Pneumonia

7172019 Pneumonia

httpslidepdfcomreaderfullpneumonia-568f5d4002e1c 117

36

PneumoniaKai Man Chan and Charles D Gomersall

The management of pneumonia is based on four nd-ings and premises

bull Pneumonia is associated with a wide range of largelynon-specic clinical features1

bull Pneumonia can be caused by over 100 organisms

bull The relationship between specic clinical featuresand aetiological organism is insufciently strong

to allow a clinical diagnosis of the causativeorganism2

bull Early administration of appropriate antibiotics isimportant2

The net result is that the differential diagnosis is wideand treatment should be started before the aetiologicalagent is known The differential diagnosis and thelikely causative organisms can be narrowed by usingepidemiological clues the most important of which arewhether the pneumonia is community-acquired orhealthcare-associated and whether the patient is immu-nocompromised Note that the ora and antibioticresistance patterns vary from country to country hos-pital to hospital and even ICU to ICU within a hospitaland this must be taken into account

COMMUNITY-ACQUIRED PNEUMONIA

Evidence-based guidelines have been issued by theBritish Thoracic Society3 the Infectious Diseases Societyof America (IDSA) and American Thoracic Society(ATS)2 and the European Respiratory Society4 Linksto these and other pneumonia-related guidelines canbe found at the following lsquolink pagersquo httpwww aiccuhkeduhkweb8Pneumonia20guidelineshtm

DEFINITION

An acute infection of the pulmonary parenchyma thatis associated with at least some symptoms of acuteinfection accompanied by an acute inltrate on a chestradiograph (CXR) or auscultatory ndings consistentwith pneumonia (eg altered breath sounds localisedcrackles) in a patient not hospitalised or residing in along-term care facility for ge14 days prior to the onset ofsymptoms

The overall incidence is 3ndash40 per 1000 inhabitantsper year with 40ndash60 requiring hospital admission

Overall 10 of patients are admitted to ICU Theoverall mortality of hospitalised patient is approxi-mately 105

AETIOLOGY

Table 361 gives possible aetiological agents based onepidemiological clues Streptococcus pneumoniae is the

most commonly isolated organism The next mostcommon bacterial pathogens in patients admitted toICU are Legionella species Haemophilus infuenzae Enterobacteriaceae species Staphylococcus aureus and Pseudomonas species2

CLINICAL PRESENTATION

Pneumonia produces both systemic and respiratorymanifestations Common clinical ndings include feversweats rigors cough sputum production pleuriticchest pain dyspnoea tachypnoea pleural rub andinspiratory crackles Classic signs of consolidationoccur in less than 25 of cases Multi-organ dysfunc-tion or failure may occur depending on the type andseverity of pneumonia

The diagnosis of pneumonia may be more difcultin the elderly Although the vast majority of elderlypatients with pneumonia have respiratory symptomsand signs over 50 may also have non-respiratorysymptoms and over a third may have no systemic signsof infection

INVESTIGATIONS24

Investigations should not delay administration of anti-biotics as delays are associated with an increase in mor-

tality2 Important investigations include

1 Chest X-ray (CXR)2 Arterial blood gases or oximetry3 Full blood count4 Serum creatinine urea and electrolytes5 Liver function tests6 Blood cultures (times2) prior to the administration of

antimicrobials7 Sputum (if immediately available) for urgent Gram

stain and culture The usefulness of sputum testsremains debatable because of contamination byupper respiratory tract commensals However a

7172019 Pneumonia


7172019 Pneumonia


416 Pneumonia

9 Urinary Legionella antigen This test is specic(gt95) In patients with severe Legionnaires diseasesensitivity is 88ndash100 for L pneumophilia serogroup1 (the most commonly reported cause of Legionella infection) Thus a positive result is virtually

single or predominant organism on a Gram stain ofa fresh sample or a heavy growth on culture ofpurulent sputum is likely to be the organismresponsible The nding of many polymorphonu-clear cells (PMN) with no bacteria in a patient whohas not already received antibiotics can reliablyexclude infection by most ordinary bacterial patho-gens Specimens should be obtained by deep coughand be grossly purulent Ideally the specimenshould be obtained before treatment with antimi-crobials if this does not delay administration ofantibiotics and be transported to the laboratoryimmediately for prompt processing to minimise thechance of missing fastidious organisms (eg Strep pneumoniae) Acceptable specimens (in patientswith normal or raised white blood cell counts)should contain gt25 PMN per low-power eld (LPF)and lt10ndash25 squamous epithelial cells (SEC)LPF orgt10 PMN per SEC These criteria should not beused for Mycobacteria and Legionella infectionCertain organisms are virtually always pathogenswhen recovered from respiratory secretions (Box 361) Patients with risk factors for tuberculosis (TB)(Box 362) and particularly those with cough for

more than a month other common symptoms of TBand suggestive radiographic changes should havesputum examined for acid-fast bacilli Sputumcannot be processed for culture for anaerobesowing to contamination by the endogenous anaero-bic ora of the upper respiratory tract In additionto the factors listed in Table 361 foul-smellingsputum lung abscess and empyema should raisesuspicion of anaerobic infection

8 Aspiration of pleural uid for Gram stain culturepH and leucocyte count ndash all patients with a pleuraleffusion gt1 cm thick on a lateral decubitus chestX-ray

Table 361 Possible aetiological agents based on epidemiological cluesmdashcontrsquod

EXPOSURE ORGANISM

Lung abscess Community-acquired meticillin-resistant S aureus oralanaerobes endemic fungi M tuberculosis atypicalmycobacteria

Endobronchial obstruction Anaerobes Strep pneumoniae H influenzae S aureus

Intravenous drug addict S aureus CA-MRSA anaerobes M tuberculosis Streppneumoniae

End-stage renal failure CA-MRSA

OTHERS

Epidemic M pneumoniae influenza virus

Air-conditioning cooling towers hot tubs or hotel or cruise shipstay in previous 2 weeks

Legionella pneumophilia

Presentation of a cluster of cases over a very short periodof time

Bioterrorist agents B anthracis F tularensis Y pestis

Box 361 Organisms that are virtually alwayspathogens when recovered fromrespiratory secretions

LegionellaChlamydiaTBInfluenza para-influenza virus RSV adenovirus hantavirus

SARS coronavirusStronglyloides stercoralisToxoplasma gondi Histoplasma capsulatum

Coccidiodes immitisBlastomycoses dermatitidisCryptococcus neoformans

Box 362 Risk factors for pulmonary tuberculosis

Living in or originating from a developing countryAge (lt5 years middle-aged and elderly men)Alcoholism andor drug addictionHIV infectionDiabetes mellitusLodging-house dwellers

ImmunosuppressionClose contact with smear-positive patientsSilicosisPoverty andor malnutritionPrevious gastrectomySmoking

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Community-acquired pneumonia 417

contamination and colonisation PCR assays are moresensitive than culture for Mycoplasma and Chlamydia species and at least as sensitive for Legionella7 PCRassays also detect Legionella strains other than sero-group 1 The BTS guidelines3 recommend PCR of lowerrespiratory tract sample or if unavailable throat swabfor the diagnosis of Mycoplasma pneumonia PCR for

Chlamydophilia should be performed when invasiverespiratory samples were collected from patients withsevere community-acquired pneumonia The role ofPCR in diagnosing PCP is mainly limited to non-HIVpatients in whom conventional microscopy and stain-ing of induced sputum and BAL have a lower sensitiv-ity than in HIV patients9

MANAGEMENT

GENERAL SUPPORTIVE MEASURES Intravenous uids may be required to correct dehydra-

tion and provide maintenance uid A general approachshould be made to organ support with an emphasis oncorrecting hypoxia

ANTIMICROBIAL REGIMENS Increased mortality among those who do not receiveempirical antibiotics that cover the infecting pathogen(s)is well documented11 Each unit should have its ownregimens tailored to the local ora and antibiotic resist-ance patterns In the absence of such regimens theregimen outlined in Figure 361 may be helpful This

diagnostic of Legionella infection but a negativeresult does not exclude it In areas (eg South Aus-tralia) where other Legionella species are morecommon this test is less helpful

