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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 RBC’s 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 host’s 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

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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 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 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: β-lactam/β-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 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)

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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

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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 host’s response once

the pathogen is

encountered o Chemoprophylaxis

o Immunizing of patients at risk

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6 Some notes by KC 