IM2: PNEUMONIA AND OTHER INFECTIONS OF PULMONARY SYSTEM

ANDRE ANGELO G. TANQUE DATE: JUNE 16, 2011

*The term hepatization is used because the affected lobe appears distinctly
Objectives red, firm, and airless, with a liver-like consistency
*Gray hepatization is the phase where the RBCs have already
Define community-acquired pneumonia and hospital-acquired
disintegrated and the fibrin deposition renders the affected lobe with a
pneumonia.
grayish tinge.
Describe the pathophysiology of pneumonia. *In resolution, the remaining exudates are enzymatically digested to allow
Identify the most common pathogen associated with community- space for healing.
acquired 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. Gross and histologic changes in Pneumonia
Enumerate ways to prevent pneumonia and its transmission.

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 Classification of Pneumonia
Mechanical and Structural
Hairs/Turbinates
Cough and Gag reflex
Airway Anatomy
Mucociliary clearance
Normal oropharyngeal flora
*Hospital Acquired Pneumonia used to be a subclass but with the
Cellular
emergence of pneumonia associated with ventilator use and the findings
Alveolar Macrophages that causative agents come from the health workers themselves, it is
Epithelial cells consolidated into Health Care Associated Pneumonia
Neutrophils
Microbial Causes of CAP, by site of care
Humoral/Molecular/Inflammatory
IgG, IgA
Cytokines
Granulocyte colony stimulating factors

Pathology
1. Edema
Presence of proteinaceous exudate (bacteria) in alveoli
Epidemiologic factors suggesting possible causes of CAP
2. Red hepatization
Presence of RBC in the cellular intraalveolar exudate
3. Gray hepatization
Neutrophil is the predominant cell
Fibrin deposition is abundant
Bacteria disappeared
4. 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 1
transcribed by: anirtahk Some notes by KC
 IPD Preferentially Affects the Young and Older Adults
Incidence of IPD per 100,000 Population, England and Wales, 1998-2006

80 1998 1999 2000

2001 2002 2003
70

Incidence/100,000
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.

**The incidence of pneumococcal disease by age has a characteristic U-

LRTIS: A leading cause of disease globally: All Ages, 2004
shaped distribution with peaks at extremes of age.
The data in the graph show the incidence of IPD by age in England and
LRTIs: A Leading Cause of Disease Globally: All Ages, 2004 Wales between 1998 and 2006. 1Approximately 5,000-6,000 cases of IPD are
reported annually to the Health Protection Agency (HPA), Centre for
TIs

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Infections (CFI) from laboratories in England and Wales.

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infants has been observed over these years, the incidence of IPD in adults
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DALYS (millions)

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Risk factors for pneumonia

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Alcoholism
20

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Asthma - due to presence of secretions in the airways
0
1 2 3 4 5 6 7 8 9 10
Immunosuppression
Institutionalization
Rank
DALYS = disease-adjusted life-years
LRTIs = lower respiratory tract infections

Age > 70 years

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 Dementia
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 disease-
Seizure disorders
adjusted life-years (DALYs). Tobacco smoking
Globally, Pneumococcal Disease is a Leading Cause of Death in Young Chronic obstructive pulmonary disease (COPD)
Children and Older Adults
Globally, Pneumococcal Disease is a Leading
Clinical manifestation
Cause of Death in Young Children and Older Adults Fever
2 ,0 0 0 ,0 0 0
Tachycardia
002)

Chills and/or sweats

O2

A ll A g e s
H

C h ild r e n < 5 y r s
s(W

1 ,5 0 0 ,0 0 0

Productive or non-productive cough

erofdeath

1 ,0 0 0 ,0 0 0

Dyspnea
mb

Pleuritic chest pain (if pleura is involved)

dnu

5 0 0 ,0 0 0
Estimate

0 Fatigue, headache, myalgias

P n e um o co ccal M e a s le s R o ta v ir u s H ib P e r tu s s is T e ta n u s O th e r M e n in g o c o c c u s
d is e a s e