10 Urinary pneumococcal antigen has moderate sensi-tivity (50ndash80) and high specicity (gt90)

11 Microimmunouorescence serology for Chlamydia

pneumoniae IgM A titre ge1 16 is signicant12 HIV serological status

Other investigations should be considered in patientswith risk factors for infection with unusual organismsBronchoalveolar lavage may be useful in immunocom-promised patients those who fail to respond to antibi-otics or those in whom sputum samples cannot beobtained6

Molecular diagnosis (eg PCR-based methods) hasthe advantages of quick results (within 3 hours)enhanced sensitivity independence from organismviability and hence previous antibiotics and theoretical

possibility for determination of antimicrobial suscepti-bility7 Of note it is important to test for genes specicfor the organism in question10 and the sampling siteremains important PCR is most useful when performedon specimens from a normally sterile site For examplePCR for Pneumococcus is positive in 62 of bloodsamples from adult patients with conrmed or proba-ble pneumococcal pneumonia8 whereas blood culturesare positive in only 37 For respiratory specimensunder most circumstances interpretation remainsproblematic due to low specicity related to oral

Figure 361 Antibiotic regimens for treatment of severe community-acquired pneumonia in critically ill patients24 Respiratory fluoroquinolones include moxifloxacin and levofloxacin Advanced macrolides include azithromycin andclarithromycin Non-antipseudomonal third-generation cephalosporins include cefotaxime and ceftriaxone

Severe CAP

Aztreonam

and

levofloxacin

Piperacillin-tazobactam or

meropenem or imipenem or

cefepime and ciprofloxacin or

aminoglycoside plus

advanced macrolide

Respiratory

fluoroquinolone

plusmn clindamycin

Non anti-pseudomonal

third-generation cephalosporin

or ampicillin-sulbactam

and respiratory fluoroquinolone

or advanced macrolide

Risk of Pseudomonas

(COPDbronchiectasis

recent hospitalisation

recent antimicrobial

therapy or gross aspiration)

β-lactam

allergy

β-lactam

allergy

NoYes

NoYesNoYes

7172019 Pneumonia


418 Pneumonia

should be modied in the light of risk factors (see Table 361) Quinolones may be less appropriate in areas witha high prevalence of TB as their use may mask concur-rent TB infection Appropriate antimicrobial therapyshould be administered within 1 hour of diagnosis412 There is controversy regarding the appropriate changeto empirical therapy based on microbiological nd-

ings24

Changing to narrower-spectrum antimicrobialcover may result in inadequate treatment of the 5ndash38of patients with polymicrobial infection Increasing evi-dence demonstrates improved outcome with combina-tion antimicrobial as compared with monotherapyparticularly in severely ill patients with bacteraemicpneumococcal pneumonia5 Odds ratio of death was15 to 6 for monotherapy as compared with com-bination therapy Benets were seen only in combina-tion therapy with macrolide as part of the regimen butnot in combination with uroquinolone regimen13 For the treatment of drug-resistant Strep pneumoniae (DRSP) the regimens in Figure 361 are probably suit-

able for isolates with a penicillin MIC lt 4 mgL2 Ifthe MIC is ge4 mgL an antipneumococcal uoroqui-nolone vancomycin teicoplanin or linezolid should begiven4

DURATION OF THERAPY No clinical trial has specically addressed this issueCourses as short as 5 days may be sufcient14 IDSAATS guidelines recommend stopping after a minimumof 5 days if the patient is afebrile for 48ndash72 hoursand organ dysfunction has largely resolved2 Shortcourses may be suboptimal for patients with bacterae-mic S aureus pneumonia meningitis or endocarditiscomplicating pneumonia or infection with less commonorganisms (eg Burkholderia pseudomallei or fungi) orPseudomonas aeruginosa Procalcitonin may be useful toguide antibiotic therapy but not all studies have dem-onstrated a benet15

RESPONSE TO THERAPY 2

This can be assessed subjectively (a response is usuallyseen within 1ndash3 days of starting therapy) or objectivelyon the basis of respiratory symptoms fever oxygena-tion WBC count bacteriology CXR changes C-reactiveprotein reduction and procalcitonin reduction of

80ndash90 from peak value The average time to deferves-cence varies with organism severity and patient age(7 days in elderly patients 25 days in young patientswith pneumococcal pneumonia 6ndash7 days in bacterae-mic patients with pneumococcal pneumonia 1ndash2 daysin patients with M pneumoniae pneumonia and 5 daysin patients with Legionella pneumonia) Both blood andsputum cultures are usually negative within 24ndash48hours of treatment although P aeruginosa and M pneu-moniae may persist in the sputum despite effectivetherapy CXR changes lag behind clinical changes withthe speed of change depending on the organism theage of the patient and the presence or absence of comor-

bid illnesses The CXR of most young or middle-aged

patients with bacteraemic pneumococcal pneumonia isclear by 4 weeks but resolution is slower in elderlypatients and patients with underlying illness extensivepneumonia on presentation or Legionella pneumophilia pneumonia

If the patient fails to respond consider the followingquestions

bull Has the patient got pneumonia

bull Are there host factors that explain the failure (egobstruction of bronchus by a foreign body or tumourinadequate host response)

bull Has a complication developed (eg empyema super-infection bronchiolitis obliterans organising pneu-monia metastatic abscess)

bull Is the right drug being given in an adequate dose bythe right route

bull Is the organism resistant to the drug being given

bull Are there other organisms

bull Is the fever a drug fever

Useful investigations include computerised tomogra-phy (CT) of the chest thoracocentesis bronchoalveolarlavage (Table 362) and transbronchial or open-lungbiopsy

PREDICTION OF ADVERSE OUTCOME ANDADMISSION TO ICU Scoring systems have been developed to predictadverse outcome and ICU admission including pneu-monia severity index (PSI) CURB-65 CRB-65 modiedATS major and minor criteria SCAP prediction ruleSMART-COP REA-ICU index and CAP-PIRO16

Although they may help identify the sicker patientsthey should not be used as a sole determinant of ICUadmission as local admission criteria will be affectedby local facilities both in and outside ICU It shouldbe noted that none of the criteria has been prospec-tively demonstrated to avoid late transfers or lowermortality

INFLUENZA PNEUMONIA

Inuenza pneumonia may present with severe respira-tory failure and multi-organ failure However the

pattern of organ failure appears to vary between strainswith H5N1 being associated with a much higher mor-tality and a higher incidence of multi-organ failure thanpandemic H1N117 which itself presented differently toseasonal inuenza In particular trophism for lowerrespiratory tract a higher rate of ICU admission18 anda higher rate of extrapulmonary complications19 wereobserved

Early initiation of oseltamivir is recommended forcritically ill patients although there is no direct evidenceof outcome benet Glucocorticoids do not appear tobe useful and may prolong viral replication20 Bacterialsuperinfection should be considered with Gram-

positive cocci being most frequently isolated21

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Healthcare-associated pneumonia 419

failure and cancer) can cause inltrates on a chest X-rayIdentication of the organism responsible is even moredifcult than in patients with community-acquiredpneumonia owing to the high incidence of oropharyn-

geal colonisation by Gram-negative bacteria Blood cul-tures are positive in only about 6 of cases of nosocomialpneumonia Ventilator-associated pneumonia (VAP) isnosocomial pneumonia arising gt48ndash72 hours after intu-bation Reported incidence of VAP is between 10 and20 for those receiving mechanical ventilation for morethan 48 hours22 It is associated with a higher incidenceof multi-drug-resistant organisms1

PATHOGENESIS

Nosocomial pneumonia is thought to result from micro-aspiration of bacteria colonising the upper respiratory

tract Other routes of infection include macroaspiration

Although there are data demonstrating that surgicalmasks are as effective as N95 (FFP 2) masks in prevent-ing transmission of seasonal inuenza in non-ICU set-tings it is important to note that the capacity for airborne

transmission (and hence the need for N95 masks) isdependent on the exact characteristics of the organismand the frequency of aerosol-generating procedures sothese data should not be extrapolated to other inuenzaviruses and ICU settings

HEALTHCARE-ASSOCIATED PNEUMONIA

Nosocomial pneumonia occurs in 05ndash5 of hospitalpatients with a higher incidence in certain groups(eg postoperative patients and patients in ICU) Diag-nosis may be difcult the clinical features of pneumo-nia are non-specic and many non-infectious conditions

