Community-Acquired Pneumonia

Shireesha Dhanireddy, MD Division of Allergy & Infectious Diseases University of Washington 12 September 2014

Objectives

 Diagnosis and management of CAP  Differentiate between healthcare-associated pneumonia (HCAP) and CAP  Identify risk factors for resistant organisms and less common causes of pneumonia

CAP - Epidemiology

 Very common   5 million cases/year in North America At least 1 million hospitalizations/year  9 th leading cause of infectious death in US  30 day morality for hospitalized patients is up to 23%  $17 billion/year in healthcare costs in US

www.cdc.gov/flu

Which of these patients have community-acquired pneumonia (CAP)?

 34 yo hospital employee, previously healthy, admitted for acute pneumonia.

 ✔ 56 yo man admitted with CHF, noted to have pneumonia the day after admission.

 76 yo bedridden man transferred from a nursing home for acute confusion, noted to have a new infiltrate on CXR.

Alphabet Soup of Terms

 CAP: Community-acquired pneumonia  Outside of hospital or extended-care facility   HCAP: Healthcare-associated pneumonia  Long-term or extended care facility, hemodialysis, outpatient chemo, wound care, etc.

HAP: Hospital-acquired pneumonia  ≥ 48 h from admission  VAP: Ventilator-associated pneumonia  ≥ 48 h from endotracheal intubation

Pneumonia - Definitions

Kollef MH et al. CID 2008:46 (suppl 4)

Case 1

70 yo man presents to ED with acute onset of cough productive of yellow sputum, R-sided pleuritic CP and lisinopril, glyburide and metformin.

1. Admit to general medical floor.

PEx: T 35 ° C, BP 110/70 HR 120 RR 36 base. NEURO: Oriented only to self.

LABS: WBC 23 (40% bands), Hct 42%, Plts 150. BUN 46, Cr 1.4.

ABG: 7.48 /30 /50 on RA. CXR shows RLL infiltrate.

Clinical Presentation

Acute cough (>90%) Fevers/chills (80%) Sputum production (66%) Dyspnea (66%) Pleuritic chest pain (50%) Tachypnea (RR > 24) Egophony Bronchial breath sounds Percussion dullness Diminished breath sounds

Clinical Presentation

Acute cough (>90%) Fevers/chills (80%) Sputum production (66%) Dyspnea (66%)

Sensitivity 47-69% ; Specificity 58-75%

Tachypnea (RR > 24) Egophony Bronchial breath sounds Percussion dullness Diminished breath sounds

CXR

To Admit or Not?

Pneumonia Severity & Deciding Site of Care

 Objective criteria to risk stratify & assist in decision re outpatient vs inpatient management  Pneumonia Severity Index (PSI)  CURB-65  Caveats  Other reasons to admit apart from risk of death   Not validated for ward vs ICU Not validated in some populations (i.e. HIV+)

70 20 15 20 10 Total 135

Criteria for Severe CAP (Admit to ICU)

Minor criteria

Respiratory rate ≥30 breaths/min PaO2/FiO2 ratio ≥ 250 Multilobar infiltrates Confusion/disorientation Uremia (BUN ≥20 mg/dL) Leukopenia (WBC <4000 cells/mm 3 ) Thrombocytopenia (platelets <100,000 cells/mm 3 ) Hypothermia (core T <36  C) Hypotension requiring aggressive fluid resuscitation

Major criteria

Invasive mechanical ventilation Septic shock with the need for vasopressors 2007 IDSA/ATS Guidelines for CAP in Adults.

Microbiology

TYPICAL

–

Streptococcus pneumoniae

–

Haemophilus influenzae

–

Moraxella catarrhalis

–

Klebsiella pneumoniae

ATYPICAL –

Mycoplasma pneumoniae

–

Chlamydophila pneumoniae

–

Legionella pneumophila

Microbiology of CAP among hospitalized patients

Outpatient

Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae

Respiratory viruses Inpatient (Ward)

S. pneumoniae M. pneumoniae H. influenzae C. Pneumoniae Legionella

species Respiratory viruses Aspiration Inpatient (ICU)

S. pneumoniae Legionella

spp.

Staphylococcus aureus

Gram-negative bacilli

Age-specific Rates of Hospital Admission by Pathogen

Marsten. Community-based pneumonia incidence study group.

