key: cord-027678-k64whepc
authors: Chan, Kai Man; Gomersall, Charles D
title: Pneumonia
date: 2020-06-22
journal: Oh's Intensive Care Manual
DOI: 10.1016/b978-0-7020-4762-6.00036-9
sha: 
doc_id: 27678
cord_uid: k64whepc

nan

• Pneumonia can be caused by over 100 organisms. • The relationship between specific clinical features and aetiological organism is insufficiently strong to allow a clinical diagnosis of the causative organism. 2 • Early administration of appropriate antibiotics is important. 2 The net result is that the differential diagnosis is wide and treatment should be started before the aetiological agent is known. The differential diagnosis and the likely causative organisms can be narrowed by using epidemiological clues, the most important of which are whether the pneumonia is community-acquired or healthcare-associated and whether the patient is immunocompromised. Note that the flora and antibiotic resistance patterns vary from country to country, hospital to hospital and even ICU to ICU within a hospital and this must be taken into account.

Evidence-based guidelines have been issued by the British Thoracic Society, 3 the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) 2 and the European Respiratory Society. 4 Links to these and other pneumonia-related guidelines can be found at the following 'link page': http://www. aic.cuhk.edu.hk/web8/Pneumonia%20guidelines.htm.

An acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection, accompanied by an acute infiltrate on a chest radiograph (CXR), or auscultatory findings consistent with pneumonia (e.g. altered breath sounds, localised crackles) in a patient not hospitalised or residing in a long-term care facility for ≥14 days prior to the onset of symptoms.

The overall incidence is 3-40 per 1000 inhabitants per year, with 40-60% requiring hospital admission.

Overall, 10% of patients are admitted to ICU. The overall mortality of hospitalised patient is approximately 10%. 5 

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 less than 25% of cases. Multi-organ 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 a third may have no systemic signs of infection.

Investigations should not delay administration of antibiotics as delays are associated with an increase in mortality. 2 Important investigations include: 416 Pneumonia 9. Urinary Legionella antigen. This test is specific (>95%). In patients with severe Legionnaires disease sensitivity is 88-100% for L. pneumophilia serogroup 1 (the most commonly reported cause of Legionella infection). Thus a positive result is virtually 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. Strep. pneumoniae). Acceptable specimens (in patients with normal or raised white blood cell 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 Mycobacteria and Legionella infection. Certain organisms are virtually always pathogens when recovered from respiratory secretions (Box 36.1). Patients with risk factors for tuberculosis (TB) (Box 36.2), 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. Sputum cannot be processed for culture for anaerobes owing to contamination by the endogenous anaerobic flora of the upper respiratory tract. In addition to the factors listed in Table 36 .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 leucocyte count -all patients with a pleural effusion >1 cm thick on a lateral decubitus chest X-ray. contamination and colonisation. PCR assays are more sensitive than culture for Mycoplasma and Chlamydia species and at least as sensitive for Legionella. 7 PCR assays also detect Legionella strains other than serogroup 1. The BTS guidelines 3 recommend PCR of lower respiratory tract sample or, if unavailable, throat swab for the diagnosis of Mycoplasma pneumonia. PCR for Chlamydophilia should be performed when invasive respiratory samples were collected from patients with severe community-acquired pneumonia. The role of PCR in diagnosing PCP is mainly limited to non-HIV patients, in whom conventional microscopy and staining of induced sputum and BAL have a lower sensitivity than in HIV patients. 9 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.

