Paras Patel MD.Paras Patel MD.

Assistant Professor of Internal Medicine, Assistant Professor of Internal Medicine, Division of Infectious disease. Division of Infectious disease. ETSUETSU

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Alphabet Soup for Pneumonia

• HAP: Hospital-acquired pneumonia– ≥ 48 h from admission

• VAP: Ventilator-associated pneumonia– ≥ 48 h from endotracheal intubation

• HCAP: Healthcare-associated pneumonia– Long-term care facility (NH), hemodialysis, outpatient chemo, wound

care, etc.

• CAP: Community-acquired pneumonia– Outside of hospital or extended-care facility

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Community Acquired Pneumonia

• Definition:

– … an acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection, accompanied by the presence of an acute infiltrate on a chest radiograph, or auscultatory findings consistent with pneumonia, in a patient not hospitalized or residing in a long term care facility for > 14 days before onset of symptoms.

Bartlett. Clin Infect Dis 2000;31:347-82.

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Community Acquired Pneumonia

• Epidemiology:– 4-5 million cases annually– ~500,000 hospitalizations– ~45,000 deaths– Mortality 2-30%

• <1% for those not requiring hospitalization

Cdc.gov/data 2007.

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Community Acquired Pneumonia

• Epidemiology: (contd)– fewest cases in 18-24 yr group– probably highest incidence in <5 and >65 yrs– mortality disproportionately high in >65 yrs

898

1071

83

1171 1207

684

0

200

400

600

800

1000

1200

1400

<5 5 to17

18-24 25-44 45-64 >65

# of cases

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Community Acquired Pneumonia

2 5.7

74.9

0

10

20

30

40

50

60

70

80

<4 5 to 14 15-24 25-44 45-64 >65

# of deaths# in 1000s

Mortality

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Age-specific Rates of Hospital Admission by Pathogen

Marsten. Community-based pneumonia incidence study group.Arch Intern Med 1997;157:1709-18

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CAP – PathogenesisCAP – Pathogenesis

• Inhalation, aspiration and hematogenous spread are the 3 main mechanisms by which bacteria reaches the lungs

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Pathogenesis

• Primary inhalation: when organisms bypass normal respiratory defense mechanisms or when the Pt inhales aerobic GN organisms that colonize the upper respiratory tract or respiratory support equipment

• Aspiration: occurs when the Pt aspirates colonized upper respiratory tract secretions– Stomach: reservoir of GNR that can ascend, colonizing the

respiratory tract.

• Hematogenous: originate from a distant source and reach the lungs via the blood stream.

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• Risk Factors for pneumonia– age– smoking– asthma– immunosuppression– institutionalization– COPD– PVD– Dementia– HIV/AIDS

Community Acquired Pneumonia

ID Clinics 1998;12:723. Am J Med 1994;96:313

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• Risk Factors in Patients Requiring Hospitalization– older, unemployed– common cold in the previous year– asthma, COPD; steroid or bronchodilator use– Chronic disease– amount of smoking

Farr BM. Respir Med 2000;94:954-63

Community Acquired Pneumonia

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• Risk Factors for Mortality– age– bacteremia (for S. pneumoniae)– extent of radiographic changes– degree of immunosuppression– amount of alcohol

Community Acquired Pneumonia

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– S. pneumoniae: 20-60%– H. influenzae: 3-10%– Chlamydia pneumoniae: 4-6%– Mycoplasma pneumonaie: 1-6%

Community Acquired Pneumonia

– Legionella spp. 2-8%– S. aureus: 3-5%– Gram negative bacilli: 3-5%– Viruses: 2-13%

40-60% - NO CAUSE IDENTIFIED

2-5% - TWO OR MORE CAUSES

Microbiology

Bartlett. NEJM 1995;333:1618-24

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Streptococcus pneumonia Streptococcus pneumonia (Pneumococcus)Pneumococcus)