Vaccine Preventable Diseases

Physical findings
Increased RR
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, Use of accessory muscles of respiration
sinusitis, or nonbacteremic pneumonia. Increased tactile fremitus, dull percussion note for consolidation
Invasive pneumococcal disease includes bacteremia, meningitis, and
Decreased tactile fremitus, flat percussion note for effusion
bacteremic pneumonia.1,2 As this graph illustrates, pneumococcal disease
(invasive and noninvasive) is the leading cause of morbidity and vaccine- Crackles, bronchial breath sounds on auscultation
preventable death worldwide, particularly in young children, individuals
with chronic cardiopulmonary disease, older adults, and Etiologic Diagnosis
immunocompromised individuals of all ages. In 2005, there were an Cannot be determined on the basis of the clinical presentation
estimated 1.6 million pneumococcal disease fatalities globally, with 0.7-1.0
million of these fatalities occurring in children <5 years of age. Laboratory test are needed to establish etiology
IPD Preferentially Affects the Young and Older Adults Allows narrowing of the initial empirical regimen
Collected data show trends in resistance
CAP mimickers
Pulmonary edema
Pulmonary infarction
Acute respiratory distress syndrome (ARDS)

2 2
transcribed by: anirtahk Some notes by KC
 Pulmonary hemorrhage Blood culture
Lung cancer/metastatic cancer Only 5-14% of cultures of blood are positive
Atelectasis No longer considered necessary for all hospitalized CAP patients
Radiation pneumonitis
Drug reactions involving the lung Should be done in certain high-risk patients
Extrinsic allergic alveolitis
Antigen tests
Pulmonary vasculitis
Pulmonary eosinophilia
Two commercially available tests detect pneumococcal and
Legionella antigens in urine
Bronchiolitis obliterans and organizing pneumonia
Sensitivity and specificity are high for both tests
Criteria for Pneumonia
Can detect antigen even after the initiation of appropriate antibiotic
Cough therapy
Tachycardia CR > 100 Limited availability
Tachypnea RR > 20
Site of Care Decision
Fever T >37.8C Must take into consideration diminishing health care resources and
At least one abnormal chest findings rising costs of treatment
o diminished breath sounds, rhonchi, crackles or wheeze Decision to where a patient should be managed is sometimes
o New x-ray infiltrate with no clear alternative such as lung difficult
cancer or pulmonary edema Use of objective tools that assess risk of adverse
outcomes and severity of the disease (i.e. PSI;
Diagnosis CURB-65)
No particular clinical symptom/physical finding is sufficiently
sensitive or specific to confirm/exclude CAP Risk Categories for CAP

Specificity of history and PE- 67% Low risk CAP

Sensitivity of history and PE- 58% Moderate risk CAP
Chest radiography is necessary to help differentiate CAP from other 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
Streptococcus pneumoniae
Haemophilus influenzae
Chlamydia pneumoniae
*The photo on the left shows lobar pneumonia and the one on the right Mycoplasma pneumoniae
Moraxella catarrhalis
show an improved CXR result after antimicrobial therapy. 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

Diagnostic Tests Alternative

Gram stain 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

3 3
transcribed by: anirtahk Some notes by KC
 Empric antimicrobial therapy for High-risk CAP
Empric antimicrobial therapy for Antibiotic Dosage

Low-risk CAP Antipseudomonal, anti-pneumococcal -lactam

(BLIC, cephalosphorin, carbapenem)
Antibiotic Dosage Antibiotic Dosage Cefoperazone-sulbactam 1.5-2 gm q 8-12 h
Piperacillin-tazobactam 2.25-4.5 gm q 6-8 h
-lactam 2nd gen
Amoxicillin 500 mg TID cephalosphorin Ticarcillin-clavulanic acid 3.2 gm q 6 h
Cefipime 2 gm q 8-12 h
Cefaclor 500 mg TID or
750 mg BID Cefpirome 2 gm q 12
Cefuroxime 500 mg BID Imipinem-cilastatin 0.5 1 gm q 6-8 h
Meropenem 1-2 gm q 8 h
Macrolides 3rd gen
Aztihromycin 500 mg OD Cephalosphorin Antipseudomonal Floroquinolones IV
Levofloxacin 400 mg q 12
dihydrate Cefdinir 300 mg BID
Clarithromycin 500 mg BID Cefixime 200 mg BID Moxifloxacin 750 mg q 24

