Pneumonia Update 2010 Management of the Hospitalized Patient Scott A. Flanders, M.D." Professor of Medicine" Director, Hospitalist Program" University of Michigan" Overview" Community Acquired Pneumonia (CAP)! Pneumonia developing outside the hospital" But not HCAP" Healthcare Associated Pneumonia (HCAP)! Pneumonia developing outside the hospital" But the patient has been touched by the healthcare system" Community-Acquired Pneumonia" Care of the Hospitalized Patient" Admission Decision" Etiologies and Etiologic Testing" Antibiotic Therapy" Discharge Decision" Prevention" 1
Community-Acquired Pneumonia" Care of the Hospitalized Patient" Admission Decision (Predicting ICU Care)" Etiologies and Etiologic Testing" Antibiotic Therapy" Prevention" Predicting the Need for ICU Care ATS / IDSA Severity Criteria MAJOR CRITERIA" Mechanical Ventilation" Shock with Pressors" MINOR CRITERIA" RR > 30 BPM" P/F ratio < 250" Multilobar Infiltrates" Confusion" BUN > 20" WBC < 4 k" PLT < 100k" Temp < 36 C" Hypotension + Fluids" 2
Admission Decision" Predicting the Need for ICU Level Care" SMART COP > 3: Sens=92%, Spec=62%" IDSA / ATS: (3 minor): PPV 55%, (4 minor): PPV 81% " Sensitivity" " "AUC! ATS / IDSA! 0.88*! SMART COP 0.87*! PSI IV&V! 0.69! CURB-65! 0.67! 1-Specificity" *Crit Care Med 2010" *CID 2008" Impact of Delayed ICU Admission" Some series have suggested that up to 45% of patients who require ICU care are initially admitted to non-icu settings! Retrospective review of 4 multicenter CAP studies" 7266 patients (315 Direct ICU / 138 Delayed)" Exclude patients requiring vent / pressors on admit" Delayed Transfers" Propensity matched; Mortality OR= 3.08 (1.5-6.5)" Crit Care Med 2010" 3
Community-Acquired Pneumonia" Care of the Hospitalized Patient" Admission Decision" Etiologies and Etiologic Testing" Antibiotic Therapy" Prevention" Etiologies in CAP (Mild-Moderate Dz)" Typical bacteria! S. Pneumo 45%" H. Flu " " 20%" S. Aureus " 10%" K. Pneumo 3%" Other 15-20%" 30-40% 40-50% CID, 2008" 20-25% Atypical bacteria! Mycoplasma 65%" Chlamydiophila 30%" Legionella 5%" Viral Pneumonia 193 patients with extensive testing for viral agents" Rank order of viruses (15%)! Viral vs. Bacterial! Influenza (n=7)" hmpv (n=7)" RSV (n=5)" Rhinovirus" Parainfluenza" Coronavirus" Adenovirus" Nothing reliable, but " Older" More frail" More cardiac disease" Less leukocytosis (74% nl)" Seasonal" No difference in outcomes" CHEST 2008" 4
Is H1N1 Really That Bad?" Active Surveillance with 30 d follow-up" 07-08 vs. 08-09 vs. May 09- Nov 09 (H1N1)" H1N1" NO significant increase rates of hospitalization" NO significant increase rates of ICU" NO significant increase rates of sinusitis / otitis" Pneumonia 4% vs. 1.1% with seasonal" Median age with serious outcome : 32 vs. 65 (H3N2)" JAMA,2010" Swine Origin Influenza A (H1N1) Virus (S-OIV): Severe Disease; 18 cases" Clinical Presentation! Temp >38" "100%" Dyspnea " "100%" LDH abnl " "100%" Bilateral patchy" basilar inflitrates "100%" CPK abnl " "63%" Lymphopenia "61%" Hypotension "50%" Comorbidities "44%" PE " " "(50% UM" Extreme Obesity (90% UM)" MMWR 2010" Clinical Course! ARDS / vent "67%" ARDS in 24 hrs "55%" Renal Failure "33%" Bacterial Infxn "<5%" Rapid Tests Insensitive " Death Associations! Pressors after fluids" Intubation in 24 hrs" Renal Failure" APACHE / SOFA / P/F ratio" NOT steroids" NEJM 2009 5
