤60mmHg

  • Hypoxaemia Respiratory failure, with PaO2 <8kPa and the need for assisted ventilation, predicts mortality

  • Urea ≥7mmol/L

  • Albumin <35g/L

  • WCC >20 or <4 × 109/L are both predictive

  • Radiology Bilateral or multilobe involvement. In patients admitted to ICU, progression of CXR changes is a poor prognostic marker

  • Microbiology Positive blood culture, whatever the pathogen isolated.

A commonly used severity assessment score is CURB-65, which aims to predict morbidity and mortality in CAP. A CURB-65 derivative CRB-65 does not rely on laboratory blood tests and may be used in the community to help assess which patients require hospital admission. The Pneumonia Severity Index (PSI) is an alternative, which may be more sensitive, but is much more complicated and includes information on comorbid disease and laboratory tests before stratifying patients into five risk classes.

CURB-65 score core factors

  • Confusion New mental confusion defined as AMTS ≤8 (see Box 40.2)

  • Urea >7mmol/L

  • RR Raised ≥30/min

  • BP Systolic BP <90 and/or diastolic BP ≤60

  • 65 Age ≥65.

The presence of the CURB-65 factors correlates with mortality:

  • 3–5 factors present gives a mortality of 15–40%, 2 factors 9%, 1 factor 2.1%, and 1.2% in the presence of no factors

  • Low risk of death: age <50, no coexisting disease, CURB-65 score 0–1 patients may be suitable for home treatment

  • CRB-65 may be used by GPs in the community to help assess patients: a score of 0 suggests patients with a low risk of death who may be appropriately treated in the community; scores of ≥1 should be considered for hospital admission

  • Pneumonia severity scores aim to contribute to, rather than supersede, a clinical judgement; they include a potential over-emphasis on age.

CAP: investigations

General investigations

are aimed at confirming the diagnosis, assessing disease severity, guiding appropriate treatment, assessing the presence of underlying disease, enabling identification of complications, and monitoring progress.

  • Oxygenation assessment Those with an O2 saturation of <92% on admission or with features of severe pneumonia should have ABGs measured. The inspired O2 concentration must be documented

  • CXR

    • Consolidation, most commonly in the lower lobes. Also interstitial infiltrates and cavitation

    • Multilobe involvement, more common in bacteraemic pneumococcal infection

    • Pleural effusion, more common in bacteraemic pneumococcal infection

    • Lymphadenopathy, uncommon, but most likely with Mycoplasma infection

    • Multilobe involvement, cavitation, or spontaneous pneumothorax suggest Staphylococcus aureus infection

    • Upper lobe preponderance suggests Klebsiella

  • CT chest Unlikely to add additional information. May be useful if the diagnosis is in doubt or the patient is severely ill and failing to respond to treatment in order to exclude abscess formation, empyema, underlying malignancy, or other interstitial disease process

  • Blood tests

    • FBC—a WCC >15 × 109 suggests bacterial (particularly pneumococcal) infection. Counts of >20 or <4 indicate severe infection

    • Deranged renal and liver function tests can be indicative of severe infection or point to the presence of underlying disease. LFTs may be abnormal, particularly with right lower lobe pneumonia. A raised urea is a marker of more severe pneumonia

    • Metabolic acidosis is associated with severe illness

    • CRP may be useful in management, with high levels being a more sensitive marker of infection than the WCC or temperature. Serial measures may be useful in assessing response to treatment.

Microbiological investigations

The microbiological cause for CAP is not found in 25–60% of patients and therefore often does not contribute to patient management. Microbiological investigations can help to aid selection of optimal antibiotics, hence limiting antibiotic resistance and the possible problems of Clostridium difficile-associated diarrhoea. They also inform public health or infection control teams, aiding in the monitoring of pathogen trends causing CAP over time.

  • Blood cultures Recommended for all patients with CAP, ideally before antibiotics are started. About 10% of patients with CAP will have positive blood cultures. The early availability of blood culture results (within 24h of admission) improves outcome

  • Sputum culture and sensitivity Useful for those patients who have failed to improve with empirical antibiotic treatment and in those with non-severe pneumonia admitted to hospital who are expectorating purulent samples and have not received prior antibiotics. Also useful in severe pneumonia. Not routinely recommended for those treated in the community. Sputum examination is recommended for possible TB in those with weight loss, a persistent cough, night sweats, and risk factors for TB, e.g. ethnic origin, social deprivation

  • Pleural fluid (if present) for M, C, & S and pH to exclude empyema (see Respiratory infection—bacterial p. [link])

  • Viral and ‘atypical’ pathogens In severe CAP only

  • Serological testing Paired samples (from within 7 days of the onset of the illness, repeated 10–14 days later) should be tested together, in those with severe CAP and in those unresponsive to β‎-lactam antibiotics. They are unlikely to guide initial treatment though.

Tests for specific pathogens

  • Pneumococcal pneumonia

    • Urinary antigen has a sensitivity of 100% and specificity of 60–90% for invasive pneumococcal disease, and testing is recommended in all patients with severe CAP

  • Legionnaires’ disease A number of immunological tests exist to aid in the prompt and accurate diagnosis of Legionella pneumophilia:

    • Urinary antigen detection is about 80% sensitive and >95% specific for serogroup A, and rapid results can be obtained early. A positive urinary antigen test correlates with subsequent ITU admission

    • Direct immunofluorescence tests (DIFs)—Legionella pneumophilia can be detected on bronchial aspirates

    • Culture is 100% specific (sputum, endotracheal aspirate, BAL, pleural fluid, lung)

    • Serology—antibody levels and PCR are also available

  • Mycoplasma pneumoniae

    • PCR is the method of choice for diagnosis. The complement fixation test (CFT) is the commonest serological assay. Culture of Mycoplasma pneumoniae is not generally available

  • Chlamydophila

    • Chlamydophila can be detected using PCR or antigen detection using DIF on respiratory samples or by CFT

  • Others

    • Influenza A and B, adenovirus, RSV—PCR or serological testing. Coxiella burnetii indirect immunofluorescence antibody test.

CAP: management

General management

  • O2 Hypoxia is due to V/Q mismatching, as blood flows through unventilated lung. Aim for O2 saturation ≥94% (PaO2 ≥8kPa). If there is severe concomitant COPD, controlled O2 therapy and close monitoring of blood gases are mandatory. A rising CO2 in a patient without prior respiratory disease may indicate they are tiring and need respiratory support—discuss with ITU early

  • Non-invasive ventilatory support A number of studies demonstrate beneficial effects of NIV in severe CAP. However, following initial improvement in physiological parameters, >50% of patients subsequently deteriorate, requiring intubation. A higher initial RR (>30) is associated with failure of NIV support (CPAP or bi-level ventilation). NIV may have a place in the management of severe CAP but should only be used in a high dependency setting, with very close observation

  • Fluids Assessment of volume status by JVP (with or without central venous access) and BP is paramount. Encourage oral fluids. IV fluids may be needed if volume-depleted and severely unwell. Monitor urine output

  • Analgesia Paracetamol or NSAIDs initially, if required. Paracetamol also has an antipyretic role

  • Nutrition Nutritional status is important to the outcome, and nutritional supplements may be of benefit in prolonged illness. Poor nutritional status may increase the risk of acquiring pneumonia

  • Physiotherapy Airway clearance techniques may be considered in patients having difficulty expectorating sputum

  • VTE prophylaxis.

Additional treatments


May be helpful, especially after intubation on ITU, to suction retained secretions, particularly if these are causing lobar collapse, to obtain further samples for culture, and to exclude an endobronchial abnormality.


