PNEUMONIA
Gerardo P. Morato, M.D. Section of Pulmonary Medicine
Department of Internal Medicine De La Salle University Medical Center
Infection of the alveoli, distal airways, and interstitium.
PNEUMONIA
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
PATHOGENESIS
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
HOST DEFENSES
Edema- Presence of
proteinaceous exudates and often bacteria
PATHOLOGY
PATHOLOGY
RED HEPATIZATION
- presence of erythrocytes in the intraalveolar exudate
- neutrophils are also present
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
PATHOLOGY
Community acquired pneumonia (CAP) - Typical
- Atypical
*Aspiration
Hospital Acquired Pneumonia (HAP)
- Early onset
- Late onset
- Ventilator associated
CLASSIFICATION (OLD)
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
RISK FACTORS FOR MDR PATHOGENS
Community acquired pneumonia (CAP)
Health Care-Associated Pneumonia (HCAP)
- Hospital-Acquired Pneumonia (HAP)
- Ventilator-Associated pneumonia (VAP)
CURRENT CLASSIFICATION
COMMUNITY-ACQUIRED PNEUMONIA
MICTROBIAL CAUSES OF COMMUNITY-ACQUIRED PNEUMONIA, BY SITE OF CARE
Hospitalization Patients
Outpatients Non-ICU ICU
Streptococcus pneumoniae S. pneumoniae S. pneumoniaeMycoplasma pneumoniae M. pneumoniae Staphylococcus aereusHaenophilus influenzae Chlamydophila Legionella spp.C. Pneumoniae pneumoniae Gram-negative bacilliRespiratory 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, Klebsiella pneumoniae, Acinetobacter spp., Mycobacterium tuberculosisCOPD and/or smoking Haemophilus influenzae, Pseudomonas aeruginosa, Legionella spp., S pneumoniae Moraxella catarrhalis, Chlamydophila pneumoniaeStructural lung disease P. aeruginosa, Burkholderia cepacia, Staphy- lococcus aureusDementia stroke, decreased Oral anaerobes, gram-negative enteric bacteria level of conciousnessLung abscess CA_MRSA, oral anaerobes, endemic fungi, M. tuberculosis, atypical mycobacteriaTravel to Ohio or St. Histoplasma capsulatum Lawrence river valleysTravel to Southwestern 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 MORBIDITYRate/100,000 PopulationPHILIPPINES, 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 MORTALITYNumber and Rate/100,000 PopulationPHILIPPINES, 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
Alcoholism Asthma Immunosuppression Institutionalization Age > 70 years Dementia Seizure disorders Tobacco smoking Chronic obstructive pulmonary disease (COPD)
RISK FACTORS FOR CAP
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
CLINICAL MANIFESTATIONS
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
PHYSICAL FINDINGS
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
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
Diagnosis, Empiric Management and Prevention of
COMMUNITY-ACQUIRED PNEUMONIAIn Immunocompetent Adult
2004 Philippine Consensus Guideline
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
CRITERIA FOR PNEUMONIA
CHEST RADIOGRAPH
Confirm the diagnosis of pneumonia
Assess severity of disease and presence of complication
Suggest possible etiology
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
ETIOLOGIC DIAGNOSIS
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
DIAGNOSTIC TESTS
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)
SITE OF CARE DECISION
Diagnosis, Empiric Management and Prevention of
COMMUNITY-ACQUIRED PNEUMONIAIn Immunocompetent Adult
2004 Philippine Consensus Guideline
Low risk CAP
Moderate risk CAP
High risk CAP
RISK CATEGORIES FOR 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)
LOW 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
MODERATE 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
HIGH RISK CAP
Any of the ff:1. RR > 30/min2. PR > 125/min3. Tº > 40ºC or < 35ºC4. Extrapulmonary
evidence of sepsis5. Suspected aspiration6. Unstable comorbid
conditions7. CXR: multilobar,
pleural effusion,abscess, progression to >50% within 24 hrs
Any of the ff:1. Shock or signsof hypoperfusion:
- Hypotension-Altered mental state
-urine output <30ml/hr2. PaO2 < 60mmHgacute hypocapneaPaCO2>50mmHg
COMMUNITY ACQUIRED PNEUMONIA
