1CAP, HAP, VAP, & HCAPJohn C. Rotschafer, Pharm. D.ProfessorCollege of PharmacyUniversity of MinnesotaFollowing the presentation, the participant will be able to:1. Identify typical, atypical, & hospital respiratory pathogens.2. Identify diagnostic criteria used to establish a diagnosis ofpneumonia3. Identify differences in pathogens causing HAP vs CAP and the required differences in antibiotic coverage.4. Identify underlying mechanisms of antibiotic resistance for typical bacterial pathogens5. Using IDSA/ATS guidelines for CAP & HAP/VAP/HCAP identify appropriate initial antibiotic therapyObjectivesPneumonia• Community acquired pneumonia (CAP)• Aspiration pneumonia• Hospital –Hospital acquired pneumonia (HAP)–Ventilator associated pneumonia (VAP)–Healthcare associated pneumonia (HCAP)2007 ATS/IDSA CAP GuidelinesMandell, LA et al CID 44(suppl 2) 2007Patient screening• Determine whether to treat as outpatient or in-patient (ICU vs Ward)• Objective scoring systems– Pneumonia Severity Index– CURB-65– Confusion– Urea > 7 mmol/L– Respiratory Rate >30 / min– Blood pressure <90 mm Hg & diastolic > 60 mm Hg – Age >65 years– ICU Admit (3 minor criteria present)– Respiratory rate > 30 / min– PaO2/FIO2< 250– Multilobar infiltrates– Confusion– Uremia– Neutropenia– Thrombocytopenia– HypothermiaPneumoniaDiagnosis• Fever, cough, SOB & pleuritic chest pain• Chest x-ray infiltrate• HAP, VAP, & HCAP– Sputum culture should be obtained prior to antibiotics– Quantitative or semiquantitative culture required• Sputum gram stain & culture – <10 epithelial cells & > 25 PMN’s per field– Appropriate cultures of blood and CSFBacterial Resistance in PneumoniaPenicillin Resistant S. pneumoniaeMacrolide Resistant S. pneumoniaeAmpicillin Resistant H. influenzaeBeta-lactamase producing M. catarrhalisMRSA & CA-MRSAMultiple Drug Resistant Gram Negative PathogensP. aeruginosaS. maltophiliaAcinetobacter sppK. pneumoniae or E. coli (ESBL positive)KPC (+) Klebsiella spp2Potential CAP PathogensTypical• S. pneumoniae• H. influenzae• M. catarrhalisAtypical• C. pneumoniae• L. pneumophila• Mycoplasma• Viruses• Fungi• Less Common pathogens– N. meningitidis– S. pyogenes– M. tuberculosis– Chlamydia psittaci– Coxiella burnetii– B. anthracis– Y. pestis– F. tularensis– CA-MRSAAm J Med 106:385-390,1999ATS Pathogen Risk Factors for Penicillin NS/R S. pneumoniae> 65 yearsMultiple co-morbiditiesAlcoholismExposure to children in day careImmunosuppressedSmokingUse of beta-lactam within last 90 daysAm J Respir Crit Care Med 163:1730-1754, 2001Nosocomial Pneumonias~80%~80%10%10%<10%<10%EarlyEarly--onset pneumoniaonset pneumoniaStreptococcus pneumoniaeStreptococcus pneumoniae(~5)(~5)HaemophilusHaemophilusinfluenzaeinfluenzae(<5%)(<5%)MiscellaneousMiscellaneousAnaerobes (Anaerobes (<<30%; may be 30%; may be present in mixed infections)present in mixed infections)LegionellaLegionella(0% (0% --10%)10%)Influenza A and B (<1%)Influenza A and B (<1%)Respiratory Respiratory syncytialsyncytialvirus virus (<1%)(<1%)AspergillusAspergillus(<1%)(<1%)PneumocystisPneumocystiscariniicarinii(<1%)(<1%)LateLate--onset pneumoniaonset pneumoniaAerobic gramAerobic gram--negative bacilli negative bacilli ((>>60%)60%)PseudomonasPseudomonasEnterobacterEnterobacterAcinetobacterAcinetobacterKlebsiellaKlebsiellaStaphylococcus aureus Staphylococcus aureus (~20%)(~20%)Adapted from Leaf HL. In: Mandell GL, Simberkoff MS, eds. Adapted from Leaf HL. In: Mandell GL, Simberkoff MS, eds. Atlas of Infectious Disease. Atlas of Infectious Disease. Philadelphia, Pa: Current Medicine. 1996;6.VI:6.16Philadelphia, Pa: Current Medicine. 1996;6.VI:6.16ATS Guidelines for HAP, VAP, & HCAPAm J Resp Crit Care Med 171:388-416, 2005•Risk for MDR Pathogens• Antibiotic therapy in previous 90 days• Current hospitalization of >5 days• High frequency of antibiotic resistance• Risk factors for HCAP– Hospitalization for > 2 days in previous 90 days– Residence in nursing home or ECF– Home infusion therapy– Chronic dialysis within 30 days– Home wound care– Family member with MDR pathogen• Immunosuppressive diseaseEffect of Mechanical Ventilation and Prior Antibiotic Use on Development of Multiresistant Pathogens63 (41.4)63 (41.4)28 (87.5)28 (87.5)14 (70)14 (70)41 (100)41 (100)Other bacteriaOther bacteria30 (19.7)30 (19.7)1 (3.1)1 (3.1)1 (5)1 (5)00MRSAMRSA6 (3.9)6 (3.9)000000S. maltophiliaS. maltophilia20 (13.2)20 (13.2)1 (3.1)1 (3.1)1 (5)1 (5)00A. baumanniiA. baumannii33 (21.7)33 (21.7)2 (6.3)2 (6.3)4 (20)4 (20)00P. aeruginosaP. aeruginosa89 (58.6)89 (58.6)4 (12.5)4 (12.5)††6 (30)6 (30)0*0*MultiresistantMultiresistantbacteriabacteriaGroup 4 Group 4 ((n=84n=84) ) MV MV ≥≥7 7 ABT = yesABT = yesGroup 3 Group 3 ((n=17n=17) ) MV MV ≥≥7 7 ABT = noABT = noGroup 2 Group 2 ((n=12n=12) ) MV < 7 MV < 7 ABT = yesABT = yesGroup 1 Group 1 ((n=22n=22) ) MV < 7 MV < 7 ABT = noABT = noOrganismsOrganisms* p < 0.02 versus Groups 2, 3, or 4* p < 0.02 versus Groups 2, 3, or 4††p < 0.0001 versus Group 4p < 0.0001 versus Group 4Adapted from Adapted from TrouilletTrouilletJL, et al. JL, et al. Am J Respir Crit Care MedAm J Respir Crit Care Med. 1998;157:531. 1998;157:531--539539Diagnosis of Suspected VAP413 patients with suspected VAP• 32% enrolled surgical patientsInvasive management• BAL or bronchoscopic protected specimen brush (PSB)• Quantitative sputum cultures– ≥104CFU/mL BAL– ≥103CFU/mL PSBClinical management• Clinical criteria• Nonquantitatve evaluation of nonbronchoscopic isolatesFagon JY et al. Ann Intern Med. 2000;132:621-630.3Diagnosis of Suspected VAPAdapted from Adapted from FagonFagonJY et alJY et al. Ann Intern Med. . Ann Intern Med. 2000;132:6212000;132:621--630.630.0.002547 (22.5)23 (11.3)Emergence of Candida spp., n (%)<0.0017.5 ± 7.611.5 ± 9.0Antibiotic-free days at 28 days<0.0012.2 ± 3.55.0 ± 5.1Antibiotic-free days at 14 days0.09981 (38.8)63 (30.9)Mortality at 28 days, n (%)0.02254 (25.8)33 (16.2)Mortality at 14 days, n (%)P valueClinical(n=209)Invasive(n=204)End PointIntention-to-Treat AnalysisBacteriology3.5%5.0%A.