Community-Acquired Pneumonia Current & Future State

Community-Acquired Pneumonia Current & Future State Brad Sharpe, M.D. Professor of Clinical Medicine Department of Medicine UCSF sharpeb@medicine.ucsf.edu I have no relevant financial relationships to disclose. 1. In 1898, William Osler described community-acquired pneumonia as: a. An ailment that often leads to suffocation and death. b. A friend of the aged. c. A common and mortal disease which can be diagnosed by simple observation and percussion of the chest. d. Bad. Really bad. 1

1. In 1898, William Osler described community-acquired pneumonia as: a. An ailment that often leads to suffocation and death. b. A friend of the aged. c. A common and mortal disease which can be diagnosed by simple observation and percussion of the chest. d. Bad. Really bad. "Pneumonia may well be called the friend of the aged. Taken off by it in an acute, short, not often painful illness, the old man escapes those cold gradations of decay so distressing of himself and to his friends. -- William Osler, M.D., 1898 2

Brad, pneumonia sucks. -- Mary R. Sharpe November 2011 Update in CAP 3

Roadmap Background Etiology Diagnosis Treatment Prevention 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 CAP: Current & Future 4

Caveats Will not talk about healthcare-associated pneumonia (HCAP) Will not discuss admission decision (complex) Syllabus or specific questions: (sharpeb@medicine.ucsf.edu) Community-Acquired Pneumonia Roadmap Background Etiology Diagnosis Treatment Prevention 5

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% Outpatient mortality < 1% CAP: Background Some evidence that quality of care for African-Americans with CAP is worse Higher mortality among Caucasians Mortensen EM, et al. BMC Health Serv Res. 2004;4:20. Mayr FB, et al. Crit Care Med. 2010;38:759. 6

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 2002;347(25):2039. Clinical Presentation: Geriatrics Less classic presentations 10% have NONE of the classic signs or symptoms Up to 35% will not have fever Up to 50% will have altered mental status Up to 50% will have asthenia Mehr DR, et al. J Fam Prac 2001;50(11):1101. Riquelme R, et al. Am J Respir Crit Care Med 1997;156:1908. Sund-Levander M, et al. Scand J Inf Dis. 2003;35:306. Simoneti AF, et al. Ther Adv ID. 2014;2:3. Community-Acquired Pneumonia 7

Roadmap Background Etiology Diagnosis Treatment Prevention Typical vs. Atypical Typical organisms S. pneumoniae, H. influenzae, M. catarrhalis, etc. 8

Typical vs. Atypical Atypical organisms M. pneumoniae, C. pneumoniae, Legionella spp, etc. Typical vs. Atypical Classic teaching is not supported by the literature Some general trends S. pneumoniae in older pts, co-morbidities Mycoplasma in patients < 50 years old Bilateral hazy opacities more likely to be atypical (but not always) 9

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) Non-ICU inpatients ICU inpatient File TM. Lancet 2003;362:1991. 10

Microbiology of CAP Jain S, et al. NEJM. 2015. Community-Acquired Pneumonia Microbiology of CAP Prospective study of 2320 patients with CAP admitted to 5 hospitals All extensive diagnostic evaluation Blood cultures, sputum cultures Urine antigen for S. pneumoniae & Legionella Nasopharyngeal PCR for viruses, Chlamydophila, Mycoplasma Some serologic testing Jain S, et al. NEJM. 2015. Community-Acquired Pneumonia 11

Microbiology of CAP Jain S, et al. NEJM. 2015. Community-Acquired Pneumonia Microbiology of CAP Jain S, et al. NEJM. 2015. Community-Acquired Pneumonia 12

Microbiology of CAP 1) Rhinovirus 2) Influenza 3) Streptococcus pneumoniae Jain S, et al. NEJM. 2015. Community-Acquired Pneumonia Microbiology of CAP No pathogen detected in > 60% of patients Real-world ~ 80-90% Many possible explanations Mainly viruses? Inadequate diagnostic testing Jain S, et al. NEJM. 2015. Community-Acquired Pneumonia 13

