7343603 Med Ppt Pneumonia for Lecture

PNEUMONIA Gerardo P. Morato, M.D. Section of Pulmonary Medicine Department of Internal Medicine De La Salle University Medical Center

PNEUMONIAInfection of the alveoli, distal airways, and interstitium.

PATHOGENESIS 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

HOST DEFENSES 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

PATHOLOGY Edema- Presence of proteinaceous exudates and often bacteria

PATHOLOGY

RED HEPATIZATION- presence of erythrocytes in the intraalveolar exudate- neutrophils are also present

PATHOLOGY 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

PATHOLOGYBRONCHOPNEUMONIA

Patchy consolidation in 1 or more lobes

PATHOLOGYINTERSTITIAL PNEUMONIA

Inflammatoryprocess involving the interstitium, alveolar walls and connective tissues

PATHOLOGYMILIARY PNEUMONIA

Numerous discrete lesions of hematogenous spread

CLASSIFICATION (OLD)Community acquired pneumonia (CAP) - Typical- Atypical*AspirationHospital Acquired Pneumonia (HAP) - Early onset- Late onset- Ventilator associated

RISK FACTORS FOR MDR PATHOGENSWidespread use of potent antibiotics Early transfer to home/low-acuity careIncreased use of outpatient IV antibiotic therapyGeneral aging of the populationMore extensive immunomodulatory therapies

CURRENT CLASSIFICATIONCommunity acquired pneumonia (CAP) Health Care-Associated Pneumonia (HCAP) - Hospital-Acquired Pneumonia (HAP)- Ventilator-Associated pneumonia (VAP)

COMMUNITY-ACQUIRED PNEUMONIA

MICTROBIAL CAUSES OF COMMUNITY-ACQUIRED PNEUMONIA, BY SITE OF CAREHospitalization PatientsOutpatients 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 PNEUMONIAFactor 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 StatesTravel to Southeast Asia Burkholderia pseudomallei, avian influennza virusStay in hotel or on cruise Legionella spp, ship in previous 2 weeksLocal influenza activity Influenza virus, 5. pneumoniae, S. aureusExposure to bats or birds H. capsulatumExposure to birds Chlamydophila psittaciExposure to rabbits Francisella tularensisExposure to sheep, goats, Coxiella burnetii parturient cats

TEN LEADING CAUSES OF MORBIDITY Rate/100,000 Population PHILIPPINES, 1999

TEN LEADING CAUSES OF MORBIDITY Rate/100,000 Population PHILIPPINES, 1999

CauseNumberRate1. Diarrheas908,454 1189.9 2. Bronchitis/Bronchiolitis717,214 939.4 3. Pneumonia693,334 908.1 4. Influenza514,198 673.5 5. Hypertension208,248 272.8 6. T.B. Respiratory144,932 189.8 7. Malaria68,155 89.3 8. Diseases of the Heart63,167 82.7 9. Chickenpox35,699 46.8 10. Typhoid Fever17,675 23.1 Source: FHSIS Annual Report 1999

TEN LEADING CAUSES OF MORTALITY Number and Rate/100,000 Population PHILIPPINES, 1997

CAUSESNUMBERRATE*1. Diseases of the Heart49,96269.82. Diseases of the Vascular System38,69354.13. Pneumonia30,81143.14. Accidents28,56339.95. Malignant Neoplasm26,84237.56. Tuberculosis, All Forms23,05632.27. Chronic Obstructive Pulmonary Diseases and Allied Condition11,80716.58. Other Diseases of the Respiratory System6,9619.79. Diabetes Mellitus6,7499.410. Nephritis, Nephrotic Syndrome and Nephrosis6,7049.4Source: Philippine Health Statistics 1997

RISK FACTORS FOR CAPAlcoholism AsthmaImmunosuppressionInstitutionalizationAge > 70 yearsDementiaSeizure disordersTobacco smokingChronic obstructive pulmonary disease (COPD)

CLINICAL MANIFESTATIONSMay vary from indolent to fulminant; from mild to fatal FeverTachycardiaChills and/or sweatsProductive or non-productive coughDyspnea (occasionally)Pleuritic chest pain (if pleura is involved)Fatigue, headache, myalgias

PHYSICAL FINDINGSIncreased RR Use of accessory muscles of respirationIncreased tactile fremitus, dull percussion note for consolidationDecreased tactile fremitus, flat percussion note for effusionCrackles, bronchial breath sounds on auscultation

Non infectious causes of fever and pulmonary infiltrates that may mimic CAPPulmonary edemaPulmonary infarctionAcute respiratory distress syndrome (ARDS)Pulmonary hemorrhageLung cancer/metastatic cancerAtelectasisRadiation pneumonitisDrug reactions involving the lungExtrinsic allergic alveolitisPulmonary vasculitisPulmonary eosinophiliaBronchiolitis obliterans and organizing pneumonia

DIAGNOSISNo particular clinical symptom/physical finding is sufficiently sensitive or specific to confirm/exclude CAPSensitivity of history and PE- 58%Specificity of history and PE- 67%Chest radiography is necessary to help differentiate CAP from other conditions