Increased mortality among those who do not receive empirical antibiotics that cover the infecting pathogen(s) is well documented. 11 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 36 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. 6 Molecular diagnosis (e.g. PCR-based methods) has the advantages of quick results (within 3 hours), enhanced sensitivity, independence from organism viability and hence previous antibiotics, and theoretical possibility for determination of antimicrobial susceptibility. 7 Of note, it is important to test for genes specific for the organism in question 10 and the sampling site remains important. PCR is most useful when per formed on specimens from a normally sterile site. For example, PCR for Pneumococcus is positive in 62% of blood samples from adult patients with confirmed or probable pneumococcal pneumonia, 8 whereas blood cultures are positive in only 37%. For respiratory specimens under most circumstances, interpretation remains problematic due to low specificity related to floral should be modified in the light of risk factors (see Table  36 .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. 4, 12 There is controversy regarding the appropriate change to empirical therapy based on microbiological findings. 2, 4 Changing to narrower-spectrum antimicrobial cover may result in inadequate treatment of the 5-38% of patients with polymicrobial infection. Increasing evidence demonstrates improved outcome with combination antimicrobial as compared with monotherapy, particularly in severely ill patients with bacteraemic pneumococcal pneumonia. 5 Odds ratio of death was 1.5 to 6 for monotherapy as compared with combination therapy. Benefits were seen only in combination therapy with macrolide as part of the regimen, but not in combination with fluroquinolone regimen. 13 For the treatment of drug-resistant Strep. pneumoniae (DRSP) the regimens in Figure 36 .1 are probably suitable for isolates with a penicillin MIC < 4 mg/L. 2 If the MIC is ≥4 mg/L an antipneumococcal fluoroquinolone, vancomycin, teicoplanin or linezolid should be given. 4

No clinical trial has specifically addressed this issue. Courses as short as 5 days may be sufficient. 14 IDSA/ ATS guidelines recommend stopping after a minimum of 5 days if the patient is afebrile for 48-72 hours and organ dysfunction has largely resolved. 2 Short courses may be suboptimal for patients with bacteraemic S. aureus pneumonia, meningitis or endocarditis complicating pneumonia or infection with less common organisms (e.g. Burkholderia pseudomallei or fungi) or Pseudomonas aeruginosa. Procalcitonin may be useful to guide antibiotic therapy, but not all studies have demonstrated a benefit. 15 

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, CXR changes, C-reactive protein reduction and procalcitonin reduction of 80-90% from peak value. The average time to defervescence 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 or 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 Legionella pneumophilia pneumonia.

If the patient fails to respond consider the following questions:

• Has the patient got pneumonia?

• Are there host factors that 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, metastatic abscess)?

• 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 computerised tomography (CT) of the chest, thoracocentesis, bronchoalveolar lavage (Table 36 .2) and transbronchial or open-lung biopsy.

Scoring systems have been developed to predict adverse outcome and ICU admission including pneumonia severity index (PSI), CURB-65, CRB-65, modified ATS major and minor criteria, SCAP prediction rule, SMART-COP, REA-ICU index and CAP-PIRO. 16 Although they may help identify the sicker patients they should not be used as a sole determinant of ICU admission as local admission criteria will be affected by local facilities, both in and outside ICU. It should be noted that none of the criteria has been prospectively demonstrated to avoid late transfers or lower mortality.

Influenza pneumonia may present with severe respiratory failure and multi-organ failure. However the pattern of organ failure appears to vary between strains with H5N1 being associated with a much higher mortality and a higher incidence of multi-organ failure than pandemic H1N1, 17 which itself presented differently to seasonal influenza. In particular, trophism for lower respiratory tract, a higher rate of ICU admission 18 and a higher rate of extrapulmonary complications 19 were observed.

Early initiation of oseltamivir is recommended for critically ill patients although there is no direct evidence of outcome benefit. Glucocorticoids do not appear to be useful and may prolong viral replication. 20 Bacterial superinfection should be considered, with Grampositive cocci being most frequently isolated. 21 failure and cancer) can cause infiltrates on a chest X-ray. Identification of the organism responsible is even more difficult than in patients with community-acquired pneumonia owing to the high incidence of oropharyngeal colonisation by Gram-negative bacteria. Blood cultures are positive in only about 6% of cases of nosocomial pneumonia. Ventilator-associated pneumonia (VAP) is nosocomial pneumonia arising >48-72 hours after intubation. Reported incidence of VAP is between 10 and 20% for those receiving mechanical ventilation for more than 48 hours. 22 It is associated with a higher incidence of multi-drug-resistant organisms. 1 

Nosocomial pneumonia is thought to result from microaspiration of bacteria colonising the upper respiratory tract. Other routes of infection include macroaspiration Although there are data demonstrating that surgical masks are as effective as N95 (FFP 2) masks in preventing transmission of seasonal influenza in non-ICU settings it is important to note that the capacity for airborne transmission (and hence the need for N95 masks) is dependent on the exact characteristics of the organism and the frequency of aerosol-generating procedures so these data should not be extrapolated to other influenza viruses and ICU settings.

