Respiratory Tract Infections

Community acquired pneumonia Introduction Pneumonia is an inflammation of the lower air passages and air sacs of the lungs resulting from infection of the parenchyma of the lungs.  It is very common and most of the infections are in elderly patients. The mortality rate is up to 50%.  Pneumonitis is an acute inflammatory process that can be difficult to differentiate from pneumonia and can arise from infection, such as cytomegalovirus, or from non-infective processes such as inhalation of vomit or smoke.  In this context ‘pneumonitis’ will be used for non-infective inflammatory processes of the lung.

Risk factors for pneumonia in the immunocompetent adult Pre-existing chest infection, especially bronchitis. Cardiac failure. Structural lung disease. Smoking. Alcoholism. Diabetes. Age over 65.

Etiology of community-acquired pneumonia Most community-acquired pneumonias are bacterial and the predominant pathogen is Streptococcus pneumoniae. Up to 13% of community-acquired pneumonias are viral in origin. Influenza A and B viruses are the predominant viral pathogens.  Viral pneumonia is more common in the autumn and winter.

Diagnosis of community-acquired pneumonia Assessment of severity Clinical assessment of disease severity is important for patient management, particularly in deciding which tests to use, where the patient should be treated (community, hospital ward or ICU), and which antibiotic regimens to use.  The key issue in patient management is distinguishing those with severe pneumonia, who are at high risk of death, from those with non-severe pneumonia.  Defining severe pneumonia accurately also has the added benefit of reducing over-prescribing. 

The British Thoracic Society guidelines recommend that the following core adverse prognostic features should be assessed for all patients (CURB score): Confusion: new mental confusion defined as an Abbreviated Mental Test score of 8 Urea: raised >7 mmol/L Respiratory rate: raised >30/min Blood pressure: low blood pressure (systolic <90 mmHg and/or diastolic <60 mmHg).

Patient stratification based on CURB score If patients have two or more of the core features they are at high risk of death and should be managed in hospital as having severe community-acquired pneumonia. If none of the above is present and the patient is aged under 50 and has no co-existing chronic illness, the patient can be managed in the community.  However, they may be admitted to hospital for social reasons, such as poor social support. For all other patients the management decision is one of clinical judgement, but most will be treated in hospital.

Microbiology Blood cultures. Serology. Sputum Gram stain and culture. Invasive sample collection. Blood tests.

Blood cultures in diagnosis of pneumonia The British Thoracic Society recommends that blood for culture be taken from all patients admitted to hospital. Blood samples for culture and sensitivity should ideally be obtained before antibiotic therapy starts. Blood culture is of most value in patients with severe pneumonia, where the result of the blood test is more likely to lead to a change in antibiotic therapy. There is controversy about the use of blood cultures, as only about 11% of blood cultures will be positive, but on the occasions when a positive blood culture is obtained, it is highly specific, as it is unlikely to be contaminated by respiratory tract commensals.  A positive blood culture in the absence of septicemia or other focus of infection is a definitive test.  Positive blood cultures are more often associated with Streptococcus pneumoniae and Haemophilus influenzae serotype B (the incidence of which has now been reduced by vaccination).

Serology and other investigations Organisms that can be detected by serology of antibodies in serum include Mycoplasma pneumonia, Coxiella burnetii, Chlamydia psittaci, Chlamydia pneumonia and Legionella spp.  Other serological tests include: Antigen tests: Sputum, blood or urine samples, or parapneumonic (pleural) effusions, for pneumococcal antigen Urinary antigen is useful for Legionella pneumophila serogroup 1 (most cases in the UK are caused by serogroup 1); the test is easy to perform and is still effective after previous antibiotic treatment.  Sensitivity is 50–60% and specificity >95% for serogroup 1.  However, because the antigen used is specific to serogroup 1, this test will miss Legionnaire’s disease caused by other serogroups.  Legionella antigen is only detectable in the first few days of infection: consult the local microbiology laboratory for the correct use of this test. HIV antibody testing is useful in cases where history or clinical suspicion suggests HIV or Pneumocystis carinii.

Gram stain and culture of sputum in diagnosis of pneumonia Gram stain of sputum The use of sputum Gram stain is controversial. It is not routinely performed but is cheap and rapid; sample collection has little risk to the patient and is non-invasive.  Gram stain must be performed within 1–2 h of sputum collection.  Gram stain provides a potential immediate clue to the classes of pathogens: staphyloccocal infection can also be rapidly identified by Gram stain. However, there are disadvantages of Gram stain.  Sensitivity for pneumococcal pneumonia is 50–60% (although specificity is >80%).  The experience of the person reading the stain can affect the results.  Often patients cannot produce sputum and hence poor quality samples are obtained where the Gram film will show commensals of the respiratory tract only.

Gram stain also provides an indication of whether subsequent culture is likely to be useful:  Fewer than 10 squamous epithelial cells and >25 polymorphonuclear neutrophils per low power (×100) field are required in a Gram stain for subsequent culture.  The high numbers of polymorphs indicate active infection, rather than the presence of bacterial contamination in the smear. (This response may be altered if the patient is immunocompromised)  Other techniques can be used in addition to Gram stain to increase the range of pathogens detected: Acid-fast stain for mycobacteria Immunofluorescence for Legionella, Pneumocystis and viruses.

