Table 32.1 gives possible aetiological agents based on epidemiological clues. Streptococcus pneumoniae is the most commonly isolated organism. The next most common pathogens in patients admitted to ICU are: Legionella species, Haemophilus influenzae, Enterobacteriaceae species, Staphylococcus aureus and Pseudomonas species.¹⁰

Table 32.1 Possible aetiological agents based on epidemiological clues ^2,^3,^7,⁹

Exposure	Organism
Exposure to animals
Handling turkeys, chickens, ducks or psittacine birds or their excreta	Chlamydia psittaci
Exposure to birds in countries in which avian flu has been identified in birds	Influenza A H5N1
Handling infected parturient cats, cattle, goats or sheep or their hides	Coxiella burnetii
Handling infected wool	Bacillus anthracis
Handling infected cattle, pigs, goats or sheep or their milk	Brucella spp.
Insect bite. Transmission from rodents and wild animals (e.g. rabbits) to laboratory workers, farmers and hunters	Francisella tularensis
Insect bites or scratches. Transmission from infected rodents or cats to laboratory workers and hunters	Yersinia pestis
Contact with infected horses (very rare)	Pseudomonas mallei
Exposure to mice or mice droppings	Hantavirus
Geographical factors
Immigration from or residence in countries with high prevalence of tuberculosis	Mycobacterium tuberculosis
North America. Contact with infected bats or birds or their excreta. Excavation in endemic areas	Histoplasma capsulatum
South-west USA	Coccidiodes species, Hantavirus
USA. Inhalation of spores from soil	Blastomyces dermatitidis
Asia, Pacific, Caribbean, north Australia. Contact with local animals or contaminated skin abrasions	Burkholderia pseudomallei
Host factors
Diabetic ketoacidosis	Streptococcus pneumoniae, Staphylococcus aureus
Alcoholism	Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, oral anaerobes, Mycobacterium tuberculosis, Acinetobacter spp.
Chronic obstructive pulmonary disease or smoking	Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella spp., Pseudomonas aeruginosa
Sickle-cell disease	Streptococcus pneumoniae
Pneumonia complicating whooping cough	Bordatella pertussis
Pneumonia complicating influenza	Streptococcus pneumoniae, Staphylococcus aureus
Pneumonia severe enough to necessitate artificial ventilation	Streptococcus pneumoniae, Legionella spp., Staphylococcus aureus, Haemophilus influenzae, Mycoplasma pneumoniae, enteric Gram-negative bacilli, Chlamydia pneumoniae, Mycobacterium tuberculosis, viral infection, endemic fungi
Nursing-home residency	Treat as health care-associated pneumonia
Poor dental hygiene	Anaerobes
Suspected large-volume aspiration	Oral anaerobes, Gram-negative enteric bacteria
Structural disease of lung (e.g. bronchiectasis, cystic fibrosis)	Pseudomonas aeruginosa, Burkholderia cepacia, Staphylococcus aureus
Lung abscess	Community-acquired methicillin-resistant Staphylococcus aureus, oral anaerobes, endemic fungi, Mycobacterium tuberculosis, atypical mycobacteria
Endobronchial obstruction	Anaerobes, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus
Intravenous drug addict	Staphylococcus aureus, anaerobes, Mycobacterium tuberculosis, Streptococcus pneumoniae
Others
Epidemic	Mycoplasma pneumoniae, influenza virus
Air-conditioning cooling towers, hot tubs or hotel or cruise ship stay in previous 2 weeks	Legionella pneumophilia
Presentation of a cluster of cases over a very short period of time	Bioterrorist agents: Bacillus anthracis, Franciscella tularensis, Yersinia pestis

CLINICAL PRESENTATION

Pneumonia produces both systemic and respiratory manifestations. Common clinical findings include fever, sweats, rigors, cough, sputum production, pleuritic chest pain, dyspnoea, tachypnoea, pleural rub and inspiratory crackles. Classic signs of consolidation occur in fewer than 25% of cases. Multiorgan dysfunction or failure may occur depending on the type and severity of pneumonia.

The diagnosis of pneumonia may be more difficult in the elderly. Although the vast majority of elderly patients with pneumonia have respiratory symptoms and signs, over 50% may also have non-respiratory symptoms and over one-third may have no systemic signs of infection.

