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New Guidelines for CAP Diagnosis and Therapy : A View from North America and Beyond. Michael S. Niederman, MD Chairman, Department of Medicine Winthrop-University Hospital Mineola, New York Professor of Medicine Vice-Chairman, Department of Medicine
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New Guidelines for CAP Diagnosis and Therapy : A View from North America and Beyond Michael S. Niederman, MD Chairman, Department of Medicine Winthrop-University Hospital Mineola, New York Professor of Medicine Vice-Chairman, Department of Medicine State University of New York at Stony Brook
Intensity of Implementation Affects CAP Guideline Success • Cluster-randomizedtrial of 32 ED’s and 3219 CAP patients and a guideline implemented with low (n=8), moderate (MI) (n=12) or high (HI) (n=12) intensity. • High intensity= real-time reminders, doctor audit and feedback, intense CQI PLUS education • More inpatients and outpatients in HI group got all 4 recommended processes (CMS core measures) of care (p<0.001). No mortality differences. • Yealy DM, et al. Ann Intern Med 2005; 143:881-894. • Figure 5 • Use of a guideline with tracking of variances and intervention to correct prospectively, reduced LOS by 3 days vs. no guideline, and guideline without variance tracking • Fishbane, Niederman, et al: Arch Intern Med , IN PRESS
North American CAP Guidelines • Development of guidelines • Canadian guidelines 1993 • ATS 1993 • IDSA 1998 • CDC 2000 • Canadian (Pulm/ID) guidelines 2000 • IDSA guidelines 2000 • ATS guidelines 2001 • IDSA update 2003 • ATS/IDSA Joint Guideline 2007
Other Global Guidelines • Europe: ERS (with ESCMID), German (pulm/ID), Spanish (pulm/ID), BTS (Pulm), Portugese (Pulm), French (ID) • Middle East: Saudi Arabia • South America: Latin America (pulm), South America, Argentina • Africa: South Africa (pulm/ID) • Australia: • Asia: Hong Kong, Japan (JRS, pulm), Phillipines (ID), Singapore,
Topics In New ATS/IDSA Guidelines • The admission decision • The value of diagnostic testing (blood cultures, sputum culture, antigen testing) • Risk factors for specific pathogens • Recommended empiric antibiotic therapy • The role of adjunctive and supportive therapies • Quality improvement and performance measures • The value of prevention efforts: smoking cessation, vaccination • Mandell LA et al. Clin Infect Dis 2007;44 Suppl 2:S27-72
Evidence Base In The New ATS/IDSA Guidelines • The admission decision • The value of diagnostic testing (blood cultures, sputum culture, antigen testing) • Risk factors for specific pathogens • Recommended empiric antibiotic therapy • The role of adjunctive and supportive therapies • Quality improvement and performance measures • The value of prevention efforts: smoking cessation, vaccination • Mandell LA et al. Clin Infect Dis 2007;44 Suppl 2:S27-72
Recommended Testing in ATS/ IDSA Guideline • Diagnose with CXR and clinical data • Look for specific pathogens that alter therapy, based on historical and epidemiologic clues • Outpatient testing optional • Blood cultures with severe illness • Sputum Gram stain and culture prior to therapy IF good quality and rapid transport and processing in lab • Legionella and pneumococcal urinary antigen for severe CAP. Endotracheal aspirate or sputum culture for severe CAP. • Mandell LA et al. Clin Infect Dis 2007;44 Suppl 2:S27-72
Predicting Bacteremia in CAP • 13,043 Medicare patients to derive rule to predict bacteremia, validate on 12,771. • Predictors of bacteremia (derivation and validation cohort): prior antibiotics (OR=0.5), liver dis (OR= 2.3,1.4), Systolic BP < 90 mm Hg (OR=1.7,1.8), T < 35 or > 40 (1.9,1.5), HR > 125 ( 1.9,1.7), BUN > 30 (2.0,2.2), Na < 130 (1.6,1.8), WBC < 5k or >20k (OR=1.7,1.9) • 0 predictors, prior abtc=3% bacteremia; no BC’s • 0 pred, no prior abtc ; 1 pred , prior abtc; 5% bacteremia; 1 BC • At least 2 predictors= 16% bacteremia; 1 pred and no prior abtc= 9% bacteremia; 2 BC’s • Metersky et al: AJRCCM 2004; 169: 342-347.
