1 / 43

CAP and HCAP

CAP and HCAP. Gary Skankey, MD, FACP, FIDSA University of Nevada School of Medicine. Community-Acquired Pneumonia (CAP) Epidemiology. Sixth leading cause of death Leading cause of death due to infectious disease More than 3 million cases of CAP per year 500,000 hospitalizations per year

anakin
Télécharger la présentation

CAP and HCAP

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CAP and HCAP Gary Skankey, MD, FACP, FIDSA University of Nevada School of Medicine

  2. Community-Acquired Pneumonia (CAP)Epidemiology • Sixth leading cause of death • Leading cause of death due to infectious disease • More than 3 million cases of CAP per year • 500,000 hospitalizations per year • 45,000 deaths per year • Cost: $21 billion Bartlett et al: Clin Inf Dis 26:811-838, 1998; File and Tan: Curr Opin Pul Med 3:89-97, 1997; Marston et al: Arch Int Med 157:1709-1718, 1997.

  3. Key Bacterial Pathogens in CAP S. pneumoniae is the primary recognized bacterial cause of respiratory infections 16% AtypicalPathogens:23% 40% S. pneumoniae 6% M. catarrhalis H. influenzae Legionella spp. 10% M. pneumoniae C. pneumoniae Others 7% 1% 20% Reimer and Carroll: Clin Infect Dis 26:742-748, 1998. Marrie: Infect Dis Clin North Am 12:723-740,1998. Bartlett et al: Clin Infect Dis 26:811-838, 1998

  4. S. pneumoniae resistance trend 50 40 30 20 10 0 Intermediate resistance High-level resistance 43.8% 36.0% 27.8% 33.5% 22.0% % Resistant 19.9% 23.6% 14.1% 17.8% 15.2% 16.0% 14.0% 13.6% 9.5% 4.0% 3.8% 2.6% 0.2% 1988–89 1992–93 1994–95 1996–97 TRUST I 1997–98 TRUST II Jan.–June 1997 SENTRY Doern et al: Clin Infect Dis 27:764-70, 1998 Thornsberry et al: Diagn Microbiol Infect Dis 29:249-257, 1997.

  5. Diagnosis of Pneumonia • MYTH: • Diagnosis of pneumonia is made by sputum culture • Diagnosis of pneumonia is made by CXR

  6. Diagnosis of Pneumonia • Clinical data points • Cough • Pleuritic chest pain • Purulent sputum, WBCs on gram stain • Fever • Leukocytosis • Abnormal CXR • Abnormal ABG • Sputum cultures identify the pathogen

  7. Diagnosis of CAP • Clinical presentation is not diagnostic of an etiology • Yield of pathogens from Gram stain of adequate expectorated sputum, blood culture, sputum culture from patients with CAP 30%–40% • Immunologic/serologic tests

  8. IDSA Guidelines for Empiric Treatment of Outpatient CAP • Previously healthy, no use of abx in past 3 months • A macrolide (Biaxin, Azithromycin) • Doxycycline • Comorbidities, immune suppression, abx in last 3 months • Respiratory FQ (Avelox, Tequin, Levaquin [750 mg]) • Beta-lactam (cefuroxime, amox/clav) plus macrolide (clarithromycin, azithromycin) • If high incidence of macrolide-resistant pneumococcus, substitute FQ for macrolide

  9. IDSA Guidelines for empiric treatment of Inpatient CAP • Non-ICU • Respiratory FQ • Beta-lactam (ceftriaxone, amp/sulb) or ertapenem plus macrolide • ICU • Beta-lactam or ertapenem plus macrolide or resp FQ • (I add vancomycin to cover cephalosporin-resistant pneumococcus or CA-MRSA)

  10. Timing and duration of therapy for CAP • First dose must be given in ER • Outcome dependent on early institution of appropriate antibiotics • Switch from IV to PO abx when pt hemodynamically stable and improving clinically, is able to ingest medications, and has a normally functioning gastrointestinal tract

