Pneumonia considerations 2017 Galia Rahav Infectious diseases unit Sheba medical center
Sir William Osler (1849 1919) "Father of modern medicine Pneumonia: The old man's friend The captain of the men of death (most common cause of infections related death) Osler died with pneumonia without benefit of a proper chest radiograph, antimicrobial therapy, or vaccine
Epidemiology Sixth leading cause of death number one cause of death from infectious disease 5.6 million cases per year in U.S >10 million physician visits 1.1 million hospitalizations 12/1000 all ages, 36/1000 2-5y, 30/1000 >65y Average rate of mortality for hospitalized patients 12% It cost $40 billion to care for patients with pneumonia Seasonal variation (winter months) M>F, black persons > Caucasians
Pathophysiology <5µm reach alveoli
Diagnosis Physical examination: Sensitivity 58% Specificity 67% Chest Imaging: CXR, CT Air Bronchogram CT not routine, is abnormal in 30% of those with normal CXR
Rationale for establishing an etiologic Dx (ID vs Pulmonary physicians) Optimal antibiotic selection Limit broad spectrum antibiotics Identify organisms of epidemiologic significance Identify drug resistant bacteria and monitor trends Identify new or emerging pathogens
Inadequate sputum saliva S. pneumopniae
Staphylococcus aureus Haemophilus influenzae
Solitaire -52%! Add -10-15%
Chicago and Nashville Age -57y ICU-21% Death-2%
Treatment CAP (IDSA, ATS, CTS, CDC, BTC ) Outpatients, inpatients, ICU Administration of antibiotics within 4 hours reduces mortality & LOS S. pneumoniae is the major pathogen (PRSP) Penicillin-resistant pneumococci may be resistant to macrolides and/or doxycycline All major guidelines recommend coverage for both typical" and atypical" organisms
CAP admitted to non-icu wards 90-day mortality: Beta-lactam monotherapy was noninferior to Beta-lactam macrolide combination or Fluoroquinolone monotherapy
IDSA/ATS recommendations for empiric therapy of CAP Ertapenem, ceftaroline
Antibiotic Resistance S. pneumoniae EU & U.S; Israel 2010 Antibiotic Europe 1 % of Drug Resistant S. pneumoniae Isolates (N=1974) US 2 (N=1647) Israel 3 (N=980) Penicillin 24.0 14.6 25.9 Ceftriaxone --- 5.9 5.5 Erythromycin 24.6 29.1 14 TMP-SMX 26.7 21.0 Tetracycline 19.8 15.8 Clindamycin --- 11.2 Chloramphenicol --- 4.9 Levofloxacin 2.0 1.1 1.6 1. Riedel S, et al. Eur J Clin Microbiol Infect Dis. 2007;26(7):485-490; 2. Richter SS, et al. Clin Infect Dis. 2009;48(3):e23-e33. 3. Regev-Yochay G. Plos one. 2014; e88406
Outpatients without comorbidity PO therapy (1) Macrolides Erythromycin Clarithromycin (Klacid) Roxithromycin (Rulid) Azithromycin (azenil) (2) Doxycycline (3) Respiratory Quinolones Levofloxacin (tavanic) Moxifloxacin Gatifloxacin
Outpatients with comorbidity PO therapy Respiratory fluoroquinolone Macrolide plus high-dose amoxicillin Macrolide plus high-dose amoxicillinclavulanate Some authorities prefer macrolides or doxycycline for patients <50 y who have no comorbidities and fluoroquinolones for patients >50 y or have comorbidities
Hospitalized patients General medical ward Extended spectrum cephalosporin (Ceftriaxone) (IV) combined with a macrolide / doxycycline (IV/PO) or ß -lactam / ß -lactamase inhibitor (augmentin) (IV) combined with a macrolide / doxycycline (IV/PO) or Fluoroquinolone (IV/PO)
Hospitalized patients ICU IV therapy Extended-spectrum cephalosporin (IV) plus either fluoroquinolone or macrolide (IV) ß lactam / ß -lactamase inhibitor (IV) plus either fluoroquinolone or macrolide (IV)
Duration of therapy No controlled trials to assess Good outcomes with 5-7 days total Consider 10-14 days if sick... S pneumoniae 7-10 days M. pneumoniae 10-14 days L. pneumophila 14-21 days
Prevention Pneumococcal vaccine pneumococcal polysaccharide vaccine (PPV) (pneumovax) 23- valent: > 65y, comorbidity, ineffective <2y pneumococcal conjugate vaccine (PCV 7, Prevenar 7) (PCV Prevenar 13) Influenza vaccine Stop smoking
PPV23- Efficacy and effectiveness Despite multiple studies conducted during >30 years, the efficacy and effectiveness of PPV23 in children and adults remain poorly defined and the subject of controversy
Capsular polysaccharide vaccine lack potency, durability, memory Limitations: No immune memory Does not induce T cell response Antibody titers and efficacy appear to wane after 5 years Effectiveness is very low in immunocompromised patients Poorly immunogenic in children younger than two years Induce Hypo responsiveness to either another dose of PPV23 or to a dose of conjugate vaccine Not effective in preventing pneumococcal pneumonia No reduction in carriage, no reduction in transmission
Surveillance of IPD in children in US following implementation of PCV7 in 2000
Surveillance of IPD in adults found Herd protection
Incidence rate of antibiotic 3 2.5 2 resistant isolates in Israel 29.7% Penicillin MIC 2.0 µg/ml MIC>0.06 µg/ml Ceftriaxone MIC 4.0 µg/ml MIC> 1 µg/ml PCV Implementation in Israel PCV7-7/2009 1.5 1 11% 18% PCV13 11/2010 0.5 5% 1.5%% 0 2009-10 2010-11 2011-12 2012-13 2009-10 2010-11 2011-12 2012-13 2009-10 2010-11 2011-12 2012-13 2009-10 2010-11 2011-12 2012-13 AB Penicillin Ceftriaxone Erythromycin Quin
CAPiTA trial (Community-Acquired Pneumonia Immunization Trial in Adults)
One of the largest double-blind, randomized, placebo-controlled vaccine efficacy trials conducted in adults
Primary and Secondary Objectives: Per Protocol 49 90 45.6 (21.8,62.5) <0.001 7 28 75.0 (41.4,90.8) <0.001
ACIP Sequential administration and recommended intervals for PCV13 and PPSV23 for aged 65y
Influenza vaccine - efficacy variable Respiratory illness Risk Reduction 56%* Hospitalization 50%* Pneumonia 53%* All cause death 68%* NNT=118 *p<0.001
CAP TYPICAL ATYPICAL Pathogens S. pneumoniae M. pneumoniae H. influenaze C. pneumoniae K. pneumoniae L. pneumophilla Onset Abrupt insidious Fever high (39-40) low grade (38) Chills yes no Cough productive (rusty) dry Sputum PMN & bacteria few PMN Extra Pulmonary signs rare common CXR lobar interstitial consolidation infiltrates WBC leukocytosis normal count General condition sick walking pneumonia Mortality high (20%) low (1-2%)
Admission decision (X20 cost ) Pneumonia severity index (PSI) (PORT study) Scoring system to risk stratify and to identify outpatient vs. inpatient treatment Fine MJ, et al. N Engl J Med 1997
years F -10 +20 +20 +10 +20 +20 +10 +30 +20 +10 +10 +20 +20 +10 +30 +10 +10 +10
CURB - 65 Confusion Uremia > 20mg/ml Respiration > 30/min Blood pressure (SBP < 90 mmhg or DBP <60 mmhg) Age > 65y
CURB - 65