What Do Other Guidelines Say? • British Thoracic Society: No blood culture unless severe. Legionella and urinary antigen testing for severe CAP. CRP of value if admitted. • Thorax 2004; 59: 364-366 • Thorax 2001; 56 (Suppl IV) • European Respiratory Society: Blood cultures for all admitted. Sputum Gram stain if purulent sputum. Legionella urinary antigen if severe, no serologic testing except for epidemiology. Possible role for CRP. • Eur Resp J 2005; 26:1138-1180.
Evidence Base In The New ATS/IDSA Guidelines • The admission decision • The value of diagnostic testing (blood cultures, sputum culture, antigen testing) • Risk factors for specific pathogens • Recommended empiric antibiotic therapy • The role of adjunctive and supportive therapies • Quality improvement and performance measures • The value of prevention efforts: smoking cessation, vaccination • Mandell LA et al. Clin Infect Dis 2007;44 Suppl 2:S27-72
Modifiers Affecting Bacteriology of CAP • DRSP • Age > 65 years, ß-lactam therapy within 3 months, alcoholism, immune suppression (including steroids), multiple medical co-morbidities, exposure to child in day care • Enteric Gram-negatives • Nursing home residence, underlying cardiopulmonary disease, multiple medical co-morbidities, recent antibiotic therapy • Pseudomonas aeruginosa • Structural lung disease (bronchiectasis), corticosteroids (> 10 mg prednisone/day), broad-spectrum antibiotics for > 7 days within the past month, malnutrition
Why Modify Therapy if DRSP Risks are Present? • To assure EFFICACY for organisms at higher levels of resistance • Only relevant for penicillin MIC of at least 4 mg/L • Maybe relevant when choosing quinolones • To MANAGE resistance and prevent selection of more resistance in the community. Theoretical, but probably important • If patients have DRSP risks: • Use a highly active anti-pneumococcal agent to minimize selection pressure for more organisms emerging with higher levels of resistance
HCAP : Now a Part of Nosocomial Pneumonia Guidelines • Inclusion of healthcare related pneumonia • Hospitalized in the preceding 90 days • Nursing home/extended care facility residence • Home infusion therapy (including antibiotics) • Chronic dialysis • Home wound care • Family member with multidrug-resistant pathogen • Treat for MDR pathogens, regardless of when in hospital stay pneumonia begins Am J Respir Crit Care Med. 2005;171:388-416.
What Do Other Guidelines Say? • British Thoracic Society: Pneumococcus is #1. Little concern for atypicals, esp in elderly and outpatients, but consider Legionella in more severe CAP. • Thorax 2004; 59: 364-366 • Thorax 2001; 56 (Suppl IV) • European Respiratory Society: Little focus on atypicals, except in ICU. Macrolide resistant pneumococcus a concern. Pseudomonas a potential pathogen in ICU. HCAP patients included, but identified as at risk for Pseudomonas aeruginosa. • Eur Resp J 2005; 26:1138-1180.