  11. Timing and duration of therapy for CAP • Rx for a minimum of 5 days, should be afebrile for 48–72 h, and should have no more than 1 CAP-associated sign of clinical instability before discontinuation of therapy • Criteria for clinical stability • 1) Temperature 37.8°C, 2) Heart rate 100 beats/min, 3) Respiratory rate 24 breaths/min, 4) Systolic blood pressure 90 mm Hg, 5) Arterial oxygen saturation 90% or pO2 60 mm Hg on room air, 6) Ability to maintain oral intake, 7) Normal mental status

  12. Healthcare Associated Pneumonia (HCAP)

  13. HCAP • Healthcare associated pneumonia (HCAP) • Any hospitalization in the past 90 days • Any IV antibiotics in the past 30 days • Resident of or transferred from a long term acute care facility or skilled nursing facility • Likely to be due to MDR hospital-acquired organisms • Pseudomonas, MDR acinetobacter, ESBL Klebsiella, MDR enterobacter, etc • MRSA • These patients are too frequently started on standard CAP empiric antibiotics

  14. VAP and HAP • VAP – ventilator associated pneumonia • Pneumonia developing >72 hrs after intubation • HAP – Hospital acquired pneumonia • Pneumonia developing > 72 hrs after hospitalization

  15. Impact, Epidemiology, Pathogenesis

  16. Impact of Hospital-Acquired Infections • Incidence • >2 million persons per year1 • 5% to 35% admitted to ICU1 • Most common causes • Pneumonia 47% • Other lower respiratory tract infections 18% • Urinary tract infection 18% • Laboratory-confirmed bloodstream infection 12% • Hospital-acquired pneumonia • A new pulmonary infiltrate after 1 week of hospitalization that resembles a bacterial pneumonia on the chest x-ray2 VAP is a leading cause of death from hospital-acquired infections in the ICU setting.3 1. Eggimann and Pittet. Chest. 2001;120:2059-2093. 2. Cunha. eMedicine. 8/31/04. 3. Kollef. Chest.1999;115:8-11.

  17. Epidemiology of HAP, VAP, and HCAP • Incidence • HAP: 5 to 10 cases per 1000 hospital admissions • VAP: 6- to 20-fold greater • Increased risk for MDR pathogens • Late-onset HAP and VAP • More likely caused by MDR pathogens • Higher crude mortality vs early-onset disease ATS. Am J Respir Crit Care Med. 2005;171:388-416.

  18. Risk Factors for MDR Pathogens in HAP, VAP, HCAP • Antimicrobial therapy in preceding 90 days • Current hospitalization of > 5 days • High frequency of antibiotic resistance in the community or in the specific hospital unit • Presence of risk factors for HCAP • Immunosuppressive disease and/or therapy ATS. Am J Respir Crit Care Med. 2005;171:388-416.

  19. VAP Pathogenesis

  20. Microbiology

  21. Microbiology of HAP, VAP, and HCAP • Gram-negative pathogens • P aeruginosa • E coli • K pneumoniae • Acinetobacter species • Stenotrophomonas • Gram-positive cocci • S aureus, much of which is MRSA • Anaerobes are an uncommon cause of VAP ATS. Am J Respir Crit Care Med. 2005;171:388-416.

  22. Prevalence of Bacterial Pathogens in Hospitalized Patients With Pneumonia – North America Other 6.4% 18 species Gm-positive Gm-negative Other Other Gm- Each <4% n=2712 S aureus 28% H influenzae 7.3% Klebsiella spp 7.5% S pneumoniae 9.1% P aeruginosa 20% Enterobacter spp 5.8% Adapted from Hoban, et al. Diagn Microbiol Infect Dis.2003 Apr;45(4):279-285.

  23. Diagnosis

  24. Clinical Diagnosis of HAP • Chest radiographic abnormality • New, progressive, or persistent for > 24 hours • More likely if… • Progressive cavitation • Air space process abutting a fissure • Air bronchograms • Infiltrate next to an empyema • Evidence of infection (> 2 of the following) • Purulent sputum • Temperature < 36 C° or > 38 C° • Leukocyte count < 5000 or > 10000 • Blood culture • Specific, but not sensitive Higgins. Curr Treat Options Infect Dis.1999;1:159-175.