Swine Origin Influenza A (H1N1) Virus (S-OIV)" Treatment! Oseltamivir (Tamiflu)" 150 mg p.o. bid x 10 days : critically ill / ICU" 75 mg p.o. bid x 5 days : non-icu" Zanamivir (Relenza)" 10 mg (2 oral inhalations) bid x 5 days" Rimantadine (If seasonal flu circulating)" 100 mg p.o. bid x 7 days" Antibiotics for Viral Respiratory Infections" -67% of 196 pts got abx" -95% continued abx for a median of 8 days" -63% of those had nl CXR" -More C-diff if cont. abx" Infect Control Hosp Epidemiol 2010" 6
Reducing Unnecessary Treatment" A Role for Procalcitonin?" Multicenter, randomized controlled trial" 6 Swiss emergency departments" 1360 patients presenting with LRTIʼs" 70% CAP, 15% COPD, 10% Acute Bronchitis" 93% hospitalized" 50% PSI risk classes IV and V" Randomized to usual care vs PCT based rx" Override allowed: ICU / severe instability, legionella" JAMA 2009" PCT Algorithm for Antibiotic Treatment" JAMA 2009" Antibiotic Exposure! All" Abx Exposure: 7d vs. 11d" CAP" Adverse effects: 23% vs. 33%" No effect on death, ICU admit, readmission, or complications" COPD" Bronchitis" Copyright restrictions Schuetz, may apply." P. et al. JAMA 2009;302:1059-1066. 7
CA-MRSA" Narrative review of published 12 studies / series" Clinical Features " "% of Patients! Flu Prodrome " " "30-75" Leucopenia " " "25-100" Shock " " " "50-100" Multi-lobar " " "50-100" Necrotizing " " "33-100" PVL + " " " "100" Mortality" " " "30-100 (avg 40)" Lancet 2009" CA-MRSA" 2010 Experience! 15 pts with CA-MRSA CAP over 30 months" <10% with influenza" 50% ICU" 60% necrosis on CT" 60% with effusions" 50% Immunodeficiency" 13% Mortality! 93% with Clindamycin or Linezolid rx! CHEST 2010" 8
CA-MRSA" Risk factors " Past skin infection (abscess)" IVDU" Influenza (concurrent with flu; resp sx 2-6 d prior to ED)" In sick patients with above risk factors consider empiric rx" Treatment:" Vancomycin or Linezolid (NOT Daptomycin)" Vanco troughs 15-20 mcg / ml" Controversial"?Clindamycin for anti-toxin effect? (rule out resistance first)" IVIG" Ann Emerg Med 2007" Lancet ID 2009" Diagnostic Testing" Pneumococcal Urinary Antigen Testing" Prospective 1 yr study in Spain! Patients " " "N (%) " " "Ag Testing! CAP " " " "474 (100) " "80% " "" Pneumococcal " "171 (36) " "90% of pts "" "Blood / pleural " "58" "Sputum " " "38" "Ag Test only " "75" "Ag Test + " " " " " "130 (85)" "Sens / Spec " " " " "70% / 96%! "Rx Narrowed " "41 (9)" (not narrowed in 89 + pts) " " " " " "" Arch Intern Med, 2010" Diagnostic Testing" RCT of Empirical vs. Targeted (Urine Ag) Rx! " " " " "Empiric " "Targeted" Patients " " "89 " " "88" Urine Ag +" " " " " "25" Rx Narrowed (Amox)" " " "25" Relapse " " " " "12%! Rx Not Narrowed" "89 " " "63" Relapse Rate " "2%!!!2% " " Thorax, 2010" 9
Community-Acquired Pneumonia" Care of the Hospitalized Patient" Admission Decision" Etiologies and Etiologic Testing" Antibiotic Therapy" Prevention" CASE" A 68 yo woman with Rheumatoid Arthritis (history of steroid use, but none in past 3 months) is admitted from the rheum clinic with 1 week F/C/S and rigors. A CXR 3 days prior showed a LLL infiltrate. She has not improved on 3 days of oral Levofloxacin. A repeat CXR re-demonstrates LLL infiltrate. She is febrile but hemodynamically stable. She is admitted to the floor after being started on Zosyn and Azithromycin in the ER. You would:" 1) keep these antibiotics going" 2) change them around" Antibiotic Therapy" The Guidelines:Inpatient" IDSA / ATS 2007" β-lactam + macrolide (or doxycycline)" (β-lactam :Ceftriaxone, Cefotaxime, Amp / Sul, Ertapenem)" Or, Respiratory fluoroquinolone" ICU: ß-lactam+macrolide, or ß-lactam+fluoroquinolone" Anti-pseudomonal (many options) or CA-MRSA Rx (Vanco or Linezolid) if risk factors: independent of ICU status" 10
