IM2: PNEUMONIA AND OTHER INFECTIONS OF PULMONARY SYSTEM

ANDRE ANGELO G. TANQUE

Objectives
Define community-acquired pneumonia and hospital-acquired
pneumonia.
Describe the pathophysiology of pneumonia.
Identify the most common pathogen associated with communityacquired and hospital-acquired pneumonia in the local setting.
Discuss the clinical manifestations of patients with pneumonia.
Describe the diagnostic tools used to confirm pneumonia.
Explain the pharmacologic strategies in pneumonia management.
Summarize the approach to management of pneumonia according
the current local guidelines.
Enumerate ways to prevent pneumonia and its transmission.

DATE: JUNE 16, 2011

*The term hepatization is used because the affected lobe appears distinctly
red, firm, and airless, with a liver-like consistency
*Gray hepatization is the phase where the RBCs have already
disintegrated and the fibrin deposition renders the affected lobe with a
grayish tinge.
*In resolution, the remaining exudates are enzymatically digested to allow
space for healing.

Gross and histologic changes in Pneumonia

Pneumonia

Infection of the pulmonary parenchyma

Results from the proliferation of microbial pathogens at the alveolar
level and the hosts response to those pathogens

Pathogenesis

Aspiration of oropharyngeal content

Inhalation of microorganisms into the lower airways
Direct extension from the mediastinum or subphrenic space
Hematogenous seeding from an extrapulmonary focus
Host Defenses
Mechanical and Structural

Hairs/Turbinates

Cough and Gag reflex

Airway Anatomy

Mucociliary clearance

Normal oropharyngeal flora

Cellular

Alveolar Macrophages

Epithelial cells

Neutrophils
Humoral/Molecular/Inflammatory

IgG, IgA

Cytokines

Granulocyte colony stimulating factors

Classification of Pneumonia

*Hospital Acquired Pneumonia used to be a subclass but with the

emergence of pneumonia associated with ventilator use and the findings
that causative agents come from the health workers themselves, it is
consolidated into Health Care Associated Pneumonia
Microbial Causes of CAP, by site of care

Pathology

1.
2.
3.

4.

Edema

Presence of proteinaceous exudate (bacteria) in alveoli

Red hepatization

Epidemiologic factors suggesting possible causes of CAP

Presence of RBC in the cellular intraalveolar exudate

Gray hepatization

Neutrophil is the predominant cell

Fibrin deposition is abundant
Bacteria disappeared
Resolution

Macrophage is the dominant cell

Debris of neturophils, bacteria, and fibrin has been cleared
*Edema is written in some books as CONGESTION wherein it is
characterized by vascular engorgement, intra-alveolar fluid with few
neutrophils, and presence of bacteria

1
transcribed by: anirtahk

1
Some notes by KC

IPD Preferentially Affects the Young and Older Adults

Incidence of IPD per 100,000 Population, England and Wales, 1998-2006

Incidence/100,000

80
70

1998

1999

2000

2001

2002

2003

2004

2005

2006

60
50
40
30
20
10
0
<2 m o

2 -5 m o

6 -1 1 m o

1 -< 2

2 -4

5 -9

1 0 -1 4

1 5 -4 4

4 5 -6 4

6 5 -7 4

7 5 -7 9

80+

Age (years)
Incidence of IPD creates a U-shaped curve with peaks at extremes of age

Adapted from: Kaye P, et al. Poster presented at ESPID Brussels,June2009.

LRTIS: A leading cause of disease globally: All Ages, 2004

DALYS (millions)

80
70
60
50
40

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LR
TIs

LRTIs: A Leading Cause of Disease Globally: All Ages, 2004

30
20
10
0
1

10

Rank

DALYS = disease-adjusted life-years

LRTIs = lower respiratory tract infections

Adapted from: WHO Global Burden of Disease Report, 2004.

http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_part4.pdf. Table 12.