Etiology of CAP Outpatients (mild) Non-ICU inpatients ICU inpatient File TM. Lancet 2003;362:1991. Etiology of CAP Outpatients (mild) Non-ICU inpatients ICU inpatient Resp. viruses S pneumoniae M pneumoniae C pneumoniae H influenzae Resp. viruses S pneumoniae M pneumoniae C pneumoniae H influenzae Legionella spp S pneumoniae Legionella H influenzae GNRs S aureus Resp. viruses (?) File TM. Lancet 2003;362:1991. Metlay JP, et al. JAMA 1997;278(17):1440. CAP: Current & Future 14

Take Home Points 1) 2) 3) 4) 5) Community-Acquired Pneumonia Take Home Points 1) Cover typical and atypical bacteria 2) 3) 4) 5) Community-Acquired Pneumonia 15

Roadmap Background Etiology Diagnosis Treatment Prevention 2. A 65-year old man presents to urgent care complaining of subjective fever, chills, and productive cough x 3 days. He reports mild shortness of breath. His temperature is 38.6 o C, RR 20, O 2 saturation 95% on RA. He has crackles at the right base on lung exam. You should: a. Treat for community-acquired pneumonia. b. Send him for a PA and lateral CXR. c. Send him for blood and sputum cultures. d. Prescribe sudafed and robitussin and send him home. e. Perform trans-tracheal aspiration f. B and C 16

Chest Radiograph Gold Standard All expert guidelines state should have positive CXR to make diagnosis History & exam not good enough (50% sensitive) In outpt setting, should see an infiltrate. Order CXR if you are concerned about CAP If CXR negative, likely should not treat for CAP In the inpatient setting, can see pneumonia with a negative CXR (~30%) Metlay J. Ann Intern Med. 2003. Community-Acquired Pneumonia Chest Radiograph Gold Standard? Should (generally) order CXR in all patients with suspected pneumonia. In the hospital, a positive CXR is not necessary to treat as CAP (but consider other diagnoses). Community-Acquired Pneumonia 18

2. A 65-year old man presents to urgent care complaining of subjective fever, chills, and productive cough x 3 days. He reports mild shortness of breath. His temperature is 38.6 o C, RR 26, O 2 saturation 95% on RA. He has crackles at the right base on lung exam. You should: a. Treat for community-acquired pneumonia. b. Send him for a PA and lateral CXR. c. Send him for blood and sputum cultures. d. Prescribe sudafed and robitussin and send him home. e. Perform trans-tracheal aspiration f. B and C 2. A 65-year old man presents to urgent care complaining of subjective fever, chills, and productive cough x 3 days. He reports mild shortness of breath. His temperature is 38.6 o C, RR 26, O 2 saturation 95% on RA. He has crackles at the right base on lung exam. You should: a. Treat for community-acquired pneumonia. b. Send him for a PA and lateral CXR. c. Send him for blood and sputum cultures. d. Prescribe sudafed and robitussin and send him home. e. Perform trans-tracheal aspiration f. B and C 19

Blood Cultures Specific organism vs. contaminants, cost Reality: No evidence of a benefit Rarely positive = ~ 7% Contaminant rate = ~ 7% More likely to be positive if sicker ICU, septic shock, etc. Community-Acquired Pneumonia Blood Cultures in CAP In general, do not get blood cultures for outpatient CAP For inpatient CAP, blood cultures are optional Consider if risk factors: ICU, severe sepsis, cavitary infiltrates, pleural effusion IDSA/ATS Guidelines. CID. 2007;44:S27-72. 20

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 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. 21

The future in CAP - biomarkers Procalcitonin: precursor of calcitonin No hormonal activity Inflammatory marker Increased in bacterial infection Diagnosing Pneumonia Procalcitonin: Bacterial vs. Non-bacterial Intl J. Lung Dz. 2006 22

Meta-analysis/systematic review Four studies, ~3500 patients with respiratory tract infections Specific algorithm 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. Take Home Points 1) Cover typical and atypical bacteria 2) 3) 4) 5) Community-Acquired Pneumonia 23