Most common cause of CAPMost common cause of CAP About 2/3 of CAP are due to S.pneumoniaeAbout 2/3 of CAP are due to S.pneumoniae These are gram positive diplococciThese are gram positive diplococci Typical symptoms (e.g. malaise, shaking chills Typical symptoms (e.g. malaise, shaking chills

fever, rusty sputum, pleuritic chest pain, cough)fever, rusty sputum, pleuritic chest pain, cough) Lobar infiltrate on CXRLobar infiltrate on CXR May be Immuno suppressed hostMay be Immuno suppressed host 25% will have bacteremia – serious effects25% will have bacteremia – serious effects

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Atypical Pneumonia

• #2 cause (especially in younger population)• Commonly associated with milder Sx’s: subacute onset, non-

productive cough, no focal infiltrate on CXR• Mycoplasma: younger Pts, extra-pulm Sx’s (anemia, rashes),

headache, sore throat• Chlamydia: year round, URI Sx, sore throat• Legionella: higher mortality rate, water-borne outbreaks,

hyponatremia, diarrhea

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Viruses and PneumoniaViruses and Pneumonia

Pneumonia in the normal hostPneumonia in the normal host• Adults or ChildrenAdults or Children• Influenza A and B, RSV, Adenovirus, Para InfluenzaInfluenza A and B, RSV, Adenovirus, Para Influenza

Pneumonia in the immuno-compromisedPneumonia in the immuno-compromised• Measles, HSV, CMV, HHV-6, Influenza virusesMeasles, HSV, CMV, HHV-6, Influenza viruses• Can cause a primary viral pneumonia. Cause partial Can cause a primary viral pneumonia. Cause partial

paralysis of “mucociliary escalator” - increased risk of paralysis of “mucociliary escalator” - increased risk of secondary bacterial LRTI. secondary bacterial LRTI. S.aureus pneumonia S.aureus pneumonia is a is a known complication following influenza infection.known complication following influenza infection.

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Other bacteria• Anaerobes

– Aspiration-prone Pt, putrid sputum, dental disease• Gram negative

– Klebsiella - alcoholics– Branhamella catarrhalis - sinus disease, otitis, COPD– H. influenza

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S. S. aureusaureus CAP – Dangerous CAP – Dangerous

This CAP is not common; Multi lobar InvolvementThis CAP is not common; Multi lobar Involvement Post Influenza complication, Class IV or VPost Influenza complication, Class IV or V Compromised host, Co-morbidities, ElderlyCompromised host, Co-morbidities, Elderly CA MRSA – A Problem; CA MSSA also occursCA MRSA – A Problem; CA MSSA also occurs Empyema and Necrosis of lung with cavitationsEmpyema and Necrosis of lung with cavitations Multiple Pyemic abscesses, Septic ArthritisMultiple Pyemic abscesses, Septic Arthritis Hypoxemia, Hypoventilation, Hypotension commonHypoxemia, Hypoventilation, Hypotension common Vancomycin, Linezolid are the drugs for MRSAVancomycin, Linezolid are the drugs for MRSA

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Diagnosis and ManagementDiagnosis and Management

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Clinical Diagnosis

• Suggestive signs and symptoms• CXR or other imaging technique• Microbiologic testing

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Signs and Symptoms

• Fever or hypothermia• Cough with or without sputum, hemoptysis• Pleuritic chest pain• Myalgia, malaise, fatigue• GI symptoms• Dyspnea• Rales, rhonchi, wheezing• Egophony, bronchial breath sounds• Dullness to percussion• Atypical Sx’s in older patients

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Clinical Diagnosis: CXR

• Demonstrable infiltrate by CXR or other imaging technique– Establish Dx and presence of complications (pleural

effusion, multilobar disease)– May not be possible in some outpatient settings– CXR: classically thought of as the gold standard

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Normal Pneumonia

Chest RadiographMay show hyper-expansion, atelectasis or infiltrates

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Infiltrate Patterns

Pattern Possible Diagnosis

Lobar S. pneumo, Kleb, H. flu, GN

Patchy Atypicals, viral, Legionella

Interstitial Viral, PCP, Legionella

Cavitary Anaerobes, Kleb, TB, S. aureus, fungi

Large effusion Staph, anaerobes, Kleb

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Clinical Diagnosis: Recommended testing• Outpatient: CXR, sputum Cx and Gram stain not

required• Inpatient: CXR, Pox or ABG, chemistry, CBC, two sets

of blood Cx’s– If suspect drug-resistant pathogen or organism not covered

by usual empiric abx, obtain sputum Cx and Gram stain. – Severe CAP: Legionella urinary antigen, consider

bronchoscopy to identify pathogen

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Community Acquired Pneumonia