Not recommended for the standard treatment of severe CAP.


Temperature, RR, HR, BP, mental status, O2 saturation, and inspired O2 concentration should be monitored twice daily, and more often in the severely ill.

ICU admission

Those fulfilling criteria for severe CAP on admission or who fail to respond rapidly to treatment should be considered for transfer for close monitoring, either to a HDU or to ICU. Persisting hypoxia (PaO2 8kPa), acidosis, hypercapnia, hypotension, or depressed conscious level, despite maximal therapy, are indications for assisted ventilation. CPAP may be of benefit whilst awaiting for the arrival of the anaesthetist (although this may just be a more effective way of delivering 100% O2).

When to discuss patient with CAP with ITU

  • Always sooner, rather than later

  • Respiratory failure (PaO2 <8kPa) despite high-flow O2

  • Tiring patient, with a rising CO2

  • Worsening metabolic acidosis, despite antibiotics and optimum fluid management

  • Hypotension despite adequate fluid resuscitation.

CAP: antibiotics

  • Most antibiotics are used empirically at diagnosis of CAP in the absence of microbiological information. The clinical scenario also guides antibiotic choice such as the addition of anaerobic cover in an alcoholic who has a high chance of aspiration

  • Severity assessment guides antibiotic therapy and the method of antibiotic administration (see Table 40.1). When pathogens are identified, consider narrowing antibiotic coverage (see Table 40.2)

  • Local protocols and antibiotic resistance patterns may also guide choice

  • Liaise closely with microbiologist.

Table 40.1 Suggested empirical antibiotics for CAP treatment

Preferred treatment

Alternative (if intolerant of, or allergic to, preferred treatment)

Community treatment

Amoxicillin 500mg–1g tds PO

Doxycycline 100mg od (after 200mg loading dose) PO or clarithromycin 500mg bd PO

Hospital treatment: low severity (CURB-65 = 0–1)

Amoxicillin 500mg tds PO (or same dose IV if oral treatment impossible)

Doxycycline 100mg od (after 200mg loading dose) PO or clarithromycin 500mg bd PO

Hospital treatment: moderate severity (CURB-65 = 2)

  • Amoxicillin 500mg–1g tds PO and clarithromycin 500mg bd PO

  • If oral treatment impossible: amoxicillin 500mg tds IV or benzylpenicillin 1.2g qds IV and clarithromycin 500mg bd IV

Doxycycline 100mg od (after 200mg loading dose) PO or levofloxacin 500mg od PO or moxifloxacin 400mg od PO

Hospital treatment: high severity (CURB-65 = 3–5)

Co-amoxiclav 1.2g tds IV and clarithromycin 500mg bd IV (add levofloxacin if Legionella strongly suspected)

  • Benzylpenicillin 1.2g qds IV and either levofloxacin 500mg bd IV or ciprofloxacin 400mg bd IV

  • OR

  • Cefuroxime 1.5g tds IV/cefotaxime 1g tds IV/ceftriaxone 2g od IV and clarithromycin 500mg bd IV (add levofloxacin if Legionella strongly suspected)

Table 40.2 Recommended antibiotic treatment of specific causative organisms


Preferred antibiotic

Alternative antibiotic

Streptococcus pneumoniae

Amoxicillin 500mg–1g tds PO or benzylpenicillin 1.2g qds IV

Clarithromycin 500mg bd PO or cefuroxime 0.75–1.5g tds IV or cefotaxime 1–2g tds IV or ceftriaxone 2g od IV

Mycoplasma pneumoniae and Chlamydophila pneumoniae

Clarithromycin 500mg bd PO/IV

Doxycycline 100mg od PO (after 200mg loading dose) or fluoroquinolone PO/IV

Chlamydophila psittaci and Coxiella burnetii

Doxycycline 100mg od PO (after 200mg loading dose)

Clarithromycin 500mg bd PO/IV

Legionella spp.

Fluoroquinolone PO/IV

Clarithromycin 500mg bd PO/IV (azithromycin may be an option)

Haemophilus influenzae

  • Non-lactamase-producing amoxicillin 500mg tds PO/IV

  • Lactamase-producing co-amoxiclav 625mg tds PO or 1.2g tds IV

Cefuroxime 750mg–1.5g tds IV or cefotaxime 1–2g tds IV or ceftriaxone 2g od IV or fluoroquinolone PO/IV

Gram-negative enteric bacilli

Cefuroxime 1.5g tds or cefotaxime 1–2g tds IV or ceftriaxone 1–2g bd IV

Fluoroquinolone IV or imipenem 500mg qds IV or meropenem 0.5–1.0g tds IV

Pseudomonas aeruginosa

Ceftazidime 2g tds IV and gentamicin or tobramycin (dose monitoring)

Ciprofloxacin 400mg bd IV or piperacillin 4g tds IV and gentamicin or tobramycin (dose monitoring)

Staphylococcus aureus

Non-MRSA flucloxacillin 1–2g qds IV ± rifampicin 600mg od/bd PO/IV

MRSA vancomycin 1g bd (dose monitoring) or linezolid 600mg bd IV or teicoplanin 400mg bd IV ± rifampicin 600mg od/bd PO/IV

Aspiration pneumonia

Co-amoxiclav 1.2g tds IV

General points

  • Early antibiotic administration is associated with an improved outcome

  • Antibiotics given before admission can influence the results of subsequent microbiological investigations, but this should not delay antibiotic administration in the community if the patient is unwell

  • It is vital there is no delay in the administration of the first antibiotic dose in patients with confirmed CAP. Confirmation of pneumonia with CXR and antibiotic administration should occur within 4h of admission

  • IV antibiotics will be needed in 30–50% of patients admitted to hospital. Consider IV antibiotics if:

    • Severe pneumonia

    • Loss of swallow reflex

    • Impaired absorption

    • Impaired conscious level

  • Oral antibiotics should be used in those with community-managed pneumonia or those with non-severe hospital-managed pneumonia, with no other contraindications

  • Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) is a rare cause of rapidly progressive necrotizing pneumonia. If strongly suspected, discuss with microbiology and add linezolid, clindamycin, and rifampicin (all IV)

  • Add anaerobic antibiotic cover, e.g. metronidazole if possible aspiration pneumonia or if suspicion of lung abscess on CXR/CT

  • Switch IV to oral antibiotics as soon as possible, usually when a patient has shown clear response to treatment, being apyrexial for 24h

  • A switch to oral co-amoxiclav, and not an oral cephalosporin, is recommended after treatment with IV cephalosporin

  • For those treated with benzylpenicillin plus levofloxacin, a switch to oral levofloxacin ± oral amoxicillin is recommended.

Length of treatment

There is no evidence to guide treatment length, but consensus suggests:

  • 7 days—non-severe, uncomplicated pneumonia

  • 7–10 days—severe microbiologically undefined pneumonia

  • 14–21 days—if Legionella, staphylococcal disease, or Gram-negative enteric bacteria suspected

  • Consult local antibiotic guidelines (also see Tables 40.1 and 40.2); concern regarding increasing rates of Clostridium difficile has led to reduced antibiotic course length and alternative empirical antibiotic choice in some centres. There is no evidence that any specific antibiotic (other than clindamycin) is more likely to cause C. difficile than any other.

Newer fluoroquinolones

Moxifloxacin is licensed in the UK for the treatment of CAP. It is not recommended for first-line treatment for CAP for community use, given the current low level of pneumococcal resistance in the UK. Levofloxacin is available in oral and IV preparations and is licensed for severe CAP. Other fluoroquinolones, e.g. gemifloxacin and gatifloxacin, are likely to extend the choice of oral antibiotics for CAP when they are licensed in the UK. The ketolides (e.g. telithromycin) are novel macrolides, with efficacy against penicillin- and erythromycin-resistant pathogens.