Take Home Points 1) Cover typical and atypical bacteria 2) Get the CXR, skip the cultures 3) 4) 5) Community-Acquired Pneumonia Roadmap Background Etiology Diagnosis Treatment Prevention 24

Roadmap Background Etiology Diagnosis Treatment Prevention 25

Etiology of CAP Outpatients (mild) Non-ICU inpatients ICU inpatient Resp. viruses S pneumoniae M pneumoniae C pneumoniae H influenzae Resp. viruses S pneumoniae M pneumoniae C pneumoniae H influenzae Legionella spp S pneumoniae Legionella H influenzae GNRs S aureus Resp. viruses (?) File TM. Lancet 2003;362:1991. Metlay JP, et al. JAMA 1997;278(17):1440. CAP: Current & Future Treatment Principle #1 Outpatients (mild) Resp. viruses S pneumoniae M pneumoniae C pneumoniae H influenzae Must cover all these organisms 26

Treatment Principle #2 Outpatients (mild) Resp. viruses S pneumoniae M pneumoniae C pneumoniae H influenzae Wimpy pneumococcus Drug-resistant angry 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 27

Treatment of CAP Treatment CAP Outpatient, healthy, no DRSP risk factors Doxycycline or macrolide Macrolide = azithro, clarithro, erythro 29

Treatment CAP Risk Factors for DRSP Age > 65 years old Chronic disease Heart, lung, renal, liver Diabetes mellitus Alcoholism Malignancy Immunosuppression Antibiotics in the last 3 months 30

Treatment CAP Outpatient, DRSP risk factors Oral fluoroquinolone OR Oral β-lactam + doxy OR β-lactam + macrolide (DRSP = drug-resistant angry strep pneumo) NOTE: macrolides are not indicated for outpatients with DRSP risk factors (US resistance > 40%) Treatment CAP Outpatient, DRSP risk factors Oral fluoroquinolone OR Oral β-lactam + doxy OR β-lactam + macrolide Oral fluoroquinolone: moxi, gemi, levofloxacin β-lactam: High-dose amoxicillin (1mg PO tid) Amoxicillin/clavulanate (875mg PO bid) 31

Take Home Points 1) Cover typical and atypical bacteria 2) Get the CXR, skip the cultures 3) 4) 5) Community-Acquired Pneumonia Take Home Points 1) Cover typical and atypical bacteria 2) Get the CXR, skip the cultures 3) Outpatient: Brad Pitt vs. Donald Rumsfeld 4) 5) Community-Acquired Pneumonia 32

3. A 72 year-old man with a PMH of gout and DJD presents to your clinic with cough and shortness of breath. Based on the history, exam, and CXR (RML infiltrate), he is diagnosed with community-acquired pneumonia. He is well enough to be treated as an outpatient. He has no allergies. Which of the following is the best treatment regimen? A. Levofloxacin PO B. Azithromycin PO C. Ertapenem D. Ampicillin/clavulanate PO and azithromycin PO E. Zosyn & Vanco & Flagyl Risk Factors for DRSP Age > 65 years old Chronic disease Heart, lung, renal, liver Diabetes mellitus Alcoholism Malignancy Immunosuppression Antibiotics in the last 3 months 33

Treatment CAP Outpatient, DRSP risk factors Oral fluoroquinolone OR Oral β-lactam + doxy OR β-lactam + macrolide Oral fluoroquinolone: moxi, gemi, levofloxacin β-lactam: High-dose amoxicillin (1mg PO tid) Amoxicillin/clavulanate (875mg PO bid) 3. A 72 year-old man with a PMH of gout and DJD presents to your clinic with cough and shortness of breath. Based on the history, exam, and CXR (RML infiltrate), he is diagnosed with community-acquired pneumonia. He is well enough to be treated as an outpatient. He has no allergies. Which of the following is the best treatment regimen? A. Levofloxacin PO B. Azithromycin PO C. Ertapenem D. Ampicillin/clavulanate PO and azithromycin PO E. Zosyn & Vanco & Flagyl 34