Sputum culture Sputum culture has the advantage of posing little risk to the patient. Ideally sputum should be obtained for culture before antibiotic therapy starts: the specimen should be processed rapidly for best results. Sputum is often not produced during the first 72 h of infection. Not all patients can produce sputum; if not, postural drainage, physiotherapy or saline nebulization may be used to produce a sample. Invasive investigations may also be used.

Invasive sampling techniques in pneumonia If the patient is in the Intensive Care Unit then protected specimen bronchial brush techniques or bronchoalveolar lavage (BAL) (via bronchoscopy or non-directed BAL) may be required to obtain a specimen. This allows specimens uncontaminated by nasopharyngeal flora to be obtained and may be warranted in severely ill patients to allow a definite aetiology to be obtained.  Fibre optic bronchoscopy is useful in patients who fail to improve. Transthoracic needle aspiration can be used to obtain material for culture. Pleural effusions can also be cultured.

Blood tests in diagnosis of pneumonia Blood count (neutrophils will usually be raised to >15 000×109/L in bacterial infection. This rise will not be seen in viral infection). Leucopenia (WBC <4,000×109/L). Leucocytosis (WBC >20,000×109/L). Serum urea is an important prognostic indicator, particularly of mortality. Blood gas analysis is important in the management of severe pneumonia: expert advice should be sought. Imaging The advantages and disadvantages of imaging are discussed in the new British Thoracic Society guidelines for the management of community-acquired pneumonia.

Management of community-acquired pneumonia It is important to initiate empirical treatment promptly without waiting for investigation results or until a scheduled drug round.  Early antibiotic administration (within eight hours of hospital arrival) improves outcome. Blood and sputum for culture and sensitivity should be taken before antibiotic treatment is started.

Antibiotic rationale Spectrum of action The choice of antibiotic, route of administration, and dose depend on the severity of the disease, probable pathogens and local resistance patterns. The agent chosen should always cover the most likely pathogen; Streptococcus pneumoniae. It should also cover Haemophilus influenza which is still the second most common pathogen causing pneumonia. Atypical pathogens such as Chlamydia pneumoniae and Mycoplasma pneumoniae are less common but are more frequent in patients <75 years. Mycoplasma pneumoniae infection tends to be more frequent in winter, in addition to its pattern of four-yearly epidemics.  Staphylococcus aureus is an uncommon cause of community-acquired pneumonia but should be considered during influenza epidemics. A cluster of atypical infections may suggest Legionnaires’ disease (although it is often not possible to distinguish atypical pathogens clinically and Legionnaires’ disease is often diagnosed in retrospect).

Tissue penetration The antibiotics chosen should be able to penetrate into alveolar tissue and fluid, and if the suspected pathogen is intracellular, such as Legionella or Mycoplasma spp., then the antibiotics chosen should also be capable of penetration into cells. Glycopeptides are ineffective in treating pneumonia, because levels in alveolar tissue are below the MICs for most Gram-positive organisms despite high plasma levels. Route of administration and duration of treatment If the patient is severely ill, unconscious or vomiting, intravenous therapy will be required. Treatment durations should be at least five days, or longer if the patient is slow to respond, with at least two to three weeks of treatment for staphylococcal pneumonia and Legionnaires’ disease.

In non-severe pneumonia: Empirical treatment The following suggestions are suitable empirical antibiotic choices but do not replace local guidelines. Refer to local guidelines. In non-severe pneumonia: First line: Oral amoxicillin with or without a macrolide Amoxicillin monotherapy can be used if patients with non-severe pneumonia; Are admitted for non-clinical reasons and/or Have not been recently treated with antibiotics in the community and/or Have no reason to suspect infection with atypical pathogens. For all other patients with non-severe pneumonia, add a macrolide. Second-line or in penicillin-allergy: high-doses of a newer quinolone with good activity against Streptococcus pneumoniae, or a newer macrolide, such as clarithromycin, or an azalide, such as azithromycin.

Severe pneumonia of unknown etiology: Combination treatment with a macrolide (consult local guidelines for choice of macrolide) plus an injectable cephalosporin (consult local policy for choice of cephalosporin).  An alternative regimen for those allergic to beta-lactams is: A newer quinolone with good activity against Streptococcus pneumoniae plus any one of the following: rifampicin, linezolid or a macrolide. Definitive treatment Once culture results are known, treatment can be adjusted accordingly. Your microbiologist will advise on suitable treatments. If the pathogen shows sensitivity to penicillin, there is an opportunity to change antibiotic therapy to one of the penicillins, thereby using minimal effective therapy and reducing the potential for antibiotic resistance.