-lactam with BLIC Cefpodoxime 200 mg BID Others

Oxacilin (staphylococcus) 1-2 gm q 4-6 h
Amoxicillin- 625 mg TID or
Clindamycin (staphylococcus/anaerobes) 600 mg q 6-8 h
clavulanic acid 1 gm BID
Metronidazole (anaerobes) 500mg q 6-8 h
Amoxicillin- 1 gm TID
sulbactam Linezolid (MRSA) 600 mg q 12 h
Sultamicillin 750 mg BID Vancomycin (MRSA) 1 gm q 12

Empric antimicrobial therapy for Moderate-risk CAP Failure to improve within 48 to 72 hours

Empric antimicrobial therapy for Noninfectious conditions

Moderate-risk CAP
Potential Pathogen Empiric Therapy
o Cancer, embolus, hemorrhage
Streptococcus pneumoniae
Haemophilus influenzae
Chlamydia pneumoniae
Mycoplasma pneumoniae
IV non-antipseudomonal -lactam
(BLIC, cephalosphorin, or
carbapenem) + extended
macrolide
Resistant pathogen
Right drug, wrong dose
Moraxella catarrhalis
Enteric Gram negative bacilli OR
Legionella pneumophila
Anaerobes (among those with risk of IV non-antipseudomonal -lactam

Unusual pathogens
aspiration) (BLIC, cephalosphorin or
carbapenem) + respiratory
floroquinolone

o Mycobacterial, anaerobic, viral, fungal

Nosocomial superinfections
Empric antimicrobial therapy for
Moderate-risk CAP Complications
Antibiotic
Macrolides (IV/PO)
Dosage Antibiotic
2nd gen
Dosage
Respiratory failure
Aztihromycin 500 mg q 24 cephalosphorin
dihydrate
Clarithromycin 500 mg q12
Cefotiam
Cefoxitin
1 gm q 8
1-2 gm q 8
Shock; Multiorgan failure
Erythromycin
Antipneumococcal
0.5-1 gm q 6 Cefuroxime
3rd gen
1.5 gm q 8
Bleeding diathesis
Floroquinolones IV/PO Cephalosphorin
Levofloxacin 500-750 mg q24 Cefotaxime 1-2 gm q 8 Exacerbation of comorbid illnesses
Moxifloxacin 400 mg q 24 Ceftizoxime 1-2 gm q 8

-lactam with BLIC IV

Ceftriaxone
Carbapenem
1-2 gm q 24
Metastatic infections
Amoxicillin- 1.2 gm q 8 Ertapenem 1 gm q 24
clavulanic acid Brain abscess; Endocarditis
Amoxicillin- 1.5 gm q 8
sulbactam
Lung abscess
o usually occurs in the setting of aspiration
Empric antimicrobial therapy for High-risk CAP
o should be drained
Empric antimicrobial therapy for High-risk CAP
Potential Pathogen Empiric Therapy
Pleural effusion

