Management of Community Acquired PneumoniaATS/IDSA Guidelines 2006

Mazen Kherallah, MD, FCCPConsultant, Infectious Disease and Critical Care

Medicine

King Faisal Specialist Hospital & Research Center

www.icumedicus.com

CAP Guidelines

BTS, Canadian, ATS (1993) IDSA, ERS (1998) DRSPTWG (2000) IDSA (2000), Canadian (2000), JRS (2000) ATS (2001), BTS (2001) IDSA (2003) Mandell et al; CID (2003) ATS/IDSA (2006)

Site of Care

Site of Care

Significant impact on: Extent of laboratory evaluation Antimicrobial therapy

Advantage of outpatient therapy: Cost Patient preference Faster convalescence and avoidance of nosocomial

complications Decisions:

Hospital vs outpatients Intensive care vs general wards

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

CURB-65 Score:

1 Confusion (new disorientation in person, time or place)

1 Elevation of blood Urea, or blood urea nitrogen (BUN) level above 7 mmol/L (urea) or 20 mg% (BUN)

1 Respiratory rate >= 30 breaths/min

1 Low Blood pressure, < 90 mm Hg systolic OR =<60 mm Hg diastolic

1 Age >= 65 years

Score % Mortality Site of Care

0 0.7 Outpt1 1-3.2 Outpt2 2-9 Hospital3 17 ICU4 41.5 ICU5 57 ICU

Lim et al. Thorax 2003;58:377

Clinical Indications for more Extensive Diagnostic Testing.

Minor criteria Major criteria

Respiratory rate 30 breaths/min Invasive mechanical ventilation

PaO2/FiO2 ratio 250 Septic shock with the need for vasopressors

Multi-lobar infiltrates

Confusion/disorientation

Uremia (BUN level, 20 mg/dL)

Leukopenia (WBC count, >4000 cells/mm3)

Thrombocytopenia (platelet count, !100,000 cells/mm3)

Hypothermia (core temperature, <36°C)

Hypotension requiring aggressive fluid resuscitation

Recommended ICU admission if either major or at least three minor criteria

Diagnostic Testing

Clinical Diagnosis

Cough, fever, sputum production, and pleuritic chest pain)

Supported by imaging of the lung, usually by chest radiography.

Clinical Indications for more Extensive Diagnostic Testing.

Pathogen Rapid Test Standard Test

Other

S. Pneumoniae Gram stainUrine antigen

Blood and respiratory cultures

H. Influenzae Gram stain Blood culture

M. Pneumoniae PCR* Ab-ELISA1 Culture

C. Pneumoniae PCR* Ab-MIF2 Culture

L. pneumophilia Urine antigena

PCR*DFA3

Respiratory cultureAb-IFA

Culture (media)

•Not FDA approved a sensitivity 60-80%; specificity >90%1 IgM (1-50 weeks),, 2 Primary infection-IgM (4-6 weeks) IgG (often >6 weeks); 3 False positives with sputum.

Recommended Diagnostic Tests for Etiology

Urinary Antigen for S. pneumoniae (UrSp)

Immunochromatographic test Sensitivity 50-80% (80-90% for bacteremia) Specificity ~ 90% In prospective study, of 269 patients with CAP and no

pathogen identified, UrSp detected in 69 (27.5%) [Gutierrez et al. CID, 2003]

False positive in children (oropharyngeal colonization); Streptococcus spp. Bacteremia

Recommended as ancillary test (not as substitute for culture)

Mandell L et al. Clin Inf Dis, 2003

Blood Cultures

Blood cultures for all inpatients probably has some benefits, but limited and associated with increased cost and inappropriate antibiotic False positive > true pathogen in less ill patients

Strategy which targets higher risk patients seems reasonable Limit number of blood cultures by

Targeting the patients at highest risk of bacteremia (Mastesky, Am J Resp Crit Care Med, 2004)

Targeting patients with highest risk of mortality (Fine, NEJM 1997)

New CMS/JCAHO All patients with severe CAP (ICU) Optional for general ward patients (but not discouraged) If drawn in ER, before administration of antibiotics

Antibiotic Treatment

Most common etiologies of community-acquiredpneumonia

Ambulatory Patients Hospitalized (Non-ICU)2

Severe (ICU)2

S. pneumoniae S. pneumoniae S. pneumoniae

M. pneumoniae M. pneumoniae Legionella spp.

H. Influenzae C. pneumoniae H. Influenzae

C. pneumoniae H. Influenzae Gram-negative bacilli

Respiratory viruses3 Legionella spp. S. aureus

Aspiration

Respiratory viruses3

1Based on collective data from recent studies 2Excluding Pneumocystis spp.3Influenza A and B, adenovirus, respiratory syncytial virus, and parainfluenza.

Adapted from File T. Lancet 2003

Risk factors for infection with b-lactam–resistant S. pneumoniae

Age <2 years or >65 years Previous b-lactam therapy within the

previous 3 months Alcoholism Medical comorbidities Immunosuppressive illness or therapy Exposure to a child in a day care center

Treatment of Respiratory Tract Infections

Empiric Historically ß-lactams have been the agent of

choice Publication of treatment guidelines for CAP in the

1990s recommend macrolides for first-line use* Increase in macrolide use worldwide Also an increase in macrolide resistance

Macrolide resistance is now more common in some areas than ß-lactam resistance

*Niederman MS et al. Am Rev Resp Dis 1993;148:1418-1426

Antibiotic Choice: Outpatient

PSI <91 (Class I, II, III) or CURB-65 score 0-1

Previously healthy and no risk factors for drug-resistant S. pneumoniae (DRSP) infection:

A. A macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation; level I evidence)B. Doxycycline (weak recommendation; level III evidence)

•Presence of comorbidities, such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; •Use of antimicrobials within the previous 3 months:

A. A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin) (strong recommendation; level I evidence)B. A b-lactam plus a macrolide (strong recommendation; level I evidence): High dose amoxicillin, amoxicillin-clavulanate ceftriaxone, cefpodoxime, and cefuroxime. Doxycycline [level II evidence] is an alternative to the macrolide.