  25. Nosocomial PneumoniaDiagnostic Studies • Sputum culture • Beware of colonization • Sputum gram stain - WBCs • Bronchoscopy • controversial • problems with accuracy • questionable contribution to outcome

  26. Nosocomial PneumoniaInterpreting Sputum Cultures • Low numbers of epithelial cells suggests a reliable specimen • High numbers of WBCs should be seen in lower respiratory tract infection. If not: • poor quality specimen (saliva) • no pulmonary infection • If one morphologic type predominates it suggests etiologic agent

  27. Sputum Gram StainS. aureus

  28. Sputum Gram StainP. aeruginosa

  29. What to do with a positive sputum culture – Must decide if it is a colonizer or pathogen Does the patient have pneumonia? • Is the WBC elevated? • Is the patient febrile? • Is there an infiltrate on CXR? • Are the respiratory secretions purulent? • Is pulmonary function impaired? • DO NOT TREAT COLONIZATION! • Don’t be a “knee-jerk” doctor

  30. Treatment

  31. Antimicrobial Therapy Definitions • Appropriate Therapy • Matches antibiotic sensitivities of the organism to the antibiotic used • Adequate Therapy • Choosing an appropriate initial antibiotic therapy • Optimal dosing • Correct route of administration to ensure antibiotic penetration at site of infection • Use of combination therapy if necessary ATS. Am J Respir Crit Care Med. 2005;171:388-416

  32. Inappropriate Antibiotic Therapy Increases Mortality Appropriate therapy Inappropriate therapy 100 90 80 70 60 Mortality (%) 50 40 30 20 10 0 Ibrahim Leibovici Luna Alvarez-Lerma Rello Nosocomial Pneumonia/VAP Bloodstream Infections Ibrahim, et al. Chest. 2000;118:146–155. Leibovici, et al. J Intern Med. 1998;244:379–386. Luna, et al. Chest. 1997;111:676–685. Alvarez-Lerma, et al. Intensive Care Med.1996;22:387–394. Rello, et al. AJRCCM.1997;156:196–200.

  33. Hospital Mortality Rate of Infected Patients • 2000 consecutive patients admitted to an MICU or SICU • Pneumonia in 411 cases • 305 with adequate therapy • 106 with inadequate therapy N = 312 P<.001 Mortality % Inadequate Adequate Antibiotic Treatment Kollef, et al. Chest. 1999;115:462–474.

  34. Management Strategies Days 2 and 3:Check Cultures and Assess Clinical Response (Temperature, WBC, Chest X-ray, Oxygenation, Purulent Sputum, Hemodynamic Changes, and Organ Function) Clinical Improvement at 48 to 72 Hours NO YES Cultures - Cultures + Cultures - Cultures + Search for Complications, or Other Pathogens, Dx, or Sites of Infection Adjust Antibiotic Tx, Search for complications, Other Pathogens, Dx, or Sites of infection Consider Stopping Antibiotics De-escalate Antibiotics, if Possible. Treat Selected Patients 7 to 8 days and Reassess ATS. Am J Respir Crit Care Med. 2005;171:388-416.

  35. Empiric Therapy for HAP, VAP and HCAP in Patients With Late-onset Disease or Risk Factors for MDR Pathogens and all Disease Severity Combination Therapy Antipseudomonal cephalosporin (cefepime, ceftazidime) or Antipseudomonal carbepenem (imipenem or meropenem) or Beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam) plus Antipseudomonal fluoroquinolone* (ciprofloxacin or levofloxacin) or Aminoglycoside (amikacin, gent, tobra) plus Linezolid or vancomycin† Potential Pathogens MDR pathogens • P aeruginosa • K pneumoniae (ESBL+) • Enterobacter • Acinetobacter sp • MRSA *If an ESBL+ strain (eg, K pneumoniae or an Acinetobacter sp) is suspected, a carbepenem is a reliable choice. If L pneumophila is suspected, the combination regimen should include a macrolide (eg, azithromycin) or a fluoroquinolone (eg, ciprofloxacin or levofloxacin) rather than an aminoglycoside. † If MRSA risk factors are present, or there is a high incidence locally. ATS. Am J Respir Crit Care Med. 2005;171:388-416.