Pneumonia caused by Staphylococcus aureus Staphylococcus aureus, and especially MRSA, is a rare cause of community-acquired pneumonia, but must be considered during influenza epidemics or if the patient presents with a history suggesting recent pneumonia.  When treating Staphylococcus aureus, the duration of treatment needs to be sufficiently long to minimise the possibility of systemic embolic complications. Treatment may need to continue for 2–3 weeks. The following antibiotics may be useful: Methicillin-sensitive strains:  Flucloxacillin with or without either fusidic acid or rifampicin. MRSA Treatment will depend on local sensitivities. Consult your local microbiologist. Treatment may include: Chloramphenicol (if the organism is sensitive) or doxycycline.

Pneumonia caused by atypical pathogens In order to adequately cover atypical pathogens including: Chlamydia psittaci, Chlamydia pneumoniae, Q fever, or Mycoplasma pneumoniae, it is important to choose antibiotics with good penetration into lung tissues and fluids and high intracellular activity. Atypical organisms lack a conventional cell wall so beta-lactam antibiotics are inappropriate. Macrolides and tetracyclines are suitable first choices. Quinolones such as ciprofloxacin achieve very high concentrations in lung tissue (many times the plasma concentration), and have good activity against atypical pathogens so make good alternatives to macrolides or tetracyclines. If used as empirical therapy, a newer quinolone with enhanced activity against the Pneumococcus would be preferable. Treatment options include: A macrolide such as erythromycin or a tetracycline such as doxycycline or a fluoroquinolone such as ciprofloxacin.

Assessment of response in management of pneumonia Assessment of response depends on: resolution of cough, dyspnoea/tachypnoea (in ventilated patients respiratory symptoms may be difficult to observe), fever, PO2 level, peripheral leukocyte count, and radiological findings. Fall in CRP of 50% over four days suggests a good response to treatment. Follow-up cultures of blood and sputum are not normally required (except in TB). Radiological findings resolve more slowly than clinical symptoms in most patients, whether ventilated or not, and may even show initial progression despite symptom improvement

Nosocomial pneumonia Introduction Nosocomial pneumonia is pneumonia acquired in the hospital (that is, manifesting at least 48 h after admission).  It is common and accounts for significant mortality and morbidity.  Nosocomial pneumonia and ventilator-associated pneumonia (a subset of nosocomial pneumonia) are often discussed together in the literature.

Risk factors for nosocomial pneumonia Increased duration of hospital stay (risk significantly increases with >14 days’ stay). Trauma (particularly head trauma). Chronic underlying diseases (eg. diabetes and chronic lung disease). Immunosuppression. General anaesthetic. Endotracheal intubation. Hospital admission during the previous month. Antibiotic history.

etiology of nosocomial pneumonia A wide range of pathogens can be implicated in nosocomial pneumonia. Several factors affect the aetiology of nosocomial pneumonia. Time of onset after hospitalisation. Stress-induced flora changes. Antibiotic-induced flora changes. Exposure to contamination with nosocomial pathogens. Nosocomial pneumonia can generally be described as ‘early nosocomial’ (appearing within five days of hospitalisation) or ‘late nosocomial’ (more than five days after hospitalisation). The organisms leading to community-acquired pneumonia, predominantly Gram-positive cocci, are seen in patients who present with pneumonia very shortly after admission to hospital (if no antibiotic therapy has so far been given) and Gram-negative bacilli predominate in patients developing pneumonia after five days of hospitalisation. Legionella infection is possible but rare.

Diagnosis of nosocomial pneumonia Clinical and laboratory signs allow a presumptive diagnosis of pneumonia. Laboratory investigations Blood cultures. Sputum Gram stain and culture. Invasive sample collection.

Management of nosocomial pneumonia Antibiotic treatment must be started promptly. If the pathogen is known or suspected, antimicrobial therapy should be guided by local sensitivities; consult your microbiologist. However, in most cases empirical antibiotic treatment will be required. Antibiotic rationale Antibiotic choices are influenced by the following factors: Time of onset of the illness after admission (‘early’ or ‘late’) Local resistance patterns Severity of the pneumonia Underlying disease Recent antibiotic treatment.

Empirical therapy Typical regimens for nosocomial pneumonia in patients previously untreated with antibiotics include: First-line: if cephalosporins have not been given in the last 7–10 days, an injectable cephalosporin such as cefuroxime but follow local policy on choice of cephalosporin Second-line: consult local treatment guidelines and/or local microbiologist.  Options include quinolones or aztreonam In penicillin-allergic patients: a quinolone If aspiration is suspected, regimens for aspiration pneumonia should be used. Empirical therapy must cover a wide range of organisms including Pseudomonas aeruginosa and maintain high concentrations in lung parenchyma. There is controversy over the ability of monotherapy vs. combination therapy to achieve this. There have been examples of treatment-sensitive strains of Pseudomonas aeruginosa developing resistance during the course of antimicrobial therapy. In cases of suspected or confirmed Pseudomonas aeruginosa pneumonia, the antibiotics chosen should have vigorous anti-pseudomonal activity. Possible anti-pseudomonal therapy includes: Combination therapy with a ureidopenicillin plus an aminoglycoside or Monotherapy with aztreonam For nosocomial pneumonia in patients previously treated with antibiotics consult your local guidelines.