4. A healthy 41 year-old woman who was recently treated (1 month ago) for cystitis with cipro presents to your clinic with fever, cough, sob. Her CXR reveals RLL infiltrate and you diagnose community-acquired pneumonia and decide to treat as an outpatient. Which of the following is the best treatment regimen? A. Levofloxacin PO B. Azithromycin PO C. Ertapenem D. Ampicillin/clavulanate PO and azithromycin PO E. Doxycycline PO and penicillin PO Risk Factors for DRSP Age > 65 years old Chronic disease Heart, lung, renal, liver Diabetes mellitus Alcoholism Malignancy Immunosuppression Antibiotics in the last 3 months 35

4. A healthy 41 year-old woman who was recently treated (1 month ago) for cystitis with cipro presents to your clinic with fever, cough, sob. Her CXR reveals RLL infiltrate and you diagnose community-acquired pneumonia and decide to treat as an outpatient. Which of the following is the best treatment regimen? A. Levofloxacin PO B. Azithromycin PO C. Ertapenem D. Ampicillin/clavulanate PO and azithromycin PO E. Doxycycline PO and penicillin PO Treatment CAP Outpatient, healthy, no DRSP risk factors Doxycycline or macrolide Outpatient, DRSP risk factors Oral fluoroquinolone OR Oral β-lactam + doxy or β-lactam + macrolide 36

Treatment Inpatient CAP Inpatient, non- ICU Fluoroquinolone OR β-lactam + macrolide OR β-lactam + doxycycline** ** At UCSF, we use ceftriaxone & doxycycline Treatment Inpatient CAP Inpatient, non- ICU Inpatient, ICU Fluoroquinolone OR β-lactam + macrolide OR β-lactam + doxycycline** IV β-lactam + macrolide + vancomycin OR IV β-lactam + fluoroquinolone + vancomycin ** At UCSF, we use ceftriaxone & doxycycline 37

Treatment CAP: New Data Treatment CAP: New Data Two European RCTs comparing β-lactam alone to either β-lactam + macrolide OR to a fluoroquinolone One study showed no difference One study showed better outcomes with atypical coverage for: 1) Sicker patients 2) Atypical pathogens 38

Treatment CAP: New Data May not be generalizable: European patient population Used amoxicillin or 2 nd -generation ceph. More than 30% got antibiotics before admission Not enough to change practice Duration of therapy 39

4. A 67 year-old man with CHF and diabetes is admitted to the hospital with CAP (non-icu). He is treated with ceftriaxone and doxycycline and does well. The cultures are all negative. On hospital day 3 he is ready for discharge. What is the optimal duration of total therapy for his CAP? A. 14 days B. 10 days C. 7 days D. 3 days E. Who cares. He probably won t take it anyway. I hate my job. 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. 40

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. Li JZ, et al. Am J Med. 2007;120:783. Duration of therapy Patients with CAP should be treated for a minimum of 5 days (level I evidence) -- IDSA/ATS Guidelines 41

Duration of therapy Minimum of 5 days If afebrile for 48-72 For most, 7 days total 4. A 67 year-old man with CHF and diabetes is admitted to the hospital with CAP (non-icu). He is treated with ceftriaxone and doxycycline and does well. The cultures are all negative. On hospital day 3 he is ready for discharge. What is the optimal duration of total therapy for his CAP? A. 14 days B. 10 days C. 7 days D. 3 days E. Who cares. He probably won t take it anyway. I hate my job. 42

Take Home Points 1) Cover typical and atypical bacteria 2) Get the CXR, skip the cultures 3) Outpatient: Brad Pitt vs. Donald Rumsfeld 4) 5) Community-Acquired Pneumonia Take Home Points 1) Cover typical and atypical bacteria 2) Get the CXR, skip the cultures 3) Outpatient: Brad Pitt vs. Donald Rumsfeld 4) Treat for 7 days (or 5) 5) Community-Acquired Pneumonia 43

Steroids in Pneumonia? CAP: Current & Future 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 Bruns AH. CID. 2007;45:983. 44

