Getting Smart About: Upper Respiratory Infections Daniel Z. Uslan, MD Assistant Clinical Professor Director, Antimicrobial Stewardship Program UCLA Health System
Disclosures None relevant to the topic
Objectives 1. Understand the epidemiology and financial impact of Community-Acquired Pneumonia (CAP) 2. Review the racial and ethnic difference in CAP 3. Review site-of-care decisions and initial assessment of severity 4. Understand the role and limitations of diagnostic testing 5. Discuss empiric and targeted antibiotics for CAP
Why Get Smart? Respiratory infections mostly viral drive antibiotic overprescribing in the outpatient setting. Outside the U.S., national reductions in antibiotic prescriptions for URIs are associated with declines in prevalence of antibiotic resistance Judicious antibiotic use minimizes adverse events and costs for our patients, while safeguarding the efficacy of antibiotics
Resistant S. pneumoniae Alarming rate of spread of resistant S. pneumoniae over the past 20 years Resistance to PCN, macrolides, TMP-SMX, cephalosporins Leading bacterial cause of CAP, meningitis, otitis media The major risk factor for spread and carriage of resistant S. pneumo is prior antibiotic use Retrospective & prospective studies Numerous countries
Outside the U.S. Decreasing community-wide antibiotic use leads to decreases in prevalence of resistant bacteria Iceland: Penicillin-resistant S. pneumo in day care centers decreased by 25% over 3-years during successful public/physician campaign to reduce antibiotic use Finland: 40% reduction in community macrolide use resulted in 48% decrease in erythromycinresistant group A strep over 4 years
Factors that Influence Outpatient Over-Prescribing Patient/parent expectations Purulence of secretions Physician workload Easier to prescribe than explain Defensive medicine The most effective intervention strategies to reduce antibiotic prescribing must also be multifactorial
Background - CAP The most common infection in hospitalized patients ~950,000 episodes per year in US in adults >65 years 8 15 per 1000 persons per year Rates higher among extremes of age Rates higher in winter Mortality rates have not changed significantly since discovery of PCN
Racial/Ethnic Disparities Rates higher for ethnic minorities than Caucasians Disparate care of underlying diseases, i.e. DM Vaccination rates Social/environmental factors (ie, smoking, crowding) Access to health care Black VA patients have better outcomes than Caucasians
Risk Factors Numerous! Altered LOC Dementia ETOH Drugs Seizures Smoking Malnutrition AGE >65 Immunosuppressed Steroids SOT Malignancy COPD Bronchiectasis
Definitions Typical S. pneumoniae H. influenzae S. aureus Moraxella catarrhalis Anaerobes Gram-negative bacilli Atypical Mycoplasma pneumoniae Legionella spp Chlamydophila pneumoniae C. psittaci In an individual patient, there are NO findings from history, physical examination, or routine laboratory studies that allow the clinician to distinguish pneumonia caused by atypical from typical organisms
Pneumonia Guidelines CAP guidelines result in improved outcomes WHICH outcomes?? Mortality? Hospitalization? Cost? Antibiotic utilization? Patient satisfaction? Goals vary by target audience Patient, insurance company, ER physician, etc Time to first antibiotic dose Everyone with CHF gets antibiotics
CAP guidelines should address a comprehensive set of elements in the process of care rather than just a single element in isolation (ie, time to antibiotics). No study has ever found that changing one metric (such as time to first dose) has decreased mortality
Signs, Symptoms, Microbiology, and Clues to Diagnosis EPIDEMIOLOGY AND PRESENTATION
CAP: Symptoms at Presentation Bochud et al Medicine 2001
Microbiological Etiology of Outpatient CAP Bochud et al Medicine 2001
Microbiological Etiology of Outpatient CAP Over 40% of CAP are caused by atypical organisms. Bochud et al Medicine 2001
Microbiological Etiology of Outpatient CAP Symptoms and clinical findings cannot reliably differentiate microbial cause. Bochud et al Medicine 2001
Microbiological Etiology of Outpatient CAP Therefore, Empirical Rx must cover both pyogenic bacteria and atypical organisms. Bochud et al Medicine 2001
CAP: Symptoms at Presentation 100 Cough 90 80 70 60 50 40 30 20 10 0 Malaise Fever Sputum Production Myalgia Dyspnea Pleurodynia
CAP: Signs at Presentation 100 90 80 70 60 50 40 30 20 10 0 Temp >38 deg C Rales Dullness to Percussion Bronchial Breath Sounds Pleural Rub* *P=.002 for pyogenic Bochud et al Medicine 2001
Outpatient CAP: Etiology by Age Bochud et al Medicine 2001
History and Clues to Dx
Physical Exam Clues to DX
CXR and Clues to DX
DIAGNOSIS
