Brice Taylor Assistant Professor Division of Pulmonary and Critical Care Medicine
Discuss advances in predicting prognosis Understand dwhat we know (and don t know) about the Microbiology Recognize important treatment principles
Epidemiology Predicting prognosis Pathogenesis/Microbiology Treatment
40 35 30 25 20 15 10 5 0 ICU Nursing Home Bacteremic Elderly Hospitalized Fine et al., JAMA 1996; 275:134
Musher et al; Clin Infect Dis 2007 170 pts with pneumonia 19.4% had major cardiac event (7% had MI) Higher mortality p<0.008 Ramirez et al; Clin Infect Dis 2008 500 CAP patients 5.8% had MI Perry et al; Am J Med 2011 50,119 veterans with pneumonia 1.5% MI, 10.2% CHF, 9.2% arrhythmia hth
Kruger et al; Am J Resp Crit Care Med 2010 728 CAP patients outcomes: 28 day and 180 day mortality MR proadm, CRP, Procalcitonin, etc Cardiac biomarkers more predictive than inflammatory markers
Need one MAJOR or three MINOR Mandell Clin Infect Mandell Clin Infect Dis 2007
Kruger; Eur Resp J 2008 1671 CAP patients PCT increased with CRB 65 score PCT higher in pts who died, similar accuracy to CRB 65 PCT < 0.228 identified low risk pts (99% NPV) Huang; Ann Emerg Med 2008 1651 CAP patients Only 2 pts with PCT <0.1 died
Epidemiology Predicting prognosis Pathogenesis/Microbiology Treatment
Sources of bacteria Aspiration from colonized oropharynx Aspiration from sinuses Aspiration from stomach Hematogenous spread (i.e. septic emboli) Aerosol (TB, legionella, viruses)
In nonsevere CAP, immune response is localized Local production of IL 1, IL 6, TNF alpha IL 8 in involved lung only In severe CAP Higher TNF and IL 6 in contralateral lung, serum Suggests role of excessive inflammatory response
Oupatient t Inpatient t S. pneumoniae M. pneumoniae H. influenza C. Pneumoniae viruses S pneumoniae M. pneumoniae C pneumoniae H. influenza Legionella Aspiration ICU S. aureus Gram negative enterics?mrsa
18% of 338 CAP patients had positive paired viral serology (4x rise in titers) Influenza (27 A, 10 B), Parainfluenza (11), RSV (5), Adenovirus (5) 100 90 80 70 60 50 40 30 20 10 Half pure viral, half 0 mixed infection De Roux et al Chest 2004 * p < 0.05 * viral mixed s. pneumo
Incidence unknown, often after viral infection Distinct from nosocomial MRSA Severe, necrotizing Panton Valentine Leukocidin USA 300 strain
95 Nursing home patients admitted for aspiration pna Cultures by bronch within 4 hours Anerobes in only 11 h % organism 60 50 40 30 6 of these responded to 20 inappropriate therapy 10 0 Anaerobes Gram Negs S. aureus
Community Acquired Health Care Associated Pneumonia (HCAP) Hospital Acquired
MRSA Pseudomonas ESBL E Coli KPC Klebsiella Acinetobacter, stenotrophomas others
HCAP criteria (any one) Hospitalization for >48 hrs in past 90 days Residence in nursing home or extended care Home infusion therapy or wound care Chronic dialysis Family member with MDR pathogen Treat like HAP/VAP with broad spectrum Abx
p p 2001: Morin & Hadler Healthcare associated infection (MRSA bacteremia) Hospitalization in past 12 months Dialysis within 12 months Indwelling catheter at home prior to admission 2002: Friedman et al Healthcare associated bloodstream infection (MRSA) IV infusion i or wound care at home in past 30 days Hemodialysis or infusion clinic visit in past 30 days Hospitalized for >2 days in past 90 days Nursing home or long term care facility 2004: Tacconelli et al 2005: ATS/IDSA guidelines Healthcare associated bacteremia (MRSA) IV therapy or nursing/wound care at home Ambulatory care visit in past 30 days Chronic Hemodialysis Hospitalized >2 days in past 6 months Nursing home or long term care facility Healthcare associated pneumonia Hospitalization >2 days in past 90 days Nursing home or extended term care facility Home infusion therapy or wound care Chronic dialysis within 30 days
Single center retrospective analysis, n=639 Primary endpoint infection with drugresistant organism The HCAP definition had a specificity of only 48.6% for drug resistant pathogens Misclassified one third of patients
