Nothing to disclose. Lisa G. Winston, MD University of California, - PDF document

Community-Acquired Pneumonia Nothing to disclose…. Lisa G. Winston, MD University of California, San Francisco San Francisco General Hospital Community-Acquired Pneumonia - Community-Acquired Pneumonia Outline  Talk will focus on adults  Epidemiology  Guideline for healthy infants and children  Diagnosis available: www.idsociety.org ( Clin Infect Dis  Microbiology 2011;53:617-30 )  Risk stratification  Treatment  Prevention Community Acquired Pneumonia CAP: Symptom Frequency (CAP): definition  At least 2 new symptoms  Cough 90% Fever or hypothermia Cough  Dyspnea 66% Rigors and/or diaphoresis Chest pain Sputum production or color change Dyspnea  Sputum 66%  New infiltrate on chest x-ray and/or  Pleuritic chest pain 50% abnormal chest exam  No hospitalization or other nursing But, only 4% of all visits for cough turn out to be pneumonia…. facility prior to symptom onset Halm EA, Teirstein AS. N Engl J Med 2002;347(25):2039 .

Epidemiology: Epidemiology: Acute Lower Respiratory Tract Infections Acute Lower Respiratory Tract Infections  In U.S., influenza and pneumonia 8 th most  Inpatient mortality rate: may be influenced by coding common cause of death per the Centers for  From 2003 – 2009, mortality rate for principal diagnosis Disease Control and Prevention (moved up from pneumonia decreased from 5.8% to 4.2% 9 th in 2010)  More patients coded with principal diagnosis sepsis or  Most common cause of death from infectious disease respiratory failure and secondary diagnosis pneumonia  Using all codes, little change in mortality rate  Among those 85 and older, at least 1 in 20 hospitalized each year Lindenauer et al, JAMA 2012;307:1405-13  Outpatient mortality < 1%; about 80% of CAP treated in 1. Diseases of heart 5. Accidents (unintentional injuries) outpatient setting 2. Malignant neoplasms 6. Alzheimer’s disease 3. Chronic lower respiratory diseases 7. Diabetes mellitus  More common in winter months 4. Cerebrovascular diseases 8. Influenza and pneumonia Health Disparities Host Defenses  Some data regarding disparities with socioeconomic  Mechanical factors  Antimicrobial factors status and race/ethnicity  IgA (and IgG, IgM)  Nasal hair  Study of 4870 adults with community acquired  Complement bacteremic pneumonia in 9 states 2003 – 2004  Turbinates  Alveolar lining fluid  Annual incidence 24.2 episodes per 100,000 Black  Mucocilliary apparatus  Cytokines (TNF, IL-1, IL- adults vs. 10.1 episodes per 100,000 White adults  Cough 8, others)  Black residents in most impoverished areas with 4.4  Macrophages  Airway branching times the incidence of White residents in least  PMNs impoverished areas  Lymphocytes Burton et al. AJPH 2010;100(10):1904-11 Microbiological Investigation Diagnosis  Chest radiograph – needed in all cases?  Sputum Gram stain and culture  Avoid over-treatment with antibiotics  Remains somewhat controversial  Differentiate from other conditions  30-40% patients cannot produce adequate sample  Specific etiology, e.g. tuberculosis  Most helpful if single organism in large numbers  Co-existing conditions, such as lung mass or pleural  Usually unnecessary in outpatients effusion  Culture (if adequate specimen < 10 squamous  Evaluate severity, e.g. multilobar cells/LPF; > 25 PMNs/LPF): antibiotic sensitivities  Unfortunately, chest physical exam not sensitive or  Limited utility after antibiotics for most common specific and significant variation between organisms observers Arch Intern Med 1999;159:1082-7

Microbiological Investigation - Inpatients  Blood cultures x 2 before antibiotics  Blood cultures positive in 5 – 14% of hospitalized patients  Severe disease most important predictor  Consider evaluation for Legionella  Urinary antigen test for L. pneumophila serogroup 1 (70%)  Culture with selective media  Pneumococcal urinary antigen test  Simple, takes apx. 15 minutes  In adults, sensitivity 50-80%, specificity ~90% but specificity poor in children, possibly due to carriage IDSA/ATS Guidelines for CAP in Adults; CID 2007:44(Suppl 2) Other diagnostics? Microbiological Investigation - Inpatients  Biomarkers - procalcitonin  Other studies as clinically indicated, e.g. influenza  Procalcitonin is produced in response to endotoxin and  M. pneumoniae serologic studies can be considered but endogenous mediators released in the setting of bacterial are uncommon in routine practice (mostly IgM-specific infections assays)  Rises in bacterial infections much more than, e.g., viral  Serologic studies of Chlamydophila largely for infections or inflammatory states epidemiology  Rises and falls quickly  For C. pneumoniae , IgM is available, titer > 1:16 considered positive  Unfortunately, probably not sensitive / specific enough to rule out / rule in bacterial CAP in individual cases in  Bronchoscopy perhaps for fulminant course, most settings unresponsive to conventional therapy, or for specific BMC Medicine 2011;9:107 pathogens (e.g. Pneumocystis )  May help limit duration of antibiotic exposure Etiology Typical vs. Atypical  Typical  Atypical  Clinical syndrome and CXR not reliably predictive  Streptococcus pneumoniae 20-60%  Visible on Gram stain,  Not visible on Gram stain, grows in routine culture special culture techniques  Haemophilus influenzae 3-10%  Susceptible to beta  Not treated with beta  Mycoplasma pneumoniae up to 10% lactams lactams  Chlamydophila pneumoniae up to 10%  S. pneumoniae , H.  M. pneumoniae , C.  Legionella up to 10% influenzae pneumoniae , Legionella  Enteric Gram negative rods up to 10% X X  Staphylococcus aureus up to 10%  Viruses up to 10%  No etiologic agent 20-70%