ETIOLOGYTYPICALS. pneumoniaeH. InfluenzaeS. aureusK. pneumoniaeP. aeruginosa

ATYPICALM. pneumoniaeC. pneumoniaeLegionella spp.Respiratory viruses

Diagnosis, Empiric Management and Prevention of COMMUNITY-ACQUIRED PNEUMONIAIn Immunocompetent Adult2004 Philippine Consensus Guideline

CRITERIA FOR PNEUMONIA 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

CHEST RADIOGRAPHConfirm the diagnosis of pneumoniaAssess severity of disease and presence of complicationSuggest possible etiology

ETIOLOGIC DIAGNOSISCannot 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

DIAGNOSTIC TESTSSputum Culture- Sensitivity and specificity is highly variable (< 50%)- Greatest benefit is to alert the physician of unsuspected and/or resistant pathogens

DIAGNOSTIC TESTSBlood 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 TESTSAntigen 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 TESTSBlood Cultures: gold standardGram stain and cultures of appropriate pulmonary secretionsSerology PCRUrine antigen testDirect antibody test

SITE OF CARE DECISIONMust take into consideration diminishing health care resources and rising costs of treatmentDecision to where a patient should be managed is sometimes difficultUse of objective tools that assess risk of adverse outcomes and severity of the disease (i.e. PSI; CURB-65)

Diagnosis, Empiric Management and Prevention of COMMUNITY-ACQUIRED PNEUMONIAIn Immunocompetent Adult2004 Philippine Consensus Guideline

RISK CATEGORIES FOR CAP

Low risk CAP

Moderate risk CAP

High risk CAP

LOW RISK CAP

Stable vital signsRR < 30/minPR < 125/minSBP > 90, DBP > 60 mmHgTemp. < 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)

MODERATE RISK CAPVital Signs: any one of the followingRR > 30/minPR > 125/minTemp. > 40 C

X-ray findings of:Multi-lobar involvementProgression of lesion to 50% within 24 hoursAbscessPleural 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

HIGH RISK CAPAll criteria under moderate risk plus

Impending or frank respiratory failureHypoxemia with PaO2 < 60 mmHgAcute hypercapnia with PaCO2 > 50 mmHg

Hemodynamic alterations and hypoperfusion:SBP < 90mmHg, DBP < 60mmHgUrine output < 30cc/hourAltered mental state

Any of the ff:Shock or signsof hypoperfusion:- Hypotension-Altered mental state-urine output 50mmHgCOMMUNITY ACQUIRED PNEUMONIALOW RISK CAPMODERATE RISK CAPHIGH RISK CAPOutpatientWard AdmissionICU AdmissionYESYESNONOAlgorithm: Management-Oriented Risk Stratification ofCommunity-Acquired PneumoniaIn Immunocompetent Adults

MICTROBIAL CAUSES OF COMMUNITY-ACQUIRED PNEUMONIA, BY SITE OF CAREHospitalization PatientsOutpatients 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

EMPIRICAL ANTIBIOTIC TREATMENTLOW RISK CAPPreviously healthy and no antibiotics in past 3 months- A macrolide (Clarithromycin 500mg BID or Azithromycin 500mg OD or- Doxycycline 100mg BIDComorbidities 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 TREATMENTMODERATE 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 TREATMENTHIGH 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 TREATMENTSPECIAL CONCERNSIf 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 fluoroquinoloneIf CA-MRSA is a consideration- Add Linezolid 600mg IV q12 or Vancomycin 1gm IV q12

LOW RISK CAPPotential pathogenS. pneumoniaeH. influenzaeC. pneumoniaeM. pneumoniaeM. catarrhalisgram negative bacilli(enteric)* If with comorid illnessEmpiric TherapyIf previously healthy:Amoxycillin orExtended MacrolideIf with stable co-morbid illness/ recent use of antibiotics:Co-amoxiclav orSultamicillin or2nd Gen. cephalosporins orExtended Macrolide

MODERATE RISK CAPPotential pathogenS. pneumoniaeH. influenzaeC. pneumoniaeM. pneumoniaeM. catarrhalisgram negative bacilliLegionella pneumophilaAnaerobes: in aspirationEmpiric therapy

IV beta lactams with orwithout anaerobiccoverage+MacrolideORAlternative: IV Antipneumococcal Fluoroquinolones alone

High risk CAP (IV)Potential pathogenS. pneumoniaeH. influenzaeL. pneumophilaC. pneumoniaeM. catarrhalisgram negative bacilliAnaerobesS. aureusP. aeroginosaEmpiric TherapyIf no risk for P. aeruginosa or aspiration:IV 3RD Gen. cephalosporins w/o anaerobic coverage + IV Macrolide ORIV antipneumococcal fluoroquinolone alone

If no risk for P. aeruginosa but with risk for aspiration:IV beta lactam/beta lactamase inhibitor + IV antipneumococcal fluoroquinolone ORIV 3RD Gen. cephalosporins with anaerobic coverage + IV Macrolide