Recent hospitalization Nursing Home Residence Chronic hemodialysis Home health/wound care Family member with MDR organism
Multicenter Prospective cohort study (n=104) Patients > 75 yo with severe pneumonia requiring mechanical ventilation Looked at microbial etiology in CAP vs NHAP Assigned ADL score as marker of functional status
Pathogen, % S. pneumoniae S. aureus MRSA Pseudomonas Nursing home Home (n = 47) (n = 57) p value (%) 9 29 6 4 (%) 14 0.380 7 0.002* 0 0.053 2 0.448 In hospital mortality (%) 57.4 52.6 0.8
ACTIVITIES OF DAILY LIVING Transfer Feeding Bathing Dressing Toileting Continence SCORING 1 = Independent 2 = Partially dependent 3 = Completely dependent 6 = fully independent 18 = fully dependent
60 50 40 30 20 S. aureus GNR and PSA S. pneumoniae 10 0 ADL I ADL II ADL III El Solh et al. 2001 Am J Resipir Crit Care Med
Recent hospitalization Nursing Home Residence Chronic hemodialysis Home health/wound care Family member with MDR organism
Retrospective cohort study 3074 pts on HD who were hospitalized for pneumonia Organism identified d in only 18.2% Gram negatives (11.1%) 1%) Gram positives (4.8%) Pseudomonas 2.8 % Klebsiella 16 1.6 % H influenzae 1.5 % S pneumoniae 3.4 % Other streptoccocci 10 1.0 % Staphylococcus sp 0.4 %
Guo et al. Nephrol Dial Transplant 2008 Retrospective cohort study (n = 60,610) Organism identified in only 15.6% Gram negatives (4.0%) Gram positives (4.73%) Pseudomonas 1.2 % Klebsiella 1.1 % H influenzae 0.47 % E coli 0.23 % S pneumoniae 2.56 % Other streptoccocci 0.43 % Staphylococcus sp 1.73 %
Retrospective cohort study (n=128) of hemodialysis patients admitted with pneumonia NO other HCAP risk factors Compared outcomes in patients treated with CAP vs HCAP guidelines Mortality Length of stay Time to oral therapy
CAP HCAP P value Age (mean, SD) 54.7 (15.7) 56.7 (15.6) 0.486 PSI (mean, SD) 93.1 (29.5) 101.7 (31.4) 0127 0.127 CCI 4.5 (1.8) 4.1 (1.5) 0.221 Outcomes Length of stay (days) Time to oral tx (days) 5.1 (3.7) 9.4 (5.5) <.0001* 3.2 (2.0) 9.2 (6.8) <.0001* Hospital mortality 0 2 0.465
Epidemiology Predicting prognosis Pathogenesis/Microbiology Treatment
NO PSEUDOMONAL RISK FACTORS PSEUDOMONAL RISK FACTORS Beta lactam (ceftriaxone) Beta lactam (cefepime, PLUS pip tazo), doripenem, Macrolide aztreonam if PCN allergy PLUS OR Cipro (or levo) OR Respiratory quinolone Beta lactam PLUS Aminoglycoside PLUS macrolide OR resp quinolone
40 515 pna patients Randomized to 35 levaquin alone vs 30 BL + M 25 Equivalent for non 20 severe CAP 15 Lower 30 day 10 mortality in severe CAP 5 0 PSI < V PSI V BL+M levo
First dose antibiotics within 6 hours Oxygenation assessment within 24 hrs Correct antibiotic/s administered d Blood cultures w/i 24 hrs Smoking cessation advice Pneumococcal and influenza vaccine
Most pts have clinical response in 3 days Switch to oral antibiotics when: Improvement in cough and dyspnea Decreasing wbc count Functional GI tract Afebrile at least 8 hrs (Ok to switch if still febrile as long as other features are present) Discharge home same day, outcomes same as if hospitalized for entire course
<7 day course similar efficacy to prolonged course in severe CAP 8 days equivalent to 14 days in HAP/VAP (except pseudomonas)
Guidelines recommend coverage for MRSA, pseudomonas, and resistant Gram negatives CAP tx may be adequate for patients with Good functional status No recent antibiotics Hemodialysis as only risk factor??
(Antibiotic) resistance it is 1 of the 3 greatest threats to human health, as well as national security and public safety of some regions Antimicrobial overuse is the key driver of resistance
Until guidelines are revised, consider subsets of HCAP pts that can be treated with CAP tx Limited role for combination therapy De escalation when clinical improvement Avoid prolonged dduration
Mortality from CAP is high and likely related to underlying cardiovascular disease Early recognition of severe CAP reduces mortality (PSI, CRB 65, PCT) PCT has high hneg pred value in CAP HCAP is clearly a heterogenous disease not all patients need MDR therapy Prompt deescalation and limited duration of antibiotics is safe and appropriate