INVESTIGATIONS ^7,⁸

Investigations should not delay administration of antibiotics as delays are associated with an increase in mortality.³ Important investigations include:

1 CXR

2 Arterial blood gases or oximetry

3 Full blood count

4 Serum creatinine, urea and electrolytes

5 Liver function tests

6 Blood cultures (×2) prior to the administration of antimicrobials

7 Sputum (if immediately available) for urgent Gram stain and culture. The usefulness of sputum tests remains debatable because of contamination by upper respiratory tract commensals. However, a single or predominant organism on a Gram stain of a fresh sample or a heavy growth on culture of purulent sputum is likely to be the organism responsible. The finding of many polymorphonuclear cells (PMN) with no bacteria in a patient who has not already received antibiotics can reliably exclude infection by most ordinary bacterial pathogens. Specimens should be obtained by deep cough and be grossly purulent. Ideally the specimen should be obtained before treatment with antimicrobials, if this does not delay administration of antibiotics, and be transported to the laboratory immediately for prompt processing to minimise the chance of missing fastidious organisms (e.g. Streptococcus pneumoniae). Acceptable specimens (in patients with normal or raised white blood cell (WBC) counts) should contain > 25 PMN per low-power field (LPF) and < 10–25 squamous epithelial cells (SEC)/LPF or > 10 PMN per SEC. These criteria should not be used for Mycobacterium and Legionella infection. Certain organisms are virtually always pathogens when recovered from respiratory secretions (Table 32.2). Patients with risk factors for tuberculosis (TB) (Table 32.3) and particularly those with cough for more than a month, other common symptoms of TB and suggestive radiographic changes should have sputum examined for acid-fast bacilli (AFB). Sputum cannot be processed for culture for anaerobes due to contamination by the endogenous anaerobic flora of the upper respiratory tract. In addition to the factors listed in Table 32.1, foul-smelling sputum, lung abscess and empyema should raise suspicion of anaerobic infection.

8 Aspiration of pleural fluid for Gram stain, culture, pH and leukocyte count – all patients with a pleural effusion > 1 cm thick on a lateral decubitus CXR.

9 Urinary Legionella antigen. This test is specific (> 95%). In patients with severe legionnaire’s disease sensitivity is 88–100% for L. pneumophilia serogroup 1 (the most commonly reported cause of Legionella infection). Thus a positive result is virtually diagnostic of Legionella infection but a negative result does not exclude it. In areas where other Legionella species are more common, this test is less helpful.

10 Urinary pneumococcal antigen has moderate sensitivity (50–80%) and high specificity (> 90%).

11 Microimmunofluorescence serology for Chlamydia pneumoniae immunoglobulin (Ig) M. A titre of 1:16 is significant.

12 Human immunodeficiency virus (HIV) serological status.

Table 32.2 Organisms which are virtually always pathogens when recovered from respiratory secretions ⁹

Legionella

Chlamydia

Tuberculosis

Influenza, para-influenza virus, respiratory syncytial virus, adenovirus, Hantavirus, severe acute respiratory syndrome (SARS), coronavirus

Stronglyloides stercoralis

Toxoplasma gondi

Pneumocystis carinii

Histoplasma capsulatum

Coccidiodes immitis

Blastomycoses dermatitidis

Cryptococcus neoformans

Table 32.3 Risk factors for pulmonary tuberculosis

Living in or originating from a developing country

Age (< 5 years, middle-aged and elderly men)

Alcoholism and/or drug addiction

Human immunodeficiency virus (HIV) infection

Diabetes mellitus

Lodging-house dwellers

Immunosuppression

Close contact with smear-positive patients

Silicosis

Poverty and/or malnutrition

Previous gastrectomy

Smoking

Other investigations should be considered in patients with risk factors for infection with unusual organisms. Bronchoalveolar lavage may be useful in immunocompromised patients, those who fail to respond to antibiotics or those in whom sputum samples cannot be obtained.¹¹

MANAGEMENT

GENERAL SUPPORTIVE MEASURES

Intravenous fluids may be required to correct dehydration and provide maintenance fluid. A general approach should be made to organ support with an emphasis on correcting hypoxia.

ANTIMICROBIAL REGIMES

Each unit should have its own regimens tailored to the local flora and antibiotic resistance patterns. In the absence of such regimens the regimen outlined in Figure 32.1 may be helpful. This should be modified in the light of risk factors (see Table 32.1). Quinolones may be less appropriate in areas with a high prevalence of TB as their use may mask concurrent TB infection. Appropriate antimicrobial therapy should be administered within 1 hour of diagnosis.^8,¹⁴ There is controversy regarding the appropriate change to empiric therapy based on microbiological findings.^7,⁸ Changing to narrower-spectrum antimicrobial cover may result in inadequate treatment of the 5–38% of patients with polymicrobial infection. Furthermore, dual therapy may be more effective than monotherapy, even when the identified pathogen is sensitive to the agent chosen, particularly in severely ill patients with bacteraemic pneumococcal pneumonia.¹⁵ For the treatment of drug-resistant Streptococcus pneumoniae, the regimes in Figure 32.1 are probably suitable for isolates with a penicillin minimum inhibitory concentration (MIC) < 4 mg/l.⁷ If the MIC is ≥ 4 mg/l an antipneumococcal fluoroquinolone, vancomycin, teicoplanin or linezolid should be given.⁸

Figure 32.1 Antibiotic regimes for treatment of severe community-acquired pneumonia in critically ill patients.^7,⁸ Respiratory fluoroquinolones include moxifloxacin and levofloxacin. Advanced macrolides include azithromycin and clarithromycin. Cefotaxime is a suitable non-antipseudomonal third-generation cephalosporin.