S. pneumoniae – drug resistance S. pneumoniae  Clinical and Laboratory Standards Institute (CLSI)  2/3 of CAP cases where etiology known minimum inhibitory standards for penicillin in  g/mL  2/3 lethal pneumonia Sensitive Intermediate Resistant  2/3 bacteremic pneumonia ≤ 2 Parenteral = 4 > 8  Apx. 20% of cases with pneumococcal pneumonia are (penicillin G) bacteremic (variable) Non-meningitis ≤ 0.06 ≥ 0.12  Risk factors include Parenteral (penicillin G) Extremes of age Influenza Meningitis Alcoholism Injection drug use ≤ 0.06 Oral (penicillin V) 0.12 - 1 > 2 COPD and/or smoking Airway obstruction Nursing home residence *HIV infection S. pneumoniae – drug resistance  ~ 25-35% penicillin non-susceptible by old standard nationwide, but most < 2  g/mL  Using the new breakpoints for patients without meningitis, 93% would be considered susceptible to IV penicillin  Other beta-lactams are more active than pencillin, especially  Ceftriaxone, cefotaxime, cefepime, amoxicillin, amoxicillin-clavulanate MMWR , 2008;57(50)1353-1355 S. pneumoniae – drug resistance Legionella  Other drug resistance more common with increasing  Geographic differences in rates penicillin minimum inhibitory concentration (MIC)  Perhaps suggested by high fever, hyponatremia,  Macrolides and doxycycline more reliable for PCN markedly elevated LDH, CNS abnormalities, susceptible pneumococcus, less for penicillin non- susceptible severe disease  Trimethoprim-sulfamethoxazole not reliable  Severe disease: fluoroquinolone or azithromycin likely drug of choice; usual rx 14-21 days  Fluoroquinolones – most S. pneumoniae are Renal disease Age susceptible  Risk factors: Liver disease Smoking  Clinical failures have been reported Diabetes Immune compromise, Malignancy cell mediated  No resistance with vancomycin, linezolid Travel

Haemophilus influenzae Mycoplasma pnuemoniae  Common cause respiratory infections in  Increased risk with smoking and children/young adults COPD  Pneumonia relatively uncommon  Beta-lactamase production ~30%  Epidemics in close quarters  With beta-lactamase production, resistant to  May have sore throat, nausea, vomiting, hemolytic ampicillin and amoxicillin anemia, rash  Active oral antibiotics include amoxicillin-  Treatment with doxycycline, macrolide, or clavulanate, fluoroquinolones, azithromycin, fluoroquinolone Pediatr Infect Dis J 2012;31:409-11 clarithromycin, doxycycline  Rising rate of macrolide resistance – U.S. 8.2%; China 90% Risk Stratification Risk Stratification  Outpatient vs. inpatient? Cost differential in CAP: Colice et al, Chest 2004  Inpatient: $10,227 / case  Pneumonia Patient Outcomes Research Team  Outpatient: $466 / case (PORT) study (Fine et al, NEJM 1997;336:243- 250) Who can be safely managed as an outpatient???  Prediction rule to identify low risk patients with CAP  Stratify into one of 5 classes • Class I: age < 50, none of 5 co-morbid conditions, apx. normal VS, normal mental status • Class II-V: assigned via a point system Risk Stratification Pneumonia Severity Index Calculator http://www.mdcalc.com/psi-port-score-  Mortality < 1% for classes I, II pneumonia-severity-index-adult-cap/  Low risk patients hospitalized more than Age and sex; resident of nursing home {yes/no} necessary Comorbid diseases {yes/no}: renal disease, liver disease,  Caveats: CHF, cerebrovascular disease, neoplasia  Does not take into account social factors Physical exam {yes/no}: altered mental status, SBP < 90, temp < 35 or >=40, RR>=30, HR>=125 Labs/studies {yes/no}: pH<7.35, PO2<60 or Sat<90, Na<130, HCT<30, gluc>250, BUN>30, pleural eff