In regions with a high rate (>25%) of infection with high-level (MIC >16 mg/mL) macrolide-resistant S. pneumoniae,

Consider the use of alternative agents listedabove for any patient, includingthose without comorbidities. (Moderate recommendation; level III evidence.)

Antibiotic Choice: Inpatient

PSI >90 (Class IV) or CURB-65 score 2-5

Inpatient: Non-ICU Treatment

• Respiratory fluoroquinolone (strong recommendation; level I evidence)• B-lactam plus a macrolide (strong recommendation; level I evidence) (cefotaxime, ceftriaxone, and ampicillin; ertapenem for selected patients)

Inpatient, ICU Treatment

• B-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin (level II evidence) or a fluoroquinolone (level I evidence) (strong recommendation)

• For Pseudomonas infection, use an antipneumococcal, antipseudomonal b lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin

orthe above b-lactam plus an aminoglycoside and azithromycin

orthe above b-lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone (Moderate recommendation; level III evidence.)

• For community-acquired methicillin resistant Staphylococcus aureus infection, add vancomycin or linezolid. (Moderate recommendation; level III evidence.)

Others

Penicillin I or R 47%

PSI >90 (Class I, II, III) or CURB-65 score 2-5

S. Pneumonia Viral

Previously well, no prior ATB Macrolide, (azithromycin, clarithromycin, or erythromycin)

Doxycycline

Medical morbidity or use of antimicrobials within the previous 3 months

Respiratory fluroquinolone* (levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin)High dose β-lactam + macrolide

Risk of aspiration Am-CL; Clindamycin

General WordICU

No risk for pseudomonas Risk for psudomonas: brinchiectasis, recent ATB, prior ICU hospitalization

Respiratory fluroquinolones

β-lactam* + macrolide

β-lactam* + macrolide or respiratory quinolone

Antipseudomonas β-lactam** + ciprofloxacin

PSI <91 (Class I, II, III) or CURB-65 score 0-1

*Amox-CL, Cefotaxime, Ceftriaxone or Ertapenem**Pipercillin, imipenem, meropenem, cefepime***Moxifloxacin, gemifloxacin, levofloxacin

Atypicals et al

IDSA:2006

H. Flu

Time to First Antibiotic Dose

Timing of Antibiotic Administration

IDSA 2000: within 8 hours (Meehan et al. JAMA, 1997) IDSA 2003: “Goal” within 4 hours (ouck et al: Arch

Intern Med 2004; 164:637-44) A problem of internal consistency is also present,

because, in both studies, patients who received antibiotics in the first 2 h after presentation actually did worse than those who received antibiotics 2–4 h after presentation.

The first antibiotic dose should be administered while still in the ED. (Moderate recommendation; level III evidence.)

Switch from Intravenous to Oral Therapy

Switch from Intravenous to Oral Therapy

Patients should be switched from intravenous to oral therapy when they are: Hemodynamically stable Improving clinically Are able to ingest medications Have a normally functioning gastrointestinal tract. (Strong recommendation; level II evidence.)

Patients should be discharged as soon as they are: clinically stable Have no other active medical problems Have a safe environment for continued care. Inpatientobservation while receiving oral therapy is not necessary.(Moderate recommendation; level II evidence.)

Criteria for clinical stability.

Temperature 37.8C Heart rate 100 beats/min Respiratory rate 24 breaths/min Systolic blood pressure 90 mm Hg Arterial oxygen saturation 90% or pO2 60 mm

Hg on room air Ability to maintain oral intake Normal mental status

Criteria for clinical stability.

Halm EA, et al.. Arch Intern Med 2002; 162:1278–84.

Duration of Therapy

Community-Acquired MRSA

Case of Severe CAP

30 year old female presents to ER at 04:00 with acute fever, dough, and dyspnea

Recent ‘viral syndrome’ Severe hypoxemia Requires immediate

intubation Treated with 3rd gen ceph

pluse fluroquinolone

Case of Severe CAP

Gram stain of ET aspirate reveals GPC in clusters

Vancomycin was added

Patient has multi-organ dysfunction expires at 16:00

CA-MRSA isolated

Case of Severe CAP

Gram stain of ET aspirate reveals GPC in clusters

Vancomycin was added

Case of Severe CAP

Patient has multi-organ dysfunction expires at 16:00

CA-MRSA isolated

CA-MRSA Pneumonia

Newly recognized pathogen: community-onset MRSAGenotypically and phenotypically distinct HA-MRSA

Often associated with severe disease Panton Valentine Leukocidin (PVL)

Associated with preceding influenzaPending new data; vancomycin or linezolid recommended for initial therapy for severe disease

Framcis et al. Clin Inf Dis. 2004;40:100-7, Wago and Eiland Clin Infect Dis. 2005;40:1376

Response to Therapy

Thank You