(eg atelectasis pulmonary embolus aspiration heart

Table 362 Procedure for obtaining microbiological samples using bronchoscopy and protected specimen brushingandor bronchoalveolar lavage3549

Infection control In patients suspected of having a disease that is transmitted by the airborne route (egtuberculosis)

bull the risk of transmission should be carefully weighed against the benefits ofbronchoscopy which may generate large numbers of airborne particles

bull perform bronchoscopy in a negative-pressure isolation room

bull consider the use of a muscle relaxant in ventilated patients to prevent coughingbull 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 poweredair-purifying respirator should be considered

General recommendations Suction through the endotracheal tube should be performed before bronchoscopyAvoid suction or injection through the working channel of the bronchoscopePerform protected specimen brushing before bronchoalveolar lavage

Ventilated patients Set F iO2 at 10

Set peak pressure alarm at a level that allows adequate ventilationTitrate ventilator settings against exhaled tidal volumeConsider neuromuscular blockade in addition to sedation in patients at high risk of

complications who are undergoing prolonged bronchoscopy

Protected specimen brushing (PSB) Sample the consolidated segment of lung at subsegmental levelIf purulent secretions are not seen advance the brush until it can no longer be seen but

avoid wedging it in a peripheral positionMove brush back and forth and rotate it several times

Bronchoalveolar lavage (BAL) Wedge tip of bronchoscope into a subsegment of the consolidated segment of lungInject 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 forother microbiological analysis

Inject aspirate and collect additional aliquots of 20ndash60 mLThe total volume of saline injected should be 60ndash200 mL

Complications Hypoxaemia (possibly less with smaller BAL volumes)Arrhythmia

Transient worsening in pulmonary infiltratesBleeding (particularly following PSB)Fever (more common after BAL)

Positive results gt5 of cells in cytocentrifuge preparations of BAL fluid contain intracellular bacteria ORge103 colony-forming unitsmL in PSB specimen ORge104 colony-forming unitsmL in BAL fluid

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420 Pneumonia

worse prognosis In 50 of patients with severehospital-acquired pneumonia and positive bloodcultures there is another source of sepsis

MANAGEMENT

Management is based on the nding that early treat-

ment with antimicrobials that cover all likely patho-gens results in a reduction in morbidity and mortality2 The initial selection of antimicrobials is made on thebasis of epidemiological clues (Fig 362 Table 363)Antimicrobials should be administered within 1 hourof diagnosis12 The results of microbiological investiga-tions are used to narrow antimicrobial cover laterTreatment should be reassessed after 2ndash3 days orsooner if the patient deteriorates (Fig 363) An outlineof management based on an invasive approach is givenin Figure 364

DURATION OF THERAPY

Current ATS guidelines recommend 7 daysrsquo treatmentprovided the aetiological agent is not P aeruginosa orother non-lactose fermenter and the patient has a goodclinical response with resolution of clinical features ofinfection1 The outcome of patients who receive appro-priate initial empirical therapy for ventilator-associatedpneumonia for 8 days is similar to those who receivetreatment for 15 days1

of gastric contents inhaled aerosols haematogenousspread spread from pleural space and direct inocula-tion from ICU personnel

CLINICAL DIAGNOSIS

Diagnosis is based on time of onset (gt48 hours afteradmission to a healthcare facility1) CXR changes (newor progressive inltrates) and either clinical featuresand simple laboratory investigations or the results ofquantitative microbiology Using a clinical approachpneumonia is diagnosed by the nding of a new inl-trate or a change in an inltrate on chest radiographand growth of pathogenic organisms from sputum plusone of the following white-blood-cell (WBC) countgreater than 12times l05L core temperature ge383degCsputum Gram stain with scores of more than two on ascale of four of polymorphonuclear leucocytes andbacteria

INVESTIGATIONSThese are broadly similar to those required incommunity-acquired pneumonia

bull Chest X-ray although studies using a histologicaldiagnosis as the gold standard have demonstratedthat pneumonia may be present despite a normalCXR most denitions of nosocomial pneumoniarequire the presence of new persistent inltrates ona CXR

bull Respiratory secretions considerable controversy sur-rounds the issue of whether invasive bronchoscopicsampling (Table 362) of respiratory secretions is nec-

essary Whether invasive sampling is employed ortracheal aspirates are used empirical broad-spectrumantibiotics should be started while results areawaited The results of microbiological analysis ofrespiratory secretions are used to either stop antibi-otics or narrow the spectrum1 Although the use ofan invasive strategy is associated with a higher like-lihood of modication of initial antimicrobials23 theeffect on important clinical outcome such as mortal-ity antibiotic-free days and organ dysfunction isvariable1 Although tracheal aspirates may predomi-nantly reect the organisms colonising the upper

airway they may be useful in indicating whichorganisms are not responsible for the pneumoniathus allowing the antimicrobial cover to be nar-rowed1 This interpretation is based on the premisethat the predominant route of infection is via theupper respiratory tract From this it can be assumedthat if the organism is not present in the upper res-piratory tract the probability of it being present inthe lung parenchyma is low Certain organisms arevirtually always pathogens when recovered fromrespiratory secretions (see Box 361)

bull Blood cultures identify the aetiological agent in8ndash20 of patients Bacteraemia is associated with a

Figure 362 An outline of initial management ofnosocomial pneumonia based on a non-invasive clinicalapproach1

Two ofuarr or darr WCC

purulent sputum

temp gt38degC

New CXR

infiltrates

Consider acute

tracheobronchitis

Obtain lower respiratory

tract specimens and blood for

microbiological investigations

Risk factorsfor multidrug-resistant

pathogens

Early broad-spectrum

antibiotic therapy

to cover multidrug-

resistant pathogens

Early limited-spectrum

antibiotic therapy

Yes

Yes

No

No

7172019 Pneumonia



inltrate in 48 hours new cavitation or a signicantnew pleural effusion should raise concern If the patientfails to respond consider the diagnosis host factors (egimmunosuppressed debilitated) bacterial factors (egvirulent organism) and therapeutic factors (eg wrongdrug inadequate dose) Review the antibiotics andrepeat cultures It may be useful to broaden the antimi-crobial cover while waiting for the results of investiga-tions Consider invasive sampling of respiratorysecretions computerised tomography or ultrasound ofthe chest (to look for an empyema or abscess) anothersource of infection open-lung biopsy to establish diag-nosis and aetiology or administration of steroids

MORTALITY AND MORBIDITY ATTRIBUTABLE TO VAP Substantial morbidity and mortality associated withVAP have previously been reported22 However acausal relationship is difcult to establish It should benoted that patients who developed VAP tend to be

more severely ill and at higher risk of death not onlyon ICU admission but throughout the course of theirillness Most of the relevant studies were observationaland failed to adequately control confounders likedisease severity evolution of disease progression andICU length of stay with mortality In addition signi-cant heterogeneity exists among these studies Althoughthe presence of VAP is associated with a signicantlylonger ICU length of stay (mean of 61 days 95 CI532ndash687) and increased healthcare cost22 more recentstudies reported that mortality attributable to VAPtends to be small if any2425 The attributable mortalityhas been reported to be 1 on the 30th day of ICU and

RESPONSE TO THERAPY Clinical improvement is usually not apparent for 48ndash72hours and therapy should not be changed during thistime The CXR is of limited value for assessing responseinitial deterioration is common and improvement oftenlags behind clinical response However a rapidly dete-riorating CXR pattern with a gt50 increase in size of

Figure 363 Subsequent management of nosocomialpneumonia based on a non-invasive clinical approach1

Pathogens isolated

from respiratory

specimen

Antibiotics

changedstarted in 7 h

prior to sampling

Adjust antibiotics

according to sensitivities

Continue antibiotics if

high clinical suspicion of

nosocomial pneumonia

Bacterial pneumonia

unlikely

Investigate for other cause

of sepsis and CXR changes

Consider unusual causes

of nosocomial pneumonia

(eg Legionella viruses fungi

Pneumocystis carinii )

Yes

Yes

No

No

Table 363 Recommended initial empirical treatment for nosocomial pneumonia1

SITUATION ANTIBIOTICS

No risk factors for multidrug-resistant pathogens Ceftriaxone or Levofloxacin moxifloxacin or ciprofloxacin or Ampicillinsulbactam or Ertapenem

