Roadmap. Community-Acquired Pneumonia. Specific Goals: Sources. Background Etiology Diagnosis Treatment Prevention

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Community-Acquired

Pneumonia

Bradley A. Sharpe, M.D. Associate Professor Medicine Department of Medicine UCSF [email protected]

Roadmap

• Background • Etiology • Diagnosis • Treatment • Prevention

CAP: A Practical Approach

Specific Goals:

• Describe the most common causes of community-acquired pneumonia in the outpatient setting

• Order appropriate diagnostic tests for CAP • Initiate appropriate antibiotics in the treatment

of community-acquired pneumonia (CAP) • State the optimal duration of therapy in CAP • State the benefits and need for preventative

measures for CAP

Sources

• Guidelines for Community-Acquired Pneumonia

♦ IDSA/ATS Consensus Guidelines 2007

(IDSA = Infectious Disease Society of America) (ATS = American Thoracic Society)

♦ BTS: British Thoracic Society

• Updated Literature Review

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Caveats

• Practical, nuts and bolts (use it tomorrow…)

• Run-of-the-mill community-acquired pneumonia • Will not talk about healthcare-associated

pneumonia (HCAP)

• Will not discuss admission decision (complex)

Community-Acquired Pneumonia

CAP: Background

• 5 million cases/year in the U.S. • 80% of CAP is treated outpatient • Sixth leading cause of death • Inpatient mortality 10-35%

▪One-year mortality = 40% (vs. 29% in controls)

• Outpatient mortality < 1%

CAP: Background

• Higher mortality among Caucasians • Some evidence that quality of care for

African-Americans with CAP is worse

CAP: A Practical Approach Mortensen EM, et al. BMC Health Serv Res. 2004;4:20.

Mayr FB, et al. Crit Care Med. 2010;38:759.

CAP: Background

Cough 90%*

Dyspnea 66%

Sputum 66%

Pleuritic chest pain 50%

* Yet, only 4% of all visits for cough are pneumonia

Halm EA, Teirstein AS. N Engl J Med

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Community-Acquired Pneumonia

Clinical Presentation: Geriatrics

• Less “classic” presentations

♦ 10% have NONE of the classic signs or symptoms

• Up to 40% will not have fever

• Up to 45% will have altered mental status

Mehr DR, et al. J Fam Prac2001;50(11):1101. Riquelme R, et al. Am J Respir Crit Care Med

1997;156:1908.

“Typical” vs. “Atypical”

• Classic teaching is not supported by the literature

• Some general trends

♦ S. pneumoniaein older pts, co-morbidities

♦ Bacterial infections more common in immune deficiencies

♦ Viruses more common in older patients

♦ Mycoplasmain patients < 50 years old

“Typical” vs. “Atypical”

• Classic teaching is not supported by the literature

• Some general trends

• But - no history, exam, laboratory, or radiographic features predict organism

♦ “Walking pneumonia”

♦ “Classic lobar pneumonia”

Etiology of CAP

Outpatients (mild) • S pneumoniae(30-50%) • Resp. viruses (10-30%) • M pneumoniae • H influenzae • C pneumoniae Non-ICU inpatients • S pneumoniae • M pneumoniae • C pneumoniae • H influenzae • Legionella spp • Resp. viruses ICU inpatient • S pneumoniae • Legionella spp • H influenzae • GNRs • S aureus File TM. Lancet2003;362:1991.

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CA-MRSA

• Community-acquired MRSA CAP • First reported in 2003; increasing • Specific strain of MRSA

-- Panton-Valentine Leukocidin (PVL) genes

CA-MRSA

Clinical Features % of Patients

• Flu Prodrome 30-75% • Shock 50-100% • Multi-lobar 50-100% • Necrotizing 33-100% • Leukopenia 25-100% • Ventilated 50-100% • Mortality ~ 40%

Diagnosis of CAP

1) Select clinical features

(e.g. cough, fever, sputum, pleuritic chest pain)

AND

2) Infiltrate by CXR or other imaging

IDSA/ATS Guidelines. CID. 2007;44:S27-72.

Diagnosis of CAP

• Clinical history and physical examination are not sensitive or specific

• All patients with suspected pneumonia should have a CXR

Wipf JE, et al. Arch Intern Med. 1999;159:1082. IDSA/ATS Guidelines. CID. 2007;44:S27-72.

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Blood Cultures

• Provides a specific diagnosis • The data:

♦ Cultures within 24 hours of arrival are associated with 10% lower odds of 30d mortality • No evidence of benefit in outpatient setting

CAP: A Practical Approach Meehan TP, et al. JAMA1997;278.

Blood Cultures in CAP

• Limitations

♦ Positive in < 10% of cases

• Medicare database of 13,000 patients

• Determined predictors of blood-culture positivity

♦ The sicker you are. . .