**Lower respiratory tract infections (LRTIs) are a leading cause of disease

burden in all age groups and income groups worldwide. In 2004, LRTIs
were the no. 1 cause of disease burden worldwide, accounting for nearly
430 million episodes of illness and nearly 95 million, or 6.2%, of all diseaseadjusted life-years (DALYs).
Globally, Pneumococcal Disease is a Leading Cause of Death in Young
Children and Older Adults
Globally, Pneumococcal Disease is a Leading
Cause of Death in Young Children and Older Adults
Estim
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**The incidence of pneumococcal disease by age has a characteristic Ushaped distribution with peaks at extremes of age.
The data in the graph show the incidence of IPD by age in England and
Wales between 1998 and 2006. 1Approximately 5,000-6,000 cases of IPD are
reported annually to the Health Protection Agency (HPA), Centre for
Infections (CFI) from laboratories in England and Wales.
Although some variation in the annual incidence of IPD in children and
infants has been observed over these years, the incidence of IPD in adults
remains consistent.
Risk factors for pneumonia

Alcoholism
Asthma - due to presence of secretions in the airways
Immunosuppression
Institutionalization
Age > 70 years
Dementia
Seizure disorders
Tobacco smoking
Chronic obstructive pulmonary disease (COPD)
Clinical manifestation
Fever
Tachycardia
Chills and/or sweats
Productive or non-productive cough
Dyspnea
Pleuritic chest pain (if pleura is involved)
Fatigue, headache, myalgias

M e n in g o c o c c u s

Vaccine Preventable Diseases

WHO Department of Immunization, Vaccines and Biologicals Data. September 2005.
WHO 2008 Global Immunization Data.

**Pneumococcal disease can be noninvasive, such as acute otitis media,

sinusitis, or nonbacteremic pneumonia.
Invasive pneumococcal disease includes bacteremia, meningitis, and
bacteremic pneumonia.1,2 As this graph illustrates, pneumococcal disease
(invasive and noninvasive) is the leading cause of morbidity and vaccinepreventable death worldwide, particularly in young children, individuals
with
chronic
cardiopulmonary
disease,
older
adults,
and
immunocompromised individuals of all ages. In 2005, there were an
estimated 1.6 million pneumococcal disease fatalities globally, with 0.7-1.0
million of these fatalities occurring in children <5 years of age.
IPD Preferentially Affects the Young and Older Adults

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
Etiologic Diagnosis

Cannot be determined on the basis of the clinical presentation

Laboratory test are needed to establish etiology
Allows narrowing of the initial empirical regimen
Collected data show trends in resistance
CAP mimickers
Pulmonary edema
Pulmonary infarction
Acute respiratory distress syndrome (ARDS)

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transcribed by: anirtahk

2
Some notes by KC

Blood culture

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

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
Antigen tests

Two

commercially available tests detect pneumococcal and

Legionella antigens in urine

Criteria for Pneumonia

Cough
Tachycardia CR > 100
Tachypnea RR > 20
Fever T >37.8C
At least one abnormal chest findings
o diminished breath sounds, rhonchi, crackles or wheeze
o New x-ray infiltrate with no clear alternative such as lung
cancer or pulmonary edema
Diagnosis

No particular clinical symptom/physical finding is sufficiently

sensitive or specific to confirm/exclude CAP

Specificity of history and PE- 67%

Sensitivity of history and PE- 58%
Chest radiography is necessary to help differentiate CAP from other

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
outcomes
and
severity
CURB-65)

that
of

assess risk of adverse

the
disease
(i.e.
PSI;

Risk Categories for CAP

Low risk CAP

Moderate risk CAP
High risk CAP

conditions

Chest radiograph

Confirm the diagnosis of

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

Empric antimicrobial therapy for Low-risk CAP

Empric antimicrobial therapy for

Low-risk CAP
Potential Pathogen

*The photo on the left shows lobar pneumonia and the one on the right
show an improved CXR result after antimicrobial therapy.
Diagnostic Tests
Gram stain

Streptococcus pneumoniae
Haemophilus influenzae
Chlamydia pneumoniae
Mycoplasma pneumoniae
Moraxella catarrhalis
Enteric Gram negative bacilli (among
those with co-morbid illness)

Empiric Therapy
Previously healthy:
amoxicillin OR extended macrolide
With stable comorbid illness:
-lactam/-lactamase inhibitor
combination (BLIC) or second
generation oral cephalosphorin +/extended macrolide
Alternative
third-generation oral
cephalosphorin +/- extended
macrolide

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

Sputum culture

Sensitivity and specificity is highly variable (< 50%)