Nosocomial pneumonia occurs in 0.5-5% of hospital patients, with a higher incidence in certain groups (e.g. postoperative patients and patients in ICU). Diagnosis may be difficult: the clinical features of pneumonia are non-specific and many non-infectious conditions (e.g. atelectasis, pulmonary embolus, aspiration, heart Table 36 .2 Procedure for obtaining microbiological samples using bronchoscopy and protected specimen brushing and/or bronchoalveolar lavage 35, 49 Infection control

In patients suspected of having a disease that 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

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 

Management is based on the finding that early treatment with antimicrobials that cover all likely pathogens results in a reduction in morbidity and mortality. 2 The initial selection of antimicrobials is made on the basis of epidemiological clues ( Fig. 36.2, Table 36 .3). Antimicrobials should be administered within 1 hour of diagnosis. 12 The results of microbiological investigations are used to narrow antimicrobial cover later. Treatment should be reassessed after 2-3 days or sooner if the patient deteriorates ( Fig. 36.3 ). An outline of management based on an invasive approach is given in Figure 36 .4.

Current ATS guidelines recommend 7 days' treatment provided the aetiological agent is not P. aeruginosa or other non-lactose fermenter and the patient has a good clinical response with resolution of clinical features of infection. 1 The outcome of patients who receive appropriate initial empirical therapy for ventilator-associated pneumonia for 8 days is similar to those who receive treatment for 15 days. 1 of gastric contents, inhaled aerosols, haematogenous spread, spread from pleural space and direct inoculation from ICU personnel.

Diagnosis is based on time of onset (>48 hours after admission to a healthcare facility 1 ), CXR changes (new or progressive infiltrates) and either clinical features and simple laboratory investigations or the results of quantitative microbiology. Using a clinical approach, pneumonia is diagnosed by the finding of a new infiltrate or a change in an infiltrate on chest radiograph and growth of pathogenic organisms from sputum plus one of the following: white-blood-cell (WBC) count greater than 12 × l0 5 /L, core temperature ≥38.3°C, sputum Gram stain with scores of more than two on a scale of four of polymorphonuclear leucocytes and bacteria.

These are broadly similar to those required in community-acquired pneumonia:

• Chest X-ray: although studies using a histological diagnosis as the gold standard have demonstrated that pneumonia may be present despite a normal CXR, most definitions of nosocomial pneumonia require the presence of new persistent infiltrates on a CXR.

• Respiratory secretions: considerable controversy surrounds the issue of whether invasive bronchoscopic sampling (Table 36. 2) of respiratory secretions is necessary. Whether invasive sampling is employed or tracheal aspirates are used, empirical broad-spectrum antibiotics should be started while results are awaited. The results of microbiological analysis of respiratory secretions are used to either stop antibiotics or narrow the spectrum. 1 Although the use of an invasive strategy is associated with a higher likelihood of modification of initial antimicrobials, 23 the effect on important clinical outcome such as mortality, antibiotic-free days, and organ dysfunction is variable. 1 Although tracheal aspirates may predominantly reflect the organisms colonising the upper airway, they may be useful in indicating which organisms are not responsible for the pneumonia, thus allowing the antimicrobial cover to be narrowed. 1 The use of dual therapy is not well supported by evidence but it does reduce the probability that the pathogen is resistant to the drugs being given. If an extended spectrum β-lactamase-producing strain or an Acinetobacter sp. is suspected a carbapenem should be given. If Legionella pneumophilia is suspected use a quinolone. Risk factors for MRSA infection in areas with a high incidence of MRSA include diabetes mellitus, head trauma, coma and renal failure.

or with enlarged cervical nodes or other manifestations of extrapulmonary disease. Clinical disease is seldom found in asymptomatic individuals, even those with strongly positive tuberculin test (Heaf grade III or IV). The outlook for patients with tuberculosis who require ICU admission is poor. In one retrospective study the in-hospital mortality for all patients with tuberculosis requiring ICU admission was 67% but in those with acute respiratory failure it rose to 81%. 31 The presentation and management of TB in HIV-positive patients are different (see below).

