Julio A. Ramirez, MD, FACP Professor of Medicine Chief, Infectious Diseases University of Louisville Chief, Infectious Diseases Veterans Affairs Medical.

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Presentation transcript:

Julio A. Ramirez, MD, FACP Professor of Medicine Chief, Infectious Diseases University of Louisville Chief, Infectious Diseases Veterans Affairs Medical Center Louisville, Kentucky, USA Clinical Outcomes in Patients with Community-Acquired Pneumonia

1. CAP Pathogenesis 2. CAP Early Clinical Outcomes 3. CAP Late Clinical Outcomes CAP Clinical Outcomes

Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Pneumonia Pathogenesis Alveolar Macrophage Capillary Pneumonia White Blood Cell Lymphatic

Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Alveolar Macrophage Capillary Pneumonia White Blood Cell Lymphatic Pneumonia Pathogenesis

Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Cytokines Pneumonia Generation of Cytokines White Blood Cell Lymphatic Pneumonia Pathogenesis

Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Cytokines Pneumonia Generation of Cytokines White Blood Cell Lymphatic Cytokines White Blood Cell Lymphatic Proinflammatory Cytokines Anti-inflammatory Cytokines Chemotactic Cytokines (Chemokines) CCL2 CCL3 CCL4 CCL5 CXCL1 (KC) CXCL10 (IP-10) IL-1 IL-1β IL-6 TNF-α G-CSF IFN-γ Interleukin-10 (IL-10) IL-1 receptor antagonist (IL-1ra) Pneumonia Pathogenesis

Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Pneumonia Activation of Neutrophils White Blood Cell Lymphatic Pneumonia Pathogenesis Local Inflammatory Response

Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Pneumonia Consolidation Phase Cytokines White Blood Cell Neutrophils Monocytes B / T cells Dendritic cells Lymphatic Fluid/Proteins Pneumonia Pathogenesis

Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Pneumonia Consolidation Phase Cytokines White Blood Cell Neutrophils Monocytes B / T cells Dendritic cells Lymphatic Fluid/Proteins Pneumonia Pathogenesis Local Inflammatory Response Systemic Inflammatory Response

Days A A ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001 Diagnosis Local Inflammatory Response Systemic Inflammatory Response Severity of Disease Pneumonia Pathogenesis

Days A A ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001 v Diagnosis FeverLeukocytosisCRPESRProcalcitonin CoughSputumTachypneaHypoxemiaInfiltrate Local Inflammatory Response Systemic Inflammatory Response Severity of Disease Pneumonia Pathogenesis

Days A A ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001 v Diagnosis FeverLeukocytosisCRPESRProcalcitonin CoughSputumTachypneaHypoxemiaInfiltrate Local Inflammatory Response Systemic Inflammatory Response Severity of Disease Pneumonia Pathogenesis

1. CAP Pathogenesis 2. CAP Early Clinical Outcomes 3. CAP Late Clinical Outcomes CAP Clinical Outcomes

Days Severity of Disease A A CAP: Clinical Outcomes

Days Severity of Disease A A Clinical Response to Therapy CAP: Clinical Outcomes ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease B B A A CAP: Clinical Outcomes ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeteriorationLateClinicalDeteriorationLateClinicalDeterioration B B A A CAP: Clinical Outcomes ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A CAP: Clinical Outcomes ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A CAP: Clinical Outcomes

Days Clinical Response Clinical Response Severity Severity of Disease of Disease CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes Point of Clinical Stability

Clinical Response Clinical Response X-ray Resolution X-ray Resolution Severity Severity of Disease of Disease Pulmonary Infiltrate Infiltrate Days CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes

Clinical Response Clinical Response X-ray Resolution X-ray Resolution Severity Severity of Disease of Disease Pulmonary Infiltrate Infiltrate Inflammatory Markers Markers Immune Response Immune Response Days CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes

Micro Response Micro Response Clinical Response Clinical Response X-ray Resolution X-ray Resolution Severity Severity of Disease of Disease Pulmonary Infiltrate Infiltrate Bacterial Bacterial Colony Colony Counts Counts Inflammatory Markers Markers Immune Response Immune Response Days CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes

Micro Response Micro Response Clinical Response Clinical Response X-ray Resolution X-ray Resolution Severity Severity of Disease of Disease Pulmonary Infiltrate Infiltrate Bacterial Bacterial Colony Colony Counts Counts Inflammatory Markers Markers Immune Response Immune Response Days Time to Switch Therapy CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes Time to Clinical Stability Point of Clinical Stability Point of Switch Therapy

