Update in Community- Update in Community- Acquired Pneumonia Acquired Pneumonia Brad Sharpe, M.D. I have no relevant financial relationships to disclose. Professor of Clinical Medicine Department of Medicine, UCSF sharpeb@medicine.ucsf.edu sharpeb@medicine.ucsf.edu Roadmap Specific Goals: • Describe the most common causes of • Background community-acquired pneumonia in the • Etiology outpatient setting • Diagnosis • Order appropriate diagnostic tests for CAP • Initiate appropriate antibiotics in the treatment • Treatment of community-acquired pneumonia (CAP) • Prevention • State the optimal duration of therapy in CAP • State the benefits and need for preventative measures for CAP CAP: Current & Future CAP: Current & Future 1
Caveats CAP: Background • Will not talk about healthcare-associated • 5 million cases/year in the U.S. pneumonia (HCAP) • 80% of CAP is treated outpatient • Will not discuss admission decision (complex) • Syllabus (sharpeb@medicine.ucsf.edu) • Sixth leading cause of death • Inpatient mortality 10-35% • Outpatient mortality < 1% CAP: Current & Future CAP: Current & Future CAP: Background CAP: Background • Higher mortality among Caucasians Cough 90%* • Some evidence that quality of care for Dyspnea 66% African-Americans with CAP is worse 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. Mortensen EM, et al. BMC Health Serv Res . 2004;4:20. CAP: Current & Future CAP: Current & Future Mayr FB, et al. Crit Care Med . 2010;38:759. 2
Clinical Presentation: Geriatrics “Typical” vs. “Atypical” • Less “classic” presentations • Classic teaching is not supported by the ♦ 10% have NONE of the classic signs or literature symptoms • Some general trends • Up to 40% will not have fever ♦ S. pneumoniae in older pts, co-morbidities • Up to 45% will have altered mental status ♦ Viruses more common in older patients ♦ Mycoplasma in patients < 50 years old Mehr DR, et al. J Fam Prac 2001;50(11):1101. Riquelme R, et al. Am J Respir Crit Care Med 1997;156:1908. CAP: Current & Future CAP: Current & Future “Typical” vs. “Atypical” Microbiology of CAP • Classic teaching is not supported by the • Prospective study of 2320 patients with literature CAP admitted to 5 hospitals • Some general trends • All extensive diagnostic evaluation Blood cultures, sputum cultures • • But - no history, exam, laboratory, or Urine antigen for S. pneumoniae & Legionella • radiographic features predict organism Nasopharyngeal PCR for viruses, • ♦ “Walking pneumonia” Chlamydophila , Mycoplasma ♦ “Classic lobar pneumonia” Some serologic testing • Jain S, et al. NEJM. 2015. CAP: Current & Future CAP: Current & Future 3
Microbiology of CAP Microbiology of CAP • Real-time PCR was applied to sputum samples from 323 patients with CAP • Pathogen confirmed in 87% of patients H. Flu and Strep pneumo most common 1) Rhinovirus • Viruses in 30% but > 80% co-infections • 2) Influenza 3) Streptococcus pneumoniae Jain S, et al. NEJM. 2015. Gadsby NJ, et al. Clin Infect Dis . 2016;April. CAP: Current & Future CAP: Current & Future Etiology of CAP Take Home Points Outpatients (mild) Non-ICU inpatients ICU inpatient 1) 2) • Resp. viruses • S pneumoniae • Resp. viruses • S pneumoniae • Legionella • S pneumoniae 3) • M pneumoniae • H influenzae • M pneumoniae 4) • C pneumoniae • GNRs • C pneumoniae • H influenzae • S aureus • H influenzae 5) • Resp. viruses (?) • Legionella spp Community-Acquired File TM. Lancet 2003;362:1991. CAP: Current & Future Pneumonia Metlay JP, et al. JAMA 1997;278(17):1440. 4
Diagnosis of CAP Chest Radiograph – Gold Standard • All expert guidelines state should have 1) Select clinical features positive CXR to make diagnosis (e.g. cough, fever, sputum, pleuritic chest pain) ● History, exam, etc. not good enough • In outpt setting, should see an infiltrate. AND ● Order CXR if you are concerned about CAP ● If CXR negative, likely should not treat for CAP 2) Infiltrate by CXR or other imaging • In the inpatient setting, the CXR can be negative IDSA/ATS Guidelines. CID . 2007;44:S27-72. CAP: Current & Future CAP: Current & Future Chest Radiograph – Gold Standard? Blood Cultures • Should order CXR in all patients with • Specific organism vs. contaminants, cost suspected pneumonia. • Reality: • In the hospital, a positive CXR is not No evidence of a benefit • necessary to treat as CAP (but consider other Rarely positive = _____ • diagnoses) . Contaminant rate = _____ • More likely to be positive if sicker • ICU, septic shock, etc. • CAP: Current & Future CAP: Current & Future 5