Greatest benefit is to alert the physician of unsuspected

and/or

resistant pathogens

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transcribed by: anirtahk

3
Some notes by KC

Empric antimicrobial therapy for

Low-risk CAP
Antibiotic

Dosage

-lactam
Amoxicillin

Antibiotic

Dosage

2nd gen
cephalosphorin
Cefaclor

500 mg TID

500 mg TID or
750 mg BID
500 mg BID

Cefuroxime
Macrolides
Aztihromycin
dihydrate
Clarithromycin

3rd gen
Cephalosphorin
Cefdinir
Cefixime

500 mg OD
500 mg BID

-lactam with BLIC

Amoxicillinclavulanic acid
Amoxicillinsulbactam
Sultamicillin

300 mg BID
200 mg BID

Cefpodoxime

200 mg BID

625 mg TID or
1 gm BID
1 gm TID
750 mg BID

Empric antimicrobial therapy for Moderate-risk CAP

Potential Pathogen

Empiric Therapy
IV non-antipseudomonal -lactam
(BLIC, cephalosphorin, or
carbapenem) + extended
macrolide
OR
IV non-antipseudomonal -lactam
(BLIC, cephalosphorin or
carbapenem) + respiratory
floroquinolone

Empric antimicrobial therapy for

Moderate-risk CAP
Antibiotic

Dosage

Macrolides (IV/PO)
Aztihromycin
dihydrate
Clarithromycin
Erythromycin

500 mg q12
0.5-1 gm q 6

Antipneumococcal
Floroquinolones IV/PO
Levofloxacin
Moxifloxacin
-lactam with BLIC IV
Amoxicillinclavulanic acid
Amoxicillinsulbactam

Antibiotic

500 mg q 24

500-750 mg q24
400 mg q 24

1.2 gm q 8

Dosage

2nd gen
cephalosphorin
Cefotiam
Cefoxitin
Cefuroxime

1 gm q 8
1-2 gm q 8
1.5 gm q 8

3rd gen
Cephalosphorin
Cefotaxime
Ceftizoxime
Ceftriaxone

1-2 gm q 8
1-2 gm q 8
1-2 gm q 24

Carbapenem
Ertapenem

1 gm q 24

1.5 gm q 8

Empric antimicrobial therapy for High-risk CAP

Empric antimicrobial therapy for High-risk CAP

Potential Pathogen
Streptococcus pneumoniae
Haemophilus influenzae
Chlamydia pneumoniae
Mycoplasma pneumoniae
Moraxella catarrhalis
Enteric Gram negative bacilli
Legionella pneumophila
Anaerobes (among those with risk of
aspiration)
Staphylococcus aureus
Pseudomonas aeroginosa

Antibiotic

Dosage

1.5-2 gm q 8-12 h
2.25-4.5 gm q 6-8 h
3.2 gm q 6 h
2 gm q 8-12 h
2 gm q 12
0.5 1 gm q 6-8 h
1-2 gm q 8 h

Antipseudomonal Floroquinolones IV
Levofloxacin
Moxifloxacin

400 mg q 12
750 mg q 24

Others
Oxacilin (staphylococcus)
Clindamycin (staphylococcus/anaerobes)
Metronidazole (anaerobes)
Linezolid (MRSA)
Vancomycin (MRSA)

1-2 gm q 4-6 h
600 mg q 6-8 h
500mg q 6-8 h
600 mg q 12 h
1 gm q 12

Failure to improve within 48 to 72 hours

Empric antimicrobial therapy for

Moderate-risk CAP
Streptococcus pneumoniae
Haemophilus influenzae
Chlamydia pneumoniae
Mycoplasma pneumoniae
Moraxella catarrhalis
Enteric Gram negative bacilli
Legionella pneumophila
Anaerobes (among those with risk of
aspiration)

Empric antimicrobial therapy for High-risk CAP

Antipseudomonal, anti-pneumococcal -lactam
(BLIC, cephalosphorin, carbapenem)
Cefoperazone-sulbactam
Piperacillin-tazobactam
Ticarcillin-clavulanic acid
Cefipime
Cefpirome
Imipinem-cilastatin
Meropenem

Empiric Therapy
No risk for Pseudomonas aeroginosa
IV non-antipseudomonal -lactam
(BLIC, cephalosphorin, or
carbapanem) + IV extended
macrolide or IV respiratory
quinolone

Noninfectious conditions
o Cancer, embolus, hemorrhage
Resistant pathogen
Right drug, wrong dose
Unusual pathogens
o 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
o usually occurs in the setting of aspiration

o should be drained
Pleural effusion
o should be tapped for diagnostic and therapeutic purposes

With risk for Pseudomonas aeroginosa

IV antipneumococal
antipseudomonal -lactam (BLIC,
cephalosphorin or carbapanem) + IV
extended macrolide + aminoglycoside
OR
IV antipneumococal antipseudomonal
-lactam (BLIC, cephalosphorin or
carbapenem) + IV
ciprofloxacin/levofloxacin (high dose)