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To Admit or Not?Pneumonia Severity & Deciding Site of Care

• Using objective criteria to risk stratify & assist in decision re outpatient vs inpatient management

• PSI• CURB-65• Caveats

– Other reasons to admit apart from risk of death– Not validated for ward vs ICU– Labs/vitals dynamic

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Pneumonia Severity Index

Class Points Mortality* Site of CareI <51 0.1% OutPatient

II 51-70 0.6% OutPatient

III 71-90 2.8% In or OutPatient

IV 91-130 9.5% Inpatient

V >130 26.7% Inpatient

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CURB 65 Rule – Management of CAPCURB 65 Rule – Management of CAP

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Who Should be Hospitalized?Who Should be Hospitalized?Class I and II Class I and II Usually do not require Usually do not require

hospitalizationhospitalization

Class IIIClass III May require brief hospitalizationMay require brief hospitalization

Class IV and VClass IV and V Usually do require hospitalizationUsually do require hospitalization

Severity of CAP with poor prognosis Severity of CAP with poor prognosis

RR > 30; PaORR > 30; PaO22/FiO2 < 250, or PO/FiO2 < 250, or PO22 < 60 on room air < 60 on room air

Need for mechanical ventilation; Multi lobar involvementNeed for mechanical ventilation; Multi lobar involvement

Hypotension; Need for vasopressorsHypotension; Need for vasopressors

Oliguria; Altered mental statusOliguria; Altered mental status

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CAP – Criteria for ICU AdmissionCAP – Criteria for ICU AdmissionMajor criteriaMajor criteria Invasive mechanical ventilation requiredInvasive mechanical ventilation required Septic shock with the need of vasopressorsSeptic shock with the need of vasopressors

Minor criteria (least 3)Minor criteria (least 3) Confusion/disorientationConfusion/disorientation Blood urea nitrogen ≥ 20 mg%Blood urea nitrogen ≥ 20 mg% Respiratory rate ≥ 30 / min; Core temperature < 36ºCRespiratory rate ≥ 30 / min; Core temperature < 36ºC Severe hypotension; PaO2/FiO2 ratio ≤ 250Severe hypotension; PaO2/FiO2 ratio ≤ 250 Multi-lobar infiltratesMulti-lobar infiltrates WBC < 4000 cells; Platelets <100,000WBC < 4000 cells; Platelets <100,000

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Traditional Treatment ParadigmTraditional Treatment Paradigm

Conservative start with ‘workhorse’ antibiotics

Reserve more potent drugs for non-responders

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New Treatment ParadigmNew Treatment Paradigm

Hit hard early with appropriate antibiotic(s)

Short Rx. Duration; De-escalate where possible

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Inappropriate therapy (%)

0

30

50

10

CAP

20

40

HAP HAP on CAP

17

34

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Kollef, et al. Chest 1999;115:462–474

The Effect of the Traditional ApproachThe Effect of the Traditional Approach

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New data – Don’t Wait for Results !New data – Don’t Wait for Results !

Switching after susceptibility results

p<0.001

Adequate treatment within ‘a few hours’

Mortality (%) n=75

Tumbarello, et al. Antimicrob Agents Chemother 2007;51:1987–1994

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New data – The Speed of Delay ! (Class 4,5)New data – The Speed of Delay ! (Class 4,5)

0

10

20

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40

50

60

70

80

90

0.5 1 2 3 4 5 6

Delay in treatment (hours) from hypotension onset

Surv

ival

(%)

Each hour of delay carries 7.6% reduction in survival

Kumar, et al. Crit Care Med 2006;34:1589–1596

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CAP – ComplicationsCAP – Complications