Evidence Base In The New ATS/IDSA Guidelines • The admission decision • The value of diagnostic testing (blood cultures, sputum culture, antigen testing) • Risk factors for specific pathogens • Recommended empiric antibiotic therapy • The role of adjunctive and supportive therapies • Quality improvement and performance measures • The value of prevention efforts: smoking cessation, vaccination • Mandell LA et al. Clin Infect Dis 2007;44 Suppl 2:S27-72
Community-acquired Pneumonia:Empiric Therapy– ATS/IDSA 2007 Outpatient Previously well:Advanced Macrolide; Doxy CoMorbidity or recent ATB use*: Resp Fluoroquinolone (Gemifloxacin, Levofloxacin750 mg or Moxifloxacin 400 mg) ; High dose Beta-lactam** + (macrolide or doxycyline); Ceftriaxone + macrolide or doxycycline *Base decision on ‘prior antimicrobial used’; use alternate **Amox 1 gm TID; Amox/clav 2 gm BID preferred: alternatives: cefpodoxime, cefuroxime (500 mg BID) Mandell LA et al. Clin Infect Dis 2007;44 Suppl 2:S27-72
Community-acquired PneumoniaEmpiric Therapy – ATS/IDSA 2007 Inpatient – general ward • Respiratory fluoroquinolone (levofloxacin, moxifloxacin) • OR • β-lactam PLUS macrolide/doxycycline • (preferred agents include: cefotaxime, ceftriaxone, amp/sulbactam; consider ertapenem in selected patients) • Cefepime, imipenem, meropenem, piperacillin/tazobactam only if pseudomonal risks present (For carefully selected patients without risk factors for DRSP or GNR, monotherapy with azithromycin can be considered) Consider ‘Other pathogens’ based on epidemiology Mandell LA et al. Clin Infect Dis 2007;44 Suppl 2:S27-72
Impact of Recent Antibiotic Exposure on Pneumococcal Resistance • Toronto Bacterial Infection Network 1995-2002 • 3339 cases of invasive pneumococcal infection in hospitalized patients • 563 with recent antibiotics and known agent • Quinolone resistance is more likely if patient is on steroids (OR 6.0), if infection is nosocomial (OR 5.8), or if patient is from a nursing home (OR 5.4) Vanderkooi et al. Clin Infect Dis. 2005;40:1288.
Discordant Therapy for Resistant Pneumococcal Bacteremia • Prospective , observational, international , 844 patients with pneumococcal bacteremia • 15% intermed R ( MIC =0.12- 1.0 mg/L), 9.6% high level R ( MIC > 2.0 mg/L) • Risks for R: underlying illness or immune suppression, prior antibiotics • Risks for mortality: age > 65, critical illness, underlying illness, NOT PCN SENS • Discordant therapy NOT a risk for mortality unless with cefuroxime (36.4% vs. 5.8%, p=0.02) • Yu et al: Clin Infect Dis 2003; 37: 230-237. None of the findings stat sig
Is Combination Therapy Needed for Pneumococcal Bacteremia? • 5 retrospective studies show a benefit for combination therapy vs. monotherapy • In 328 adults, those > age 50 with macrolide plus beta-lactam had a 6 % mortality vs. 20% for the entire group • Mufson et al: Am J Med 1999; 107: 34 S-43 S. • 225 bacteremic patients. OR mortality =3 for SET vs DET • Waterer et al: Arch Intern Med 2001; 161:1837. • 409 patients: reduced mortality for 238 with beta-lactam/macrolide vs. 171 with beta-lactam and no macrolide (OR=3.1) • Martinez et al: Clin Infect Dis 2003; 36: 389-395. • Combination therapy of benefit only in those with severe illness ( 23.4% vs. 55.3% mortality). Beta-lactam used with a wide variety of second agents • Baddour et al: Am J Respir Crit Care Med 2004; 170: 440-444. • 7.5% mortality for 53 with combination vs. 26% for 42 with monotherapy • Weiss et al: Chest 2005; 128: 940-946.
