Objectives
Define community-acquired pneumonia and hospital-acquired pneumonia.
Describe the pathophysiology of pneumonia.
Identify the most common pathogen associated with community-acquired and hospital-community-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. Pneumonia
•
Infection of the pulmonary parenchyma•
Results from the proliferation of microbial pathogens at the alveolar level and the host’s response to those pathogensPathogenesis
•
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 DefensesMechanical 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 Pathology1.
Edema•
Presence of proteinaceous exudate (bacteria) in alveoli2.
Red hepatization•
Presence of RBC in the cellular intraalveolar exudate3.
Gray hepatization•
Neutrophil is the predominant cell•
Fibrin deposition is abundant•
Bacteria disappeared4.
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
*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
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
Epidemiologic factors suggesting possible causes of CAP
IM2: PNEUMONIA AND OTHER INFECTIONS OF PULMONARY SYSTEM ANDRE ANGELO G. TANQUE DATE: JUNE 16, 2011
LRTI’S: A leading cause of disease globally: All Ages, 2004 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 2 3 4 5 6 7 8 9 1 0
Adapted from: WHO Global Burden of Disease Report, 2004.
http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_part4.pdf. Table 12.
LRTIs: A Leading Cause of Disease Globally: All Ages, 2004
LRTI s Dia rrhe al d isea ses Uni pola r de pres sive diso rder s Isch aem ic h eart dis ease HIV /AID S Cer ebro vasc ular dis ease Pre mat urity , low bir th w eigh t Bir th a sphy xia, bir th tr aum a Neo nata l inf ectio ns, o ther Roa d tr affic acc iden ts Rank D A LY S ( m ill io n s)
DALYS = disease-adjusted life-years LRTIs = lower respiratory tract infections
**Lower respiratory tract infections (LRTIs) are a leading cause of disease burden in all age groups and income groups worldwide. In 2004, LRTIs were the no. 1 cause of disease burden worldwide, accounting for nearly 430 million episodes of illness and nearly 95 million, or 6.2%, of all disease-adjusted life-years (DALYs).
Globally, Pneumococcal Disease is a Leading Cause of Death in Young Children and Older Adults
0 5 0 0 , 0 0 0 1 , 0 0 0 , 0 0 0 1 , 5 0 0 , 0 0 0 2 , 0 0 0 , 0 0 0 P n e u m o c o c c a l d is e a s e M e a s l e s R o t a v i r u s H i b P e r t u s s i s T e t a n u s O t h e r M e n i n g o c o c c u s A l l A g e s C h i l d r e n < 5 y r s
Globally, Pneumococcal Disease is a Leading Cause of Death in Young Children and Older Adults
WHO Department of Immunization, Vaccines and Biologicals Data. September 2005. WHO 2008 Global Immunization Data.
E st im at ed n u m b er o f d ea th s (W H O 2 00 2)
Vaccine Preventable Diseases
**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 vaccine-preventable 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 <5 years of age.
IPD Preferentially Affects the Young and Older Adults
0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 < 2 m o 2 - 5 m o 6 - 1 1 m o 1 - < 2 2 - 4 5 - 9 1 0 - 1 4 1 5 - 4 4 4 5 - 6 4 6 5 - 7 4 7 5 - 7 9 8 0 + 1 9 9 8 1 9 9 9 2 0 0 0 2 0 0 1 2 0 0 2 2 0 0 3 2 0 0 4 2 0 0 5 2 0 0 6
Adapted from: Kaye P, et al. Poster presented at ESPID Brussels,June2009.
Age (years)
IPD Preferentially Affects the Young and Older Adults
Incidence of IPD creates a “U-shaped” curve with peaks at extremes of age
In ci d ence /1 00 ,0 00
Incidence of IPD per 100,000 Population, England and Wales, 1998-2006
**The incidence of pneumococcal disease by age has a characteristic “U-shaped” distribution with peaks at extremes of age.
The data in the graph show the incidence of IPD by age in England and Wales between 1998 and 2006.1Approximately 5,000-6,000 cases of IPD are reported annually to the Health Protection Agency (HPA), Centre for Infections (CFI) from laboratories in England and Wales.
Although some variation in the annual incidence of IPD in children and infants has been observed over these years, the incidence of IPD in adults remains consistent.