  36. Wrong Diagnosis Atelectasis, Pulmonary Embolus, ARDS,* Pulmonary Hemorrhage, Underlying Disease, Neoplasm Wrong Organism Drug-resistant pathogen (bacteria, mycobacteria, virus, fungus) Inadequate Antimicrobial Therapy Complication Empyema or Lung Abscess Clostridium difficile Colitis Occult Infection, Drug Fever Assessment of Nonresponders *ARDS = adult respiratory distress syndrome ATS. Am J Respir Crit Care Med. 2005;171:388-416.

  37. MRSA Pneumonia - Treatment

  38. Concentration Versus MIC90 of Linezolid Against Gram-Positive Organisms Pharmacokinetics in healthy adult volunteers and in vitro activity do not necessarily imply a correlation with clinical effectiveness. MIC90 = minimum concentration needed to inhibit 90% of organisms. Adapted from Conte JE Jr et al. Antimicrob Agents Chemother. 2002;46:1477. Please see full prescribing information available in this kit.

  39. 100 80 60 Linezolid 600 mg q12h Vancomycin 1 g q12h 40 20 0 MRSA NP Linezolid Versus Vancomycin in the Treatment of Nosocomial Pneumonia Clinical cure rates in NP patients with MRSA 59% Clinical Cure (%) 36% P<.01 22/62 36/61 A post hoc analysis of 2 identical, randomized, double-blind, multicenter, multinational, comparator-controlled trials that compared the safety and efficacy of linezolid IV and vancomycin IV for 7 to 21 days in 1019 patients with nosocomial pneumonia, including ventilator-associated pneumonia. Patients were treated for 7 to 21 days with optional aztreonam 1 g to 2 g q12h. Excludes missing and indeterminate. MRSA = methicillin-resistant Staphylococcus aureus. Adapted from Wunderink RG et al. Chest. 2003;124:1789-1797. Please see full prescribing information available in this kit.

  40. 100 90 80 70 Linezolid 600 mg q12h 60 50 Vancomycin 1 g q12h 40 30 20 10 0 MRSA VAP Linezolid Versus Vancomycin in the Treatment of VAP Clinical cure rates in VAP patients with MRSA 62% Clinical Cure (%) 21% P=.001 23/37 7/33 A post hoc analysis of 2 identical, randomized, double-blind, multicenter, multinational, comparator-controlled trials that compared the safety and efficacy of linezolid IV and vancomycin IV for 7 to 21 days in 1019 patients with nosocomial pneumonia, including VAP. Patients were treated for 7 to 21 days with optional aztreonam 1 g to 2 g q12h. VAP = ventilator-associated pneumonia; MRSA = methicillin-resistant Staphylococcus aureus. Adapted from Kollef MH et al. Intensive Care Med. 2004;30:388-394. Please see full prescribing information available in this kit.

  41. Empiric therapy for Hospital-Acquired Pneumonia - notes • MRSA coverage • Vancomycin, Zyvox recommended • Lean towards Zyvox • Lung penetration: Zyvox > Vancomycin • Don’t use Daptomycin for pneumonia – inactivated by surfactant • Synercid not mentioned – possible last ditch drug • Gram Negative coverage • Don’t use ceftriaxone or ertapenem for patient in hospital longer than 3 days – no pseudomonas coverage • Anaerobic coverage – don’t need

  42. Tygecycline – New Antibiotic Class • New class of antibiotic – glycacycline • Similar to tetracyclines • Broad spectrum coverage: MRSA, VRE, MDR gram negatives, ESBL gram negatives, Anaerobes • Low side effect profile • 50 mg IV Q12 • Current indications for intraabdominal infections and skin and soft tissue infections • Soon may have indication for hosp-acquired pneumonia – highly concentrated in lung tissue

  43. Tygecycline - Disadvantages • Recommended dose had to be reduced to 50 mg Q12 because of nausea • May not result in serum concentrations high enough to overcome some infections • Not exceeding MPC • Bacterostatic • Does not cover pseudomonas

More Related