Roadmap Background Etiology Diagnosis Treatment Prevention Vaccinations In general, follow the national guidelines Pneumococcal and influenza vaccine 45

Pneumovax Updated meta-analysis of 18 RCTs (~64,000 pts) and 7 non-rcts (~62,000 pts) 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 CAP: Current & Future 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 CAP: Current & Future 46

Pneumovax - Efficacy Variable ICU admission Inpt complications LOS Inpt mortality Outcome Decreased Decreased Decreased Decreased CAP: Current & Future Pneumovax - Efficacy Pneumococcal vaccine likely prevents invasive pneumococcal disease. Probably reduces death, ICU admission, complications, and LOS in patients hospitalized with CAP ( makes pneumonia less bad ) CAP: Current & Future 47

Influenza Vaccine - Efficacy Adults aged < 65 years Prevents influenza illness in ~ 70-90% Adults aged > 65 years Prevents influenza illness in ~ 30-70% ACIP Recs. MMWR 2003;52:1. CAP: Current & Future Influenza Vaccine - Efficacy Hospitalization Risk Reduction Hospitalization for pna/flu 27%* All cause death 48%* * All p values < 0.001 Nichol KL, et al. N Engl J Med 2007;357:1373. (Oct 4, 2007) CAP: Current & Future 48

Roadmap Background Etiology Diagnosis Treatment Prevention Avoid the purple pill! 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) 49

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) CAP: Current & Future Take Home Points 1) Cover typical and atypical bacteria 2) Get the CXR, skip the cultures 3) Outpatient: Brad Pitt vs. Donald Rumsfeld 4) Treat for 7 days (or 5) 5) Community-Acquired Pneumonia 50

Take Home Points 1) Cover typical and atypical bacteria 2) Get the CXR, skip the cultures 3) Outpatient: Brad Pitt vs. Donald Rumsfeld 4) Treat for 7 days (or 5) 5) Vaccines = good Community-Acquired Pneumonia Roadmap Background Etiology Diagnosis Treatment Prevention 51

Take Home Points 1) Cover typical and atypical bacteria 2) Get the CXR, skip the cultures 3) Outpatient: Brad Pitt vs. Donald Rumsfeld 4) Treat for 7 days (or 5) 5) Vaccines = good Community-Acquired Pneumonia Community-Acquired Pneumonia Current & Future State Brad Sharpe, M.D. Professor of Clinical Medicine Department of Medicine UCSF sharpeb@medicine.ucsf.edu 52

Urine Pneumococcal Antigen Rapid test, specificity > 90% If positive, tx for pneumococcal disease May not reduce antibiotic spectrum -- > 70% with no change Sorde R, et al. Arch Intern Med. 2011;171:166. 53

Doxycycline Similar spectrum to macrolides Much cheaper! Good side effect profile (GI upset) Less Clostridium difficile infection Rates 27% lower in hospitalized patients with CAP vs. other regimens Doernberg SB, et al. Clin Infect Dis. 2012 Sep;55:615. 54

CURB-65 Score Validated severity-of-illness scoring system Retrospective then prospective Advocated by the British Thoracic Society Based on five easily measurable clinical factors Lim WS. Thorax 2003; 58:377 82 55

CURB-65 Score C Confusion (disoriented) U BUN > 20mg/dL R RR > 30/min B SBP < 90mmHg or DBP < 60mmHg 65 Age > 65 Lim WS. Thorax 2003; 58:377 82 CURB65 Score CURB65 Score Mortality 0 0.7% 1 2.5% 2 11.0% 3 15.5% 4 40.6% 5 57.0% Lim WS. Thorax 2003; 58:377 82 56

CURB65 Score CURB65 Mortality Treatment 0 0.7% Outpatient 1 2.3% Outpatient 2 11.0% Inpatient 3 15.5% Inpatient 4 40.6% ICU 5 57.0% ICU Lim WS. Thorax 2003; 58:377 82 Admission Decision Consider using a prognostic score in CAP Especially useful in borderline cases CURB65 easy to use 57