PNEUMONIA

Gerardo P. Morato, M.D.

Section of Pulmonary Medicine
Department of Internal Medicine
De La Salle University Medical Center

PNEUMONIA

Infection of the alveoli, distal airways, and

interstitium.

PATHOGENESIS

Microbial pathogens may enter the lungs

by:
- Direct extension from the mediastinum or
subphrenic space
- Hematogenous seeding from an
extrapulmonary focus
- Inhalation of microorganisms into the
lower airways
- Aspiration of oropharyngeal contents

HOST DEFENSES

Mechanical and structural

- nose
- cough/gag reflex
- Airway branching
- Mucociliary clearance
- Normal oropharyngeal flora

Cellular
- Macrophages
- Epithelial cells
- Neutrophils

Humoral / Molecular / Inflammatory

- IgG, IgA
- Cytokines
- Colony stimulating factors

PATHOLOGY

Edema
- Presence of
proteinaceous exudates and
often bacteria

PATHOLOGY

RED HEPATIZATION
- presence of
erythrocytes in the
intraalveolar
exudate
- neutrophils are
also present

PATHOLOGY

GRAY HEPATIZATION
- no new extravasating
erythrocytes
- neutrophils are the
predominant cells
- fibrin deposition is
abundant
- bacteria have
disappeared

PATHOLOGY

RESOLUTION
- macrophages are the
dominant cells
- inflammatory debris
cleared

CLASSIFICATION (OLD)

Community acquired pneumonia (CAP)

- Typical
- Atypical
*Aspiration

Hospital Acquired Pneumonia

- Early onset
- Late onset
- Ventilator associated

(HAP)

RISK FACTORS FOR MDR

PATHOGENS

Widespread use of potent antibiotics

Early transfer to home/low-acuity care
Increased use of outpatient IV antibiotic therapy
General aging of the population
More extensive immunomodulatory therapies

CURRENT
CLASSIFICATION

Community acquired pneumonia (CAP)

Health Care-Associated Pneumonia

(HCAP)
- Hospital-Acquired Pneumonia (HAP)
- Ventilator-Associated pneumonia (VAP)

COMMUNITY-ACQUIRED
PNEUMONIA

MICTROBIAL CAUSES OF
COMMUNITY-ACQUIRED
PNEUMONIA, BY SITE OF CARE
Hospitalization Patients

Outpatients
Streptococcus pneumoniae
Mycoplasma pneumoniae
Haenophilus influenzae
C. Pneumoniae
Respiratory viruses

Non-ICU

ICU

S. pneumoniae
S. pneumoniae
M. pneumoniae
Staphylococcus aereus
Chlamydophila
Legionella spp.
pneumoniae
Gram-negative bacilli
H. influenzae
H. influenzae
Legionella spp.
Respiratory viruses

EPIDEMIOLOGIC FACTORS
SUGGESTING POSSIBLE CAUSES OF
COMMUNITY-ACQUIRED PNEUMONIA
Factor
Alcoholism

COPD and/or smoking

Structural lung disease

Dementia stroke, decreased
level of conciousness
Lung abscess
Travel to Ohio or St.
Lawrence river valleys
Travel to Southwestern

Possible Pathogen(s)
Streptococcus pneumoniae, oral anaerobes,
Klebsiella pneumoniae, Acinetobacter spp.,
Mycobacterium tuberculosis
Haemophilus influenzae, Pseudomonas
aeruginosa, Legionella spp., S pneumoniae
Moraxella catarrhalis, Chlamydophila
pneumoniae
P. aeruginosa, Burkholderia cepacia, Staphylococcus aureus
Oral anaerobes, gram-negative enteric bacteria
CA_MRSA, oral anaerobes, endemic fungi,
M. tuberculosis, atypical mycobacteria
Histoplasma capsulatum
Hantavirus, Coccidioides spp.

United States
Travel to Southeast Asia
Stay in hotel or on cruise
ship in previous 2 weeks
Local influenza activity
Exposure to bats or birds
Exposure to birds
Exposure to rabbits
Exposure to sheep, goats,
parturient cats

Burkholderia pseudomallei, avian influennza

virus
Legionella spp,
Influenza virus, 5. pneumoniae, S. aureus
H. capsulatum
Chlamydophila psittaci
Francisella tularensis
Coxiella burnetii

TEN LEADING CAUSES OF MORBIDITY

Rate/100,000 Population
PHILIPPINES, 1999

Cause

Number

Rate

1. Diarrheas

908,454

1189.9

2. Bronchitis/Bronchiolitis

717,214

939.4

3. Pneumonia

693,334

908.1

4. Influenza

514,198

673.5

5. Hypertension

208,248

272.8

6. T.B. Respiratory

144,932

189.8

7. Malaria

68,155

89.3

8. Diseases of the Heart

63,167

82.7

9. Chickenpox

35,699

46.8

10. Typhoid Fever

17,675

23.1

Source: FHSIS Annual Report 1999

TEN LEADING CAUSES OF MORTALITY

Number and Rate/100,000 Population
PHILIPPINES, 1997

CAUSES

NUMBER

RATE*

1. Diseases of the Heart

49,962

69.8

2. Diseases of the Vascular System

38,693

54.1

3. Pneumonia

30,811

43.1

4. Accidents

28,563

39.9

5. Malignant Neoplasm

26,842

37.5

6. Tuberculosis, All Forms

23,056

32.2

7. Chronic Obstructive Pulmonary Diseases and Allied Condition

11,807

16.5

8. Other Diseases of the Respiratory System

6,961

9.7

9. Diabetes Mellitus

6,749

9.4

10. Nephritis, Nephrotic Syndrome and Nephrosis

6,704

9.4

Source: Philippine Health Statistics 1997

RISK FACTORS FOR CAP

Alcoholism
Asthma
Immunosuppression
Institutionalization
Age > 70 years
Dementia
Seizure disorders
Tobacco smoking

Chronic obstructive pulmonary disease (COPD)

CLINICAL MANIFESTATIONS

May vary from indolent to fulminant; from mild to fatal

Fever
Tachycardia
Chills and/or sweats
Productive or non-productive cough
Dyspnea (occasionally)
Pleuritic chest pain (if pleura is involved)

Fatigue, headache, myalgias

PHYSICAL FINDINGS

Increased RR
Use of accessory muscles of respiration
Increased tactile fremitus, dull percussion note for
consolidation
Decreased tactile fremitus, flat percussion note for
effusion
Crackles, bronchial breath sounds on auscultation

Non infectious causes of fever and

pulmonary infiltrates that may mimic
CAP

Pulmonary edema
Pulmonary infarction
Acute respiratory distress syndrome (ARDS)
Pulmonary hemorrhage
Lung cancer/metastatic cancer
Atelectasis
Radiation pneumonitis
Drug reactions involving the lung
Extrinsic allergic alveolitis
Pulmonary vasculitis
Pulmonary eosinophilia
Bronchiolitis obliterans and organizing pneumonia

DIAGNOSIS

No particular clinical symptom/physical finding is

sufficiently sensitive or specific to
confirm/exclude CAP
Sensitivity of history and PE- 58%
Specificity of history and PE- 67%
Chest radiography is necessary to help
differentiate CAP from other conditions

Diagnosis, Empiric Management and Prevention of

COMMUNITY-ACQUIRED
PNEUMONIA
In Immunocompetent Adult

2004 Philippine Consensus Guideline

CRITERIA FOR PNEUMONIA

Cough

Tachycardia CR > 100

Tachypnea RR > 20

Fever T >37.8C

At least one abnormal chest findings

- diminished breath sounds, rhonchi, crackles or wheeze

New x-ray infiltrate with no clear alternative such as lung

cancer or pulmonary edema

CHEST RADIOGRAPH

Confirm the diagnosis

of pneumonia
Assess severity of
disease and presence
of complication
Suggest possible
etiology