Antibiotic resistance

Studies suggest that the UK prevalence of penicillin-resistant S. pneumoniae is now about 6–8%. Macrolide-resistant organisms may be as high as 12–15%. Worldwide prevalence of pneumococcal resistance to fluoroquinolones is low, at <2%, though this has increased substantially in some countries (e.g. Hong Kong) in recent years (because of the spread of a fluoroquinolone-resistant clone).

CAP: treatment failure

A CRP that does not fall by >50% at 3–4 days suggests either treatment failure or the development of a complication such as a lung abscess or empyema.

Causes of failure to improve

  • Slow clinical response, particularly in the elderly patient

  • Incorrect initial diagnosis:

    • Pulmonary thromboembolic disease

    • Pulmonary oedema

    • Bronchial carcinoma

    • Bronchiectasis

    • Also consider eosinophilic pneumonia, foreign body aspiration, alveolar haemorrhage, COP, vasculitis or connective tissue disease, drug-induced lung disease

    • Review the history, examination, and radiology

    • Consider repeat imaging, e.g. CT chest

  • 2° complication:

    • Pulmonary, e.g. parapneumonic effusion (occurs in 36–57%, simple effusions resolve spontaneously, chest drainage for complicated parapneumonic effusions), empyema, abscess formation, ARDS

    • Extrapulmonary, e.g. septicaemia, metastatic infection (e.g. meningitis, endocarditis, septic arthritis), sequelae of initial insult, e.g. renal failure, MI

  • Inappropriate antibiotics or unexpected pathogen:

    • Review dose, compliance, and route of administration. Send further microbiological specimens

    • Review microbiological data; exclude less common pathogens, e.g. Legionella, Mycoplasma, staphylococcal disease

    • Pathogen may be resistant to common antibiotics; 10% of CAP will have a mixed infection

    • Consider TB, fungal infection

  • Impaired immunity

    • Systemic, e.g. hypogammaglobulinaemia, HIV infection, myeloma

    • Local, e.g. bronchiectasis, aspiration, underlying bronchial carcinoma

    • Overwhelming infection.

CAP: follow-up

CXR resolution

Radiographic improvement lags behind clinical improvement. There is no need to repeat a CXR before hospital discharge in those who have made a satisfactory clinical recovery.

  • In one study of CAP, complete radiographic resolution occurred after 6 weeks in 73% of patients, but only in 51% at 2 weeks

  • Radiographic resolution is slower in the elderly, those with multi-lobe involvement at presentation, smokers, and hospital inpatients

  • Legionella and pneumococcal pneumonia are slower to resolve (may take 12 weeks or more).

CXR follow-up

is recommended around 6 weeks after CAP:

  • In all patients with persisting symptoms or clinical signs

  • In all patients at higher risk of underlying lung malignancy, i.e. smokers and those over the age of 50.

This is to exclude an underlying condition that may have led to CAP such as lung cancer. Further investigations, such as bronchoscopy, should be considered at this time in patients with persisting symptoms and/or a persistently abnormal CXR.

  • One study showed lung cancer is diagnosed on follow-up in 17% of smokers aged over 60 treated for CAP in the community

  • Other studies have shown a prevalence of lung cancer of 11% in current and ex-smokers aged over 50, who are inpatients with CAP and who undergo bronchoscopy prior to discharge.


Influenza vaccination

This reduces hospital deaths from pneumonia and influenza by about 65% and respiratory deaths by 45%. It also leads to fewer hospital admissions.

Recommended for ‘high-risk’ individuals

  • Chronic lung disease

  • Cardiac, renal, and liver disease

  • Diabetes

  • Immunosuppression due to disease or treatment

  • Those aged over 65

  • Long-stay residential care

  • Health care workers

  • Contraindicated in people with hen egg hypersensitivity (the virus is cultured in chick embryos).

The vaccination contains both A and B subtype viruses and provides partial protection against influenza illnesses. It is modified annually, based on recent viral strains. The protection rate from influenza by vaccination is over 75% for influenza A and 51–97% for influenza B. Antibody levels appear to reduce about 6y after vaccination.

Pneumococcal vaccination

Recommended for:

  • Those aged over 65

  • Asplenic individuals (including coeliac disease and sickle cell disease)

  • Chronic renal, cardiac, and liver disease

  • Diabetes

  • Immunodeficiency or immunosuppression (due to disease, including HIV infection, or drugs).

It should not be given during acute infection or in pregnancy. Re-immunization is contraindicated within 3y.

Further information

Lim WS et al. British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update 2009 Thorax 2009;64(Suppl III):iii1–55.Find this resource:

Thomas MF. Community acquired pneumonia. Lancet 2003;362:1991–2001.Find this resource:

Hospital-acquired pneumonia: clinical features


New radiographic infiltrate in the presence of evidence of infection (fever, purulent sputum, leucocytosis), with onset at least 48h after hospital admission. It represents around 15% of hospital-acquired infections. Most occur outside the ICU, but those at highest risk are mechanically ventilated patients. Hospital-acquired pneumonia is expensive and prolongs the hospital stay. It requires different antibiotic treatment to CAP and is the leading cause of death from hospital-acquired infection. It is also known as nosocomial pneumonia.


Hospital-acquired pneumonia occurs from aspiration of infected upper airway secretions, from the inhalation of bacteria from contaminated equipment, or haematogenous spread of organisms.

Aspiration is thought to be the most important cause. Around 45% of normal people aspirate during sleep, and this is increased in hospital inpatients (who may be more frail) and in those with chronic disease. These patients’ upper airways become colonized with Gram-negative bacteria (in up to 75% within 48h of admission), and this proportion is even higher in those who have received broad-spectrum antibiotics. In addition, the severely ill may have impaired host defences, making them more susceptible to hospital-acquired pneumonia. Alteration in the gastric pH with illness and various drugs means that the GI tract is no longer sterile, thereby providing a potential source of bacterial infection. A cerebrovascular event and reduced conscious level are the major risk factors for aspiration.

Risk factors for nosocomial pneumonia

  • Age >70

  • Chronic lung disease and/or other comorbidity (especially diabetes)

  • Reduced conscious level/cerebrovascular accident

  • Chest/abdominal surgery

  • Mechanical ventilation

  • NG feeding

  • Previous antibiotic exposure

  • Poor dental hygiene

  • Steroids and cytotoxic drugs.

Risk factors for specific organisms

  • Streptococcus pneumoniae and Haemophilus influenzae Increased risk in trauma

  • Staphylococcus aureus Increased risk in ventilated neurosurgical patients (especially closed head injury), blunt trauma, and coma

  • Pseudomonas aeruginosa Increased risk with intubation >8 days, COPD, prolonged antibiotics

  • Acinetobacter spp. Increased risk with prolonged ventilation and previous broad-spectrum antibiotics

  • Anaerobic bacteria Increased with recent abdominal surgery, aspiration.

Clinical features

It presents typically with:

  • Fever

  • Productive cough

  • Raised inflammatory parameters

  • New CXR infiltrate

  • Deterioration in gas exchange.


is often a clinical one, and identification of the infecting agent can be difficult, especially if the patient has already received broad-spectrum antibiotics.


  • CXR usually shows a non-specific infiltrate

  • Blood, sputum, and pleural fluid should be cultured

  • ABG to determine severity

  • Renal and liver function tests to assess other organ dysfunction

  • Serological tests are of little use in nosocomial pneumonia.