IDENTIFICATION OF MYCOBACTERIA Multiple 32,33 sputum samples should be collected, preferably on different days, for microscopy for acid-fast bacilli and culture. If sputum is not available bronchial washings taken at bronchoscopy and gastric lavage or aspirate samples should be obtained. Gastric aspirates need to be neutralised immediately on collection. Bronchoscopy and transbronchial biopsy may be useful in patients with suspected TB but negative sputum smear. Pleural biopsy is often helpful and mediastinoscopy is occasionally needed in patients with mediastinal lymphadenopathy. Part of any biopsy specimen should always be sent for culture. Nucleic acid amplification tests on sputum have sensitivity similar to culture in 1.5% on the 60th day of ICU in a recent study using a multicentre high-quality database and incorporating novel statistical methodology to control evolution of severity of illness. 25 

Several guidelines for prevention of ventilatorassociated pneumonia and hospital-acquired pneumonia have been published. [26] [27] [28] [29] [30] Interventions can be divided into general infection control measures and specific measures. General measures include alcoholbased hand disinfection, hospital education programme on infection control, the use of microbiological surveillance and a programme to reduce antibiotic prescription. The major specific recommendations are summarised in Table 36 .4. There is no evidence that 'bundles' of recommendations are more effective than the sum of the individual components.

The main risk factors are listed in Box 36.2. Typical clinical features include fever, sweating, weight loss, lassitude, anorexia, cough productive of mucoid or purulent sputum, haemoptysis, chest wall pain, dyspnoea, localised wheeze and apical crackles. Patients may also present with unresolved pneumonia, pleural effusions, spontaneous pneumothorax and hoarseness 28, 29 No effect on VAP, mainly for staff safety 5. Chlorhexidine oral decontamination 27, 29, 30 6. Sedation vacation and weaning protocol 27,28 7. Judicious use of stress ulcer prophylaxis 27 Mortality reduction demonstrated when topical antimicrobials combined with short-course systemic antibiotics, BSAC recommended SDD in patients expected to require mechanical ventilation for >48 hours, ETF discourage routine use due to concern of emergence of resistant organisms Not yet reviewed by guidelines 50 1. High-volume low-pressure ultrathin membrane endotracheal tube cuff with SSD 2. Ultrathin membrane cuff with tapered shape and SSD 3. Low-volume low-pressure endotracheal tube cuff with SSD 4. Balloon device for biofilm removal 5. Saline instillation before tracheal suctioning HME = heat moist exchanger; SSD = subglottic secretion drainage.

smear-negative patients with pulmonary tuberculosis but have the advantage of a much more rapid result. There is, however, a significant false-negative rate. 32

A normal CXR almost excludes TB (except in HIV-infected patients) but endobronchial lesions may not be apparent and early apical lesions can be missed. Common appearances include patchy/nodular shadowing in the upper zones (often bilateral), cavitation, calcification, hilar or mediastinal lymphadenopathy (may cause segmental or lobar collapse), pleural effusion, tuberculomas (dense round or oval shadows) and diffuse fine nodular shadowing throughout the lung fields in miliary TB. Inactivity of disease cannot be inferred from the CXR alone. This requires three negative sputum samples and failure of any lesion seen on CXR to progress. CXR appearances in HIV-positive fit-tested negative-pressure respirator (N95, FFP2 or higher). Use of a powered air-purifying respirator should be considered when bronchoscopy is being performed. 35 Detailed infection control advice can be obtained via the 'link page' (http://www.aic.cuhk. edu.hk/web8/Pneumonia%20guidelines.htm.).

The lungs are amongst the most frequent target organs for infectious complications in the immunocompromised. The incidence of pneumonia is highest amongst patients with haematological malignancies, bone marrow transplant (BMT) recipients and patients with AIDS.

The speed of progression of pneumonia, the CXR changes ( Table 36 .5) and the type of immune defect provide clues to the aetiology. Bacterial pneumonias progress rapidly (1-2 days) whereas fungal and protozoal pneumonias are less fulminant (several days to a week or more). Viral pneumonias are usually not fulminant, but on occasions may develop quite rapidly. Bronchoscopy is a major component of the investigation of these patients. Empirical management based on CXR appearances is outlined in Table 36 .5. Early noninvasive ventilation may improve outcome amongst immunocompromised patients with fever and bilateral infiltrates. 36 PNEUMOCYSTIS JIROVECI PNEUMONIA (PCP) 37 The incidence of this common opportunistic infection has fallen substantially in patients with AIDS who are receiving prophylaxis and effective antiretroviral therapy, with most cases occurring in patients who are not receiving HIV care or among patients with advanced immunosuppression. The onset is usually insidious with dry cough, dyspnoea and fever on a background of fatigue and weight loss. Crackles in the chest are rare. Approximately 15% of patients have a concurrent cause for respiratory failure (e.g. Kaposi sarcoma, TB, bacterial pneumonia). Useful investigations are:

1. CXR: classical appearance is diffuse bilateral perihilar interstitial shadowing, but in the early stages this is very subtle and easily missed. The initial CXR is normal in 10%. In a further 10% the changes are atypical with focal consolidation or coarse patchy shadowing. None of the changes are specific for PCP and may be seen in other lung diseases associated with AIDS. Pleural effusions, hilar or mediastinal lymphadenopathy are unusual in PCP but common in mycobacterial infection or Kaposi's sarcoma or lymphoma.

Induced sputum: in this technique the patient inhales nebulised hypertonic saline from an ultrasonic nebuliser. This provokes bronchorrhoea and the patient patients with TB differ from those in non-HIV-infected patients.

The decision to initiate anti-TB treatment should be based on level of clinical suspicion, results of AFB smear and sometimes mycobacterial culture. If the initial clinical suspicion is strong and the patient is seriously ill attributable to possible TB, treatment should be initiated promptly, sometimes before the result of AFB smear. Subsequent positivity of AFB smear or nucleic acid amplification test provides support to the continuation of treatment. Combination chemotherapy consisting of four drugs is necessary for maximal efficacy. Treatment is divided into initial phase and continuation phase. The most commonly used initial regimen consists of 8 weeks of rifampicin 600 mg daily (450 mg for patients <50 kg), isoniazid 300 mg daily, pyrazinamide 2 g daily (1.5 g for patients <50 kg) and ethambutol 15 mg/kg daily as initial phase treatment.

Ethambutol should be used only in patients who have reasonable visual acuity and who are able to appreciate and report visual disturbances. This mandates careful consideration in patients who require heavy sedation. Visual acuity and colour perception must be assessed (if ethambutol is to be used) and liver and renal function checked before treatment is started. Steroids are recommended for children with endobronchial disease and, possibly, for patients with tuberculous pleural effusions. Pyridoxine 10 mg daily should be given to prevent isoniazid-induced neuropathy to those at increased risk (e.g. patients with diabetes mellitus, chronic renal failure or malnutrition or alcoholic or HIV-positive patients). Negative AFB smear should not delay initial treatment if clinical suspicion remains high. Supporting features included chronic cough, weight loss, characteristic chest X-ray findings, emigration from a high-incidence country, no other immediate diagnosis, and positive tuberculin test.

Patients admitted to an ICU with infectious TB or suspected of having active pulmonary TB should be managed in an isolation room with special ventilation characteristics, including negative pressure. Patients should be considered infectious if they are coughing or undergoing cough-inducing procedures or if they have positive AFB smears and they are not on or have just started chemotherapy, or have a poor clinical or bacteriological response to chemotherapy. 32, 35 Patients with non-drug-resistant TB should be non-infectious after 2 weeks of treatment which includes rifampicin and isoniazid. 32 As TB spreads through aerosols it is probably appropriate to isolate patients who are intubated even if only their bronchial washings are smear-positive. Staff caring for patients who are smear-positive should wear personal protective equipment including a and/or diuretics (patients often fluid-overloaded). Approximately 40% of patients with HIV-related PCP who require mechanical ventilation survive to hospital discharge. 38 Initiation of antiretroviral therapy in patients presenting with HIV-related PCP is controversial. The Centers for Disease Control and Prevention (CDC) recommend against doing so in the acute phase, but recent data suggest that the outcome may be improved by initiation within the first 4 days of ICU admission. 39 

This is the most common cause of acute respiratory failure in HIV-positive patients. Bacterial pneumonia is more common in HIV-infected patients than in the general population and tends to be more severe. Strep. pneumoniae, H. influenza, Pseudomonas aeruginosa and S. aureus are the commonest organisms. Nocardia and Gram negatives should also be considered. Atypical pathogens (e.g. Legionella) are rare. Response to appropriate antibiotics is usually good but may require protracted courses of antibiotics because of high tendency to relapse. Patients with severe immunodeficiency (CD4 + T lymphocyte count <100/µL) and a history of Pseudomonas infection or bronchiectasis or neutropenia should receive antibiotics that cover P. aeruginosa as well as other Gram negatives. The possibility of concurrent PCP or tuberculosis should be excluded.