LOW RISK CAP
MODERATE RISK CAP
HIGH RISK CAP
Outpatient Ward Admission
ICU Admission
YES YES
NO
NO
Algorithm: Management-Oriented Risk Stratification of
Community-Acquired PneumoniaIn Immunocompetent Adults
MICTROBIAL CAUSES OF COMMUNITY-ACQUIRED PNEUMONIA, BY SITE OF CARE
Hospitalization Patients
Outpatients Non-ICU ICU
Streptococcus pneumoniae S. pneumoniae S. pneumoniaeMycoplasma pneumoniae M. pneumoniae Staphylococcus aereusHaenophilus influenzae Chlamydophila Legionella spp.C. Pneumoniae pneumoniae Gram-negative bacilliRespiratory viruses H. influenzae H. influenzae Legionella spp. Respiratory viruses
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
EMPIRICAL ANTIBIOTIC TREATMENT
Adequate hydration Oxygen therapy for hypoxemia Assisted ventilation when necessary
GENERAL CONSIDERATIONS
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
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
COMPLICATIONS
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 hrs2. Temperature normalizes within 5 days3. 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 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 CARE-ASSOCIATED PNEUMONIA
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
DEFINITIONS
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
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
Pathogen
Colonization of the oropharynx with pathogenic microorganisms
Aspiration from the oropharynx into the lower respiratory tract
Compromise of the normal host defense mechanisms
PATHOGENESIS
Fever Leukocytosis Increase in respiratory secretions PE findings of consolidation New or changing radiographic infiltrate Tachypnea Tachycardia Worsening oxygenation Increased minute ventilation
CLINICAL MANIFESTATIONS
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
FACTORS CAUSING OVERDIAGNOSIS OF VAP
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 PATHOGENS1. A beta-lactam:Ceftazidime 2 gm IV q8 hours or Cefepime 2 gm IV q8-q12 hours orPiperacillin/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 orCiprofloxacin 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 orVancomycin 15mg/kg q12 hours
EMPIRICAL ANTIBIOTIC TREATMENT OF HCAP
Due to MDR pathogens Reintroduction of the microorganisms Superinfection Extrapulmonary infections Drug toxicity
FAILURE TO IMPROVE
Death Prolonged mechanical ventilation Prolonged hospital stay Development of necrotizing pneumonia Long-term pulmonary complications Inability of the patient to return to
independent function
COMPLICATIONS
HCAP is associated with significant mortality (50%-70%)
Presence of underlying diseases increases mortality rate
Causative pathogen also plays a major role
PROGNOSIS
PATHOGENIC MECHANISMS AND CORRESPONDING PREVENTION STRATEGIES FOR VENTILATOR-
ASSOCIATED PNEUMONIAPathogenic Mechanism Prevention StrategyOropharyngeal colonization withpathogenic 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 intubationGastroesophageal reflux Postpyloric enteral feeding; avoidance of high gastric residuals, prokinetic agentsBacterial 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 Prevention StrategyCross-infection from other Hand washing, especially with alcohol colonized patients based hand rub; intensive infection control education; isolation; proper cleaning of reusable equipmentLarge-volume aspiration Endotracheal intubation; avoidance of sedation; decompression of small-bowel obstructionMicroaspiration around endotracheal tube Endotracheal intubation Noninvasive ventilation Prolonged duration of Daily awakening from sedation ventilation weaning protocols Abnormal swallowing function Early percutaneous tracheostomy Secretions pooled above Head of bed elevated; continuous endotracheal tube aspiration of subglottic secretions
Pathogenic Mechanism Prevention Strategy
with specialized endotracheal tube
avoidance of reintubation;
minimization of sedation and
patient transport
Altered lower respiratory host Tight glycemic control; lowering of
defenses hemoglobin transfusion threshold;
specialized enteral feeding formula