Hospital-acquired pneumonia: management

Severity assessment

The CURB-65 pneumonia severity score (see Respiratory infection—bacterial pp. [link][link]) for CAP has not been validated in hospital-acquired pneumonia but may be useful in guiding the treatment needed.


  • About 50% are mixed infections

  • 30% are due to aerobic bacteria alone (most commonly, Gram-negative enteric bacilli and Pseudomonas)

  • Anaerobes alone are found in about 25%

  • Pseudomonas aeruginosa and Staphylococcus aureus are common causes

  • Peptostreptococcus, Fusobacterium, and Bacteroides spp. are commonly isolated, as well as Enterobacter spp., Escherichia coli, Serratia marcescens, Klebsiella, and Proteus spp.

  • Acinetobacter is a new emerging pathogen

  • MRSA is increasing in prevalence

  • Viruses are recognized as causes.


  • Patients developing pneumonia within 48h of arrival in hospital can be treated with standard CAP antibiotics (see Respiratory infection—bacterial p. [link]), as the pneumonia is likely to be due to bacteria acquired in the community

  • Patients developing pneumonia >48h after hospital admission need antibiotics to cover different organisms

  • Prolonged IV treatment is usually needed, with cover for Gram-negative bacteria. Empirical antibiotics are chosen, based on knowledge of local microbial resistance patterns, but typical choices include co-amoxiclav, ceftriaxone, piperacillin-tazobactam, or a carbapenem. A stat (or ongoing) dose of gentamicin (e.g. 5–7mg/kg, guided by renal function) may be appropriate for severe sepsis. Addition of an antibiotic with MRSA coverage should be considered, particularly if the patient is known to be recently colonized with MRSA

  • Supportive treatment is also required, with O2, fluids, and ventilation, if necessary

  • In penicillin-allergic patients, clindamycin or ciprofloxacin can be used (as long as Streptococcus pneumoniae is not thought to be the infecting agent). Levofloxacin has better pneumococcal cover

  • Complications of nosocomial pneumonia are the same as for CAP, including lung abscess and empyema. Drug fever, sepsis with multi-organ failure, and PE with 2° infection are all more common in nosocomial pneumonia

  • In this situation, chest US (to look for empyema) or CT scanning may demonstrate abscess, underlying tumour, or infection at extrathoracic sites.


Associated with a high mortality, ranging between 20 and 50%.


Meticulous hygiene and hand washing by medical staff, in addition to careful infection control measures, have been shown to reduce hospital-acquired pneumonia.

Post-operatively, early mobilization, careful cleaning and maintenance of respiratory equipment, and preoperative smoking cessation reduce infection rates. Some ICUs use antibiotics to selectively decontaminate the GI tract of Gram-negative bacilli. This has been shown to reduce infection rates, but there is no proven effect on mortality or length of ICU admission.

Ventilator-associated pneumonia (VAP)


Pneumonia in a mechanically ventilated patient, developing 48h after intubation. It has a prevalence of up to 65% in some units. It is an independent predictor of mortality and is the commonest nosocomial infection in ITU. Up to two-thirds of patients requiring mechanical ventilation for >48h will develop VAP. It has a mortality of 15–50%, increasing the length of ITU stay by an average of 6.1 days.

The major cause is bacterial contamination of the lower respiratory tract from the aspiration of oropharyngeal secretions, which is not prevented by cuffed endotracheal tube or tracheostomy.


is suggested by:

  • New or progressive CXR infiltrate

  • Association with fever, high WCC, purulent secretions, and worsening ventilatory parameters (increasing RR, decreasing tidal volumes, and increasing O2 requirements)

  • There are many non-infectious causes of fever and CXR infiltrate in ITU patients, so the diagnosis is not always straightforward. Other sources of fever are also common in ventilated patients, including infected lines, sinusitis, UTI, and pseudomembranous colitis, and may warrant further investigation.

Differential diagnosis of fever and CXR infiltrate in ITU

  • Chemical aspiration without infection

  • Atelectasis

  • ARDS

  • LVF

  • PE with lung infarction

  • Pulmonary haemorrhage

  • COP

  • Drug reaction

  • Tumour

  • Lung contusion.


  • CXR often shows a non-specific infiltrate, with air bronchograms being the best predictor of the disease

  • Airway sampling for microbiology:

    • Bronchoscopic sampling Protected specimen brush (PSB) samples (with the tip of the bronchoscope placed opposite the orifice of an involved segmental bronchus, and PSB advanced through its protective sheath into the airway) or BAL samples (from a subsegmental bronchus, with the end of the bronchoscope wedged into the airway, ideally >150mL saline wash) are the best methods to obtain lower airway samples with minimal contamination. VAP is diagnosed when an arbitrary threshold of organisms are grown on a BAL or PSB sample. The usual cut-offs are 1, 000 colony-forming units/mL (cfu/mL) for PSB samples and 10, 000 cfu/mL for BAL samples. Thresholds vary between units, as do thresholds for starting treatment. Meta-analysis of three RCTs showed no significant mortality differences between quantitative and qualitative culture assessments. Airway neutrophil counts may also aid in making the diagnosis

    • Non-bronchoscopic airway sampling, e.g. blind bronchial sampling of lower respiratory tract secretions (so-called ‘mini-BAL’) is cheaper and does not need an expert operator. A catheter is advanced through the endotracheal tube until there is resistance, and saline (~20mL) is infused and then aspirated. A meta-analysis of five RCTs showed no significant differences in mortality with non-invasive vs. invasive (bronchoscopic) airway sampling; further, there were no significant differences in number of days of mechanical ventilation, length of ICU stay, or antibiotic changes (Berton DC et al. Cochrane Database Syst Rev 2012;1:CD006482)

    • Serial sampling is favoured in some units. Regular non-invasive serial airway sampling may aid early diagnosis of VAP. It needs careful interpretation, as the microbiology of the respiratory tract changes over time in critically ill mechanically ventilated patients

    • Tracheal aspiration samples are easy to obtain but non-specific in diagnosing VAP, as upper airway colonization is very common.

Antibiotic treatment

Problems with the emergence of resistant bacteria mean that empirical treatment with antibiotics is used less commonly. Local policies are often in place, and advice should always be sought from microbiology. The most common drug-resistant pathogens are P. aeruginosa, MRSA, Acinetobacter spp., and Klebsiella spp. Delay in commencing antibiotics is associated with a poorer outcome.

Risk factors for resistant organisms include:

  • Hospitalization in the previous 90 days

  • Nursing home residence

  • Current hospital admission >5 days

  • Mechanical ventilation >7 days

  • Prior broad-spectrum antibiotic use (e.g. third-generation cephalosporin)

  • High frequency of local antibiotic resistance.

Antibiotics should be chosen on the basis of:

  • Recent antibiotic treatment

  • Local policy and known local flora

  • Culture data.

Empirical antibiotic choice often includes coverage for anaerobes and MRSA, Legionella (if long stay), P. aeruginosa, and Acinetobacter.

Length of treatment depends on the clinical response, with one trial showing that 8-day treatment had similar efficacy to 15-day treatment, although patients with P. aeruginosa infection had a greater risk of recurrence following discontinuation of antibiotics at 8 days. Failure to respond should lead to a change of antibiotics and a search for additional infection or another cause for the radiographic infiltrate. Further cultures should be sent.

Aspiration pneumonia


Pneumonia that follows the aspiration of exogenous material or endogenous secretions into the lower respiratory tract.


Aspiration pneumonia is the commonest cause of death in patients with dysphagia due to neurological disorders and is the cause of up to 20% of pneumonias in nursing home residents. It occurs in about 10% of patients admitted to hospital with a drug overdose.