Blood Cultures in CAP Sputum for CAP • Complicated and controversial • In general, do not get blood cultures for outpatient CAP • Simple, inexpensive, specific for pneumococcus • For inpatient CAP, blood cultures are • Problems include: optional • Consider if risk factors: Up to 30% could not produce adequate • sputum • ICU, severe sepsis, cavitary infiltrates, pleural effusion Good quality available in only 14% • Most don’t narrow antibiotics • IDSA/ATS Guidelines. CID . 2007;44:S27-72. CAP: Current & Future CAP: Current & Future The future in CAP - biomarkers Sputum Cultures in CAP • Procalcitonin: precursor of calcitonin • In general, sputum cultures are not indicated in outpatient CAP ● No hormonal activity ● Inflammatory marker ● Increased in sepsis, bacterial infection • 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. CAP: Current & Future CAP: Current & Future 6
Meta-analysis/systematic review Take Home Points • Four studies, ~3500 patients with 1) Cover typical and atypical bacteria respiratory tract infections 2) • Less antibiotic exposure** 3) A 22% decrease in prescriptions • 4) Average 2.3 days less abx overall • 5) • No difference in mortality/clinical outcomes Soni NJ, et al. JHM . 2013;8:530. CAP: Current & Future CAP: Current & Future Treatment Principle #1 Roadmap • Background Outpatients (mild) • Etiology • Resp. viruses • S pneumoniae • Diagnosis Must cover all these organisms* • M pneumoniae • Treatment • C pneumoniae • H influenzae • Prevention • Come back on Friday for a review of new data on atypical coverage CAP: Current & Future CAP: Current & Future 7
Treatment Principle #2 Risk Factors for DRSP • Age > 65 years old Outpatients (mild) • Chronic disease • Resp. viruses ▪ Heart, lung, renal, liver • S pneumoniae “Wimpy” pneumococcus • Diabetes mellitus • M pneumoniae • C pneumoniae • Alcoholism • H influenzae Drug-resistant S. pneumoniae • Malignancy (active) (DRSP) • Immunosuppression • Antibiotics in the last 3 months Penicillin, erythromycin, macrolides, etc. CAP: Current & Future CAP: Current & Future Treatment CAP Treatment CAP Outpatient, Oral fluoroquinolone Outpatient, healthy, no Doxycycline or macrolide OR DRSP risk factors DRSP risk factors Oral -lactam + doxy or -lactam + macrolide ● Oral fluoroquinolone: moxi, gemi, levofloxacin ● -lactam: High-dose amoxicillin (1gm PO tid) Augmentin (875mg PO bid) Macrolide = azithro, clarithro, erythro CAP: Current & Future CAP: Current & Future 8
Treatment CAP Take Home Points 1) Cover typical and atypical bacteria Inpatient, non-ICU Fluoroquinolone OR 2) Get the CXR, skip the cultures -lactam + macrolide 3) IV -lactam + macrolide + 4) Inpatient, ICU vancomycin OR 5) IV -lactam + fluoroquinolone + vancomycin CAP: Current & Future CAP: Current & Future Duration of therapy? Duration of therapy? • Meta-analysis of 15 RCTs, 2796 patients • No difference in clinical failure with mild to moderate CAP • No difference in bacterial eradication • Compared short-course (< 7 days) with • No difference in mortality longer courses. • Looked at clinical failure, bacterial • In subgroup analysis, trend toward eradication, and mortality. favorable efficacy with short-course. Li JZ, et al. Am J Med . 2007;120:783. Li JZ, et al. Am J Med . 2007;120:783. CAP: Current & Future CAP: Current & Future 9
Duration of therapy? Duration of therapy • RCT of 312 pts. admitted with CAP • Start at 5 days total • Randomized to 5 days vs. usual care • If afebrile x 48 hours and clinically well • Can extend at your discretion If afebrile x 48 hours • Most will only need 7 days or less • No difference in cure rates or mortality Uranga A, et al. JAMA Int Med . 2016;176:1257. CAP: Current & Future CAP: Current & Future Steroids in 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) CAP: Current & Future CAP: Current & Future 10
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