The role of zanamivir and oseltamivir in severe influenza pneumonia is not clear but early treatment of patients with less severe symptoms results in a reduction of the duration of symptoms if treatment is started early (< 48 hours from onset).¹⁶ Oseltamivir is recommended as first-line therapy for patients with suspected avian influenza A/H5N1.¹⁷

DURATION OF THERAPY

There are no clinical trials that have specifically addressed this issue. Courses as short as 5 days may be sufficient ¹⁸ but antibiotics should be continued until the patient has been afebrile for 48–72 hours and organ dysfunction has largely resolved.⁷ Short courses may be suboptimal for patients with bacteraemic Staphylococcus aureus pneumonia, meningitis or endocarditis complicating pneumonia or infection with less common organisms (e.g. Burkholderia pseudomallei or fungi) or Pseudomonas aeruginosa.

RESPONSE TO THERAPY ^7,^9,¹⁹

This can be assessed subjectively (a response is usually seen within 1–3 days of starting therapy) or objectively on the basis of respiratory symptoms, fever, oxygenation, WBC count, bacteriology and CXR changes. The average time to defevescence varies with organism, severity and patient age (7 days in elderly patients, 2.5 days in young patients with pneumococcal pneumonia, 6–7 days in bacteraemic patients with pneumococcal pneumonia, 1–2 days in patients with M. pneumoniae pneumonia and 5 days in patients with Legionella pneumonia). Both blood and sputum cultures are usually negative within 24–48 hours of treatment, although P. aeruginosa and M. pneumoniae may persist in the sputum despite effective therapy. CXR changes lag behind clinical changes with the speed of change depending on the organism, the age of the patient and the presence and absence of comorbid illnesses. The CXR of most young or middle-aged patients with bacteraemic pneumococcal pneumonia is clear by 4 weeks but resolution is slower in elderly patients and patients with underlying illness, extensive pneumonia on presentation or L. pneumophilia pneumonia.

If the patient fails to respond, consider the following questions:

• Does the patient have pneumonia?

• Are there host factors which explain the failure (e.g. obstruction of bronchus by a foreign body or tumour, inadequate host response)?

• Has a complication developed (e.g. empyema, superinfection, bronchiolitis obliterans organising pneumonia)?

• Is the right drug being given in an adequate dose by the right route?

• Is the organism resistant to the drug being given?

• Are there other organisms?

• Is the fever a drug fever?

Useful investigations include computed tomography of the chest, bronchoalveolar lavage (Table 32.4) and transbronchial or open-lung biopsy.

Table 32.4 Procedure for obtaining microbiological samples using bronchoscopy and protected specimen brushing (PSB) and/or bronchoalveolar lavage (BAL)^12,¹³

Infection control

In patients suspected of having a disease which is transmitted by the airborne route (e.g. tuberculosis):

• the risk of transmission should be carefully weighed against the benefits of bronchoscopy, which may generate large numbers of airborne particles

• perform bronchoscopy in a negative-pressure isolation room

• consider the use of a muscle relaxant in ventilated patients, to prevent coughing

• staff should wear personal protective equipment which should include a fit-tested negative-pressure respirator (N95, FFP2 or above) as a minimum. Use of a powered air-purifying respirator should be considered

General recommendations Suction through the endotracheal tube should be performed before bronchoscopy Avoid suction or injection through the working channel of the bronchoscope Perform protected specimen brushing before bronchoalveolar lavage Ventilated patients Set FiO₂ at 1.0 Set peak pressure alarm at a level that allows adequate ventilation Titrate ventilator settings against exhaled tidal volume Consider neuromuscular blockade in addition to sedation in patients at high risk of complications who are undergoing prolonged bronchoscopy Protected specimen brushing Sample the consolidated segment of lung at subsegmental level If purulent secretions are not seen, advance the brush until it can no longer be seen but avoid wedging it in a peripheral position Move brush back and forth and rotate it several times Bronchoalveolar lavage Wedge tip of bronchoscope into a subsegment of the consolidated segment of lung Inject, aspirate and collect 20 ml of sterile isotonic saline. Do not use this sample for quantitative microbiology or identification of intracellular organisms. It can be used for other microbiological analysis Inject, aspirate and collect additional aliquots of 20–60 ml

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