Duration of Therapy for CAP • For many patients, duration of therapy can be 5-7 days (3 days with oral azithromycin in outpatients) • Adjust duration to clinical response in inpatients • 48-72 hours after afebrile, minimum of 5 days • May have slower response with more severe illness • Can even do with pneumococcal bacteremia • Identity of pathogen may not matter if: • Good clinical response • Sensitive to therapy • Proper dose of correct therapy used • Not S. aureus, P. aeruginosa • No extrapulmonary infection (meningitis)
Serial PCT To Guide Duration of CAP Therapy • Prospective, randomized trial of 302 patients with radiographic CAP : PCT guided vs. standard rx • PCT by commercial assay (Kryptor) • PCT-guided Rx: <0.1 strongly discouraged, <0.25 discouraged, > 0.25 encouraged, > 0.5 mcg/L strongly encouraged • No PCT data available to doctors of control patients • Measure PCT on admit, 6-24 hours (if withheld), day 4,6,8. • PCT with 55% shorter duration rx. • Christ-Crain M, et al: Am J Respir Crit Care Med 2006; 174:84-93
How Can We Make CAP Care More Cost-Effective? • Careful consideration of admission decision • PSI, CURB-65 combined • PCT to guide whether to treat and how long • Outpatient oral therapy if not very ill (role of oral quinolones) • Even for nursing home patients • Short duration therapy if admitted • As short as 3 days if mild-moderate illness and good clinical response • Moussaoui R, et al. BMJ 2006; 332 : 1355 • No inpatient observation after switch to oral therapy, if otherwise stable
What Do Other Guidelines Say? • British Thoracic Society: • Inpatient, ward: Most get oral therapy. Monotherapy with amoxicillin unless more ill or a non-response to outpt rx with this agent, then macrolide alone or in combination. Quinolone an alternative. 7-21 day therapy. • ICU: Beta-lactam (incl. Cefuroxime) plus macrolide. Quinolone is an alternative if intolerance. • Thorax 2004; 59: 364-366 • Thorax 2001; 56 (Suppl IV)
What Do Other Guidelines Say? • European Respiratory Society: • Inpatient, ward: Oral therapy if more mild. Beta –lactam (including cefuroxime) with optional macrolide; quinolone monotherapy an alternative. 7-14 day therapy. • ICU: Combination therapy, routine macrolide. Quinolone if Pseudomonal concerns, or as an alternative to a macrolide. • Eur Resp J 2005; 26:1138-1180.
No Quinolone Monotherapy of Severe CAP • Current CAP guidelines do not recommend qunolone monotherapy for ICU admitted CAP • Prospective randomized, open trial of levofloxacin 500 mg q12 h (196 patients) vs. ofloxacin/cefotaxime (202 patients) in 398 ICU patients • Exclude if in septic shock • 51% on MV and trend to less cure with monotherapy • 63% clinical cure with L vs. 72% with C/O • Conclude equivalent efficacy in severe CAP EXCEPT if in shock or on ventilator • Leroy et al: Chest 2005; 128: 172-183.
Moxifloxacin Treatment IV (MOTIV) in Serious CAP: Monotherapy vs. Combination Therapy • Multicenter, prospective, randomized, double-blind comparison of Moxifloxacin 400 mg IV/oral daily (n=371)vs. Cefotaxime 2 g IV daily PLUS Levofloxacin 500 mg IV bid to oral BID levofloxacin for 7-14 days (n=367) • CAP: 60% PSI IV and V, 40% PSI III; 5% mechanically ventilated; 14% failed prior antibiotic therapy • Comparable duration of IV and total therapy in both arms • Comparable safety and efficacy of both regimens • Torres A, et al. ECCMID 2006 • Read RC et al. ERS 2006
No Pseudomonal Risk Factors Selected Beta –lactam (cefotaxime, ceftriaxone, ampicillin/sulbactam )PLUS IV MacrolideOR IV Quinolone Pseudomonal Risk Factors Present Selected Beta-lactam (cefepime, piperacillin/tazobactam, imipenem, meropenem); aztreonam if PCN allergicPLUSCiprofloxacin or High Dose Levofloxacin (750 mg) Selected Beta-lactam PLUS AminoglycosidePLUS IV macrolide OR IV anti-pneumococcal quinolone Therapy of Severe CAP: ATS /IDSA 2007 • CONSIDER CA-MRSA IN SELECTED PATIENTS POST INFLUENZA • IDSA/ATS Guidelines. Clin Infect Dis February 2007
Key Differences Between American and European CAP Guidelines • AMERICAN GUIDELINES vs EUROPEAN GUIDELINES • All patients require therapy for atypical pathogens • Less oral therapy for admitted patients • Macrolides still have a role • Usually with a beta-lactam • In selected patients as monotherapy • Less Reliance on beta-lactams (esp cefuroxime) • Quinolones used more widely as first line therapy • Use of Performance Measures • Importance of Time to Initial Therapy • Possibly shorter duration of therapy • Separation of HCAP from CAP, esp in those with Pseudomonal risks. • File et al. Chest 2004; 125: 1888-1901.