TB may be the initial presentation of AIDS, particularly in sub-Saharan Africa. The pattern of TB in HIV patients coughs up material containing cysts and trophozoites. The technique is time-consuming and requires meticulous technique and is less sensitive than bronchoscopy but less invasive. The possibility of concurrent tuberculosis should be considered and steps taken to minimise the risk of spread of infection.

the diagnosis in over 90% of cases. Specimens should be sent for cytology. Transbronchial biopsy is not necessary in most cases. PCR using bronchial lavage specimens may be useful in non-HIV patients with suspected PCP.

Antipneumocystis treatment should be started as soon as the diagnosis is suspected. Treatment of choice is trimethoprim plus sulfamethoxazole (co-trimoxazole) 20 mg/kg/day + 100 mg/kg/day for 3 weeks plus prednisolone 40 mg orally twice daily for 5 days followed by 20 mg twice daily for 5 days and then 20 mg per day until the end of PCP treatment. Side-effects of co-trimoxazole are common in HIV patients (nausea, vomiting, skin rash, myelotoxicity). The dose should be reduced by 25% if the WBC count falls. Patients who are intolerant of co-trimoxazole should be treated with:

• pentamidine 4 mg/kg/day i.v. or • primaquine with clindamycin or • trimetrexate with leucovorin (±oral dapsone).

Response to treatment is usually excellent, with a response time of 4-7 days. If the patient deteriorates or fails to improve: consider (re-)bronchoscopy (is the diagnosis correct?), treat co-pathogens and consider a short course of high-dose i.v. methylprednisolone 

Fungi are rare but important causes of pneumonia. They can be divided into two main groups based on the immune response required to combat infection with these organisms. Histoplasma, blastomycosis, coccidioidomycosis, paracoccidioidomycosis and Cryptococcus require specific cell-mediated immunity for their control and thus, in contrast to infections that are controlled by phagocytic activity, the diseases caused by these organisms can occur in otherwise healthy individuals although they cause much more severe illness in patients with impaired cell-mediated immunity (e.g. patients infected with HIV and organ transplant recipients). With the exception of Cryptococcus these organisms are rarely seen outside North America. Aspergillus and Mucor spores are killed by non-immune phagocytes and as a result these fungi rarely result in clinical illness in patients with normal neutrophil numbers and function.

This is effectively a combination of the two types of fungal infection in which impaired cell-mediated immunity predisposes to mucosal overgrowth with Candida but impaired phagocytic function or numbers is usually required before deep invasion of tissues occurs. Primary Candida pneumonia (i.e. isolated lung infection) is uncommon 41, 45 and more commonly pulmonary lesions are only one manifestation of disseminated candidiasis. Even more common is benign colonisation of the airway with Candida. In most reported cases of primary Candida pneumonia amphotericin B has been used. In disseminated candidiasis treatment should be directed to treatment of disseminated disease rather than Candida pneumonia per se. 45 

