1. Yong Lee ICU Registrar John Hunter Hospital
Pneumonia
Yong Lee
ICU Registrar
John Hunter Hospital

2. Objectives Pathogenesis Pathophysiology Clinical features
Community acquired pneumonia, investigations, assessments of severity, empirical therapy
MRSA Influenza
Nosocomial pneumonia

3. Pathogenesis 3 major routes of entry Upper airway colonisation
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

4. 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)

5. 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

6. Clinical features Systemic response Pulmonary symptoms Physical
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

8. Community Acquired Pneumonia

9. 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

10. 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

11. 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.

12. SMART-COP

13. 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.
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

14. Empirical management Mild CAP If no improvement in 48 hrs
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

15. 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

16. 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

17. 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

18. Non MRSA 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

19. 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.

20. 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.

21. Treatment High risk groups If treatment indicated
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

22. 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

23. Early onset HAP Late 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)

24. 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

25. 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.

26. 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 re-evaluation of antibiotic therapy and consideration of non-infectious diagnoses

27. Low risk MDRO Mild disease Moderate to severe disease
Amoxycillin with clavulanic acid oral OR
Benzylpenicillin + single dose gentamicin
Moderate to severe disease
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

28. 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.

29. References
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: