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 (HAP)

- Early onset
- Late onset
- Ventilator associated
 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 Non-ICU ICU

Streptococcus pneumoniae S. pneumoniae S. pneumoniae

Mycoplasma pneumoniae M. pneumoniae Staphylococcus aereus
Haenophilus influenzae Chlamydophila Legionella spp.
C. Pneumoniae pneumoniae Gram-negative bacilli
Respiratory viruses H. influenzae H. influenzae
Legionella spp.
Respiratory viruses
 EPIDEMIOLOGIC FACTORS
SUGGESTING POSSIBLE CAUSES OF
COMMUNITY-ACQUIRED PNEUMONIA
Factor Possible Pathogen(s)

Alcoholism Streptococcus pneumoniae, oral anaerobes,

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
Klebsiella pneumoniae, Acinetobacter spp.,
Mycobacterium tuberculosis
Haemophilus influenzae, Pseudomonas
aeruginosa, Legionella spp., S pneumoniae
Moraxella catarrhalis, Chlamydophila
pneumoniae
P. aeruginosa, Burkholderia cepacia, Staphy-
lococcus 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 Burkholderia pseudomallei, avian influennza
virus
Stay in hotel or on cruise Legionella spp,
ship in previous 2 weeks
Local influenza activity Influenza virus, 5. pneumoniae, S. aureus
Exposure to bats or birds H. capsulatum
Exposure to birds Chlamydophila psittaci
Exposure to rabbits Francisella tularensis
Exposure to sheep, goats, Coxiella burnetii
parturient cats
 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 risk CAP

 High 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 Algorithm: Management-Oriented
ACQUIRED PNEUMONIA Risk Stratification of
Community-Acquired Pneumonia
In Immunocompetent Adults
Any of the ff:
1. RR > 30/min
2. PR > 125/min
3. Tº > 40ºC or < 35ºC Any of the ff:
4. Extrapulmonary 1. Shock or signs
evidence of sepsis of hypoperfusion:
5. Suspected aspiration YES - Hypotension YES
6. Unstable comorbid -Altered mental state HIGH RISK CAP
conditions -urine output <30ml/hr
7. CXR: multilobar, 2. PaO2 < 60mmHg
pleural effusion, acute hypocapnea
ICU Admission
abscess, PaCO2>50mmHg
progression
to >50% NO
within 24 hrs
NO MODERATE RISK CAP

LOW RISK CAP

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

Outpatients Non-ICU ICU

Streptococcus pneumoniae S. pneumoniae S. pneumoniae

Mycoplasma pneumoniae M. pneumoniae Staphylococcus aereus
Haenophilus influenzae Chlamydophila Legionella spp.
C. Pneumoniae pneumoniae Gram-negative bacilli
Respiratory viruses 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 : < 5%

 Moderate risk : 21%
 High risk : 36%
 IMMUNIZATION
 PNEUMOCOCCAL  INFLUENZA VACCINE
VACCINE
 > 60 yrs old
 Chronic illness:
cardiovascular disease,
lung disease, DM, alcohol
abuse, chronic liver
disease, asplenia
 Immune system disorder:
HIV, malignancy
 > 50 yrs old
 Chronic illness
 Immune system disorder
 Residents of nursing
homes
 Health care workers
 Persons in contact with
high risk patients
HEALTH CARE-
ASSOCIATED 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 MDR Pathogens

Streptococcus pneumoniae Pseudomonas aeruginosa

Other Streptococcus spp. MRSA
Haemophilus influenzae Acinetobacter spp.
MSSA Antibiotic-resistant Enterobacteriaceae
Antibiotic-sensitive Enterobacteriaceae Enterobacter spp.
Escherichia coli ESBL-positive strains
Klebsiella pneumoniae Klebsiella spp.
Proteus spp. Legionella pneumophila
Enterobacter spp. Burkholderia cepacia
Serratia marcescens Aspergillus
 CLINICAL CONDITIONS ASSOCIATED
WITH AND LIKELY PATHOGENS IN
HEALTH CARE-ASSOCIATED PNEUMONIA
Pathogen

Pseudomonas Acinetobacter MDR

Condition MRSA aeruginosa spp. Enterobacteriacease

Hospitalization for ≥48 h x x x x

Hospitalization for ≥2 x x x x
days in prior 3 months
Nursing home or extended- x x x x
care facility residence
Antibiotic therapy in x x
preceding 3 months
Chronic dialysis x
Home infusion therapy x
Home wound care x
Family member with x x
MDR infection
 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 VENTILATOR-
ASSOCIATED PNEUMONIA
Pathogenic Mechanism Prevention Strategy
Oropharyngeal colonization with
pathogenic bacteria
Elimination of normal flora Avoidance of prolonged antiobiotic
courses
Large-volume oropharyngeal Short course of prophylactic antibiotics
aspiration around time of for comatose patients
intubation
Gastroesophageal reflux Postpyloric enteral feeding; avoidance
of high gastric residuals, prokinetic
agents
Bacterial overgrowth of Avoidance of gastrointestinal bleeding due to
stomach 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
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 formula