Micro-aspiration is common in healthy individuals, but, for an aspiration pneumonia to occur, there must be compromise of the normal defences protecting the lower airways (i.e. glottic closure, cough reflex), with inoculation of the lower respiratory tract of a significant amount of material. Most pneumonias are a result of aspiration of micro-organisms from the oral cavity or nasopharynx.

Situations predisposing to aspiration pneumonia

  • Reduced conscious level (cough reflex and impaired glottic closure)

    • Alcohol

    • Drug overdose

    • Post-seizure

    • Post-anaesthesia

    • Massive cerebrovascular accident (CVA)

  • Dysphagia

    • Motor neurone disease (MND)

    • Following a neurological event; those with impaired swallow reflex post-CVA are seven times more likely to develop a pneumonia than those in whom the gag reflex is unimpaired

  • Upper GI tract disease

    • Surgery to the stomach or oesophagus

    • Mechanical impairment of glottic or cardiac sphincter closure, e.g. tracheostomy, nasogastric feeding, bronchoscopy

    • Pharyngeal anaesthesia

  • Increased reflux

    • Large-volume vomiting

    • Large-volume NG feed

    • Feeding gastrostomy

    • Recumbent position

  • Nursing home residents

    • The risk of aspiration is lower in those without teeth, who receive aggressive oral hygiene

    • There is a higher incidence of silent aspiration in the otherwise healthy elderly

    • Strong correlation between volume of aspirate and the risk of developing pneumonia.

Aspiration pneumonia: clinical features

Three pulmonary syndromes result from aspiration. The amount and nature of the aspirated material, the site and frequency of the aspiration, and the host’s response to it will determine which pulmonary syndrome occurs.

Chemical pneumonitis

This is aspiration of substances toxic to the lower airways, in the absence of bacterial infection.

This causes a chemical burn of the tracheobronchial tree, causing an intense parenchymal inflammatory reaction, with release of inflammatory mediators that may lead to ARDS. Animal studies show that an inoculum with a pH <2.5 of relatively large volume (about 25mL in adults) is needed to initiate an inflammatory reaction. Animal models show rapid pathological changes within 3min, with atelectasis, pulmonary haemorrhage, and pulmonary oedema. (This was first described by Mendelson, referring to the aspiration of sterile gastric contents and its toxic effects. The original case series was in obstetric anaesthesia.)

Clinical features

  • Rapid onset of symptoms, with breathlessness (within 1–2h)

  • Low-grade fever

  • Severe hypoxaemia and diffuse lung infiltrates involving dependent segments

  • CXR changes within 2h.


  • If aspiration is observed—suction and/or bronchoscopy to clear aspirated secretions or food. This may not prevent chemical injury from acid, which is similar to a flash burn

  • Support of cardiac and respiratory function—with IV fluids, O2± ventilation

  • Steroids—controversial. No benefit has been shown in human studies

  • Antibiotics—usually given, even in the absence of evidence of infection, because 2° bacterial infection is common and may be a contributing or 1° factor in the aspiration. Acid-damaged lung is more susceptible to the effects of 2° bacterial infection; up to 25% will develop 2° bacterial infection. Activity against Gram-negative and anaerobic organisms is needed, e.g. cefuroxime plus metronidazole, or penicillin plus clindamycin.

Bacterial infection

Aspiration of bacteria normally resident in the upper airways or stomach. The normal bacterial flora are anaerobes, in a host susceptible to aspiration, and less virulent than the bacteria causing CAP.

Clinical features

depend on the infecting organism:

  • Cough, fever, purulent sputum, breathlessness

  • The process may evolve over weeks and months, rather than hours

  • May be more chronic, with weight loss and anaemia

  • Absence of fever or rigors

  • Foul-smelling sputum

  • Periodontal disease

  • Involvement of dependent pulmonary lobes

  • Anaerobic bacteria are more difficult to culture so may be present, but not identified in microbiological culture

  • May present with later manifestations, e.g. empyema, lung abscess.

Major pathogens are Peptostreptococcus, Fusobacterium nucleatum, Prevotella, and Bacteroides spp. Mixed infection is common.


  • Antibiotics to include anaerobic cover, e.g. co-amoxiclav, clindamycin, or a carbapenem

  • Swallow assessment/neurological review if no obvious underlying cause found.

Mechanical obstruction

Aspiration of matter that is not directly toxic to the lung may lead to damage by causing airway obstruction or reflex airway closure. Causative agents include:

  • Saline

  • Barium

  • Most ingested fluids, including water

  • Gastric contents with a pH >2.5

  • Mechanical obstruction, such as occurs in drowning, or those who are unable to clear a potential inoculum, e.g. neurological deficit, impaired cough reflex, reduced conscious level

  • Inhalation of an object, with the severity of the obstruction depending on the size and site of the aspirated particle. This is commoner in children but does occur in adults, e.g. teeth, peanuts.


  • Tracheal suction

  • Remove obstructing object if necessary

  • No further treatment is needed if no CXR infiltrates.

Lung abscess: clinical features


A localized area of lung suppuration leading to necrosis of the pulmonary parenchyma, with or without cavity formation.

Lung abscesses may be single or multiple, acute or chronic (>1 month), 1° or 2°. They may occur spontaneously, but, more commonly, an underlying disease exists. Lung abscess is now rare in the developed world but has a high mortality of 20–30%. They are most common in alcoholic men aged >50.


Most are the result of aspiration pneumonia. Predisposing factors for abscess are those for aspiration pneumonia (see Respiratory infection—bacterial p. [link]).

  • Dental disease

  • Impaired consciousness—alcohol, post-anaesthesia, dysphagia

  • Diabetes

  • Bronchial carcinoma (with bronchial obstruction)

  • 2° to pneumonia (cavitation occurs in about 16% of Staphylococcus aureus pneumonia)

  • Immunocompromise—abscesses due to Pneumocystis jirovecii (PCP), Cryptococcus neoformans, Rhodococcus spp., and fungi in HIV-positive patients

  • Septic embolization (right heart endocarditis due to, e.g. Staphylococcus aureus in IV drug abusers).

The bacterial inoculum reaches the lung parenchyma, often in a dependent lung area. Pneumonitis, followed by necrosis, occurs over 7–14 days. Cavitation occurs when parenchymal necrosis leads to communication with the bronchus, with the entry of air and expectoration of necrotic material leading to the formation of an air-fluid level. Bronchial obstruction leads to atelectasis with stasis and subsequent infection, which can predispose to abscess formation.


  • Often insidious onset

  • Productive cough, haemoptysis

  • Breathlessness

  • Fevers

  • Night sweats

  • Non-specific feature of chronic infection—anaemia, weight loss, malaise (especially in the elderly)

  • Foul sputum or purulent pleural fluid.

Lemierre’s syndrome (necrobacillosis)

Jugular vein suppurative thrombophlebitis. This is a rare pharyngeal infection in young adults, most commonly due to the anaerobe Fusobacterium necrophorum. It presents with a classical history of painful pharyngitis, in the presence of bacteraemia. Infection spreads to the neck and carotid sheath, often leading to thrombosis of the internal jugular vein. This may not be obvious clinically (neck vein USS or Doppler may be needed). Septic embolization to the lung, with subsequent cavitation, leads to abscess formation. Empyema and abscesses in the bone, joints, liver, and kidneys can complicate.

Lung abscess: diagnosis

The diagnosis is usually made from the history, along with the appearance of a cavity with an associated air-fluid level on CXR.


