Brice Taylor Assistant Professor Division of Pulmonary and Critical Care Medicine

Transcription

1 Brice Taylor Assistant Professor Division of Pulmonary and Critical Care Medicine

2 Discuss advances in predicting prognosis Understand dwhat we know (and don t know) about the Microbiology Recognize important treatment principles

3 Epidemiology Predicting prognosis Pathogenesis/Microbiology Treatment

4 ICU Nursing Home Bacteremic Elderly Hospitalized Fine et al., JAMA 1996; 275:134

5 Musher et al; Clin Infect Dis pts with pneumonia 19.4% had major cardiac event (7% had MI) Higher mortality p<0.008 Ramirez et al; Clin Infect Dis CAP patients 5.8% had MI Perry et al; Am J Med ,119 veterans with pneumonia 1.5% MI, 10.2% CHF, 9.2% arrhythmia hth

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7 Kruger et al; Am J Resp Crit Care Med CAP patients outcomes: 28 day and 180 day mortality MR proadm, CRP, Procalcitonin, etc Cardiac biomarkers more predictive than inflammatory markers

8 Need one MAJOR or three MINOR Mandell Clin Infect Mandell Clin Infect Dis 2007

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11 Kruger; Eur Resp J CAP patients PCT increased with CRB 65 score PCT higher in pts who died, similar accuracy to CRB 65 PCT < identified low risk pts (99% NPV) Huang; Ann Emerg Med CAP patients Only 2 pts with PCT <0.1 died

12 Epidemiology Predicting prognosis Pathogenesis/Microbiology Treatment

13 Sources of bacteria Aspiration from colonized oropharynx Aspiration from sinuses Aspiration from stomach Hematogenous spread (i.e. septic emboli) Aerosol (TB, legionella, viruses)

14 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

15 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

16 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) Half pure viral, half 0 mixed infection De Roux et al Chest 2004 * p < 0.05 * viral mixed s. pneumo

17 Incidence unknown, often after viral infection Distinct from nosocomial MRSA Severe, necrotizing Panton Valentine Leukocidin USA 300 strain

18 95 Nursing home patients admitted for aspiration pna Cultures by bronch within 4 hours Anerobes in only 11 h % organism of these responded to 20 inappropriate therapy 10 0 Anaerobes Gram Negs S. aureus

19 Community Acquired Health Care Associated Pneumonia (HCAP) Hospital Acquired

20 MRSA Pseudomonas ESBL E Coli KPC Klebsiella Acinetobacter, stenotrophomas others

21 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

22 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

23 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

24 Recent hospitalization Nursing Home Residence Chronic hemodialysis Home health/wound care Family member with MDR organism

25 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

26 Pathogen, % S. pneumoniae S. aureus MRSA Pseudomonas Nursing home Home (n = 47) (n = 57) p value (%) (%) * In hospital mortality (%)

27 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

28 S. aureus GNR and PSA S. pneumoniae 10 0 ADL I ADL II ADL III El Solh et al Am J Resipir Crit Care Med

29 Recent hospitalization Nursing Home Residence Chronic hemodialysis Home health/wound care Family member with MDR organism

30 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 % H influenzae 1.5 % S pneumoniae 3.4 % Other streptoccocci % Staphylococcus sp 0.4 %

31 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 %

32 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

33 CAP HCAP P value Age (mean, SD) 54.7 (15.7) 56.7 (15.6) PSI (mean, SD) 93.1 (29.5) (31.4) CCI 4.5 (1.8) 4.1 (1.5) 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

34 Epidemiology Predicting prognosis Pathogenesis/Microbiology Treatment

35 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

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37 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

38 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

39 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

40 <7 day course similar efficacy to prolonged course in severe CAP 8 days equivalent to 14 days in HAP/VAP (except pseudomonas)

41 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??

42 (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

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44 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

45 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