Hypotension and septic shockHypotension and septic shock 3-5% Pleural effusion; Clear fluid + pus cells3-5% Pleural effusion; Clear fluid + pus cells 1% Empyema thoracis pus in the pleural space 1% Empyema thoracis pus in the pleural space Lung abscess – destruction of lung .Lung abscess – destruction of lung . Single (aspiration) anaerobes, Single (aspiration) anaerobes, PseudomonasPseudomonas Multiple (metastatic) Multiple (metastatic) Staphylococcus aureusStaphylococcus aureus Septicemia – Brain abscess, Liver AbscessSepticemia – Brain abscess, Liver Abscess Multiple Pyemic AbscessesMultiple Pyemic Abscesses

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IDSA: Outpt Management in Previously Healthy Pt• Organisms: S. pneumo, Mycoplasma, viral, Chlamydia pneumo,

H. flu• Recommended abx:

– Advanced generation macrolide (azithro or clarithro) or doxycycline

• If abx within past 3 months:– Respiratory quinolone (moxi-, levo-, gemi-), OR– Advanced macrolide + amoxicillin, OR– Advanced macrolide + amoxicillin-clavulanate

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IDSA: Outpt Management in Pt with comorbidities• Comorbidities: cardiopulmonary dz or immunocompromised

state• Organisms: S. pneumo, viral, H. flu, aerobic GN rods, S. aureus• Recommended Abx:

– Respiratory quinolone, OR advanced macrolide

• Recent Abx:– Respiratory quinolone OR– Advanced macrolide + beta-lactam

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IDSA: Inpt Management-Medical Ward

• Organisms: all of the above plus polymicrobial infections (+/- anaerobes), Legionella

• Recommended Parenteral Abx: – Respiratory fluoroquinolone, OR– Advanced macrolide plus a beta-lactam

• Recent Abx:– As above. Regimen selected will depend on nature of recent antibiotic

therapy.

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IDSA: Inpt Management-Severe/ICU

• One of two major criteria:– Mechanical ventilation– Septic shock, OR

• Two of three minor criteria:– SBP≤90mmHg, – Multilobar disease– PaO2/FIO2 ratio < 250

• Organisms: S. pneumo, Legionella, GN, Mycoplasma, viral, ?Pseudomonas

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IDSA: Inpt Management: Severe/ICU

• No risk for Pseudomonas– IV beta-lactam plus either

• IV macrolide, OR IV fluoroquinolone

• Risk for Pseudomonas– Double therapy: selected IV antipseudomonal beta-lactam (cefepine,

imipenem, meropenem, piperacillin/tazobactam), plus• IV antipseudomonal quinolone

-OR-

– Triple therapy: selected IV antipseudomonal beta-lactam plusIV aminoglycoside plus either

IV macrolide, OR IV antipseudomonal quinolone

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Switch to Oral Therapy

• Four criteria:– Improvement in cough and dyspnea– Afebrile on two occasions 8 h apart– WBC decreasing– Functioning GI tract with adequate oral intake

• If overall clinical picture is otherwise favorable, can can switch to oral therapy while still febrile.

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Duration of TherapyDuration of Therapy

• Minimum of 5 daysMinimum of 5 days• Afebrile for at least 48 to 72 hAfebrile for at least 48 to 72 h• No > 1 CAP-associated sign of clinical instabilityNo > 1 CAP-associated sign of clinical instability• Longer duration of therapy Longer duration of therapy

If initial therapy was not active against the identified If initial therapy was not active against the identified

pathogen or complicated by extra pulmonary infectionpathogen or complicated by extra pulmonary infection

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Prevention

• Smoking cessation• Vaccination per ACIP recommendations

– Influenza• Inactivated vaccine for people >50 yo, those at risk for influenza

compolications, household contacts of high-risk persons and healthcare workers

• Intranasal live, attenuated vaccine: 5-49yo without chronic underlying dz

– Pneumococcal• Immunocompetent ≥ 65 yo, chronic illness and

immunocompromised ≤ 64 yo

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Epidemiology of Pneumococcal Infection in Immunocompromised Adults

• Streptococcus pneumoniae remains a leading cause of serious illness, including bacteremia, meningitis, and pneumonia among adults in the United States.

• An estimated 4,000 deaths occur annually in USA primarily among adults.