CAP: A Practical Approach Metersky ML, et al. Am J Respir Crit Care Med

2004;169(3):342-7

Blood Cultures in CAP

• Limitations

♦ Positive in < 10% of cases

♦ High percentage of contaminants

♦ Cultures change antibiotics in < 5% of patients

♦ Costly

CAP: A Practical Approach Metersky ML, et al. Am J Respir Crit Care Med

2004;169(3):342-7

Blood Cultures in CAP

• In general, blood cultures are not indicated in the management of outpatient CAP

• For inpatient CAP, blood cultures are optional

unless clear risk factors for positive blood cultures

▪ICU, Severe liver disease, Cavitary infiltrates, Pleural effusion

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Sputum for CAP

• Complicated and Controversial • Simple, inexpensive, specific for

pneumococcus • Problems include:

♦Up to 30% could not produce adequate sputum

♦Good quality available in only 14%

♦Most don’t narrow antibiotics

Sputum Cultures in CAP

• In general, sputum cultures are not indicated in the management of outpatient CAP

• For inpatient CAP, sputum is indicated:

▪High-quality specimen, right to the lab

▪ICU, Cavitary infiltrates, Underlying lung disease

IDSA/ATS Guidelines. CID. 2007;44:S27-72.

The future in CAP

• Pneumococcal urinary antigen • Rapid test, specificity > 90%

• If positive, tx for pneumococcal disease • Probably does not reduce antibiotic spectrum

-- > 70% with no change

Sorde R, et al. Arch Intern Med. 2011;171:166.

The future in CAP - biomarkers

• Procalcitonin: precursor of calcitonin

● No hormonal activity

● Inflammatory marker

● Increased in sepsis, bacterial infection

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Meta-analysis/systematic review

• Four studies, ~3500 patients with respiratory tract infections

• Less antibiotic exposure**

• A 22% decrease in prescriptions • Average 2.3 days less abx overall

• No difference in mortality/clinical outcomes

Soni NJ, et al. JHM. 2013;8:530.

Treatment Principle #1

Outpatients (mild) • S pneumoniae • M pneumoniae • H influenzae • C pneumoniae • Resp. viruses

Must cover all these organisms

Treatment Principle #2

Outpatients (mild) • S pneumoniae • M pneumoniae • H influenzae • C pneumoniae • Resp. viruses

“Wimpy” pneumococcus

Drug-resistant S. pneumoniae

(DRSP)

Penicillin, erythromycin, macrolides, etc.

Risk Factors for DRSP

• Age > 65 years old • Chronic disease

▪Heart, lung, renal, liver

• Diabetes mellitus • Alcoholism

• Malignancy (active) • Immunosuppression

• Antibiotics in the last 3 months

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Treatment CAP

Outpatient, healthy, no

DRSP risk factors Doxycycline or macrolide

Macrolide = azithro, clarithro, erythro

Treatment CAP

Outpatient,

DRSP risk factors

Oral fluoroquinolone OR

Oral -lactam + doxy or macrolide

● Oral fluoroquinolone: moxi, gemi, levofloxacin

● -lactam: High-dose amoxicillin (1mg PO tid) Augmentin (875mg PO bid)

UCSF Outpatient CAP

• Patients with no co-morbidities and not recently exposed to antibacterials:

First choice: doxycycline Second choice: azithromycin Third choice: clarithromycin • “High risk” (DRSP risk factors):

First choice: respiratory fluoroquinolone

Second choice: combination B-lactam + doxycycline

Treatment CAP

Inpatient, non-ICU Fluoroquinolone OR -lactam + macrolide

Inpatient, ICU IV -lactam + macrolide + vancomycin OR

IV -lactam + fluoroquinolone

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“Guideline Concordant Abx”

Benefits

• Frei CR, et al. Am J Med. 2006;119:865 - Retrospective study of 631 pts with CAP - Early switch to orals, shorter LOS, lower mortality • Mortensen EM, et al. Am J Med. 2006;119:859.

- Retrospective study of 787 pts with CAP - Decreased mortality at 48 hours

• Mortensen EM, et al. Am J Med. 2004;117:726-31 - Improved 30-day mortality

CAP: A Practical Approach CAP: A Practical Approach

“Guideline Concordant Abx”

Benefits

• Arnold FW, et al. Arch Intern Med. 2009;169:1515. - Retrospective study of 1725 pts with CAP; - Shorter LOS, mortality 10% lower (NNT = 10) • Mccabe C, et al. Arch Intern Med. 2009;169:1525.

- Retrospective study of > 50,000 with CAP - Decreased mortality by 30%

• Asadi L, et al. Respir Med. 2012;106:451.

- Retrospective study of 2973 outpatients with CAP - Decreased mortality by 77%

Duration of therapy?