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A CAP: Clinical Outcomes

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A CAP: Clinical Outcomes

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A CAP: Clinical Outcomes

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes CAP Severe CAP

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Aliberti S et al. Chest. 2008;134:

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Aliberti S et al. Chest. 2008;134: Etiology of Failure 1. Severe Sepsis (33%)

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Etiology of Failure 1. Severe Sepsis (33%) 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days LateClinicalDeteriorationLateClinicalDeterioration B B

LIR Local Infection Clinical Outcomes

LIRSIRS Local Infection CAP Clinical Outcomes

LIRSIRS Organ Dysfunction/FailureMODS Local Infection CAP Severe CAP Clinical Outcomes

LIRSIRS Organ Dysfunction/FailureMODS Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, Local Infection Sepsis Severe Sepsis Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Mortality rates increase in patients >65yo (↓immunologic response to infection) Clinical Outcomes

LIRSIRS Organ Dysfunction/FailureMODS Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Mortality rates increase in patients >65yo (↓immunologic response to infection) Local Infection CAP Severe CAP Clinical Outcomes

Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG LIRSIRS Organ Dysfunction/FailureMODS Mortality rates increase in patients >65yo (↓immunologic response to infection) Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, CURB-65 Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Local Infection CAP Severe CAP PSI Clinical Outcomes

Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG LIRSIRS Organ Dysfunction/FailureMODS Mortality rates increase in patients >65yo (↓immunologic response to infection) Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Local Infection CAP Severe CAP CURB-65 PSI Clinical Outcomes

Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG LIRSIRS Organ Dysfunction/FailureMODS Mortality rates increase in patients >65yo (↓immunologic response to infection) Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, Local Infection CAP Severe CAP CURB-65 PSI Clinical Outcomes

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Clinical Failure: Severe Sepsis 30%

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Clinical Failure: AMI 20%

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Ramirez J et al. Clin Infec Dises. 2008;47:182-7 Clinical Failure: AMI 20%

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Ramirez J et al. Clin Infec Dises. 2008;47:182-7 Clinical Failure: AMI 20%

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Clinical Failure: AMI 20%

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Clinical Failure: Males vs Females

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes Clinical Failure: Males vs Females

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes CAP due to Mycobacterium tuberculosis CAP due to Mycobacterium tuberculosis CAP complicated with empyema CAP complicated with empyema CAP associated with deterioration of CAP associated with deterioration of preexisting medical conditions (COPD, CHF) preexisting medical conditions (COPD, CHF)

EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration B B A A Clinical Outcomes 100% 15% 45%25% 5% 10%

1. CAP Pathogenesis 2. CAP Early Clinical Outcomes 3. CAP Late Clinical Outcomes CAP Clinical Outcomes

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP: Clinical Outcomes

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP: Clinical Outcomes 2 3 4

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP Re-hospitalization CAP: Clinical Outcomes Death 2 3 4

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP Re-hospitalization CAP: Clinical Outcomes Death Weeks ClinicalImprovementClinicalImprovement B B AMI (+): 31% AMI (-): 10%

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP Clinical Cure: Resolution of S&S with resolution of pulmonary infiltrate CAP: Clinical Outcomes

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP (+) 624 CAP (-) 6,347 Long Term Survival: 5 years CAP: Clinical Outcomes

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP: Clinical Outcomes

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP (-) 6,347 CAP (+) 624 CAP: Clinical Outcomes

Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP: Clinical Outcomes

Weeks Years Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement C C ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP Mortality: Days after diagnosis CAP Mortality: Weeks after diagnosis CAP Mortality: Years after diagnosis Weeks Years Days Acute Systemic Inflammatory Disease CAP: Clinical Outcomes

Weeks Years Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement C C ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP Mortality: Days after diagnosis CAP Mortality: Weeks after diagnosis CAP Mortality: Years after diagnosis Weeks Years Days Acute Systemic Inflammatory Disease Chronic Systemic Inflammatory Disease? CAP: Clinical Outcomes

Pneumonia: Clinical Outcomes

1. CAP Pathogenesis 2. CAP Early Clinical Outcomes 3. CAP Late Clinical Outcomes CAP Clinical Outcomes