This is a highly lethal condition in the immunocompromised despite treatment and therefore investigation and treatment should be prompt and aggressive. It is associated with exposure to construction work. Definitive diagnosis requires both histological evidence of acute-angle branching, septated non-pigmented hyphae measuring 2-4 µm in width, and cultures yielding Aspergillus species from biopsy specimens of involved organs. Recovery of Aspergillus species from respiratory secretions in immunocompromised, but not immunocompetent, patients may indicate invasive disease with a positive predictive value as high as depends on the degree of immunosuppression. In patients with CD4 + T lymphocytes >350 cells/µL the clinical presentation is similar to TB in non-HIV-infected patients, although extrapulmonary disease is more common. In patients with CD4 + T lymphocytes <350 cells/µL extrapulmonary disease (pleuritis, pericarditis, meningitis) is common. Severely immunocompromised patients (CD4 + T lymphocytes <100 cells/µL) may present with severe systemic disease with high fever, rapid progression and systemic sepsis. In these patients lower and middle lobe disease is more common, miliary disease is common and cavitation is less common. Sputum smears and culture may be positive even with a normal CXR. Response to treatment is usually rapid. Management of TB in HIV is complex owing to numerous drug interactions; consultation with an expert in treatment of HIV-related TB should be strongly considered. Complex interactions occur between rifamycins (e.g. rifampicin and rifabutin) and protease inhibitors and nonnucleoside reverse transcriptase inhibitors used to treat patients infected with HIV. The choice of rifampicin or rifabutin depends on a number of factors including the unique and synergistic adverse effects for each individual combination of rifampicin and anti-HIV drugs, and consultation with a physician with experience in treating both TB and HIV is advised. 40 IDSArecommended dosage adjustment for patients receiving antiretrovirals and rifabutin 37 can be obtained via the 'link page' (http://www.aic.cuhk.edu.hk/web8/ Pneumonia%20guidelines.htm.). The optimal time for initiating antiretroviral therapy in patients with TB is controversial. Early therapy may decrease HIV disease progression but may be associated with a high incidence of adverse effects and an immune reconstitution reaction. 37 CMV PNEUMONITIS 41, 42 Risk of infection is highest following allogeneic stem cell transplantation, followed by lung transplantation, pancreas transplantation and then liver, heart and renal transplantation and advanced AIDS. If both the recipient and the donor are seronegative then the risk of both infection and disease are negligible. If the recipient is seropositive the risk of infection is approximately 70% but the risk of disease is only 20%, regardless of the serostatus of the donor. However if the recipient is seronegative and the donor is seropositive the risk of disease is 70%. If steroid pulses and antilymphocyte globulin are given for treatment of acute rejection the risk of developing disease is markedly increased. Infection may be the result of primary infection or reactivation of latent infection. It is clinically important, but often difficult to distinguish between CMV infection and CMV disease and a definitive diagnosis can be made only histologically. Detection of CMV-pp65 antigen in peripheral WBC and detection of CMV DNA or RNA in the blood by quantitative polymerase chain needle aspiration or, if there is debris within the fluid, drainage using an intercostal drain. The diagnosis is confirmed by aspiration of pus.

The mainstay of treatment is drainage either by intercostal drain or by surgical intervention. Patients who present before the pus is loculated and a fibrinous peel has formed on the lung can usually be treated by simple drainage. The combination with intrapleural fibrinolysis may be beneficial. Optimal surgical management, which consists of decortication (open or thoracoscopic), is indicated if the empyema is more advanced or if simple drainage fails. This is a major procedure and many patients with cardiac or chronic respiratory disease will not tolerate it. Alternatives for these patients are instillation of thrombolytics into the pleural space or thoracostomy. Antibiotics have only an adjunctive role. Broad-spectrum antibiotic regimens with anaerobic cover should be used until the results of microbiological analysis of the aspirated pus are available.

All tables and figures are reproduced from ICU web (www.aic.cuhk.edu.hk/web8) with permission of the authors. 80-90% in patients with leukaemia or bone marrow transplant recipients. Bronchoalveolar lavage with smear, culture and antigen detection has excellent specificity and reasonably good positive predictive value for invasive aspergillosis in immunocompromised patients. Although radiological features may give a clue to the diagnosis they are not sufficiently specific to be diagnostic.

In acutely ill immunocompromised patients intravenous therapy should be initiated if there is suggestive evidence of invasive aspergillosis while further investigations to confirm or refute the diagnosis are carried out. First-line therapy is voriconazole. 47 Echinocandins and amphotericin are alternatives.

This may be an uncomplicated effusion that resolves with appropriate treatment of the underlying pneumonia or a complicated effusion that develops into an empyema unless drained. Complicated effusions tend to develop 7-14 days after initial fluid formation. They are characterised by increasing pleural fluid volume, continued fever and pleural fluid of low pH (<7.3) that contains a large number of neutrophils and may reveal organisms on Gram staining or culture. An outline of management is given in Figure 36 .5.

Collection of pus in the pleural space.

Follows infection of the structures surrounding the pleural space, including subdiaphragmatic structures, and chest trauma, or may be associated with malignancy. Anaerobic bacteria, usually streptococci or Gram-negative rods, are responsible for 76% of cases.