Risk factors for pneumonia
•
Alcoholism•
Asthma - due to presence of secretions in the airways•
Immunosuppression•
Institutionalization•
Age > 70 years•
Dementia•
Seizure disorders•
Tobacco smoking•
Chronic obstructive pulmonary disease (COPD) Clinical manifestationFever Tachycardia Chills and/or sweats
Productive or non-productive cough Dyspnea
Pleuritic chest pain (if pleura is involved) Fatigue, headache, myalgias
Physical findings 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 Etiologic Diagnosis
•
Cannot be determined on the basis of the clinical presentation•
Laboratory test are needed to establish etiology•
Allows narrowing of the initial empirical regimen•
Collected data show trends in resistance CAP mimickersPulmonary edema Pulmonary infarction
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 Criteria for Pneumonia
•
Cough•
Tachycardia CR > 100•
Tachypnea RR > 20•
Fever T >37.8C•
At least one abnormal chest findingso
diminished breath sounds, rhonchi, crackles or wheezeo
New x-ray infiltrate with no clear alternative such as lung cancer or pulmonary edemaDiagnosis
•
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 conditionsChest radiograph
•
Confirm the diagnosis of pneumonia•
Assess severity of disease and presence of complication•
Suggest possible etiology*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
•
May help identify pathogens by their appearance•
Main purpose is to ensure suitability of sputumfor culture (> 25 neutrophils and <10 squamous epithelial cells per LPF
Sputum culture
•
Sensitivity and specificity is highly variable (< 50%)•
Greatest benefit is to alert the physician of unsuspected and/or resistant pathogensBlood 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 patientsAntigen 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 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 that assess risk of adverse outcomes and severity of the disease (i.e. PSI; CURB-65)Risk Categories for CAP
•
Low risk CAP•
Moderate risk CAP•
High risk CAPEmpric antimicrobial therapy for Low-risk CAP
Empric antimicrobial therapy for Low-risk CAP
Potential Pathogen Empiric Therapy Streptococcus pneumoniae
Haemophilus influenzae Chlamydia pneumoniae Mycoplasma pneumoniae Moraxella catarrhalis
Enteric Gram negative bacilli (among those with co-morbid illness)
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
Empric antimicrobial therapy for Low-risk CAP
Antibiotic Dosage Antibiotic Dosage β-lactam Amoxicillin 500 mg TID 2 nd gen cephalosphorin Cefaclor Cefuroxime 500 mg TID or 750 mg BID 500 mg BID Macrolides Aztihromycin dihydrate Clarithromycin 500 mg OD 500 mg BID 3rd gen Cephalosphorin Cefdinir
Cefixime 300 mg BID 200 mg BID β-lactam with BLIC
Amoxicillin- clavulanic acid Amoxicillin- sulbactam Sultamicillin 625 mg TID or 1 gm BID 1 gm TID 750 mg BID Cefpodoxime 200 mg BID
Empric antimicrobial therapy for Moderate-risk CAP
Empric antimicrobial therapy for Moderate-risk CAP
Potential Pathogen Empiric Therapy
Streptococcus pneumoniae Haemophilus influenzae Chlamydia pneumoniae Mycoplasma pneumoniae Moraxella catarrhalis Enteric Gram negative bacilli Legionella pneumophila
Anaerobes (among those with risk of aspiration) IV non-antipseudomonal β-lactam (BLIC, cephalosphorin, or carbapenem) + extended macrolide OR IV non-antipseudomonal β-lactam (BLIC, cephalosphorin or carbapenem) + respiratory floroquinolone
Empric antimicrobial therapy for Moderate-risk CAP
Antibiotic Dosage Antibiotic Dosage Macrolides (IV/PO) Aztihromycin dihydrate Clarithromycin Erythromycin 500 mg q 24 500 mg q12 0.5-1 gm q 6 2nd gen cephalosphorin Cefotiam Cefoxitin Cefuroxime 1 gm q 8 1-2 gm q 8 1.5 gm q 8 Antipneumococcal Floroquinolones IV/PO Levofloxacin Moxifloxacin 500-750 mg q24 400 mg q 24 3rd gen Cephalosphorin Cefotaxime Ceftizoxime Ceftriaxone 1-2 gm q 8 1-2 gm q 8 1-2 gm q 24 β-lactam with BLIC IV