ETIOLOGIC DIAGNOSIS

Cannot be determined on the basis of the clinical

presentation

Laboratory tests are needed to establish etiology

Identification of an etiologic agent allows

narrowing of the initial empirical regimen

Collected data show trends in resistance

DIAGNOSTIC TESTS

Gram Stain
- May help identify pathogens by their
appearance
- Main purpose is to ensure suitability of
sputum for culture (> 25 neutrophils and
<10 squamous epithelial cells per LPF

DIAGNOSTIC TESTS

Sputum Culture
- Sensitivity and specificity is highly
variable (< 50%)
- Greatest benefit is to alert the physician
of unsuspected and/or resistant
pathogens

DIAGNOSTIC TESTS

Blood Culture
- Only 5-14% of cultures of blood are positive
- No longer considered necessary for all
hospitalized CAP patients
- Should be done in certain high-risk patients
(i.e. severe CAP; chronic liver disease

DIAGNOSTIC TESTS

Antigen tests
- Two commercially available tests detect
pneumococcal and Legionella antigens in urine
- Sensitivity and specificity are high for both tests
- Can detect antigen even after the initiation of
appropriate antibiotic therapy
- Limited availability

SITE OF CARE DECISION

Must take into consideration diminishing health

care resources and rising costs of treatment
Decision to where a patient should be managed
is sometimes difficult
Use of objective tools that assess risk of adverse
outcomes and severity of the disease (i.e. PSI;
CURB-65)

Diagnosis, Empiric Management and Prevention of

COMMUNITY-ACQUIRED
PNEUMONIA
In Immunocompetent Adult

2004 Philippine Consensus Guideline

RISK CATEGORIES FOR CAP

Low

risk CAP

Moderate
High

risk CAP

risk CAP

LOW RISK CAP

Stable vital signs

RR < 30/min
PR < 125/min
SBP > 90, DBP > 60 mmHg
Temp. < 40 C

No or stable co-morbid conditions

- DM, neoplastic disease, neurologic disease, CHF
Class I, CAD, immunosuppresive therapy (Grade A)
- Renal insufficiency (Grade B)
- COPD, chronic liver disease, or chronic alcohol
abuse (Grade C)

MODERATE RISK CAP

Vital Signs: any one of the following

-

RR > 30/min
PR > 125/min
Temp. > 40 C

X-ray findings of:

-

Multi-lobar involvement
Progression of lesion to 50% within 24 hours
Abscess
Pleural effusion

Those with suspected aspiration

Those with extra-pulmonary findings of sepsis: hepatic, hematologic,

gastrointestinal, endocrine

Unstable comorbid condition: uncontrolled DM, active malignacies,

neurologic disease in evolution, CHF Class II-IV, unstable CAD, renal failure
on dialysis, uncompensated COPD, decompensated liver disease

HIGH RISK CAP

All criteria under moderate risk plus

Impending or frank respiratory failure

- Hypoxemia with PaO2 < 60 mmHg
- Acute hypercapnia with PaCO2 > 50 mmHg

Hemodynamic alterations and hypoperfusion:

- SBP < 90mmHg, DBP < 60mmHg
- Urine output < 30cc/hour
- Altered mental state

COMMUNITY
ACQUIRED PNEUMONIA
Any of the ff:
1. RR > 30/min
2. PR > 125/min
3. T > 40C or < 35C
4. Extrapulmonary
evidence of sepsis
5. Suspected aspiration
6. Unstable comorbid
conditions

7. CXR: multilobar,
pleural effusion,
abscess,
progression
to >50%
within 24 hrs
NO
LOW RISK CAP

Algorithm: Management-Oriented
Risk Stratification of
Community-Acquired Pneumonia
In Immunocompetent Adults

Any of the ff:

1. Shock or signs
of hypoperfusion:
YES
- Hypotension
-Altered mental state
HIGH RISK CAP
-urine output <30ml/hr
2. PaO2 < 60mmHg
acute hypocapnea
ICU Admission
PaCO2>50mmHg

YES

NO
MODERATE RISK CAP
Outpatient

Ward Admission

MICTROBIAL CAUSES OF
COMMUNITY-ACQUIRED
PNEUMONIA, BY SITE OF CARE
Hospitalization Patients

Outpatients
Streptococcus pneumoniae
Mycoplasma pneumoniae
Haenophilus influenzae
C. Pneumoniae
Respiratory viruses

Non-ICU

ICU

S. pneumoniae
S. pneumoniae
M. pneumoniae
Staphylococcus aereus
Chlamydophila
Legionella spp.
pneumoniae
Gram-negative bacilli
H. influenzae
H. influenzae
Legionella spp.
Respiratory viruses

EMPIRICAL ANTIBIOTIC
TREATMENT
LOW RISK CAP
Previously healthy and no antibiotics in past 3 months
- A macrolide (Clarithromycin 500mg BID or Azithromycin 500mg OD
or
- Doxycycline 100mg BID
Comorbidities or antibiotics in past 3 months: select an alternative from
a different class
-A respiratory fluoroquinolone (Moxifloxacin 400mg OD,
Gemifloxacin 320mg OD, Levofloxacin 750mg OD) or
-A beta-lactam (Amoxicillin 1gm TID, Amoxicillin/Clavulanate 2gm
BID, Cefpodoxime 200mg BID, Cefuroxime 500mg BID) plus
macrolide

EMPIRICAL ANTIBIOTIC
TREATMENT

MODERATE RISK CAP

- A fluoroquinolone (Moxifloxacin 400mg PO or
IV OD, Gemifloxacin 320mg PO OD,
Levofloxacin 750mg PO or IV OD)
- A beta-lactam (Cefotaxime 1-2gm IV q8h,
Ceftriaxone 1-2gm IV OD, Ampicillin 1-2gm IV
q4-q6) plus a macrolide

EMPIRICAL ANTIBIOTIC
TREATMENT

HIGH RISK CAP (no risk for Pseudomonas)

- A beta-lactam (Cefotaxime 1-2gm IV q8h,
Ceftriaxone 2gm IV OD, Ampicillin-Sulbactam
2gm IV q8) plus
- Azithromycin or a fluoroquinolone

EMPIRICAL ANTIBIOTIC
TREATMENT
SPECIAL CONCERNS
If Pseudomonas is a consideration
- An antipseudomonal, antipneumococcal beta-lactam
(Piperacillin/Tazobactam 4.5 gm IV q4-q6, Cefepime 1-2gm IV q12,
Imipinem 500mg IV q6, Meropenem 1 g IV q8)plus either
Ciprofloxacin 400mg IV q12 or Levofloxacin 750mg IV OD
- The above beta-lactams plus an aminoglycoside (Amikacin
15mg/kg OD or Tobramycin 1.7 mg/kd OD) and Azithromycin
-The above beta-lactams plus an aminoglycoside plus an
antipneumococcal fluoroquinolone
If CA-MRSA is a consideration
- Add Linezolid 600mg IV q12 or Vancomycin 1gm IV q12

GENERAL CONSIDERATIONS
Adequate hydration
Oxygen therapy for hypoxemia
Assisted ventilation when necessary

Failure to improve within 48 to 72

hours following therapy

Noninfectious conditions
- Cancer, embolus, hemorrhage
Resistant pathogen
Wrong drug
Right drug, wrong dose
Unusual pathogens

- Mycobacterial, anaerobic, viral, fungal

Nosocomial superinfections

COMPLICATIONS

Respiratory failure
Shock; Multiorgan failure
Bleeding diathesis
Exacerbation of comorbid illnesses
Metastatic infections
- Brain abscess; Endocarditis
Lung abscess
- usually occurs in the setting of aspiration
- should be drained
Pleural effusion
- should be tapped for diagnostic and therapeutic
purposes

Rate of resolution of physical and

laboratory abnormalities
Abnormalities

Duration

Fever

2 to 4 days

Cough

4 to 9 days

Crackles

3 to 6 days

Leukocytosis

3 to 4 days

C-reactive protein

1 to 3 days

CXR abnormalities

4-12 weeks

Patient is considered to have responded if:

1. Fever declines within 72 hrs
2. Temperature normalizes within 5 days
3. Respiratory signs (tachypnea) return to normal

Risk Categories of CAP and its

associated mortality rate

Low risk
Moderate risk
High risk

: < 5%
: 21%
: 36%

IMMUNIZATION

PNEUMOCOCCAL
VACCINE

> 60 yrs old

Chronic illness:
cardiovascular disease,
lung disease, DM, alcohol
abuse, chronic liver
disease, asplenia
Immune system disorder:
HIV, malignancy

INFLUENZA VACCINE

> 50 yrs old

Chronic illness
Immune system disorder
Residents of nursing
homes
Health care workers
Persons in contact with
high risk patients

HEALTH CAREASSOCIATED PNEUMONIA

DEFINITIONS

Health Care-Associated Pneumonia (HCAP)

- Hospitalization for 2 or more days within 90 days of the
present infection
- Resident of a nursing home or long-term care facility
- Received recent IV antibiotic therapy, chemotherapy or
wound care in the past 30 days of the current infection
- Attended a hospital or hemodialysis clinic

DEFINITIONS

Ventilator Associated Pneumonia (VAP)

- Pneumonia that arises more than 48-72
hours after endotracheal intubation

DEFINITIONS

Hospital Acquired Pneumonia (HAP)

-Defined as pneumonia that occurs 48
hours or more after admission, which was
not incubating at the time of admission

MICROBIOLOGIC CAUSES OF
HCAP
Non-MDR Pathogens
Streptococcus pneumoniae
Other Streptococcus spp.
Haemophilus influenzae
MSSA
Antibiotic-sensitive Enterobacteriaceae
Escherichia coli
Klebsiella pneumoniae
Proteus spp.
Enterobacter spp.
Serratia marcescens

MDR Pathogens
Pseudomonas aeruginosa
MRSA
Acinetobacter spp.
Antibiotic-resistant Enterobacteriaceae
Enterobacter spp.
ESBL-positive strains
Klebsiella spp.
Legionella pneumophila
Burkholderia cepacia
Aspergillus

CLINICAL CONDITIONS ASSOCIATED

WITH AND LIKELY PATHOGENS IN
HEALTH CARE-ASSOCIATED PNEUMONIA
Pathogen
Condition
Hospitalization for 48 h
Hospitalization for 2
days in prior 3 months
Nursing home or extendedcare facility residence
Antibiotic therapy in
preceding 3 months
Chronic dialysis
Home infusion therapy
Home wound care
Family member with
MDR infection

MRSA

Pseudomonas
aeruginosa

Acinetobacter MDR
spp.
Enterobacteriacease

x
x

x
x

x
x

x
x

x
x
x
x
x

PATHOGENESIS
Colonization of the oropharynx with
pathogenic microorganisms
Aspiration from the oropharynx into the
lower respiratory tract
Compromise of the normal host defense
mechanisms

CLINICAL MANIFESTATIONS

Fever
Leukocytosis
Increase in respiratory secretions
PE findings of consolidation
New or changing radiographic infiltrate
Tachypnea
Tachycardia
Worsening oxygenation
Increased minute ventilation

FACTORS CAUSING
OVERDIAGNOSIS OF VAP

Tracheal colonization with pathogenic bacteria in

patients with ET tubes

Multiple alternative causes of radiographic

infiltrates in mechanically ventilated patients

High frequency of other sources of fever in

critically ill patients

EMPIRICAL ANTIBIOTIC
TREATMENT OF HCAP

PATIENTS W/O RISK FACTORS FOR

MDR PATHOGENS
- Ceftriaxone 2g IV q24 hours or
- Moxifloxacin 400mg IV q24 hours,
Ciprofloxacin 400mg IV q8 hours,
Levofloxacin 750mg IV q24 hours or
- Ampicillin/Sulbactam 3 gm IV q6 hours or
- Ertapenem 1gm IV q24 hours

EMPIRICAL ANTIBIOTIC
TREATMENT OF HCAP
PATIENTS WITH RISK FACTORS FOR MDR PATHOGENS
1. A beta-lactam:
Ceftazidime 2 gm IV q8 hours or Cefepime 2 gm IV q8-q12 hours or
Piperacillin/Tazobactam 4.5 gm IV q6 hours, Imipinem 500mg IV q6
hours or 1 gm IV q8 hours, Meropenem 1 gm IV q8 hours plus

2. A second agent active against gram-negative bacterial pathogens:

Gentamicin or Tobramycin 7 mg/kg IV q24 hours or Amikacin 20 mg/kg
IV q24 hours or
Ciprofloxacin 400mg IV q8 hours or Levofloxacin 750mg IV q24 hours
plus
3. An agent active against gram-positive bacterial pathogens:
Linezolid 600 mg IV q 24 hours or
Vancomycin 15mg/kg q12 hours

FAILURE TO IMPROVE
Due to MDR pathogens
Reintroduction of the microorganisms
Superinfection
Extrapulmonary infections
Drug toxicity

COMPLICATIONS
Death
Prolonged mechanical ventilation
Prolonged hospital stay
Development of necrotizing pneumonia
Long-term pulmonary complications
Inability of the patient to return to
independent function

PROGNOSIS
HCAP is associated with significant
mortality (50%-70%)
Presence of underlying diseases
increases mortality rate
Causative pathogen also plays a major
role

PATHOGENIC MECHANISMS AND

CORRESPONDING PREVENTION
STRATEGIES FOR VENTILATORASSOCIATED PNEUMONIA
Pathogenic Mechanism
Oropharyngeal colonization with
pathogenic bacteria
Elimination of normal flora
Large-volume oropharyngeal
aspiration around time of
intubation
Gastroesophageal reflux

Bacterial overgrowth of
stomach

Prevention Strategy

Avoidance of prolonged antiobiotic

courses
Short course of prophylactic antibiotics
for comatose patients
Postpyloric enteral feeding; avoidance
of high gastric residuals, prokinetic
agents
Avoidance of gastrointestinal bleeding due to
prophylactic agents that raise gastric pH;
selective decontamination of digestive tract
with nonabsorbable antibiotics

Pathogenic Mechanism
Cross-infection from other
colonized patients

Large-volume aspiration

Microaspiration around
endotracheal tube
Endotracheal intubation
Prolonged duration of
ventilation
Abnormal swallowing function
Secretions pooled above
endotracheal tube

Prevention Strategy
Hand washing, especially with alcohol
based hand rub; intensive infection
control education; isolation; proper
cleaning of reusable equipment
Endotracheal intubation; avoidance
of sedation; decompression of
small-bowel obstruction

Noninvasive ventilation
Daily awakening from sedation
weaning protocols
Early percutaneous tracheostomy
Head of bed elevated; continuous
aspiration of subglottic secretions

Pathogenic Mechanism

Altered lower respiratory host

defenses
formula

Prevention Strategy
with specialized endotracheal tube
avoidance of reintubation;
minimization of sedation and
patient transport
Tight glycemic control; lowering of
hemoglobin transfusion threshold;
specialized enteral feeding