Empric antimicrobial therapy for

High-risk CAP
Antibiotic
Macrolides (IV)
Aztihromycin
dihydrate
Clarithromycin
Erythromycin
Antipneumococcal
Floroquinolones IV
Levofloxacin
Moxifloxacin
-lactam with BLIC IV
Amoxicillinclavulanic acid
Amoxicillinsulbactam

Dosage
500 mg q 24
500 mg q12
0.5-1 gm q 6

500-750 mg q24
400 mg q 24

1.2 gm q 8
1.5 gm q 8

Antibiotic

Dosage

Aminoglycosides
Amikacin
Gentamicin
Netilmicin
Tobramicin

15 mg/kg q 24
3 mg/kg q 24
7 mg/kg q 24
3 mg/kg q 24

3rd gen
Cephalosphorin
Cefotaxime
Ceftizoxime
Ceftriaxone

1-2 gm q 8
1-2 gm q 8
1-2 gm q 24

Carbapenem
Ertapenem

1 gm q 24

*To confirm if its pleural effusion, always look for the meniscus on the AP or
lateral view. The second and third photos show the meniscus, which reflect
the presence of fluid. Always remember that a lateral decubitus view will
allow confirmation as the fluid will be displaced in the CXR,
Immunization
INFLUENZA VACCINE

> 50 yrs old

Chronic illness

Immune system disorder

Residents of nursing homes

Health care workers

Persons in contact with high risk patients

PNEUMOCOCCAL VACCINE

> 60 yrs old

Chronic illness: cardiovascular disease, lung disease,

DM, alcohol abuse, chronic liver disease, asplenia

Immune system disorder: HIV, malignancy

Health Care-Associated Pneumonia (HCAP)

4
transcribed by: anirtahk

4
Some notes by KC

 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

Ventilator Associated Pneumonia (VAP)

Pneumonia that arises more than 48-72 hours after endotracheal

intubation

Occurs in 9-27% of intubated patients

Hospital Acquired Pneumonia (HAP)
Defined as pneumonia that occurs 48 hours or more after admission,
which was not incubating at the time of admission

Accounts for 25% of all ICU infections

Pathogenesis

Colonization of the oropharynx with pathogenic microorganisms

Aspiration from the oropharynx into the lower respiratory tract
Compromise of the normal host defense mechanisms

Empirical Antibiotic Treatment of HCAP

PATIENTS W/O RISK FACTORS FOR MDR PATHOGENS

Ceftriaxone 2g IV q24 hoursor

Moxifloxacin 400mg IV q24 hours,
Ciprofloxacin 400mg IV q8 hours,
Levofloxacin 750mg IV q24 hoursor
Ampicillin/Sulbactam 3 gm IV q6 hoursor
Ertapenem 1gm IV q24 hours
Empirical Antibiotic Treatment of HCAP
PATIENTS WITH RISK FACTORS FOR MDR PATHOGENS

1.

Clinical manifestation

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

Risk factors for MDR pathogens

Widespread use of potent antibiotics

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

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
Assessment of Nonresponders

ASSESSMENT OF NONRESPONDERS

WRONG ORGANISM
Drug resistant pathogen;
inadequate antimicrobial
therapy

WRONG DIAGNOSIS
Atelectasis; Pulmonary
Embolus; ARDS;
Pulmonary hemmorhage;
underlying disease;
neoplasm

COMPLICATION
Empyema or Lung Abscess
Clostridium difficile colitis,
occult infectiuon, drug
fever

5
transcribed by: anirtahk

5
Some notes by KC

Complications

Death
Prolonged mechanical ventilation
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
Streamlining of Empiric Antibiotic Therapy
There is less cough and resolution of respiratory distress
(normalization of RR)
The patient is afebrile for > 24 hours.
The etiology is not a high risk (virulent/resistant) pathogen.
There is no unstable co-morbid condition or life-threatening
complication such as MI, CHF, complete heart block, new atrial
fibrillation, supraventricular tachycardia, etc.
There is no obvious reason for continued hospitalization such
as hypotension, acute mental changes, BUN: Cr of >10:1,
hypoxemia, metabolic acidosis, etc
Prevention

Decreasing likelihood of encountering the pathogen

o hand washing
o use of gloves
o Use of face mask
o Negative pressure room
o Prompt institution of effective chemotherapy for patients with
contagious illnesses

Correction of condition that facilitate aspiration

o Maintenance of gastric acidity
o Strengthening the hosts response once

the pathogen is

encountered
o Chemoprophylaxis

o Immunizing of patients at risk

6
transcribed by: anirtahk

6
Some notes by KC