Antibiotic Therapy" The Guidelines:Inpatient" IDSA / ATS 2007 Pseudomonal Risk: Non-ICU" Bronchiectasis" Structural lung disease (COPD / ILD) AND documented history of repeated antibiotics or long term chronic steroids in past 3 months" MD documentation of psuedomonal risk: will cover for psudomonas " As of Oct 1, 2010, no longer required for ICU patients! Antibiotic Therapy" ICU: β-lactam+ macrolide vs. β-lactam + fluoro! 218 pts, 27 ICUs in Europe" 20% monotherapy" 80% combination therapy" 46% with rx c/w IDSA / ATS guidelines" 50% β-lactam+ macrolide " 50% β-lactam+ fluoro" Intensive Care Med, 2010" ICU: β-lactam+ macrolide vs. β-lactam + fluoro" ICU Mortality! (censored at 60 days) " Intensive Care Med 2010" 11
ICU: β-lactam+ macrolide vs. β-lactam + fluoro" Overall Survival! Fig. 3 Survival graph for severe sepsis/septic shock patients treated in accordance with IDSA/ATS guideline in combination with a macrolide or a quinolone (censored at 60 days) Intensive Care Med 2010" Antibiotic Therapy" Stopping Antibiotics" Rx > 7 days no better than Rx < 7 days" Pts should be afebrile for 48-72 hours" Have no more than 1 CAP-associated instability*" Usually this is after 5 days of therapy" *HR<100" SBP>90" RR<24" Temp <37.8" O2 Sat >90" Mental status at baseline" Taking orals" Am J Med, 2007" Case" A 78 yo woman is being discharged after 5 days of treatment for CAP. Her course was complicated by a brief episode of delirium and hyperglycemia in the ICU. She had a swallowing study showing moderate aspiration of thin liquids. She is being discharged on augmentin, metformin, a PPI, and an atypical antipsychotic. The intervention MOST LIKELY to reduce her chance of developing recurrent pneumonia is:" 1) Pneumococcal vaccination" 2) Stopping her PPI and antipsychotics" 3) Enteral feeding to maintain caloric intake and reduce aspiration" 4) Tight glycemic control after discharge to keep hgba1c < 6.5" 12
Community-Acquired Pneumonia" Care of the Hospitalized Patient" Admission Decision" Etiologies and Etiologic Testing" Antibiotic Therapy" Prevention" Preventing CAP" Pneumococcal Vaccination! 3000 pts admitted with CAP; 4 yr f/u" 1000 pts vaccinated before or during hospitalization" 55% of patients with death or recurrent CAP" Pneumovax had no effect (HR=0.91; 0.81-1.05)" CID 2010" Preventing CAP" Pneumococcal Vaccination! Meta-analysis of 22 trials" Of high quality, blinded studies" " " " " " "Relative Risk (RR)! All cause pneumonia " "1.19 (0.95-1.49)" Elderly / ill pts" "Pneumonia " " "0.90 (0.70-1.14)" "Mortality" " " "1.00 (0.87-1.14)" CMAJ 2009" 13
Preventing CAP" Pneumococcal Vaccination! Pneumococcal vaccination does not appear to be effective in preventing pneumonia, even in populations for whom the vaccine is currently recommended " Huss, et. al. CMAJ 2010" Preventing CAP" Proton Pump Inhibitors (PPIs)! 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" Recurrent CAP after CAP admit" Starting PPIs in-house: OR=2.1 (7 % inc. absolute risk)" Numbers needed to harm (NNH)=14" Incidence of CAP Readmission" Am J. Med, 2010" 14
Proton Pump Inhibitors" Potential Adverse Effects" Community Acquired Pneumonia" Hospital Acquired Pneumonia" Hip Fractures" Clostridium difficile! Increased Mortality" Elderly, Nursing Home Population" Arch Intern Med, 2010" Preventing CAP" The Risk of Antipsychotics! JAGS, 2008" Recent antipsychotic start (1 wk), OR=4.3 (2.9-7.2)" Ann Intern Med, 2010" Population based Dutch study of 2000 patients" " " " " " "Risk of Pneumonia" Current Use" "Typical antipsychotic" "OR= 2.6 (1.4-4.6)" "Atypical " " " "OR= 1.8 (1.2-5.3)" " " " " " "(risk is dose-dependent)! Pneumococcal Vaccination and Value Based Purchasing" 15
