Pneumonia
Yong Lee
ICU Registrar
John Hunter Hospital
Objectives
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Pathogenesis
Pathophysiology
Clinical features
Community acquired pneumonia,
investigations, assessments of severity,
empirical therapy
• MRSA Influenza
• Nosocomial pneumonia
Pathogenesis
• 3 major routes of entry
– Oropharyngeal or gastric aspiration *
– Inhalation of aerosols
– Haematogenous
• Upper airway colonisation
– S.Pneumoniae, H. Influenzae, Mixed aerobic and anaerobic
bacteria
– E.Coli, Klebsiella more frequent in alcoholics,
institutionalised elderly, poor oral hygiene
• Normal host defenses
– Bronchial mucociliary clearance, phagocytic cells in alveoli
and bronchial mucosa
• Quantity of material aspirated
– Uncontrolled seizures, abnormal airway motor control
periodontal disease, bronchial obstruction
• Nature of bacteria in aspirated material
– Highly efficient pathogens (legionella, mycoplasma,
chlamydia, coxiella, fungal)
• Efficiency of host’s pulmonary defense mechanisms
– Post viral respiratory infection, alcoholics, COPD with
impaired mucociliary clearance, relative immunologic
impairment
• Haematogenous spread
– Established infection elsewhere (IV drug user)
– From damaged skin (brucellosis, melioidosis)
Pathophysiology
• Proliferation of microorganisms within pulmonary
parenchyma elicit host’s acute inflammatory response
– Exudation of protein rich fluid and phagocytic cells
• Local mechanical consequences
– Impaired distribution of ventilation, decrease in lung
compliance -> dyspnoea
– V/Q mismatch
• Systemic changes
– Activation of acute inflammatory response (interleukin 1,
cytokines) result in fever, leukocytosis
– Bacteremia or microbial antigenemia may activate
systemic inflammatory response leading to septic shock
Clinical features
• Systemic response
– Fever, increased WCC, other sepsis syndromes
• Pulmonary symptoms
– Cough, sputum production, dyspnoea, pleuritic chest pain
• Physical
– Inflammatory pulmonary parenchymal process (rales,
tachypnoea)
– Consolidation (bronchial breathing, dullness to percussion
– Abnormal lung function (arterial hypoxaemia, hypocapnia)
• Radiographic pulmonary infiltrate c/w pneumonia
Community Acquired Pneumonia
Assessment
• Clinical features c/w pneumonia
– Consider patient’s age and co-morbidities
– The presence of clinical features of organ system failures
• CXR demonstrating consolidation
• Consider mild (outpatient with appropriate follow up), moderate or
severe
• Investigation for causal pathogen
– Sputum gram stain*, blood cultures
– Pneumococcal and legionella urinary antigen assay, nose and throat
swab for respiratory viral nucleic acid testing (PCR)
– Mycoplasma IgM serology, acute and convalescent serology for
mycoplasma, legionella, chlamydophilia and influenza
– Procalcitonin*
– *BAL
Assessment of severity
• PSI (Pneumonia Severity Index)
• CURB 65 (Confusion, Urea, Resp rate, Blood pressure,
age <65)
– Both developed from statistical analyses of features c/w 30
mortality
– However majority of patients who die of CAP are elderly
persons with multiple co-morbidity
– Tools predicting mortality are less accurate in identifying
patients who will benefit from admission to ICU
• CORB
• SMART-COP
CORB
C = acute confusion
O = oxygen saturation 90% or less
R = respiratory rate 30 breaths or more per minute
B = systolic blood pressure less than 90 mm Hg or diastolic blood pressure
60 mm Hg or less
Interpretation of CORB score
• 'Severe CAP' = the presence of at least two of these features.
• In the Australian study cohort, the accuracy of CORB for predicting need
for IRVS using presence of at least two features was:
• sensitivity = 81%, specificity = 68%
• positive predictive value (PPV) = 18%
• negative predictive value (NPV) = 98%
• area under the receiver operating characteristic (ROC) curve = 0.74.
SMART-COP
SMART-COP
Interpretation of SMART-COP score
• 0 to 2 points—low risk of needing intensive respiratory or vasopressor support (IRVS)
• 3 to 4 points—moderate risk (1 in 8) of needing IRVS
• 5 to 6 points—high risk (1 in 3) of needing IRVS
• 7 or more points—very high risk (2 in 3) of needing IRVS
Severe CAP = a SMART-COP score of 5 or more points.
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In the Australian Community-Acquired Pneumonia Study (ACAPS) cohort, the accuracy for
predicting receipt of IRVS with a SMART-COP score of 3 or more points was:
sensitivity = 92%
specificity = 62%
PPV = 22%
NPV = 99%
area under ROC curve = 0.87.