Streptococcus pneumoniae No risk for Pseudomonas aeroginosa

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
o should be tapped for diagnostic and therapeutic purposes
IV non-antipseudomonal -lactam
(BLIC, cephalosphorin, or
carbapanem) + IV extended
macrolide or IV respiratory
quinolone
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 *To confirm if its pleural effusion, always look for the meniscus on the AP or
ciprofloxacin/levofloxacin (high dose)
lateral view. The second and third photos show the meniscus, which reflect
the presence of fluid. Always remember that a lateral decubitus view will
Empric antimicrobial therapy for allow confirmation as the fluid will be displaced in the CXR,
High-risk CAP
Antibiotic
Macrolides (IV)
Dosage Antibiotic
Aminoglycosides
Dosage
Immunization
Aztihromycin 500 mg q 24 Amikacin 15 mg/kg q 24
dihydrate Gentamicin 3 mg/kg q 24 INFLUENZA VACCINE
Clarithromycin 500 mg q12 Netilmicin 7 mg/kg q 24
Erythromycin
Antipneumococcal
0.5-1 gm q 6 Tobramicin
3rd gen
3 mg/kg q 24
> 50 yrs old
Floroquinolones IV
Levofloxacin
Moxifloxacin
500-750 mg q24
400 mg q 24
Cephalosphorin
Cefotaxime
Ceftizoxime
1-2 gm q 8
1-2 gm q 8
Chronic illness
-lactam with BLIC IV
Ceftriaxone
Carbapenem
1-2 gm q 24
Immune system disorder
Amoxicillin-
clavulanic acid
Amoxicillin-
1.2 gm q 8

1.5 gm q 8
Ertapenem 1 gm q 24
Residents of nursing homes
sulbactam
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 4
transcribed by: anirtahk 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 Empirical Antibiotic Treatment of HCAP
intubation
PATIENTS W/O RISK FACTORS FOR MDR PATHOGENS
Occurs in 9-27% of intubated patients Ceftriaxone 2g IV q24 hoursor
Hospital Acquired Pneumonia (HAP)
Defined as pneumonia that occurs 48 hours or more after admission, Moxifloxacin 400mg IV q24 hours,
which was not incubating at the time of admission Ciprofloxacin 400mg IV q8 hours,
Accounts for 25% of all ICU infections Levofloxacin 750mg IV q24 hoursor
Pathogenesis Ampicillin/Sulbactam 3 gm IV q6 hoursor
Colonization of the oropharynx with pathogenic microorganisms Ertapenem 1gm IV q24 hours
Aspiration from the oropharynx into the lower respiratory tract Empirical Antibiotic Treatment of HCAP
Compromise of the normal host defense mechanisms PATIENTS WITH RISK FACTORS FOR MDR PATHOGENS
1. A beta-lactam:
Clinical manifestation Ceftazidime 2 gm IV q8 hours or
Fever Cefepime 2 gm IV q8-q12 hours or

Leukocytosis Piperacillin/Tazobactam 4.5 gm IV q6 hours,

Imipinem 500mg IV q6 hours or 1 gm IV q8 hours, Meropenem
Increase in respiratory secretions 1 gm IV q8 hours plus

PE findings of consolidation 2. A second agent active against gram-negative bacterial

pathogens:
New or changing radiographic infiltrate Gentamicin or Tobramycin 7 mg/kg IV q24 hours or
Tachypnea Amikacin 20 mg/kg IV q24 hours or

Tachycardia Ciprofloxacin 400mg IV q8 hours or

Levofloxacin 750mg IV q24 hours plus
Worsening oxygenation 3. An agent active against gram-positive bacterial pathogens:
Increased minute ventilation Linezolid 600 mg IV q 24 hours or
Vancomycin 15mg/kg q12 hours
Factors causing overdiagnosis of VAP
Tracheal colonization with pathogenic bacteria in patients with ET Failure to Improve
tubes Due to MDR pathogens
Multiple alternative causes of radiographic infiltrates in Reintroduction of the microorganisms
mechanically ventilated patients
Superinfection
High frequency of other sources of fever in critically ill patients
Extrapulmonary infections
Risk factors for MDR pathogens Drug toxicity
Widespread use of potent antibiotics
Assessment of Nonresponders
Early transfer to home/low acuity care
ASSESSMENT OF NONRESPONDERS
Increased use of outpatient IV antibiotic
General aging population WRONG DIAGNOSIS
WRONG ORGANISM
More extensive immunomodulatory therapies
Atelectasis; Pulmonary
Drug resistant pathogen; Embolus; ARDS;
inadequate antimicrobial Pulmonary hemmorhage;
therapy underlying disease;
neoplasm

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

5 5
transcribed by: anirtahk 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 6
transcribed by: anirtahk Some notes by KC