• For adults aged 18–64 years with hematologic cancer, the rate of IPD in 2010 was 186 per 100,000, and for persons with human immunodeficiency virus (HIV) the rate was 173 per 100,000 (CDC, unpublished data, 2012).

• The disease rates for adults in these groups can be more than 20 times those for adults without high-risk medical conditions.

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• PCV13 has been used for children since 2010, when it replaced an earlier version targeting seven serotypes (PCV7; Prevnar, Pfizer) that had been in use since 2000.

• The routine use of PCV7 in infants and young children resulted in significant reductions in IPD caused by vaccine serotypes in children, and because of indirect effects, also in adults.

• Rates of IPD caused by vaccine serotypes in adults aged 18–64 years without HIV decreased from six cases to one case per 100,000 during 2000–2007.

• However, even after indirect effects of the pediatric immunization had been realized fully, the incidence of IPD caused by the serotypes included in PCV7 remained high in HIV-infected persons aged 18–64 years at 64 cases per 100,000 persons with acquired immunodeficiency syndrome (AIDS) .

• Moreover, 50% of IPD cases among immunocompromised adults in 2010 were caused by serotypes contained in PCV13; an additional 21% were caused by serotypes only contained in PPSV23.

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• In two randomized, multicenter immunogenicity studies conducted in the United States and Europe, immunocompetent adults aged ≥50 years received a single dose of PCV13 or PPSV23.

• In adults aged 60–64 years and aged >70 years, PCV13 elicited opsonophagocytic activity (OPA) geometric mean antibody titers (GMTs) that were comparable with, or higher than, responses elicited by PPSV23.

• OPA GMTs elicited by PCV13 in adults aged 50–59 years for all 13 serotypes were comparable with the corresponding GMTs elicited by administration of PCV13 in adults aged 60–64 years.

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PCV13 Vaccine in Adults

• PCV13 was licensed by the Food and Drug Administration (FDA) for prevention of IPD and otitis media in infants and young children in February 2010, supplanting PCV7

• One dose of PCV13 is recommended by ACIP for children aged 6–18 years with high-risk conditions such as functional or anatomic asplenia, immunocompromising conditions, cochlear implants, or CSF leaks.

• In December 2011, FDA licensed PCV13 for prevention of pneumonia and IPD in adults aged ≥50 years .

• Approval of PCV13 for adults was based on immunogenicity studies that compared antibody responses to PCV13 with antibody responses to PPSV23

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ACIP Recommendations for PCV13 and PPSV23 Use

• Pneumococcal vaccine-naïve persons. • ACIP recommends that adults aged ≥19 years with

immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, and who have not previously received PCV13 or PPSV23, should receive a dose of PCV13 first, followed by a dose of PPSV23 at least 8 weeks later (Table).

• Subsequent doses of PPSV23 should follow current PPSV23 recommendations 5 years after the first PPSV23 dose for persons aged 19–64 years with functional or anatomic asplenia and for persons with immunocompromising conditions.

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• Previous vaccination with PPSV23. • Adults aged ≥19 years with immunocompromising

conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, who previously have received ≥1 doses of PPSV23 should be given a PCV13 dose ≥1 year after the last PPSV23 dose was received.

• For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23

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CAP – So How Best to Win the War?CAP – So How Best to Win the War?

Early antibiotic administration within 4-6 hoursEarly antibiotic administration within 4-6 hours Empiric antibiotic Rx. as per guidelines (IDSA / ATS)Empiric antibiotic Rx. as per guidelines (IDSA / ATS) PORT – PSI scoring and Classification of casesPORT – PSI scoring and Classification of cases Early hospitalization in Class IV and VEarly hospitalization in Class IV and V Decrease smoking cessation - advice / counselingDecrease smoking cessation - advice / counseling Arterial oxygenation assessment in the first 24 hArterial oxygenation assessment in the first 24 h Blood culture collection in the first 24 h prior to Abx.Blood culture collection in the first 24 h prior to Abx. Pneumococcal & Influenza vaccination; Smoking Pneumococcal & Influenza vaccination; Smoking XX

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Thank you