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