The SMART-COP severity scoring tool can be modified to make it suitable for use by primary care
physicians
A modified version has also been developed for use in tropical Australia
Empirical management
• Mild CAP
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Reasonable for single shot benzylpenicillin 1.2g
Amoxycillin 5 – 7 days
Or if atypical is suspected
Doxycycline or Clarithromycin (as single agents)
• If no improvement in 48 hrs
– Consider dual therapy of amoxycillin + doxycycline or
clarithromycin
– Some resistant strains of doxycycline and clarithromycin
streptococcus pneumoniae in some regions, consider
switching to cefuroxime or moxifloxacin or assess need for
hospital admission
Empirical management
• Moderate CAP
• Tropical or non tropical region, risk factors for
Burholderia pseudomallei, Acinetobacter
baumannei (DM, chronic lung disease, heavy
ETOH, chronic renal failure)
– Non tropical, no risk factors
• Benzylpenicillin IV PLUS Doxycycline/ Clarithromycin Oral
• Add Gentamicin or change to ceftrixone if GN Bacilli
identified
– Tropical, risk factors
• Ceftriaxone PLUS initial dose of Gentamicin
Empirical management
• Severe Pneumonia
– Non tropical region
• Ceftriaxone IV
• Benzylpenicillin IV + Gentamicin*(short term empirical
or directed therapy only)
• Cefotaxime IV
• PLUS Azithromycin IV in all cases
– Tropical region
• Meropenem IV or Imipenem IV
• PLUS Azithromycin IV in call cases
Staphylococcal pneumonia
• Clinical presentation is suggestive of staphylococcal pneumonia
– R sided endocarditis, IVDU, gram stain positive cluster, CXR with
cavitatory pneumonia
• cMRSA (different from hMRSA)
– Increasing esp. in indigenous and pacific islander, IVDU
– More clinically aggressive but may be susceptible to routine Abx
(clindamycin and bactrim)
– Appropriate susceptibility testing is therefore crucial
• Hospitalised patients
– Intubated patients and late-onset nosocomial infections
• Severely ill patients should be treated for BOTH non-MRSA and
MRSA (e.g flucloxacillin & Vancomycin) until susceptibility results
available
• Non MRSA
– Flucloxacillin IV
– Cephalothin or cephazolin IV (if penicillin
hypersensitive)
– Vancomycin (if immediate penicillin
hypersensitive)
• MRSA
– Vancomycin IV
– *Linezolid, if VISA or hVISA
– Consider additional if severe (clindamycin,
linezolid, rifampicin + fusidic acid) depending on
susceptibility
Influenza
• Influenza A and B viruses
– Usually cause seasonal minor or major epidemics
– Novel strains (e.g H5N1, H1N1) also with potential to cause
epidemics due to lack of pre-existing immuniity in humans
– Infection is spread by droplets and fomite contact so
appropriate infection control are important
– Rapid specific testing such as nucleic acid tests (eg
polymerase chain reaction [PCR]) for influenza on nose or
throat swab specimens are the most useful tests to make
the diagnosis
– Clinical features alone may be reliable enough for
diagnosis when the pre-test probability of influenza is high,
for example during known epidemics.
Treatment
• Treatment with a neuraminidase inhibitor (oseltamivir or zanamivir)
has been associated with a reduced rate of complications of
influenza in observational studies
• Observational studies have also shown an increase in mortality if
hospitalised patients retrospectively shown to have had influenza
were not treated with oseltamivir.
• Treatment is generally thought to be of greatest benefit if
commenced early (ideally within 48 hours of symptom onset), and
if targeted to people at highest risk of complications.
• Where severe illness (eg pneumonitis) is already present, treatment
should be offered regardless of the patient's risk group or duration
of symptoms
• Treatment should be prioritised for people with risk factors for poor
outcomes. For these people treatment may be considered even if
commenced more than 48 hours after the onset of symptoms.