Pneumonia Key Points" START" Risk assessment for ICU" Considering viral organisms / CA- MRSA as etiologies" STOP" Panicking over H1N1" Treating viral URIs with antibiotics (will procalcitonin help?)" Routinely treating CAP beyond 7 days" Unnecessary PPIs / Anti-Psychotics" Consider" Urine antigen testing for S. Pneumo not that helpful" Macrolides may be superior to fluoroquinolones" Overview" Community Acquired Pneumonia (CAP)! Pneumonia developing outside the hospital" But not HCAP" Healthcare Associated Pneumonia (HCAP)! Pneumonia developing outside the hospital" But the patient has been touched by the healthcare system" 16
Healthcare Associated Infections" Home Therapy! IV" Wound Care" Nursing care through health agency" Hospital or Dialysis Clinic in past 30 days for! Dialysis / Any IV therapy" Hospitalized 2 days in past 90? days! Nursing Home or Long-Term Care Facility! MDR Pathogens" Pseudomonas aeruginosa! Drug resistant gram negatives! ESBL producing Klebsiella! Enterobacter! Serratia! Acinetobacter spp.! MRSA! MDR= Multidrug-resistant Risk Factors for MDR Infections" Antimicrobial rx in past 90 days! Current hospitalization > 5 days! High rates of resistance in community or ward! Risk factors for HCAP! Home Therapy" Hospital or Dialysis Clinic in past 30 days" Hospitalized 2 days in past 90? days! Nursing Home or Long-Term Care Facility! Family member with multidrug resistant pathogen! Immunosuppressive disease or therapy! MDR= Multidrug-resistant 17
Etiologies (HEALTH CARE ASSOCIATED PNEUMONIA)" (Culture + CAP at an Academic Medical Center)! " " " "CAP!!!HCAP! Patients " "208 (33%) " "431 (67%) " "" S. Pneumo " "41% " " "10%" MRSA" " "12% " " "30%" Psuedomonas "4% " " "25%" Other GNR " "2% " " "10%" Inapprop. RX" "13% " " "30%" Mortality " "9% " " "25%" (HCAP: 70% hospitalized in past 90 days, 20% in past 180d)! *As of 2005 CMS excludes HCAP from CAP GL Recs*! AAC, 2007! HCAP Outcomes" Prospective cohort study! 55 Italian hospitals! 2 active 1 week surveillance periods! HCAP:! Dialysis or hospital clinic in past 30days! Chemo in past 30 days! 2 days of hospitalization in past 6 months! Nursing home or long term care! Annals Intern Med 2009" HCAP Outcomes" " " " "CAP!!!HCAP! Patients " "223 (62%) " "90 (25%)" Recent Hosp "0% " " "80%" (6 months)" Antacids " "23% " " "53%" Bilat Infiltrate "20% " " "34%" GL Adherent "59% " " "27%" Hosp Mortality "6.7%" " "17.8% " "" (Death assoc with low consciousness, leucopenia, no GL rx)! Annals Intern Med 2009" 18
Antimicrobial Therapy" Treatment for Patients at Risk for MDR Organisms! Anti-pseudomonal beta-lactam" " " " "+" Aminoglycoside or Fluoroquinolone" " " " "+" Vancomycin or Linezolid" IDSA/ATS 2005" Kollef CID 2008" Treating HCAP by the Guidelines" Why Did They (we) Fail?" Survey of 1300 faculty" Hospitalists, Pulm/Crit 1. Single Agent for GNRs" Care, ED" 9 clinical case questions" 2. No MRSA coverage" Also asked:" Are you familiar with the HCAP guidelines? " Do you agree with the HCAP guidelines? " Seymann, et al. CID, 2009" Predicting MDR Infections" Retrospective review" 640 culture + pneumonia pts" MDR Variables!OR! Recent Hosp" "4.2" NH or LTC " "2.8" Dialysis " "2.1" ICU " " "1.6" MRSA Risk! Recent Hosp" "2.4" NH " " "1.9" ICU " " "1.7 "" Arch Intern Med, 2008" Points:" 4pts-recent hosp" 3pts-NH" 2pts-HD" 1pt-ICU" 10pts max" (Of all patients with HCAP criteria only 50% had MDR organisms)" 19