Arch Intern Med 1997;157:1709-18

Comorbidities & Associated Pathogens

Alcoholism COPD and/or Tobacco 

Strep pneumoniae

    Oral anaerobes

Klebsiella pneumoniae Acinetobacter M. tuberculosis

spp      

Haemophilus influenzae Pseudomonas aeruginosa Legionella

spp

S. pneumoniae Moraxella catarrhalis Chlamydophila pneumoniae

Aspiration Lung Abscess Structural lung disease (e.g. bronchiectasis) Advanced HIV   Gram-negative enteric pathogens Oral anaerobes    

CA-MRSA

Oral anaerobes, microaerophilic streptococci,

Actinomyces

,

Nocardia spp

Endemic fungi

M. tuberculosis,

atypical mycobacteria 

P. aeruginosa



Burkholderia cepacia



S. aureus

     

Pneumocystis jirovecii Cryptococcus Histoplasma

Tuberculosis

Aspergillus P. aeruginosa

MRSA Modern-day CAP pathogen

      51

Staphylococcus aureus

reported 2006-2007 CAP cases in 19 states 79% MRSA Median age 16 yrs (range <1 to 81) 47% antecedent viral illness 11 of 33 (33%) tested had lab-confirmed influenza 51% died a median of 4 days from symptom onset Lesson: Must consider MRSA, MSSA coverage in severe CAP, esp during flu season!

Kallen,

Ann Emerg Med.

2009 Mar;53(3):358-65.

MRSA CAP Clinical Features

         Cavitary infiltrate or necrosis Rapidly increasing pleural effusion Gross hemoptysis (not just blood-streaked) Concurrent influenza Neutropenia Erythematous rash Skin pustules Young, previously healthy patient Severe pneumonia during summer months Wunderink,

N Engl J Med.

2014;370:543-51.

Is sputum culture helpful?

 Sputum Gram stain and culture   Low sensitivity (25-40%) Considered optional for outpatients  Blood culture   Positive < 10% May help guide antibiotic therapy textbookofbacteriology.net

Diagnosis: Cultures

    Pre-abx Blood Cultures    Yield 5-15% Stronger indication for severe CAP Host factors: cirrhosis, asplenia, complement deficiencies, leukopenia Pre-abx expectorated sputum Gs & Cx    Yield can be variable Depends on multiple factors: specimen collection, transport, speed of processing, use of cytologic criteria Adequate sample w/ predominant morphotype seen in only 14% of 1669 hospitalized CAP pts (Garcia-Vasquez,

Arch Intern Med

2004) Pre-abx endotracheal aspirate Gs & Cx Pleural effusions >5 cm on lateral upright CXR

Diagnosis: Other testing



Urinary antigen tests



S. pneumoniae



L. pneumophila

serogroup 1  60-80% sensitive, >90% specific in adults  Pros: rapid (15 min), simple, more sensitive than Cx, can detect

Pneumococcus

after abx started  Cons: no susceptibility data, not helpful in patients with recent CAP (prior 3 months)

Diagnosis: Other testing

 

Acute-phase serologies

 

C. pneumoniae, Mycoplasma, Legionella

spp Not practical given slow turnaround & single acute-phase result unreliable

Influenza testing

 Hospitalized patients: Severe respiratory illness (T> 37.8

without

should get screened during season ° C with SOB, hypoxia, or radiographic evidence of pneumonia) other explanation and suggestive of infectious etiology   NP swab or nasal wash/aspirate Rapid flu test (15 min) - Distinguishes A vs B     Sensitivity 50-70%; specificity >90% Respiratory virus DFA & culture - reflex subtyping for A Respiratory viral PCR panel - reflex subtyping for A Epidemic Influenza PCR panel reflex subtyping for A – screens for A & B with

Case

29 yo previously healthy but morbidly obese woman admitted in March with 5 days of progressive SOB, intubated in field after being found home unresponsive, hypoxic with Sat 80%. Initial BP 100/80, HR 120. PaO2 60 on 80% FiO2.

CXR reveals diffuse patchy infiltrates with some lower lobar consolidation R>L.

Sputum could not be obtained but endotracheal aspirate shows 3+ polys and 3+GPC in clusters. Which of the following abx would you start empirically?

1.

2.

3.

4.

5.

Ceftriaxone + azithromycin Zanamavir + vancomycin + azithromycin Oseltamavir + vancomycin + azithromycin Oseltamavir + vancomycin + piperacillin-tazobactam Oseltamavir + daptomycin + azithromycin

Outpatient Empiric CAP Abx

 Healthy; no abx x past 3 months  Macrolide: azithromycin  2nd choice: doxycycline  Comorbidities; abx x past 3 mon   Respiratory fluoroquinolone: Moxifloxacin, levofloxacin 750 mg, gemifloxacin Beta-lactam (preferred: amoxicillin 1 g 3 or amox/clav 2 g 2 ; alternative: ceftriaxone, cefuroxime 500 mg 2 ), + macrolide  Regions with >25% high-level macrolide-resistant

S. pneumo

(MIC ≥16), consider alternative agents 2007 IDSA/ATS Guidelines for CAP in Adults.

Inpatient Empiric CAP Abx

1

     Inpatients in ward   Respiratory fluoroquinolone ß-lactam (cefotaxime/ceftriaxone or ampicillin/sulbactam) + macrolide Inpatients in ICU  ß-lactam + macrolide  Respiratory fluoroquinolone for PCN-allergic pts

Pseudomonas

(if concerns exists)  Anti-pneumococcal & anti pseudomonal ß-lactam + azithromycin + cipro/levofloxacin (750 mg)   Can substitute quinolone with aminoglycoside PCN-allergic: can substitute aztreonam CA-MRSA: Add vanco or linezolid* (or ceftaroline 2 ) CA-MSSA: Nafcillin or cefazolin or ceftriaxone 1 2007 IDSA/ATS Guidelines for CAP in Adults.