Antimicrobial therapy in previous 90 days or Current hospitalization for ge5 days or High frequency of antibiotic resistance in the specific

hospital unit or Hospitalisation for 2 days or more in previous 90 days or Residence in nursing home or extended care facility or Home infusion therapy (including antibiotics) or Chronic dialysis within 30 days or Home wound care or Family member with multidrug-resistant pathogen o rImmunosuppression or Bronchiectasis

One ofAntipseudomonal cephalosporin (cefepime or ceftazidime) or Antipseudomonal carbapenem (meropenem or imipenemndash

cilastin) or szlig-lactamszlig-lactamase inhibitor (eg piperacillinndashtazobactam or

cefaperazonendashsulbactam)plus one ofAminoglycoside or Antipseudomonal quinolone (levofloxacin or ciprofloxacin)plus one of the following for patients at high risk of meticillin-

resistant Staphylococcus aureus (MRSA) infectionLinezolid or Vancomycin or

TeicoplaninThe use of dual therapy is not well supported by evidence but it does reduce the probability that the pathogen is resistant to the drugsbeing given If an extended spectrum β-lactamase-producing strain or an Acinetobacter sp is suspected a carbapenem should be givenIf Legionella pneumophilia is suspected use a quinolone Risk factors for MRSA infection in areas with a high incidence of MRSA includediabetes mellitus head trauma coma and renal failure

7172019 Pneumonia


422 Pneumonia

or with enlarged cervical nodes or other manifestationsof extrapulmonary disease Clinical disease is seldomfound in asymptomatic individuals even those withstrongly positive tuberculin test (Heaf grade III or IV)The outlook for patients with tuberculosis who requireICU admission is poor In one retrospective study thein-hospital mortality for all patients with tuberculosisrequiring ICU admission was 67 but in those withacute respiratory failure it rose to 8131 The presenta-tion and management of TB in HIV-positive patientsare different (see below)

INVESTIGATION OF PULMONARYTUBERCULOSIS

IDENTIFICATION OF MYCOBACTERIA

Multiple

3233

sputum samples should be collected pref-erably on different days for microscopy for acid-fastbacilli and culture If sputum is not available bronchialwashings taken at bronchoscopy and gastric lavage oraspirate samples should be obtained Gastric aspiratesneed to be neutralised immediately on collection Bron-choscopy and transbronchial biopsy may be useful inpatients with suspected TB but negative sputum smearPleural biopsy is often helpful and mediastinoscopyis occasionally needed in patients with mediastinallymphadenopathy Part of any biopsy specimen shouldalways be sent for culture Nucleic acid amplicationtests on sputum have sensitivity similar to culture in

15 on the 60th day of ICU in a recent study using amulticentre high-quality database and incorporatingnovel statistical methodology to control evolution ofseverity of illness25

PREVENTION

Several guidelines for prevention of ventilator-associated pneumonia and hospital-acquired pneumo-nia have been published26ndash30 Interventions can bedivided into general infection control measures andspecic measures General measures include alcohol-based hand disinfection hospital education programmeon infection control the use of microbiological sur-veillance and a programme to reduce antibiotic pre-scription The major specic recommendations aresummarised in Table 364 There is no evidence that

lsquobundlesrsquo of recommendations are more effective thanthe sum of the individual components

TUBERCULOSIS

The main risk factors are listed in Box 362 Typicalclinical features include fever sweating weight losslassitude anorexia cough productive of mucoid orpurulent sputum haemoptysis chest wall pain dysp-noea localised wheeze and apical crackles Patientsmay also present with unresolved pneumonia pleuraleffusions spontaneous pneumothorax and hoarseness

Figure 364 Management of suspected nosocomial pneumonia based on invasive sampling of respiratory secretions

Bacteria onGram stain

Yes

Yes

No

Yes No Yes No

No

Start antibiotics immediatelyusing PSBBAL specimen

and Gram stain results

Start antibioticsimmediately based onepidemiological clues

Observe look forother infection

Signs ofsevere sepsis

Immediate PSB or BAL beforechangingstarting antimicrobial therapy

+ve cultures +ve cultures

Adjust therapybased on

culture results

Continueadjustantibiotics Look for

other infection

Start antibioticson basisof results

Look forother infection

7172019 Pneumonia


Tuberculosis 423

Table 364 Strategies for prevention of ventilator-associated pneumonia

LEVELS OF

RECOMMENDATIONS SPECIFIC INTERVENTIONS REMARKS

Universally recommendedby all guidelines27ndash30

1 Semirecumbent position to 45deg At least 30ndash45deg2 Avoidance of endotracheal intubation3 Preference of oral tracheal route

4 New circuit for a new patient and noschedule change unless soiled or damaged5 Avoidance of flushing of condensate into

lower airway or in-line medication6 HME changes no more frequently than 5ndash7

days7 Continuous aspiration of subglottic suctioning For patients expected to require mechanical

ventilation for gt72 hours

Generally recommendedby most guidelines

1 Preferential use of non-invasiveventilation272830

2 Avoidance of unplanned re-intubation272830

3 Maintenance of endotracheal cuff pressureof about 20 mmHg (266 kPa)272830

4 Closed suctioning2829

No effect on VAP mainly for staff safety5 Chlorhexidine oral decontamination272930

6 Sedation vacation and weaning protocol2728

7 Judicious use of stress ulcer prophylaxis272830

8 Restrictive blood transfusion28

Benefits less clear 1 Preference of HME over heatedhumidifier2830

HME associated with reduction in VAP inpatients ventilated for gt7 days lower cost

2 Silver-sulfadiazine-coated endotrachealtube272830

3 Early tracheostomy (within 7 days ofmechanical ventilation)29

4 Selective decontamination of digestive tract(SDD)272830

Mortality reduction demonstrated when topicalantimicrobials combined with short-course

systemic antibiotics BSAC recommendedSDD in patients expected to requiremechanical ventilation for gt48 hours ETFdiscourage routine use due to concern ofemergence of resistant organisms

Not yet reviewed byguidelines50

1 High-volume low-pressure ultrathin membraneendotracheal tube cuff with SSD

2 Ultrathin membrane cuff with tapered shapeand SSD

3 Low-volume low-pressure endotracheal tubecuff with SSD

4 Balloon device for biofilm removal5 Saline instillation before tracheal suctioning

HME= heat moist exchanger SSD= subglottic secretion drainage

smear-negative patients with pulmonary tuberculosisbut have the advantage of a much more rapid resultThere is however a signicant false-negative rate32

CHEST X-RAY (CXR)A normal CXR almost excludes TB (except inHIV-infected patients) but endobronchial lesionsmay not be apparent and early apical lesions can bemissed Common appearances include patchynodular

shadowing in the upper zones (often bilateral) cavita-tion calcication hilar or mediastinal lymphadenopa-thy (may cause segmental or lobar collapse) pleuraleffusion tuberculomas (dense round or oval shadows)and diffuse ne nodular shadowing throughout thelung elds in miliary TB Inactivity of disease cannot beinferred from the CXR alone This requires three nega-tive sputum samples and failure of any lesion seen onCXR to progress CXR appearances in HIV-positive

7172019 Pneumonia


424 Pneumonia

t-tested negative-pressure respirator (N95 FFP2 orhigher) Use of a powered air-purifying respiratorshould be considered when bronchoscopy is being per-formed35 Detailed infection control advice can beobtained via the lsquolink pagersquo (httpwwwaiccuhk eduhkweb8Pneumonia20guidelineshtm)

PNEUMONIA IN THEIMMUNOCOMPROMISED

The lungs are amongst the most frequent targetorgans for infectious complications in the immuno-compromised The incidence of pneumonia is highestamongst patients with haematological malignanciesbone marrow transplant (BMT) recipients and patientswith AIDS

The speed of progression of pneumonia the CXRchanges (Table 365) and the type of immune defectprovide clues to the aetiology Bacterial pneumonias

progress rapidly (1ndash2 days) whereas fungal and proto-zoal pneumonias are less fulminant (several days to aweek or more) Viral pneumonias are usually not ful-minant but on occasions may develop quite rapidlyBronchoscopy is a major component of the investiga-tion of these patients Empirical management based onCXR appearances is outlined in Table 365 Early non-invasive ventilation may improve outcome amongstimmunocompromised patients with fever and bilateralinltrates36