Treatment
• High risk groups
– Pregnant women, morbidly obese, underlying chronic disease,
immunosuppressed, homeless, nursing home residents, indigenous
Australians, the elderly and very young
• If treatment indicated
– Oseltamivir oral for 5 days OR
– Zanamivir inhalation for 5 days
• Antibacterials if clinical presentation suggests bacterial or secondary
bacterial infection develops
• Vaccination with current influenza vaccine provides protection and
complications in ~70% of those vaccinated
– Recommended for all health care worker, age >65, Aboriginal/ TSI > 15y
• Prophylaxis should be considered for close contacts of proven cases,
particularly if those contacts are themselves in high-risk groups
Nocosomial Pneumonia or Hospital
Acquired Pneumonia HAP
• Presentation often unusual because it is affected by
advanced age, co-morbidity and neurological disorders
– Classic respiratory symptoms often mild and
extrapulmonary manifestations (e.g. GI disorder,
confusion) are frequeny
• Pneumonia that is not incubating at time of admission
to hospital and develops in patients hospitalised for 48
h or longer
• VAP is usually defined as pneumonia developing ≥48 h
after implementing ET intubation and/or mechanical
ventilation that was not present before intubation
• Divided to early or late onset
• Early onset HAP
– Within 4 -5 days of hospital admission and tends to be
caused by antibiotic sensitive community acquired
pathogens
– However, increasing frequency of early onset HAP caused
by nosocomial pathogens (? Related to concept of
healthcare – associated pneumonia)
– HCAP - any patient admitted to an acute care hospital for 2
or more days within 90 days of the infection; nursing home
resident; attended a hospital or haemodialysis clinic;
received recent intravenous antibiotic therapy,
chemotherapy, or wound care within the past 30 days of
the current infection
• Late onset HAP
– Tends to be caused by antibiotic resistant hospital
opportunists (e.g. Pseudomonas, MRSA)
Diagnosis of HAP
• Reliable diagnosis is hard
• If one or more of the following criteria are present,
pneumonia should be considered in the differential
diagnosis:
– purulent sputum or tracheal secretions, and new and/or
persistent infiltrate on chest X-ray, which is otherwise
unexplained
– increased oxygen requirement
– temperature greater than 38.3 ºC
– blood leucocytosis (greater than 11 x 109/L) or leucopenia (less
than 4 x 109/L)
• The presence of bacteria in expectorated sputum or ETT
aspirate usually represent colonisation only, and on its own
does not justify a diagnosis of HAP
HAP aetiology
• Hospitalised patients frequently develop colonisation
of the oropharynx with aerobic GN bacilli, and may also
be exposed to multiresistant hospital pathogens
e.g.(MRSA), drug-resistant Enterobacteriaceae,
Pseudomonas aeruginosa, Acinetobacter species and
Stenotrophomonas maltophilia
• Recent antibiotic therapy is a distinct risk factor for
HAP due to drug-resistant bacteria and/or
Pseudomonas aeruginosa
• In cases admitted to intensive care for pneumonia
management, also consider testing for Legionella (in
adults) and influenza infection.
HAP Treatment
• Treatment stratification
– Low risk of MDR (Low risk ward, high risk area of < 5 days)
– High risk of MDR (High risk ward >5 days, consider HCAP)
• Antibiotic susceptibility will differ between institutions
• Recommended initial antibiotic regimen may need to
cover local pathogens and take account of the patient’s
recent Abx exposure and culture results
• Failure to control infection should prompt reevaluation of antibiotic therapy and consideration of
non-infectious diagnoses
Low risk MDRO
• Mild disease
– Amoxycillin with clavulanic acid oral OR
– Benzylpenicillin + single dose gentamicin
• Moderate to severe disease
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Ceftriaxone IV OR
Benzylpenicillin + Gentamicin OR
Cefotaxime IV
Tazocin IV
Timentin IV
• Antibiotic susceptibility to guide ongoing therapy
• Switch to oral Abx after significant improvement
• Consider early cessation of therapy in patients who are shown to
have alternative diagnosis
High risk MDR organism
• Little evidence
• Tazocin IV or Timentin IV or Cefepime IV
• If ventilated patient, add Gentamicin for 1 dose and determine
subsequent 1 or 2 doses dependant of renal function
• If predominant GPC (clusters) on gram stain or known to be
colonised
– Vancomycin IV
• Consider risk factors and extrapulmonary symptoms consider
Legionella’s
• There is evidence that the response to appropriate ABx Rx for
ventilated patients occurs within the first 6 days and that prolonged
therapy results in colonisation and re-infection with resistant
organisms. Treatment for 8 days is recommended except for
Pseudomonas aeruginosa or Acinetobacter species when treatment
may be needed for up to 15 days.
References
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Principles of Critical Care 3rd ed. - J. Hall, G. Schmidt, L. Wood (eds) (Mc-Graw-Hill,
2005)
Therapeutic guidelines, Antibiotics, 2010
Buising KL, Thursky KA, Black JF, MacGregor L, Street AC, Kennedy MP, et al.
Identifying severe community-acquired pneumonia in the emergency department:
a simple clinical prediction tool. Emerg Med Australas 2007;19(5):418-26
Charles PG, Wolfe R, Whitby M, Fine MJ, Fuller AJ, Stirling R, et al. SMART-COP: a
tool for predicting the need for intensive respiratory or vasopressor support in
community-acquired pneumonia. Clin Infect Dis 2008;47(3):375-84
Davis JS, Cross GB, Charles PG, Currie BJ, Anstey NM, Cheng AC. Pneumonia risk
stratification in tropical Australia: does the SMART-COP score apply? Med J
Aust;192(3):133-6
Charles PGP, Whitby M, Fuller AJ, Stirling R, Wright AA, Korman TM, et al, the
ACAPS Collaboration, Grayson ML. The eitiology of community-acquired
pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most
appropriate therapy. Clin Infect Dis 2008; 46:1513-21