  • Microbiological culture, ideally before commencing antibiotics. Useful to exclude TB

    • Blood cultures

    • Sputum or bronchoscopic specimen (BAL or brushings rarely needed)

    • Transthoracic percutaneous needle aspiration (CT- or US-guided) may provide samples. Risk of bleeding, pneumothorax, and seeding of infection to pleural space, if abscess not adjacent to the pleura.

In practice, blood cultures and sputum microbiology usually suffice. Samples are usually only obtained by more invasive means if appropriate antibiotics are not leading to an adequate clinical response.

  • Imaging—exclude aspirated foreign body, underlying neoplasm, or bronchial stenosis and obstruction

    • CXR may show consolidation, cavitation, air-fluid level (if the patient is unwell, the CXR is likely to be taken in a semi-recumbent position, so an air-fluid level may not be visible). 50% of abscesses are in the posterior segment of the right upper lobe or the apical basal segments of either lower lobe

    • CT is useful if the diagnosis is in doubt and cannot be confirmed from the CXR appearance or if the clinical response to treatment is inadequate. It can also help to define the exact position of the abscess (which may be useful for physiotherapy or if surgery is being considered—rarely needed)

CT also is useful to differentiate an abscess from a pleural collection—a lung abscess appears as a rounded intrapulmonary mass, with no compression of adjacent lung, with a thickened irregular wall, making an acute angle at its contact with the chest wall. An empyema typically has a ‘lenticular’ shape and compresses adjacent lung, which creates an obtuse angle as it follows the contour of the chest wall.

CT can determine the presence of obstructing endobronchial disease, due to malignancy or foreign body, and may be useful in defining the extent of disease in a very sick patient who has had significant haemoptysis. Even with CT, differentiating an abscess from a cavitating malignancy can be very difficult (no radiological features differentiate them).


Commonly mixed infection, usually anaerobes.

  • The most common organisms are those colonizing the oral cavity and gingival crevices—Peptostreptococcus, Prevotella, Bacteroides, and Fusobacterium spp.

  • Aerobes—Streptococcus ‘milleri’ group, Staphylococcus aureus, Klebsiella spp., Streptococcus pyogenes, Haemophilus influenzae, Nocardia

  • Non-bacterial pathogens are also reported—fungi (Aspergillus, Cryptococcus, Histoplasma, Blastomyces) and mycobacteria

  • Opportunistic infections in immunocompromised—Nocardia, mycobacteria, Aspergillus.

Differential diagnosis of a cavitating mass, with or without an air-fluid level

  • Cavitating carcinoma—1° or metastatic

  • Cavitatory TB

  • GPA (Wegener’s)

  • Infected pulmonary cyst or bulla (can produce a fluid level, usually thinner-walled)

  • Aspergilloma

  • Pulmonary infarct

  • Rheumatoid nodule

  • Sarcoidosis

  • Bronchiectasis.

Lung abscess: management


to cover aerobic and anaerobic infection, including β‎-lactam/ β‎-lactamase inhibitors, e.g. co-amoxiclav and clindamycin. Long courses are needed. Risk of Clostridium difficile diarrhoea.

  • Infections are usually mixed, therefore antibiotics to cover these

  • Metronidazole to cover anaerobes

  • No data to guide length of treatment. Common practice would be 1–2 weeks IV treatment, with a further 2–6 weeks oral antibiotics, often until outpatient clinic review.


Spontaneous drainage is common, with the production of purulent sputum. This can be increased with postural drainage and physiotherapy.

  • No data to support use of bronchoscopic drainage

  • Percutaneous drainage with radiologically placed small percutaneous drains for peripheral abscesses may be useful in those failing to respond to antibiotic and supportive treatment. These are usually placed under US guidance (though are rarely indicated).


is rarely required if appropriate antibiotic treatment is given. It is usually reserved for complicated infections failing to respond to standard treatment after at least 6 weeks of treatment.

May be needed if:

  • Very large abscess (>6cm diameter)

  • Resistant organisms

  • Haemorrhage

  • Recurrent disease

  • Lobectomy or pneumonectomy is occasionally needed if severe infection with an abscess leaves a large volume of damaged lung that is hard to sterilize.


Haemorrhage (erosion of blood vessels as the abscess extends into the lung parenchyma). This can be massive and life-threatening (see Respiratory infection—bacterial p. [link]) and is an indication for urgent surgery.

If slow to respond, consider:

  • Underlying malignancy

  • Unusual microbiology, e.g. mycobacterium, fungi

  • Immunosuppression

  • Large cavity (>6cm) may rarely require drainage

  • Non-bacterial cause, e.g. cavitating malignancy, GPA (Wegener’s)

  • Other cause of persistent fever, e.g. Clostridium difficile diarrhoea, antibiotic-associated fever.


85% cure rate in the absence of underlying disease. Mortality is reported as high as 75% in immunocompromised patients. The prognosis is much worse in the presence of underlying lung disease, with increasing age and large abscesses (>6cm) with Staphylococcus aureus infection.



Nocardia are Gram-positive, partially acid-fast, aerobic bacilli that form branching filaments. They are found in soil, decaying organic plant matter, and water and have been isolated from house dust, garden soil, and swimming pools. Infection typically follows inhalation, although percutaneous inoculation also occurs. The Nocardia asteroides spp. complex accounts for the majority of clinical infections.

Consider Nocardia infection when soft tissue abscesses and/or CNS manifestations occur in the setting of a pulmonary infection. The combination of respiratory, skin, and/or CNS involvement may lead to a misdiagnosis of vasculitis, and the respiratory manifestations may mimic cancer, TB, or fungal disease.


Nocardia occurs worldwide, and the frequency of subclinical exposure is unknown. Clinically apparent infection is rare and usually occurs in patients with immunocompromise (haematological malignancy, steroid therapy, organ transplant, diabetes, alcoholism, and HIV infection, especially IVDUs) or pre-existing lung disease (particularly pulmonary alveolar proteinosis, TB). Infection also occurs in apparently healthy people (10–25% of cases). Nosocomial infection and disease outbreaks have been reported.

Clinical features

Pulmonary disease

  • The lung is the most common site of involvement

  • Patients typically present with productive cough, fever, anorexia, weight loss, and malaise; dyspnoea, pleuritic pain, and haemoptysis may occur but are less common

  • Empyema occurs in up to a quarter of cases, and direct intrathoracic spread causing pericarditis, mediastinitis, rib osteomyelitis, or SVCO is also reported

Extrapulmonary disease

  • Dissemination from the lungs occurs in 50% of patients

  • CNS is the most common site of dissemination, occurring in 25% of pulmonary nocardiosis cases. Single or multiple abscesses occur and may be accompanied by meningitis

  • Other sites include the skin and subcutaneous tissues, kidneys, bone, joints and muscle, peritoneum, eyes, pericardium, and heart valves.


  • Identification by smear and culture is the principal method of diagnosis. Nocardia grows on routine media, usually within 2–7 days, although more prolonged culture (2–3 weeks) may be required

  • Direct smear of appropriate specimens (e.g. aspirates of abscesses, biopsies) is highly sensitive and typically shows Gram-positive beaded branching filaments, which are usually acid-fast on modified Ziehl–Neelsen (ZN) stain. Examination of BAL fluid may also be diagnostic

  • Sensitivity testing of isolates and identification to species level is done by reference laboratories

  • Biopsies typically show a mixed cellular infiltrate; granulomata occur rarely and may result in misdiagnosis as TB or histoplasmosis

  • CXR and CT may demonstrate parenchymal infiltrates, single or multiple nodules (sometimes with cavitation), or features of pleural infection

  • Sputum smear is usually unhelpful. Sputum culture has a greater yield, but Nocardia growth may be obscured in mixed cultures. The significance of Nocardia growth on sputum culture in asymptomatic patients is unclear; it may represent contamination or colonization in the setting of underlying lung disease

  • Blood cultures are almost always negative, although Nocardia bacteraemia may occur in the setting of profound immunocompromise

  • Consider MRI of the brain to exclude asymptomatic CNS involvement in patients with pulmonary nocardiosis.