PNEUMOCYSTIS JIROVECI PNEUMONIA (PCP)37

The incidence of this common opportunistic infectionhas fallen substantially in patients with AIDS whoare receiving prophylaxis and effective antiretroviraltherapy with most cases occurring in patients who arenot receiving HIV care or among patients with advancedimmunosuppression The onset is usually insidiouswith dry cough dyspnoea and fever on a backgroundof fatigue and weight loss Crackles in the chest are rareApproximately 15 of patients have a concurrent causefor respiratory failure (eg Kaposi sarcoma TB bacte-rial pneumonia) Useful investigations are

1 CXR classical appearance is diffuse bilateral perihi-

lar interstitial shadowing but in the early stages thisis very subtle and easily missed The initial CXR isnormal in 10 In a further 10 the changes areatypical with focal consolidation or coarse patchyshadowing None of the changes are specic for PCPand may be seen in other lung diseases associatedwith AIDS Pleural effusions hilar or mediastinallymphadenopathy are unusual in PCP but commonin mycobacterial infection or Kaposirsquos sarcoma orlymphoma

2 Induced sputum in this technique the patient inhalesnebulised hypertonic saline from an ultrasonic neb-uliser This provokes bronchorrhoea and the patient

patients with TB differ from those in non-HIV-infectedpatients

TREATMENT OF PULMONARY TB32ndash34

The decision to initiate anti-TB treatment should bebased on level of clinical suspicion results of AFBsmear and sometimes mycobacterial culture If the

initial clinical suspicion is strong and the patient is seri-ously ill attributable to possible TB treatment shouldbe initiated promptly sometimes before the result ofAFB smear Subsequent positivity of AFB smear ornucleic acid amplication test provides support to thecontinuation of treatment Combination chemotherapyconsisting of four drugs is necessary for maximal ef-cacy Treatment is divided into initial phase and con-tinuation phase The most commonly used initialregimen consists of 8 weeks of rifampicin 600 mg daily(450 mg for patients lt50 kg) isoniazid 300 mg dailypyrazinamide 2 g daily (15 g for patients lt50 kg) and

ethambutol 15 mgkg daily as initial phase treatmentEthambutol should be used only in patients who havereasonable visual acuity and who are able to appreciateand report visual disturbances This mandates carefulconsideration in patients who require heavy sedationVisual acuity and colour perception must be assessed(if ethambutol is to be used) and liver and renal func-tion checked before treatment is started Steroids arerecommended for children with endobronchial diseaseand possibly for patients with tuberculous pleuraleffusions Pyridoxine 10 mg daily should be given toprevent isoniazid-induced neuropathy to those atincreased risk (eg patients with diabetes mellitus

chronic renal failure or malnutrition or alcoholic orHIV-positive patients) Negative AFB smear should notdelay initial treatment if clinical suspicion remainshigh Supporting features included chronic coughweight loss characteristic chest X-ray ndings emigra-tion from a high-incidence country no other immediatediagnosis and positive tuberculin test

INFECTION CONTROL

Patients admitted to an ICU with infectious TB or sus-pected of having active pulmonary TB should bemanaged in an isolation room with special ventilation

characteristics including negative pressure Patientsshould be considered infectious if they are coughing orundergoing cough-inducing procedures or if they havepositive AFB smears and they are not on or have juststarted chemotherapy or have a poor clinical or bacte-riological response to chemotherapy3235 Patients withnon-drug-resistant TB should be non-infectious after 2weeks of treatment which includes rifampicin and iso-niazid32 As TB spreads through aerosols it is probablyappropriate to isolate patients who are intubated evenif only their bronchial washings are smear-positiveStaff caring for patients who are smear-positive shouldwear personal protective equipment including a

7172019 Pneumonia


Pneumonia in the immunocompromised 425

andor diuretics (patients often uid-overloaded)Approximately 40 of patients with HIV-related PCPwho require mechanical ventilation survive to hospitaldischarge38

Initiation of antiretroviral therapy in patients pre-senting with HIV-related PCP is controversial TheCenters for Disease Control and Prevention (CDC) rec-ommend against doing so in the acute phase but recent

data suggest that the outcome may be improved byinitiation within the rst 4 days of ICU admission39

BACTERIAL PNEUMONIA37

This is the most common cause of acute respiratoryfailure in HIV-positive patients Bacterial pneumonia ismore common in HIV-infected patients than in thegeneral population and tends to be more severe Strep pneumoniae H infuenza Pseudomonas aeruginosa and Saureus are the commonest organisms Nocardia andGram negatives should also be considered Atypicalpathogens (eg Legionella) are rare Response to appro-

priate antibiotics is usually good but may require pro-tracted courses of antibiotics because of high tendencyto relapse Patients with severe immunodeciency(CD4+ T lymphocyte count lt100983221L) and a history ofPseudomonas infection or bronchiectasis or neutropeniashould receive antibiotics that cover P aeruginosa aswell as other Gram negatives The possibility of concur-rent PCP or tuberculosis should be excluded

TUBERCULOSIS

TB may be the initial presentation of AIDS particularlyin sub-Saharan Africa The pattern of TB in HIV patients

coughs up material containing cysts and tropho-zoites The technique is time-consuming and requiresmeticulous technique and is less sensitive thanbronchoscopy but less invasive The possibility ofconcurrent tuberculosis should be consideredand steps taken to minimise the risk of spread ofinfection

3 Bronchoscopy with bronchoalveolar lavage leads to

the diagnosis in over 90 of cases Specimens shouldbe sent for cytology Transbronchial biopsy is notnecessary in most cases PCR using bronchial lavagespecimens may be useful in non-HIV patients withsuspected PCP

Antipneumocystis treatment should be started as soonas the diagnosis is suspected Treatment of choice istrimethoprim plus sulfamethoxazole (co-trimoxazole)20 mgkgday+ 100 mgkgday for 3 weeks plusprednisolone 40 mg orally twice daily for 5 days fol-lowed by 20 mg twice daily for 5 days and then 20 mgper day until the end of PCP treatment Side-effects of

co-trimoxazole are common in HIV patients (nauseavomiting skin rash myelotoxicity) The dose should bereduced by 25 if the WBC count falls Patients whoare intolerant of co-trimoxazole should be treated with

bull pentamidine 4 mgkgday iv or

bull primaquine with clindamycin or

bull trimetrexate with leucovorin (plusmnoral dapsone)

Response to treatment is usually excellent with aresponse time of 4ndash7 days If the patient deteriorates orfails to improve consider (re-)bronchoscopy (is thediagnosis correct) treat co-pathogens and considera short course of high-dose iv methylprednisolone

Table 365 Causes of CXR changes and empirical treatment of pneumonia in the immunocompromised

CHEST X-RAY

APPEARANCE CAUSES

EMPIRICAL TREATMENT FOR

SUSPECTED PNEUMONIA

Diffuse infiltrate CMV and other herpes virusesPneumocystis carinii Bacteria

Aspergillus (advanced)Cryptococcus (uncommon)Non-infectious causes eg drug reaction non-specific

interstitial pneumonitis radiation pneumonitis(uncommon) malignancy leucoagglutinin reaction

Broad-spectrum antibiotics for at least 48 h(eg 3rd-generation cephalosporin andaminoglycoside)

Co-trimoxazoleLung biopsy or lavage within 48 h or full2-week course of co-trimoxazole (dependson patient tolerance of invasive procedure)

Focal infiltrate Gram-negative rodsS aureusAspergillusCryptococcusNocardiaMucorP carinii (uncommon)Tuberculosis

LegionellaNon-infectious causes (eg malignancy non-specificinterstitial pneumonitis radiation pneumonitis)