Diagnosis of CAP Constellation of clinical features: Cough, fever, sputum production, etc -PLUS- Demonstrable infiltrate by chest radiograph Physical findings not sensitive or specific Clinical features and PE findings often lacking in elderly Routine microbiologic tests often negative History can be helpful
The presence of normal vital signs and absence of abnormalities on examination minimize the likelihood of pneumonia and further diagnostic testing is unnecessary Cough in elderly patients requires further evaluation PNA often characterized by absence of signs/symptoms >75 year olds: 30% with T >38 C 37% HR >100 Numerous RCTs and meta-analyses have failed to support the use of antibiotics in the absence of an identified treatable pathogen
In the presence of vital sign abnormalities, a clear chest exam cannot exclude pneumonia and a chest radiograph should be obtained High risk group lowers the threshold for obtaining chest radiograph Purulent secretions as an indicator by itself are not sensitive or specific to aid in the decision to obtain a chest radiograph
Microbiologic Testing? Should you get blood or sputum cultures for CAP? Microbiologic diagnosis reached in ~60% of research studies, ~20% everyday practice Patients with CAP should be investigated for specific pathogens that would significantly alter standard empiric management decisions, when the presence of such pathogens is suspected on the basis of clinical or epidemiologic data (Strong recommendation, II data)
Microbiologic Testing? Will antibiotic management change? Broadened, narrowed, or altered completely? Unusual pathogens (Cocci, TB) or resistance (MRSA) Inappropriate treatment with usual guidelines De-escalation unlikely to change mortality, but can change costs, LOS, adverse effects, etc Will infection control change? IE, need for isolation? (TB, H1N1 influenza) Diagnostic tests for CAP are POOR
Diagnosis - Summary Pre-treatment blood and sputum cultures should be obtained in hospitalized patients with certain clinical conditions (in whom diagnostic testing has potential to alter treatment) Testing for outpatients probably unnecessary ALWAYS test severe CAP patients If they are sick enough to admit, you should probably test them (at least, blood and sputum cultures)
Outpatient, Ward, ICU ADMISSION DECISIONS
Site of Care Decisions To admit or not? To admit to ICU or not? Inpatient care >25 x more costly $8-10 billion annual costs for inpatient pneumonia 80% of surveyed patients prefer outpatient therapy Hospitalization increases: Risks of nosocomial complications (C. diff, DVT, etc) Cost Physicians overestimate who needs hospitalization Prognostic models
Prediction Models Pneumonia Severity Index (PSI) CURB-65 (British Thoracic Society) Confusion, Uremia, Respiratory rate, Low blood pressure, age >65 30 day mortality for 0, 1, 2 risk factors: 0.7%, 2.1%, 9.2% 5 risk factors = 57% mortality Outpatient: 0 or 1 Inpatient: 2 ICU: 3 or more CRB-65 (no U) may be useful for PCP offices Unclear if PSI or CURB-65 is better Bauer TT et al. J Intern Med 2006; 260 (1)
Pneumonia Severity Index (PSI) Derivation, validation cohorts of >14,000 and >38,000 hospitalized patients with CAP Stratifies patients into 5 mortality risk classes Ability to predict mortality has been confirmed in multiple prospective studies Outpatient: Class I and II Inpatient: Class IV and V Class III: Observation unit or short hospitalization
Risk of Mortality in CAP If No to all of the following: Age >50 Underlying Diseases: CHF, Liver, Renal, CNS Altered Mental Status VS abnormality: RR>30, BP<90, Temp <35 or >40, Pulse >125 Then Risk Level = I, and mortality = 0.1% If Yes to any of the above, then calculate Risk Level (II through V) by points Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997;336:243-250
Points Determining Mortality Demographics Physical Exam Labs & Radiology Male: Age in Years Altered MS: +20 Art ph <7.35: +30 Female: Age -10 Resp R >30: +20 BUN >30mg/dl: +20 NH Resident: +10 Sy BP <90mm: +20 Sodium <130: +20 Cancer: +30 T <35 or >40: +15 Glucose > 250: +10 Liver Disease: +20 Pulse >125 +10 Hct <30: +10 CHF: +10 PaO2 <60mmHg - or - Renal Disease: +10 OxySat <90%: +10 Cerebrovasc: +10 Pleural Effusion: +10 Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997;336:243-250
Risk of Mortality by Points Risk Class Score Mortality Low I Algorithm 0.1% Low II 70 0.6% Low III 71-90 0.9% Moderate IV 91-130 9.3% High V >130 27% Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997;336:243-250
PSI Pros & Cons CONS 20 variables: Tough to use in busy ERs or PCP office Difficult to remember (vs CURB-65) PROS Extensively validated and prospectively studied Different patient populations, ie inner cities Works better among patients with chronic medical illness (ie, dialysis)