2 File, et. al.

CID

2010. 51(12): 1395-1405.

Risk Factors for Multidrug Resistance (MDR)

Antibiotics in the past 90 days High frequency of antibiotic resistance in community Immunosuppressive disease or medications HCAP Risk Factors: • Hospitalization for at least 2 days in the past 90 days • Residence in a SNF • Home infusion therapy • Dialysis within 30 days • Family member with MDR infection Kollef MH et al. CID 2008:46 (suppl 4)

Kollef MH et al. CID 2008:46 (suppl 4)

Influenza pneumonia Treatment

 First-line Tx is neuroaminidase inhibitors for both influenza A and B:  Oseltamavir 75-150* mg PO BID x 5+ days  Zanamavir 10 mg INH BID x 5+ days  NOTE: influenza A resistant to adamantanes (amantadine, rimantadine) * There is limited data in support of double dosing. But we do it anyway.

Antiviral Therapy for Influenza

Should be started ASAP in:  Anyone hospitalized with suspected or confirmed influenza  Anyone with severe, complicated or progressive respiratory illness  Anyone at higher risk of complications from influenza CDC Guidelines for Influenza 2012-2013

Individuals at Higher Risk for Influenza Complications

        Extremes of age: children <2, adults ≥65 years Comorbid conditions:     Chronic pulmonary Cardiovascular (except HTN alone) Renal, hepatic, hematologic, metabolic (DM) Neurologic, neuromuscular (cerebral palsy, epilepsy, CVA, SCI) Immunosuppression (caused by meds, HIV infection) Pregnant or post-partum (<2 wks) women Persons <19 years on long-term aspirin American Indians & Alaskan Natives Morbidly obese (BMI ≥40) Residents in NH or chronic-care facilities CDC Guidelines for Influenza 2012-2013

Influenza pneumonia What about the 48-hr rule?

 Antiviral treatment within 48 hrs   Reduce likelihood of lower tract complications & antibacterial use in outpatients Hospitalized patients likely benefit even if started up to 3 5 days from illness onset 1,2,3  Additional exceptions to <48 h rule:   Immunocompromised patients Severe, complicated or progressive illness 1 Siston, et. al.

JAMA

2 Yu,

Clin Infect Dis

2009.

2011.

3 Louie,

Clin Infect Dis

2012.

Follow-up Response Expected improvement?

 Clinical improvement w/ effective abx: 48-72 hrs  Fever can last 2-5 days with Pneumococcus, longer with other etiologies, esp Staph aureus  CXR clearing   If healthy & <50 yo, 60% have clear CXR x 4 wks If older, COPD, bacteremic, alcoholic, etc. only 25% with clear CXR x 4 wks  Switch from IV to PO   Hemodynamically stable, improving clinically Able to ingest meds with working GI tract

Question…

What is far & away the most common reason for non-response to antibiotics in CAP?

1.

2.

3.

4.

5.

Cavitation Pleural effusion Multilobar involvement Discordant antibiotic/etiology Host factors

• May. Kennewick, WA.

• A 58 y/o man with advanced liver disease, construction worker in outdoor excavation • C/O acute fever, cough, pleuritic chest pain, WBC 23,000.

• CXR and chest CT show RML nodule and effusion. No response to Unasyn + Levo.

• Concern for pneumococcal pneumonia. Thoracentesis and BAL are performed….

NW Infections: Coccidioides

Coccidioides immitis

- Endemic to the desert southwest - Dissemination more common in non-Caucasians, pregnant, immunocompromised Acute & chronic pulmonary syndromes (“valley fever”—fever, cough, arthralgias, Erythema nodosum) - Diagnosis based on serology, culture, or histopathology

Exposures & Associated Pathogens

Hotel or cruise ship, built water sources  Travel or residence in SW US Travel or residence in SE or E Asia Travel or residence in Arabian Peninsula Influenza active in community    

Coccidioides

spp

Hantavirus pulmonary syndrome (Sin Nombre virus) Burkolderia pseudomallei

Avian influenza A (H7N9)     

Legionella

spp MERS-CoV Influenza

S. pneumoniae Staph aureus (MSSA, MRSA) H. influenzae

Cough >2 wks with whoop or posttussive vomitting 

Bordetella pertussis

Zoonotic Exposures & Associated Pathogens

Bat or bird droppings 

Histoplasma capsulatum

Birds  

Chlamydophila psittaci

Avian influenza (H7N9) Rabbits Farm animals or parturient cats 

Francisella tularensis

 Coxiella burnetti (Q fever)

Take Home Points

 Ask patients about co-morbidities and travel/other potential exposures when they present with a respiratory illness  Evaluate patients for MDR risk factors when managing patients in the community with respiratory illness