Broad-spectrum antibioticsIf response seen continue treatment for

2 weeksIf disease progresses lung biopsyaspirate

within 48ndash72 hours or empirical trial ofantifungalplusmn macrolide

7172019 Pneumonia


426 Pneumonia

reaction are the most useful tests for demonstratingCMV disease Using thresholds of 10300 000ndash50200 000 positive circulating peripheral WBC the posi-tive predictive value for CMV-pp65 ranges from64 to 82 and the negative predictive value from70 to 954344 Treatment consists of intravenous gan-ciclovir for at least 14 days Foscarnet can be used if

ganciclovir fails

FUNGAL PNEUMONIA

Fungi are rare but important causes of pneumoniaThey can be divided into two main groups based on theimmune response required to combat infection withthese organisms Histoplasma blastomycosis coccidi-oidomycosis paracoccidioidomycosis and Cryptococcus require specic cell-mediated immunity for their controland thus in contrast to infections that are controlled byphagocytic activity the diseases caused by these organ-isms can occur in otherwise healthy individuals

although they cause much more severe illness inpatients with impaired cell-mediated immunity (egpatients infected with HIV and organ transplant recipi-ents) With the exception of Cryptococcus these organ-isms are rarely seen outside North America Aspergillus and Mucor spores are killed by non-immune phago-cytes and as a result these fungi rarely result in clinicalillness in patients with normal neutrophil numbers andfunction

CANDIDIASIS This is effectively a combination of the two types offungal infection in which impaired cell-mediatedimmunity predisposes to mucosal overgrowth withCandida but impaired phagocytic function or numbersis usually required before deep invasion of tissuesoccurs Primary Candida pneumonia (ie isolated lunginfection) is uncommon4145 and more commonly pul-monary lesions are only one manifestation of dissemi-nated candidiasis Even more common is benigncolonisation of the airway with Candida In mostreported cases of primary Candida pneumonia ampho-tericin B has been used In disseminated candidiasistreatment should be directed to treatment of dissemi-nated disease rather than Candida pneumonia per se45

INVASIVE ASPERGILLOSIS 46

This is a highly lethal condition in the immunocom-promised despite treatment and therefore investiga-tion and treatment should be prompt and aggressiveIt is associated with exposure to construction workDenitive diagnosis requires both histological evidenceof acute-angle branching septated non-pigmentedhyphae measuring 2ndash4 983221m in width and cultures yield-ing Aspergillus species from biopsy specimens ofinvolved organs Recovery of Aspergillus species fromrespiratory secretions in immunocompromised butnot immunocompetent patients may indicate invasive

disease with a positive predictive value as high as

depends on the degree of immunosuppression Inpatients with CD4+ T lymphocytes gt350 cells983221L theclinical presentation is similar to TB in non-HIV-infectedpatients although extrapulmonary disease is morecommon In patients with CD4+ T lymphocytes lt350cells983221L extrapulmonary disease (pleuritis pericardi-tis meningitis) is common Severely immunocompro-

mised patients (CD4+

T lymphocytes lt100 cells983221L)may present with severe systemic disease with highfever rapid progression and systemic sepsis In thesepatients lower and middle lobe disease is more commonmiliary disease is common and cavitation is lesscommon Sputum smears and culture may be positiveeven with a normal CXR

Response to treatment is usually rapid Managementof TB in HIV is complex owing to numerous druginteractions consultation with an expert in treatment ofHIV-related TB should be strongly considered Complexinteractions occur between rifamycins (eg rifampicinand rifabutin) and protease inhibitors and non-

nucleoside reverse transcriptase inhibitors used to treatpatients infected with HIV The choice of rifampicin orrifabutin depends on a number of factors includingthe unique and synergistic adverse effects for each indi-vidual combination of rifampicin and anti-HIV drugsand consultation with a physician with experiencein treating both TB and HIV is advised40 IDSA-recommended dosage adjustment for patients receivingantiretrovirals and rifabutin37 can be obtained viathe lsquolink pagersquo (httpwwwaiccuhkeduhkweb8Pneumonia20guidelineshtm) The optimal time forinitiating antiretroviral therapy in patients with TB iscontroversial Early therapy may decrease HIV disease

progression but may be associated with a high inci-dence of adverse effects and an immune reconstitutionreaction37

CMV PNEUMONITIS4142

Risk of infection is highest following allogeneic stemcell transplantation followed by lung transplantationpancreas transplantation and then liver heart and renaltransplantation and advanced AIDS If both the recipi-ent and the donor are seronegative then the risk of bothinfection and disease are negligible If the recipient is

seropositive the risk of infection is approximately 70but the risk of disease is only 20 regardless of theserostatus of the donor However if the recipient isseronegative and the donor is seropositive the risk ofdisease is 70 If steroid pulses and antilymphocyteglobulin are given for treatment of acute rejection therisk of developing disease is markedly increased Infec-tion may be the result of primary infection or reactiva-tion of latent infection It is clinically important butoften difcult to distinguish between CMV infectionand CMV disease and a denitive diagnosis can bemade only histologically Detection of CMV-pp65antigen in peripheral WBC and detection of CMV DNA

or RNA in the blood by quantitative polymerase chain

7172019 Pneumonia


Parapneumonic effusion 427

needle aspiration or if there is debris within the uiddrainage using an intercostal drain The diagnosis isconrmed by aspiration of pus

TREATMENT The mainstay of treatment is drainage either by inter-costal drain or by surgical intervention Patients whopresent before the pus is loculated and a brinous peelhas formed on the lung can usually be treated bysimple drainage The combination with intrapleuralbrinolysis may be benecial Optimal surgical man-agement which consists of decortication (open or tho-racoscopic) is indicated if the empyema is moreadvanced or if simple drainage fails This is a majorprocedure and many patients with cardiac or chronicrespiratory disease will not tolerate it Alternatives forthese patients are instillation of thrombolytics into thepleural space or thoracostomy Antibiotics have onlyan adjunctive role Broad-spectrum antibiotic regimenswith anaerobic cover should be used until the resultsof microbiological analysis of the aspirated pus areavailable

AcknowledgementsAll tables and gures are reproduced from ICU web(wwwaiccuhkeduhkweb8) with permission of theauthors

80ndash90 in patients with leukaemia or bone marrowtransplant recipients Bronchoalveolar lavage withsmear culture and antigen detection has excellent spe-cicity and reasonably good positive predictive valuefor invasive aspergillosis in immunocompromisedpatients Although radiological features may give a clueto the diagnosis they are not sufciently specic to be

diagnosticIn acutely ill immunocompromised patients intrave-nous therapy should be initiated if there is suggestiveevidence of invasive aspergillosis while further investi-gations to conrm or refute the diagnosis are carriedout First-line therapy is voriconazole47 Echinocandinsand amphotericin are alternatives

PARAPNEUMONIC EFFUSION

This may be an uncomplicated effusion that resolveswith appropriate treatment of the underlying pneumo-nia or a complicated effusion that develops into an

empyema unless drained Complicated effusions tendto develop 7ndash14 days after initial uid formation Theyare characterised by increasing pleural uid volumecontinued fever and pleural uid of low pH (lt73) thatcontains a large number of neutrophils and may revealorganisms on Gram staining or culture An outline ofmanagement is given in Figure 365

EMPYEMA48

DEFINITION Collection of pus in the pleural space

AETIOLOGY Follows infection of the structures surrounding thepleural space including subdiaphragmatic structuresand chest trauma or may be associated with malig-nancy Anaerobic bacteria usually streptococci orGram-negative rods are responsible for 76 of cases

DIAGNOSIS The diagnosis is usually simple The patient is usuallyseptic and may have a productive cough and chest painThe chest X-ray may show features suggestive of apleural effusion and underlying consolidation but may

also show an abscess cavity with a uid level in whichcase CT scanning will be required to distinguishbetween an abscess and an empyema Ultrasound canbe useful to conrm the presence of uid in the pleuralspace and to determine whether it can be drained by

Figure 365 An approach to the management of

parapneumonic effusions

Parapneumonic effusion

gt 1 cm thick

on lateral decubitus

film

Pleural aspirate

turbid or purulent or

Gram stain +ve

Pleural aspirate

pH

Serial thoracocentesis Treat as empyemaObserve

No

gt72 lt70

70ndash72

No

Yes

Yes

httpwwwexpertconsultcomAccess the complete references list online at

1 American Thoracic Society and Infectious Diseases Society of America Guidelines for the manage-ment of adults with hospital-acquired ventilator-associated and healthcare associated pneumonia

Am J Respir Crit Care Med 2005171388ndash416

2 Mandell LA Wunderink RG Anzueto A et al Infec-tious Diseases Society of AmericaAmerican Tho-racic Society consensus guidelines on the management of community-acquired pneumonia in adults Clin