If with risk for P. aeruginosa:IV anti-pseudomonal beta lactams +/- AminogylcosidesANDIV macrolide orIV antipneumococcal fluroquinolone

GENERAL CONSIDERATIONSAdequate hydrationOxygen therapy for hypoxemiaAssisted ventilation when necessary

Failure to improve within 48 to 72 hours following therapyNoninfectious conditions- Cancer, embolus, hemorrhageResistant pathogenWrong drugRight drug, wrong doseUnusual pathogens- Mycobacterial, anaerobic, viral, fungalNosocomial superinfections

COMPLICATIONSRespiratory failureShock; Multiorgan failureBleeding diathesisExacerbation of comorbid illnessesMetastatic infections- Brain abscess; EndocarditisLung abscess- usually occurs in the setting of aspiration- should be drainedPleural effusion- should be tapped for diagnostic and therapeutic purposes

Rate of resolution of physical and laboratory abnormalitiesPatient is considered to have responded if:Fever declines within 72 hrsTemperature normalizes within 5 daysRespiratory signs (tachypnea) return to normal

Risk Categories of CAP and its associated mortality rate

Low risk : < 5%Moderate risk : 21%High risk: 36%

IMMUNIZATIONPNEUMOCOCCAL VACCINE> 60 yrs oldChronic illness: cardiovascular disease, lung disease, DM, alcohol abuse, chronic liver disease, aspleniaImmune system disorder: HIV, malignancyINFLUENZA VACCINE> 50 yrs oldChronic illnessImmune system disorderResidents of nursing homesHealth care workersPersons in contact with high risk patients

HEALTH CARE-ASSOCIATED PNEUMONIA

DEFINITIONSHealth 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

DEFINITIONSVentilator Associated Pneumonia (VAP)- Pneumonia that arises more than 48-72 hours after endotracheal intubation

DEFINITIONSHospital Acquired Pneumonia (HAP)-Defined as pneumonia that occurs 48 hours or more after admission, which was not incubating at the time of admission

MICROBIOLOGIC CAUSES OF HCAPNon-MDR Pathogens MDR Pathogens

Streptococcus pneumoniae Pseudomonas aeruginosaOther Streptococcus spp. MRSAHaemophilus influenzae Acinetobacter spp.MSSA Antibiotic-resistant EnterobacteriaceaeAntibiotic-sensitive Enterobacteriaceae Enterobacter spp.Escherichia coli ESBL-positive strainsKlebsiella pneumoniae Klebsiella spp.Proteus spp. Legionella pneumophilaEnterobacter spp. Burkholderia cepaciaSerratia marcescens Aspergillus

CLINICAL CONDITIONS ASSOCIATED WITH AND LIKELY PATHOGENS IN HEALTH CARE-ASSOCIATED PNEUMONIA Pseudomonas Acinetobacter MDRCondition MRSA aeruginosa spp. Enterobacteriacease

Hospitalization for 48 h x x x xHospitalization for 2 x x x x days in prior 3 monthsNursing home or extended- x x x x care facility residenceAntibiotic therapy in x x preceding 3 monthsChronic dialysis x Home infusion therapy xHome wound care xFamily member with x x MDR infectionPathogen

PATHOGENESISColonization of the oropharynx with pathogenic microorganismsAspiration from the oropharynx into the lower respiratory tractCompromise of the normal host defense mechanisms

CLINICAL MANIFESTATIONSFeverLeukocytosisIncrease in respiratory secretionsPE findings of consolidationNew or changing radiographic infiltrateTachypneaTachycardiaWorsening oxygenationIncreased minute ventilation

FACTORS CAUSING OVERDIAGNOSIS OF VAPTracheal 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

EMPIRICAL ANTIBIOTIC TREATMENT OF HCAPPATIENTS 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 HCAPPATIENTS 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

FAILURE TO IMPROVEDue to MDR pathogensReintroduction of the microorganismsSuperinfectionExtrapulmonary infectionsDrug toxicity

COMPLICATIONSDeathProlonged mechanical ventilation Prolonged hospital stayDevelopment of necrotizing pneumoniaLong-term pulmonary complicationsInability of the patient to return to independent function

PROGNOSISHCAP is associated with significant mortality (50%-70%)Presence of underlying diseases increases mortality rateCausative pathogen also plays a major role

Streamlining of Empiric Antibiotic Therapy

PreventionDecreasing likelihood of encountering the pathogenhand washinguse of glovesUse of face maskNegative pressure roomPrompt institution of effective chemotherapy for patients with contagious illnessesCorrection of condition that facilitate aspirationMaintenance of gastric acidity

Strengthening the hosts response once the pathogen is encounteredChemoprophylaxisImmunizing of patients at risk

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 transportAltered lower respiratory host Tight glycemic control; lowering of defenses hemoglobin transfusion threshold; specialized enteral feeding formula

DIAGNOSISBlood cultureEndotracheal aspirationPSB or BAL via bronchoscopy

PREVENTIONHand washingSurveillance of pneumoniaFor mechanically ventilated: extubate rapidly, minimize circuit changes, drain tubings regularlySmall bore feeding tubeElevation of head to 30