Amoxicillin- clavulanic acid Amoxicillin- sulbactam 1.2 gm q 8 1.5 gm q 8 Carbapenem Ertapenem 1 gm q 24
Empric antimicrobial therapy for High-risk CAP
Empric antimicrobial therapy for High-risk CAP
Potential Pathogen Empiric Therapy Streptococcus pneumoniae
Haemophilus influenzae Chlamydia pneumoniae Mycoplasma pneumoniae Moraxella catarrhalis Enteric Gram negative bacilli Legionella pneumophila
Anaerobes (among those with risk of aspiration)
Staphylococcus aureus Pseudomonas aeroginosa
No risk for Pseudomonas aeroginosa IV non-antipseudomonal β-lactam (BLIC, cephalosphorin, or carbapanem) + IV extended macrolide or IV respiratory quinolone
With risk for Pseudomonas aeroginosa IV antipneumococal antipseudomonal β-lactam (BLIC, cephalosphorin or carbapanem) + IV extended macrolide + aminoglycoside OR
IV antipneumococal antipseudomonal β-lactam (BLIC, cephalosphorin or carbapenem) + IV
ciprofloxacin/levofloxacin (high dose)
Empric antimicrobial therapy for High-risk CAP
Antibiotic Dosage Antibiotic Dosage Macrolides (IV) Aztihromycin dihydrate Clarithromycin Erythromycin 500 mg q 24 500 mg q12 0.5-1 gm q 6 Aminoglycosides Amikacin Gentamicin Netilmicin Tobramicin 15 mg/kg q 24 3 mg/kg q 24 7 mg/kg q 24 3 mg/kg q 24 Antipneumococcal Floroquinolones IV Levofloxacin Moxifloxacin 500-750 mg q24 400 mg q 24 3rd gen Cephalosphorin Cefotaxime Ceftizoxime Ceftriaxone 1-2 gm q 8 1-2 gm q 8 1-2 gm q 24 β-lactam with BLIC IV
Amoxicillin- clavulanic acid Amoxicillin- sulbactam 1.2 gm q 8 1.5 gm q 8 Carbapenem Ertapenem 1 gm q 24
Empric antimicrobial therapy for High-risk CAP
Antibiotic Dosage Antipseudomonal, anti-pneumococcal β-lactam
(BLIC, cephalosphorin, carbapenem) Cefoperazone-sulbactam Piperacillin-tazobactam Ticarcillin-clavulanic acid Cefipime Cefpirome Imipinem-cilastatin Meropenem 1.5-2 gm q 8-12 h 2.25-4.5 gm q 6-8 h 3.2 gm q 6 h 2 gm q 8-12 h 2 gm q 12 0.5 – 1 gm q 6-8 h 1-2 gm q 8 h Antipseudomonal Floroquinolones IV Levofloxacin Moxifloxacin 400 mg q 12 750 mg q 24 Others Oxacilin (staphylococcus) Clindamycin (staphylococcus/anaerobes) Metronidazole (anaerobes) Linezolid (MRSA) Vancomycin (MRSA) 1-2 gm q 4-6 h 600 mg q 6-8 h 500mg q 6-8 h 600 mg q 12 h 1 gm q 12
Failure to improve within 48 to 72 hours
•
Noninfectious conditionso
Cancer, embolus, hemorrhage•
Resistant pathogen•
Right drug, wrong dose•
Unusual pathogenso
Mycobacterial, anaerobic, viral, fungal•
Nosocomial superinfectionsComplications
Respiratory failure Shock; Multiorgan failure Bleeding diathesis
Exacerbation of comorbid illnesses Metastatic infections
Brain abscess; Endocarditis Lung abscess
o
usually occurs in the setting of aspirationo
should be drained Pleural effusiono
should be tapped for diagnostic and therapeutic purposes*To confirm if it’s pleural effusion, always look for the meniscus on the AP or lateral view. The second and third photos show the meniscus, which reflect the presence of fluid. Always remember that a lateral decubitus view will allow confirmation as the fluid will be displaced in the CXR,
Immunization
INFLUENZA VACCINE
❧
> 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•
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 orwound care in the past 30 days of the current infection
•
Attended a hospital or hemodialysis clinicVentilator 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 mechanismsClinical 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 therapiesEmpirical 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 hoursEmpirical Antibiotic Treatment of HCAP
PATIENTS WITH RISK FACTORS FOR MDR PATHOGENS
1.
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 plus2.
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 plus3.
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 toxicityAssessment 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
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 roleStreamlining 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