Infect Dis 200744S27ndash72

7172019 Pneumonia


428 Pneumonia

3 Pneumonia Guidelines Committee of the BTS Stand-ards of Care Committee British Thoracic Society guidelines for the management of community acquired pneumonia in adults update 2009 Thorax200964(Suppl III)iii1ndash55

16 Waterer GW Rello J Management of community-acquired pneumonia in adults Am J Respir Crit Care Med 2011183157ndash64

34 American Thoracic Society CDC and Infectious Dis-eases Society of America Treatment of tuberculosis Am J Respir Crit Care Med 2003167603ndash62

49 Meduri GU Chastre J The standardization of bron-choscopic techniques for ventilator-associated pneu-monia Chest 1992102557Sndash64S

50 Lorente L Blot S New issues and controversies in the prevention of ventilator-associated pneumonia Am

J Respir Crit Care Med 2010182870ndash6

7172019 Pneumonia


References 428e1

REFERENCES 1 American Thoracic Society and Infectious Diseases

Society of America Guidelines for the management of adults with hospital-acquired ventilator-associated and healthcare associated pneumonia Am J Respir Crit Care Med 2005171388ndash416

2 Mandell LA Wunderink RG Anzueto A et al Infec-tious Diseases Society of AmericaAmerican Tho-racic Society consensus guidelines on the management of community-acquired pneumonia in adults Clin Infect Dis 200744S27ndash72


4 Woodhead M Blasi F Ewig S et al Guidelines for the management of adult lower respiratory tract infections Eur Respir J 2005261138ndash80

5 Torres A Rello J Update in community-acquired and nosocomial pneumonia 2009 Am J Respir Crit

Care Med 2010181782ndash76 Van der Eerden MM Vlaspolder F de Graaff CS et

al Value of intensive diagnostic microbiological investigation in low- and high-risk patients with community-acquired pneumonia Eur J Clin Micro Infect Dis 200524241ndash9

7 Murdoch DR Nucleic acid amplication tests for the diagnosis of pneumonia Clin Infect Dis 2003361162ndash70

8 Blaschke AJ Interpreting assays for the detection of Streptococcus pneumonia Clin Infect Dis 201152(S4)S331ndash7

9 Rello J Lisboa T Lujan M Severity of pneumococcal

pneumonia associated with genomic bacterial load Chest 2009136832ndash4010 Azoulay E Bergeron A Polymerase chain reaction

for diagnosing pneumocystis pneumonia in non-HIV immunocompromised patients with pulmonary inl-trates Chest 2009135(3)655

11 Garcia-Vidal C Fernandez-Sabe N Carratala J Early mortality in patients with community-acquired pneumonia causes and risk factors Eur Respir J200832733ndash9

12 Dellinger RP Carlet JM Masur H et al Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock Intensive Care Med200430536ndash55

13 Metersky ML Ma A Houck PM et al Antibiotics for bacteremic pneumonia improved outcomes with macrolides but not uoroquinolones Chest 2007131466ndash73

14 Dunbar LM Wunderink RG Habib MP High-dose short-course levooxacin for community-acquired pneumonia a new treatment paradigm Clin Infect Dis 200337752ndash60

15 Matthaiou DK Ntani G An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients Intensive Care Med 201238940ndash9


17 Gruber PC Gomersall CD Joynt GM Avian inu-enza (H5N1) implications for intensive care Inten-sive Care Med 200632823ndash9

18 Belongia EA Irving SA Clinical characteristics and 30-day outcomes for inuenza A 2009 (H1N1) 2008ndash2009 (H1N1) and 2007ndash8 (H3N2) infections JAMA2010304(10)1091

19 Lee N Chan PKS Complications and outcomes of pandemic 2009 inuenza A (H1N1) virus infection in hospitalized adults how do they differ from those in seasonal inuenza J Infect Dis 20112031739ndash47

20 Kim SH Hong SB Corticosteroid treatment in critically ill patients with pandemic inuenza AH1N1 2009 infection analytic strategy using pro-pensity scores Am J Respir Crit Care Med 20111831207ndash14

21 Centers for Disease Control and Prevention (CDC) Bacterial coinfections in lung tissue specimens from

fatal cases of 2009 pandemic inuenza A (H1N1) ndash United States MayndashAugust 2009 MMWR 2009581071ndash4

22 Safdar N Dezfulian C Clinical and economic conse-quences of ventilator-associated pneumonia A sys-tematic review Crit Care Med 200533(10)2184ndash93

23 Shorr AF Sherner JH Invasive approaches to the diagnosis of ventilator-associated pneumonia A meta-analysis Crit Care Med 200533(1)46ndash53

24 Melsen WG Rovers MM Ventilator-associated pneumonia and mortality A systematic review of observational studies Crit Care Med 2009372709ndash18

25 Bekaert M Timsit JF Attributable mortality of ventilator-associated pneumonia A reappraisal using causal analysis Am J Respir Crit Care Med20111841133ndash9

26 CDC Healthcare Infection Control Practices AdvisoryCommittee Guidelines for preventing health-care-associated pneumonia 2003 Recommendations ofCDC and the Healthcare Infection Control PracticesAdvisory Committee Online Available httpwwwcdcgovmmwrpreviewmmwrhtmlrr5303a1htm

27 Cofn SE Klompas M SHEAIDSA practice recom-mendation strategies to prevent ventilator-associated pneumonia in acute care hospitals Infect Control

Hosp Epidemiol 200829S31ndash4028 Masterton RG Galloway A Guidelines for the man-

agement of hospital-acquired pneumonia in the UK Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy J Antimicrob Chemother 2008625ndash34

29 VAP Guidelines Committee and the Canadian Critical Care Trials Group Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia prevention J Crit Care 200823126ndash37

7172019 Pneumonia


428e2 Pneumonia

30 Torres A Ewig S Dening treating and preventing hospital acquired pneumonia European perspective Intensive Care Med 2009359ndash29

31 Frame RN Johnson MC Eichenhorn MS et al Active tuberculosis in the medical intensive care unit a 15-year retrospective analysis Crit Care Med 1987151012ndash14

32 National Collaborating Centre for Chronic Condi-tions Tuberculosis Clinical diagnosis and manage-ment of tuberculosis and measures for its prevention and control London Royal College of Physicians 2006

33 Small PM Fujiwara PI Management of tuberculosis in the United States N Engl J Med 2001345189ndash200


35 Centers for Disease Control and Prevention Guide-lines for preventing the transmission of Mycobacte-rium tuberculosis in health-care settings 2005 MMWR

2005541ndash11936 Hilbert G Gruson D Vargas F et al Noninvasive

ventilation in immunosuppressed patients with pul-monary inltrates fever and acute respiratory failure N Engl J Med 2001344481ndash7

37 Benson CA Kaplan JE Masur H Treating oppor-tunistic infections among HIV-infected adults and adolescents recommendations from CDC the National Institutes of Health and the HIV Medicine AssociationInfectious Diseases Society of America Clin Infect Dis 200540S131ndash235

38 Randall CJ Yarnold PR Schwartz DN et al Improve-ments in outcomes of acute respiratory failure for

patients with human immunodeciency virus-related Pneumocystis carinii pneumonia Am J Respir Crit Care Med 2000162393ndash8

39 Croda J Croda MG Neves A et al Benet of antiret-roviral therapy on survival of human immunode-ciency virus-infected patients admitted to an intensive care unit Crit Care Med 200937(5)1605

40 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 MMWR 200049185ndash9

41 Tamm M The lung in the immunocompromised patient Infectious complications part 2 Respiration199966199ndash207

42 Van der Bij W Speich R Management of cytomega-lovirus infection and disease after solid-organ trans-plantation Clin Infect Dis 200133(Suppl 1)S32ndash7

43 Schaumlfer P Tenschert W Cremaschi L et al Area under the viraemia curve versus absolute viral load utility for predicting symptomatic cytomegalovirus infections in kidney transplant patients J Med Virol20016585ndash9

44 Meyer-Koenig U Weidmann M Kirste G et al Cytomegalovirus infection in organ-transplant recip-ients diagnostic value of pp65 antigen test qualita-tive polymerase chain reaction (PCR) and quantitative