Culture Negative HCAP" 900 HCAP patients" Prior Hosp 12 months! Nursing home" Outpt HD / wound care / infusion center" Immunosuppressed! 50% culture +; 50% culture -, or no culture" Of culture +" 30% with MRSA" 25% with pseudomonas" Culture Negative HCAP" " " " "Culture + " " "Culture! APACHE " "20 " " " "12" Approp Rx " "72% " " " "15% (CAP rx)" LOS " " "12 days " " "7 days" RX " " "9 days " " "5 days" De-escalate "30% " " " "20%" Mortality " "25% " " " "7%" (Culture + predictors: APACHE, Vent, Age, Nursing home)" (Mortality predictors: APACHE, Immunosuppress, Escalation)" Nursing Home Acquired Pneumonia (NHAP)" Predictors of Drug Resistant Bacteria" 135 nursing home patients admitted to ICU" Antibiotic use > 48 hrs in past 6 months! Poor functional status (ADL score > 12.5)*! Both positive: 90% MDRs" Both negative: 0% MDRs" ADL Score: 6 components, score each" 1 point=independent, 2=partial, 3=independent" El Solh CID 2004" Niederman Clin Chest Med 2007 " 20
Nursing Home Acquired Pneumonia (NHAP)" Treating NHAP like CAP" Retrospective 10 yr review of 150 cases of NHAP" Median age 82, 40% no disability, mild-mod dz" 95% treated with CAP rx" Mortality 8.7% (comparable to CAP)" 38% with etiology (S.pneumo (60%), GNB, atypicals )! Pts with GNB, MRSA were sicker" Polverino et. al. Thorax, 2010" AND NO Proton Pump β-lactam + macrolide Inhibitor for me, thanks!" for me, Thanks!" HCAP Treatment Recommendations Too Much Too Fast?! Lancet 2010" 21
HCAP Treatment Algorithm" Cur Opinion Infect Dis 2009" HCAP Treatment Algorithm" ADD! Indwelling Devices! (PICC, urinary Catheter, feeding tube)! Advanced Respiratory Disease! (Severe COPD, Bronchiectasis)! Cur Opinion Infect Dis 2009" Case" A 70 yo woman with a history of CHF, DM, COPD, and CKD is admitted with pneumonia. She has been hospitalized twice in the past 3 months and received broad spectrum antibiotics each time for an average of 3 days. No cultures were positive. She has a fever and mild hypoxia with a RLL infiltrate on CXR. She is admitted to the hospital floor and is started on Vanco, Zosyn, and Levofloxacin. After three days she is markedly improved. All cultures are negative. What do you do?" "1) Continue current regimen for 7 days" "2) Continue current regimen for 10 days" "3) Stop Vanco and Levo and continue Zosyn for 7 days total" "4) Switch to oral Fluoroquinolone alone" "5) Switch to oral Augmentin alone" 22
HCAP: De-escalation" Single Center Retrospective Chart Review" 102 cases of HCAP" " " "De-escalation " "No De-escalation! Patients " "77 " " " "25" Culture+ " "28% " " " "28%" LOS " " "7 days " " "13 days" Mortality " "3% " " " "28%" Antibiotic " "62% Moxifloxacin" Time to de-esc "4 days "" (culture neg. pts more likely to get moxi)" " " "" Infection 2010" CAP / HCAP Key Points" START" CAP: Risk assessment for ICU" CAP: Considering viral organisms as a possible etiology" HCAP: Risk stratifying for MDR pathogens" HCAP: Treating those at low risk with narrow spectrum abx" HCAP: Treating those at high risk with broad spectrum abx" STOP" CAP: Routinely treating beyond 7 days" HCAP: Treating all NHAP with broad spectrum abx" HCAP: Routinely treating beyond 8 days" CAP / HCAP Key Points" CONSIDER" CAP: SMART-COP to risk stratify for ICU admissions" CAP: Procalcitonin / Biomarkers may be coming soon" CAP/HCAP: Avoiding / Stopping unnecessary PPIs, antipsychotics" 23