Use of Scores MUST be supplemented by physician judgment Ability to obtain and take oral antibiotics Social situation/support Outpatient resources/availability Underlying medical problems may be exacerbated (ie, asthma, CHF) Scores assume rationale for admission is to prevent death = not always valid Scores assume static variables Dynamic observation may be necessary (i.e. BP)
http://pda.ahrq.gov/clinic/psi/psicalc.asp
Effectiveness of PSI Scoring CAPITAL Trial 19 Canadian ERs Randomized to PSI implementation or usual care 1743 patients enrolled 18% decrease in admissions for low risk (I, II, III) patients versus control arm No negative effects (mortality, complications, readmissions) Marrie, TJ et al. JAMA 2000; 283:749
Emergency Department CAP Trial (EDCAP) 32 US EDs 3219 patients with CAP Practice guideline recommending outpatient treatment for low risk (I-III) patients Implemented using random low, moderate, high intensity guideline implementation strategies More low risk patients (62%) treated as outpatients in mod or high implementation groups than low (37%). No differences in safety outcomes (mortality, complications, etc) Yealey, et al. Ann Intern Med. 2005 Dec 20;143(12):881-94
Conclusions: Prediction Tools Tools exist that accurately can predict bad outcome (death) from CAP Can assist with selecting appropriate site of care Outpatient management (generally) associated with improved patient satisfaction and lower costs CURB-65, CRB-65, PSI IDSA guidelines (2007) prefer CURB-65 due to ease of calculation
Exceptions Low-risk patients who require admission: Complications of CAP itself Exacerbation of underlying disease (ie, CHF) Inability to take oral medications or receive outpatient care Multiple risk factors but falling below cutoffs necessary Vomiting, homelessness, psychiatric illness, poor functional status, cognitive dysfunction
Antibiotic choice, duration, special cases TREATMENT OF CAP
Empiricism Diagnostic tests for CAP are poor CAP caused by a WIDE variety of pathogens Treatment therefore almost always empiric Most recently FDA-approved antibiotics have an indication for CAP (since it is the most common infectious disease in the hospital) Treatment not only which is best, but need to consider cost, tolerability, pharmacokinetics, selection of resistance
Empirical Antibiotics for Outpatient CAP Host Variable Regimen Normal Co- Morbidities No Recent Antibiotic Recent Antibiotic No Recent Antibiotic Recent Antibiotic Macrolide or Doxycycline Antipneumococcal Fluoroquinolone - or Macrolide plus either High Dose Ampiciliin (1 GM tid) or Amp/Clav Acid (2 GM bid) antipneumococcal Fluoroquinolone -or - Beta-lactam* (e.g., HD Amp/CA, Cefpodoxime) plus macrolide The alternative from above that had not been used Mandell et al: CID, 2003: 37: 1405-1433
Empirical Antibiotics for Inpatient CAP
Severe CAP and the ICU Severe CAP often associated with multiorgan failure Severe Pneumonia = with mortality risk >20%, has 2 or more of: Respiratory rate >30/minute Diastolic blood pressure <60 mm Hg Urea >7 mmol/l Any one of the following ~ doubles the rate of death: Altered mental status, confusion or an Abbreviated Mental Test score of <8/10 Hypoxaemia (PO2 <60 mmhg or O2 saturation <90%) Bilateral or multilobar (more than two lobes) shadowing on CXR Baudouin SV Critical care management of CAP. Thorax 2002;57;267-271
Resolution of Symptoms and Signs -- in an otherwise healthy host Abnormality Fever WBC Other VS abnormalities Cough Crackles CXR Slower CXR clearance Time to Resolution/Normal 2.5 days 4 days 2 to 6 days About 7 days 8 to 10 days 4 to 10 weeks St. pneumoniae up to 6 weeks, Legionella up to 6 months,
Criteria for Determining the Appropriateness of Discharge Vital Signs stable for 24 hours RR <24 HR <100 Syst BP >90 mmhg Ox Sat >90% on room air Able to take PO antibiotics Able to maintain adequate hydration and nutrition Mental Status normal/baseline No other clinical or psychosocial problems requiring hospitalization Halm, E. A. et al. N Engl J Med 2002;347:2039-2045
Duration of Antibiotics Minimum of 5 days treatment Afebrile x 48-72 h No signs of clinical instability Average = ~7-10 days Azithromycin has been used in clinical trials for 3-5 days with good results (Zpak)
Non-responding CAP Failure to improve: Early (<72 hours) NORMAL Delayed Resistant microorganism (PCP/HIV) Parapneumonic effusion/empyema Nosocomial superinfection (MDR) Pneumonia, others (UTI, BSI) Noninfectious Pneumonia complications (BOOP, ARDS, Eosinophilic PNA) Misdiagnosis (CHF, PE, Vasculitis/SLE) Drug fever
Conclusions Appropriate triage/assessment of CAP PSI, CURB-65 Epidemiologic & H&P clues to Dx Empiric antibiotics in according with guidelines Duration Evaluation of nonresponding CAP