• Meta-analysis of 15 RCTs, 2796 patients with mild to moderate CAP

• Compared short-course (< 7 days) with longer courses.

• Looked at clinical failure, bacterial eradication, and mortality.

Li JZ, et al. Am J Med. 2007;120:783.

Duration of therapy?

• No difference in clinical failure • No difference in bacterial eradication • No difference in mortality

• In subgroup analysis, trend toward favorable efficacy with short-course.

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Duration of therapy

• Minimum of 5 days

▪ If afebrile for 48-72

• For most, 7 days total

Follow-up CXR?

• Standard practice?

• Prior ATS guidelines said yes, recent guidelines do not address

• CXR resolution:

▪At 28 days, ~ 50% had not resolved

• Can consider in “high-risk” patients ▪Significant smoking history, etc.

▪Probably should wait > 3 months

CAP: A Practical Approach Bruns AH. CID. 2007;45:983..

Pneumovax

• Updated meta-analysis of 18 RCTs (~64,000 pts) and 7 non-RCTs (~62,000 pts) trials,

• Only high-quality studies

Relative Risk All-cause pneumonia 0.70(0.45-1.12) All-cause mortality 0.90 (0.74-1.09) ** No difference for elderly or chronic illness

Moberly S, et al. Cochrane. 2013; 1:CD000422

Pneumovax - Efficacy

• Four different trials looking at benefits of pneumovax in patients hospitalized with CAP.

• Compared vaccinated vs. non-vaccinated • Looked at impact on ICU admission,

inpatient mortality, inpatient complications, and LOS.

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Pneumovax - Efficacy

Variable Outcome ICU admission Decreased Inpt complications Decreased

LOS Decreased

Inpt mortality Decreased

Pneumovax - Efficacy

• Pneumococcal vaccine likely prevents invasive pneumococcal disease.

• Probably reduces death, ICU admission, complications, and LOS in patients hospitalized with CAP.

Pneumovax - Who

• Patients > 65 years old

• Patients < 65 with chronic medical conditions • Respiratory: COPD, asthma

• Cardiovascular disease

• Metabolic diseases: diabetes, renal failure, liver failure

• Immunocompromised (HIV, malignancy, etc.) • Residing in long-term care facilities

Influenza Vaccine - Efficacy

• Adults aged < 65 years

• Prevents influenza illness in ~ 70-90%

• Adults aged > 65 years

• Prevents influenza illness in ~ 30-70%

CAP: A Practical Approach ACIP Recs. MMWR2003;52:1.

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Influenza Vaccine - Efficacy

CAP: A Practical Approach Gross PA, et al. Ann Intern Med. 1995;123:518-27.

Hospitalization Risk Reduction

Resp. Illness 56%* Hospitalization 50%*

Pneumonia 53%*

All cause death 68%*

(NNT = 118) * All p values < 0.001

Influenza Vaccine - Efficacy

CAP: A Practical Approach Nichol KL, et al. N Engl J Med2007;357:1373. (Oct 4, 2007)

Hospitalization Risk Reduction

Hospitalization

for pna/flu 27%*

All cause death 48%*

* All p values < 0.001

Smoking Cessation Counseling

• Should provide it to all of our patients that smoke

• Some evidence that tobacco is a risk factor for pneumonia

Proton Pump Inhibitors

• Gulmez, et al. Arch Intern Med. 2007.

-- Current use of PPI: CAP OR = 1.5 -- Recent start: CAP OR = 5.0 • Sarkar, et al. Ann Intern Med. 2008.

-- Recent PPI start: CAP OR = 3.8 • Herzig, et al. JAMA. 2009.

-- 52% of hosp pts got PPI, HAP OR = 1.3 • Eurich, et al. Am J Med. 2010.

-- Rates recurrent CAP after CAP admit -- Starting PPI: OR 2.1% (7% abs risk)

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Anti-psychotics

• Knol W, et al. JAGS. 2009.

-- Recent anti-psychotic start (1 wk); OR 4.3** • Trifiro, et al. Ann Intern Med. 2010.

-- Population based study, 2000 patients. Current Use Risk of pneumonia

Typical anti-psychotic OR = 2.6 (1.4-4.6)

Atypical OR = 1.8 (1.2-5.3)

Take-Home Points

• Etiology: No predictors for “typical” or “atypical” – need to treat both • Etiology: Recognize CA-MRSA as a cause for

severe CAP

• Diagnosis: Do not routinely get blood or sputum cultures in outpt CAP

Take-home Points

• Treatment: doxycycline or macrolide for healthy outpatient with no DRSP risk-factors

• Treatment: fluoroquinolone or -lactam + macrolide/doxy for outpt with DRSP risk factors

• Prevention: pneumovax, flu vax, smoking, avoid PPIs