  • Discuss treatment with an infectious diseases specialist

  • Drug treatment choices include sulfonamides/co-trimoxazole, minocycline, imipenem, cefotaxime, ceftriaxone, or amikacin. Sulfa drugs, in particular co-trimoxazole, have traditionally been the mainstay of therapy. Imipenem and amikacin combination therapy has been shown to be active in vitro and in animal models and is recommended for pulmonary nocardiosis and for very ill patients. Extended-spectrum cephalosporins, such as ceftriaxone and cefotaxime, have the advantages of good CNS penetration and low toxicity

  • Optimal treatment duration is unclear: typically given for 6 months in non-immunocompromised patients, and for 12 months or longer for CNS involvement or immunocompromised patients

  • Surgery may be required for abscess drainage.


Clinical outcome is dependent on the site and extent of disease and on underlying host factors. Disease remissions and exacerbations are common. Cure rates are ~90% in pleuropulmonary disease and 50% in brain abscess. Mortality of Nocardia infection is generally low, although it approaches 50% in cases of bacteraemia.

Further information

Saubolle MA, Sussland D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol 2003;41:4497–501.Find this resource:

Lerner PI. Nocardiosis. Clin Inf Dis 1996;22:891–905.Find this resource:



Actinomycosis is caused by a group of anaerobic Gram-positive bacilli, of which Actinomyces israelii is the commonest. These organisms are present in the mouth, GI tract, and vagina. Clinical infection may follow dental procedures or aspiration of infected secretions. Infection is slowly progressive and may disseminate via the bloodstream or invade tissue locally, sometimes resulting in sinus tract formation.

Consider this diagnosis particularly in patients with pulmonary disease accompanied by soft tissue infection of the head and neck. The diagnosis of actinomycosis is often unsuspected, and the clinical and radiological features may mimic cancer, TB, or fungal disease.


Actinomycosis is rare. It can occur at any age and is more common in men. Predisposing factors include corticosteroid use, chemotherapy, organ transplant, and HIV infection.

Clinical features

Thoracic disease

Thoracic disease occurs in about 15% of cases. Symptoms of pulmonary involvement are non-specific and include cough, chest pain, haemoptysis, fever, anorexia, and weight loss. Chest wall involvement may occur, with sinus formation or rib infection, and empyema is common. Mediastinal involvement is documented.

Extrathoracic disease

Soft tissue infection of the head and neck, particularly the mandible, is the commonest disease presentation (about 50% of cases). Discharging sinuses may form. Other extrathoracic disease sites include the abdomen (particularly the ileocaecal region), pelvis, liver, bone, and CNS (manifest as single or multiple abscesses).


  • CXR and CT appearances are variable, including masses (sometimes with cavitation), parenchymal infiltrates, consolidation, mediastinal disease, and/or pleural involvement

  • Diagnosis is based on the microscopy and anaerobic culture of infected material. Warn the microbiology laboratory if the diagnosis is suspected, as specific stains and culture conditions are required. Examination of infected material may reveal yellow ‘sulfur granules’ containing aggregated organisms. Sample sputum, pleural fluid, and pus from sinus tracts; inoculate into anaerobic transport media, and rapidly transport to lab. Endobronchial biopsies have a low sensitivity. Most infections are polymicrobial, with accompanying aerobic or anaerobic bacteria.


  • Discuss treatment with an infectious diseases specialist

  • Drug treatment choices include penicillin, amoxicillin, clindamycin, or erythromycin. Administration should initially be IV. Optimal treatment duration is unclear (typically given for 6–12 months)

  • Surgery may be required for abscess drainage

  • Monitor response to treatment with serial CT or MRI scans

  • Treat any associated periodontal disease.


Disease relapse is common if prolonged treatment is not administered.

Further information

Mabeza GF, Mcfarlane J. Pulmonary actinomycosis. Eur Resp J 2003;21:545–51.Find this resource:


Definition and epidemiology

  • Bacillus anthracis is an aerobic Gram-positive spore-forming bacterium that causes human disease, principally following either inhalation or cutaneous contact. Spores can survive in soil for many years. Person-to-person transmission does not occur

  • Considerable recent interest has focused on the use of anthrax in bioterrorism; five envelopes containing anthrax spores were sent through the USA postal service in 2001, and there were 11 confirmed cases of inhalational anthrax (including five deaths) and seven confirmed cases of cutaneous anthrax. A previous outbreak occurred in Sverdlovsk in the former Soviet Union in 1979, following the release of spores from a biological weapons plant, and resulted in 68 deaths

  • Anthrax infection also occurs very rarely in association with occupational exposure to Bacillus anthracis in animal wool or hides. The majority of occupational cases result in cutaneous disease, and a diagnosis of inhalational anthrax strongly suggests a bioterrorist attack.

Clinical features

Inhalational anthrax

  • Incubation period is variable, although, in the USA, in 2001, it typically ranged 4–6 days following exposure from opening mail

  • Patients typically experience a prodrome of flu-like symptoms such as fever and cough. GI symptoms (vomiting, diarrhoea, abdominal pain), drenching sweats, and altered mental status are often prominent symptoms. Breathlessness, fever, and septic shock develop several days later. Haemorrhagic meningitis is a common complication

  • Large haemorrhagic pleural effusions are a characteristic feature.

Cutaneous anthrax

  • Initial symptoms include itch and development of a papule at the infection site. A necrotic ulcer with a black centre, and often surrounding oedema, subsequently develops. Systemic symptoms, such as fever and sweats, may be present.


  • Bacillus anthracis grows on conventional media and is readily cultured if sampling precedes antibiotic treatment; a definitive diagnosis requires specialized laboratory tests (e.g. PCR, immunohistochemistry of biopsy samples, or serological studies)

  • Blood tests typically reveal leucocytosis

  • Blood cultures are positive in nearly all cases of inhalational anthrax when taken prior to antibiotic treatment. Staining and culture of pleural fluid may be diagnostic

  • CXR in inhalational anthrax classically shows a widened mediastinum (due to necrosis of mediastinal lymph nodes and haemorrhagic mediastinitis); pleural effusions and pulmonary infiltrates may be present. CT may also demonstrate mediastinal and hilar lymphadenopathy

  • Gram stain and culture of the ulcer is usually diagnostic in cutaneous anthrax, although biopsy is sometimes required.


  • Discuss with infectious diseases and public health specialists if the diagnosis is suspected

  • Antibiotic treatment should be administered immediately after taking blood cultures. Recommendations are for initial treatment with either ciprofloxacin or doxycycline IV, in combination with 1–2 additional antibiotics (choices include clindamycin, vancomycin, meropenem, or penicillin). Subsequent treatment should be with either ciprofloxacin or doxycycline orally for 60 days. Oral treatment alone may be sufficient in cases of mild cutaneous disease

  • Corticosteroid treatment should be considered in patients with meningitis or severe neck or mediastinal oedema

  • Supportive care, including ventilatory support, treatment of shock with IV fluids and/or inotropes, and chest tube drainage of large pleural effusions may be needed.


Inhalational anthrax is associated with a high mortality; five of the recent 11 cases in the USA died. The mortality of previously documented cases has been even higher, perhaps reflecting a delay or lack of antibiotic treatment.