Taqman PCR Transplantation 2004771692ndash8

45 Pappas PG Rex JH Sobel JD Guidelines for treat-ment of candidiasis Clin Infect Dis 200438161ndash89

46 Stevens DA Kan VL Judson MA Practice guidelines for diseases caused by Aspergillus Clin Infect Dis200030696ndash709

47 Herbrecht R Denning DW Patterson TF Voricona-zole versus amphotericin B for primary therapy of invasive aspergillosis N Engl J Med 2002347408ndash15

48 Peek GJ Morcos S Cooper G The pleural cavity BMJ20003201318ndash21




7172019 Pneumonia


7172019 Pneumonia


416 Pneumonia






EXPOSURE ORGANISM





OTHERS













7172019 Pneumonia





MANAGEMENT












Severe CAP

Aztreonam

and

levofloxacin




aminoglycoside plus

advanced macrolide

Respiratory

fluoroquinolone

plusmn clindamycin






Risk of Pseudomonas

(COPDbronchiectasis




β-lactam

allergy

β-lactam

allergy

NoYes

NoYesNoYes

7172019 Pneumonia


418 Pneumonia


ings24




















INFLUENZA PNEUMONIA





7172019 Pneumonia





PATHOGENESIS


























7172019 Pneumonia


420 Pneumonia


MANAGEMENT



DURATION OF THERAPY



CLINICAL DIAGNOSIS










purulent sputum

temp gt38degC

New CXR

infiltrates

Consider acute

tracheobronchitis





pathogens


antibiotic therapy

to cover multidrug-

resistant pathogens


antibiotic therapy

Yes

Yes

No

No

7172019 Pneumonia








Pathogens isolated

from respiratory

specimen

Antibiotics


prior to sampling

Adjust antibiotics





Bacterial pneumonia

unlikely







Yes

Yes

No

No











7172019 Pneumonia


422 Pneumonia




Multiple

3233



PREVENTION



TUBERCULOSIS




Yes

Yes

No

Yes No Yes No

No









culture results


other infection



7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



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CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











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426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


416 Pneumonia






EXPOSURE ORGANISM





OTHERS













7172019 Pneumonia





MANAGEMENT












Severe CAP

Aztreonam

and

levofloxacin




aminoglycoside plus

advanced macrolide

Respiratory

fluoroquinolone

plusmn clindamycin






Risk of Pseudomonas

(COPDbronchiectasis




β-lactam

allergy

β-lactam

allergy

NoYes

NoYesNoYes

7172019 Pneumonia


418 Pneumonia


ings24




















INFLUENZA PNEUMONIA





7172019 Pneumonia





PATHOGENESIS


























7172019 Pneumonia


420 Pneumonia


MANAGEMENT



DURATION OF THERAPY



CLINICAL DIAGNOSIS










purulent sputum

temp gt38degC

New CXR

infiltrates

Consider acute

tracheobronchitis





pathogens


antibiotic therapy

to cover multidrug-

resistant pathogens


antibiotic therapy

Yes

Yes

No

No

7172019 Pneumonia








Pathogens isolated

from respiratory

specimen

Antibiotics


prior to sampling

Adjust antibiotics





Bacterial pneumonia

unlikely







Yes

Yes

No

No











7172019 Pneumonia


422 Pneumonia




Multiple

3233



PREVENTION



TUBERCULOSIS




Yes

Yes

No

Yes No Yes No

No









culture results


other infection



7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



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CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia





MANAGEMENT












Severe CAP

Aztreonam

and

levofloxacin




aminoglycoside plus

advanced macrolide

Respiratory

fluoroquinolone

plusmn clindamycin






Risk of Pseudomonas

(COPDbronchiectasis




β-lactam

allergy

β-lactam

allergy

NoYes

NoYesNoYes

7172019 Pneumonia


418 Pneumonia


ings24




















INFLUENZA PNEUMONIA





7172019 Pneumonia





PATHOGENESIS


























7172019 Pneumonia


420 Pneumonia


MANAGEMENT



DURATION OF THERAPY



CLINICAL DIAGNOSIS










purulent sputum

temp gt38degC

New CXR

infiltrates

Consider acute

tracheobronchitis





pathogens


antibiotic therapy

to cover multidrug-

resistant pathogens


antibiotic therapy

Yes

Yes

No

No

7172019 Pneumonia








Pathogens isolated

from respiratory

specimen

Antibiotics


prior to sampling

Adjust antibiotics





Bacterial pneumonia

unlikely







Yes

Yes

No

No











7172019 Pneumonia


422 Pneumonia




Multiple

3233



PREVENTION



TUBERCULOSIS




Yes

Yes

No

Yes No Yes No

No









culture results


other infection



7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


418 Pneumonia


ings24




















INFLUENZA PNEUMONIA





7172019 Pneumonia





PATHOGENESIS


























7172019 Pneumonia


420 Pneumonia


MANAGEMENT



DURATION OF THERAPY



CLINICAL DIAGNOSIS










purulent sputum

temp gt38degC

New CXR

infiltrates

Consider acute

tracheobronchitis





pathogens


antibiotic therapy

to cover multidrug-

resistant pathogens


antibiotic therapy

Yes

Yes

No

No

7172019 Pneumonia








Pathogens isolated

from respiratory

specimen

Antibiotics


prior to sampling

Adjust antibiotics





Bacterial pneumonia

unlikely







Yes

Yes

No

No











7172019 Pneumonia


422 Pneumonia




Multiple

3233



PREVENTION



TUBERCULOSIS




Yes

Yes

No

Yes No Yes No

No









culture results


other infection



7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia





PATHOGENESIS


























7172019 Pneumonia


420 Pneumonia


MANAGEMENT



DURATION OF THERAPY



CLINICAL DIAGNOSIS










purulent sputum

temp gt38degC

New CXR

infiltrates

Consider acute

tracheobronchitis





pathogens


antibiotic therapy

to cover multidrug-

resistant pathogens


antibiotic therapy

Yes

Yes

No

No

7172019 Pneumonia








Pathogens isolated

from respiratory

specimen

Antibiotics


prior to sampling

Adjust antibiotics





Bacterial pneumonia

unlikely







Yes

Yes

No

No











7172019 Pneumonia


422 Pneumonia




Multiple

3233



PREVENTION



TUBERCULOSIS




Yes

Yes

No

Yes No Yes No

No









culture results


other infection



7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


420 Pneumonia


MANAGEMENT



DURATION OF THERAPY



CLINICAL DIAGNOSIS










purulent sputum

temp gt38degC

New CXR

infiltrates

Consider acute

tracheobronchitis





pathogens


antibiotic therapy

to cover multidrug-

resistant pathogens


antibiotic therapy

Yes

Yes

No

No

7172019 Pneumonia








Pathogens isolated

from respiratory

specimen

Antibiotics


prior to sampling

Adjust antibiotics





Bacterial pneumonia

unlikely







Yes

Yes

No

No











7172019 Pneumonia


422 Pneumonia




Multiple

3233



PREVENTION



TUBERCULOSIS




Yes

Yes

No

Yes No Yes No

No









culture results


other infection



7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia








Pathogens isolated

from respiratory

specimen

Antibiotics


prior to sampling

Adjust antibiotics





Bacterial pneumonia

unlikely







Yes

Yes

No

No











7172019 Pneumonia


422 Pneumonia




Multiple

3233



PREVENTION



TUBERCULOSIS




Yes

Yes

No

Yes No Yes No

No









culture results


other infection



7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


422 Pneumonia




Multiple

3233



PREVENTION



TUBERCULOSIS




Yes

Yes

No

Yes No Yes No

No









culture results


other infection



7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


Tuberculosis 423


LEVELS OF

































7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


424 Pneumonia

















INFECTION CONTROL



7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia









TUBERCULOSIS












CHEST X-RAY

APPEARANCE CAUSES


SUSPECTED PNEUMONIA











7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


426 Pneumonia


ganciclovir fails

FUNGAL PNEUMONIA













CMV PNEUMONITIS4142




7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia











EMPYEMA48








gt 1 cm thick


film

Pleural aspirate


Gram stain +ve

Pleural aspirate

pH


No

gt72 lt70

70ndash72

No

Yes

Yes






7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


428 Pneumonia







7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


References 428e1



































7172019 Pneumonia


428e2 Pneumonia


























7172019 Pneumonia


428e2 Pneumonia


























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Pneumonia