The diagnosis is usually simple. The patient is usually septic and may have a productive cough and chest pain. The chest X-ray may show features suggestive of a pleural effusion and underlying consolidation but may also show an abscess cavity with a fluid level, in which case CT scanning will be required to distinguish between an abscess and an empyema. Ultrasound can be useful to confirm the presence of fluid in the pleural space and to determine whether it can be drained by 

Guidelines for the management of adults with hospital-acquired, ventilatorassociated, and healthcare associated pneumonia

Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults

Pneumonia Guidelines Committee of the BTS Standards of Care Committee. British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update

Management of communityacquired pneumonia in adults

CDC, and Infectious Diseases Society of America. Treatment of tuberculosis

The standardization of bronchoscopic techniques for ventilator-associated pneumonia

New issues and controversies in the prevention of ventilator-associated pneumonia

Guidelines for the management of adults with hospital-acquired, ventilatorassociated, and healthcare associated pneumonia

Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults

Pneumonia Guidelines Committee of the BTS Standards of Care Committee. British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update

Guidelines for the management of adult lower respiratory tract infections

Update in community-acquired and nosocomial pneumonia 2009

Value of intensive diagnostic microbiological investigation in low-and high-risk patients with community-acquired pneumonia

Nucleic acid amplification tests for the diagnosis of pneumonia

Interpreting assays for the detection of Streptococcus pneumonia

Severity of pneumococcal pneumonia associated with genomic bacterial load

Polymerase chain reaction for diagnosing pneumocystis pneumonia in non-HIV immunocompromised patients with pulmonary infiltrates

Early mortality in patients with community-acquired pneumonia: causes and risk factors

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock

Antibiotics for bacteremic pneumonia: improved outcomes with macrolides but not fluoroquinolones

High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm

An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients

Management of communityacquired pneumonia in adults

Avian influenza (H5N1): implications for intensive care

Clinical characteristics and 30-day outcomes for influenza A 2009 (H1N1)

Complications and outcomes of pandemic 2009 influenza A (H1N1) virus infection in hospitalized adults: how do they differ from those in seasonal influenza?

Corticosteroid treatment in critically ill patients with pandemic influenza A/H1N1 2009 infection analytic strategy using propensity scores

Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) -United States

Clinical and economic consequences of ventilator-associated pneumonia: A systematic review

Invasive approaches to the diagnosis of ventilator-associated pneumonia: A meta-analysis

Ventilator-associated pneumonia and mortality: A systematic review of observational studies

Attributable mortality of ventilator-associated pneumonia. A reappraisal using causal analysis

Guidelines for preventing health-careassociated pneumonia 2003. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee

SHEA/IDSA practice recommendation. strategies to prevent ventilator-associated pneumonia in acute care hospitals

Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy

VAP Guidelines Committee and the Canadian Critical Care Trials Group. Comprehensive evidencebased clinical practice guidelines for ventilatorassociated pneumonia: prevention

Defining, treating and preventing hospital acquired pneumonia: European perspective

Active tuberculosis in the medical intensive care unit: a 15-year retrospective analysis

National Collaborating Centre for Chronic Conditions. Tuberculosis. Clinical diagnosis and management of tuberculosis and measures for its prevention and control

Management of tuberculosis in the United States

CDC, and Infectious Diseases Society of America. Treatment of tuberculosis

Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings

Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure

Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America

Improvements in outcomes of acute respiratory failure for patients with human immunodeficiency virusrelated Pneumocystis carinii pneumonia

Centers for Disease Control. Updated guidelines for the use of rifabutin or rifampicin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors

The lung in the immunocompromised patient

Management of cytomegalovirus infection and disease after solid-organ transplantation

Area under the viraemia curve versus absolute viral load: utility for predicting symptomatic cytomegalovirus infections in kidney transplant patients

Cytomegalovirus infection in organ-transplant recipients: diagnostic value of pp65 antigen test, qualitative polymerase chain reaction (PCR) and quantitative Taqman PCR

Guidelines for treatment of candidiasis

Practice guidelines for diseases caused by Aspergillus

Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis

The pleural cavity

The standardization of bronchoscopic techniques for ventilator-associated pneumonia

New issues and controversies in the prevention of ventilator-associated pneumonia