USA recommendations advise prophylaxis with oral ciprofloxacin or doxycycline for individuals considered to have been exposed to anthrax spores in contaminated areas. A vaccine is available, although its value in post-exposure prophylaxis is unknown.


Definition and epidemiology

Tularaemia is a rare zoonosis caused by infection with the Gram-negative bacteria Francisella tularensis. Two major subspecies are described: subspp. tularensis (type A) is highly virulent and found in North America; subspp. holarctica (type B) is less virulent and found in North America, Europe, and Asia. Small mammals (particularly rabbits and hares) acquire infection from arthropod bites and act as reservoirs; human infection follows inhalation, direct contact with infected rodents, ingestion of contaminated food, or arthropod bites. Tularaemia is most frequently encountered in rural areas, following activities, such as farming and hunting, although laboratory workers are also at risk. There has been considerable interest in the development of F. tularensis as a biological weapon, and more recently concerns have arisen as to its possible use in bioterrorism.

Clinical features

Typically abrupt onset of fever, headache, dry cough, and malaise. Development of a tender ulcer and regional lymphadenopathy (‘ulceroglandular tularaemia’) around an infected arthropod bite is common. Tularaemia pneumonia, following infection with type A, is characterized by cough (productive or dry), breathlessness, and sweating, with often minimal signs on examination; may progress rapidly to respiratory failure and death. Symptoms of pneumonia are milder after infection with type B.


  • Serology is the principal method of diagnosis, although PCR-based techniques are increasingly used

  • F. tularensis may be identified in culture of wound specimens, although the laboratory should be warned—type A is sufficiently virulent for some laboratories not to perform culture. Sputum cultures may be diagnostic

  • CXR may demonstrate parenchymal infiltrates, often progressing to lobar consolidation. Pleural effusions, hilar lymphadenopathy, and lung abscess may occur.


  • Discuss treatment with an infectious diseases specialist

  • Drug treatment choices include streptomycin or gentamicin for 10 days. Doxycycline or chloramphenicol are alternatives, although treatment failure rates are higher and a course of 14 days is recommended

  • In the setting of a large-scale outbreak (e.g. following use in bioterrorism), doxycycline or ciprofloxacin may be used for treatment or following exposure.


Mortality is 1–2% from type A; type B is benign in humans.

Further information

Tarnvik A, Berglund L. Tularaemia. Eur Resp J 2003;21:361–73.Find this resource:


Definition and epidemiology

Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus that is found in soil and water in South-East Asia, northern Australia, China, and India; clinical disease is particularly common in Thailand where it may account for up to a third of all pneumonia deaths. Infection is thought to follow entry via skin abrasions or inhalation, and pneumonia is the most common clinical presentation. Most cases represent recent infection; reactivation of infection is rare but can occur many years after exposure. Risk factors for melioidosis include diabetes, alcohol excess, renal disease, and chronic lung disease (including CF).

Consider melioidosis in returning travellers from Asia or Australia with CAP or a subacute/chronic ‘TB-like’ respiratory illness.

Clinical features


  • Acute septicaemic melioidosis Patients present acutely unwell, with a severe pneumonia and widespread nodular consolidation on CXR, may progress rapidly to death

  • Localized subacute melioidosis Subacute cavitating lobar (often upper) pneumonia, mimicking TB

  • Chronic suppurative melioidosis Chronic lung abscess ± empyema; suppurative infection may involve other organs, including skin, brain, joints, bones, liver, spleen, kidney, adrenal, prostate, lymph nodes.


Identification by culture is the principal method of diagnosis. Blood cultures may be diagnostic; alert the laboratory to the possibility of this infection. ELISAs are relatively insensitive.


  • B. pseudomallei is resistant to multiple antibiotics. Treat with high-dose IV ceftazidime, meropenem, or imipenem for at least 10–14 days (longer if severe pulmonary disease or organ abscesses), then oral antibiotic (e.g. co-trimoxazole, alone or in combination with doxycycline) for at least 12 weeks to ensure eradication

  • Supportive care, with ITU admission for septic shock or severe pneumonia.


Documented mortality rates range 19–46%.

Further information

Currie BJ. Melioidosis: an important cause of pneumonia in residents of and travelers returned from endemic regions. Eur Resp J 2003;22:542–50.Find this resource:


Definition and epidemiology

Leptospirosis is a zoonosis transmitted from water or soil contaminated with urine of infected animals (e.g. rats, dogs, cats, pigs, cattle, hamsters, bats) through skin abrasions or mucosa. Present worldwide, more common in tropical countries, but well described in UK. Individuals most at risk in the UK include farmers, vets, sewage workers, returning travellers from the topics, military personnel, and canoeists. Incidence peaks in spring/summer. In the tropics, epidemics may occur following storms or floods.

Consider leptospirosis in all patients with diffuse alveolar haemorrhage and in at-risk individuals with pneumonia or ARDS.

Clinical features

Disease manifestations are highly variable, ranging from asymptomatic infection to multi-organ failure, pulmonary haemorrhage, and death. Patients may present solely with pulmonary haemorrhage, without other features of Weil’s disease. Manifestations include:

  • Acute (anicteric) leptospirosis Self-limiting flu-like illness; myalgia, rash, and aseptic meningitis may occur

  • Weil’s disease (icterohaemorrhagic fever) Classic form of leptospirosis. Features include fever, myalgia, conjunctival haemorrhage, rash, jaundice/hepatic failure, renal failure, coagulopathy, and thrombocytopenia, shock, myocarditis/cardiac arrhythmias

  • Pulmonary disease Occurs in at least a third of hospitalized patients with acute leptospirosis or Weil’s disease. Manifestations include mild symptoms/signs (cough, wheeze, and crackles), pneumonia, pulmonary oedema 2° to myocarditis, and ARDS or fulminant alveolar haemorrhage syndrome.


  • May be isolated in blood cultures

  • Serology confirms the diagnosis and is performed in a single Leptospira Reference Unit in the UK. Both ELISA and microscopic agglutination tests may be performed

  • CXR and CT typically demonstrate patchy consolidation and ground-glass shadowing, commonly bilateral with lower lobe predominance.


  • Discuss treatment with infectious diseases and renal specialists. Antibiotic choices include penicillin, ceftriaxone, or doxycycline

  • Ventilatory support required for alveolar haemorrhage and ARDS

  • Ensure adequate hydration; blood products may be required

  • High-dose glucocorticoids are occasionally used, although there is no convincing evidence of benefit. Plasma exchange and desmopressin infusions have been tried.


Acute leptospirosis typically resolves spontaneously after about 14 days. Severe pulmonary disease can progress very rapidly (over hours), with reported mortality rates approaching 50%.

Differential diagnosis of zoonotic microbial causes of CAP (with exposures)

  • Avian influenza virus (birds, animals)

  • Bacillus anthracis (anthrax; animals)

  • Brucellosis (animals)

  • Chlamydophila psittaci (psittacosis; poultry, birds)

  • Coxiella burnetii (Q fever; parturient cats, cattle, sheep, goats, rabbits)

  • Cryptococcus neoformans (birds)

  • Francisella tularensis (tularaemia; rabbits, cats, rodents)

  • Hantavirus (rodents, the Americas)

  • Histoplasma capsulatum (histoplasmosis; birds or bats, the Americas)

  • Leptospirosis (water contaminated with infected animal urine)

  • Pasteurella multocida (pasteurellosis; animals, birds)

  • Ricketsia rickettsii (Rocky mountain spotted fever; tick bite or exposure to tick-infested habitats, USA)

  • Yersinia pestis (pneumonic plague; rodents, cats).