Healthcare-Associated Pneumonia: Refining the HCAP Criteria Pharmacotherapy Conference November 20, 2009 Russell T. Attridge, Pharm.D. Master’s Candidate / Specialty Resident in Pharmacotherapy The University of Texas at Austin College of Pharmacy The University of Texas Health Science Center at San Antonio OBJECTIVES At the end of this presentation, audience members will be able to: Define healthcare-associated pneumonia (HCAP). Describe the origin of the term “healthcare-associated infection.” Briefly summarize the findings of current HCAP evidence. Discuss the published evidence regarding individual HCAP risk factors. Further specify the population of pneumonia patients that should be considered HCAP. INTRODUCTION Table 1: Definitions1, 2 Pneumonia Type “Signs, symptoms, and radiologic evidence of pneumonia . . .” Community-acquired pneumonia (CAP) Healthcare-associated pneumonia (HCAP) Hospital-acquired pneumonia (HAP) Ventilator-associated pneumonia (VAP) In the first 48 hours of hospital admission In CAP patients with recent contact with the health system 48-72 hours after hospital admission 48-72 hours after endotracheal intubation Adapted from: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388-416. Epidemiology – pneumonia is… The leading cause of infectious disease-related death globally and in the United States3-5 WHO (2004) 4.2 million deaths worldwide (7.1% of total global death)3 CDC (2006) more than 56,000 deaths in the United States4 Responsible for 1.2 million of the 35 million annual U.S. hospitalizations 5 Community-acquired pneumonia (CAP)6, 7 Incidence: 4 million cases annually in the United States o 80% outpatient: low risk of mortality o 18% non-ICU inpatient: 5-7% mortality o 2% ICU inpatient: 10-15% mortality U.S. expenditures: greater than $8 billion annually Table 2: Expected CAP Pathogen Distribution, By Site of Care8 Outpatient Inpatient, non-ICU Inpatient, ICU S pneumoniae M pneumoniae H influenzae C pneumoniae Resp viruses S pneumoniae M pneumoniae C pneumoniae H influenzae Legionella sp Aspiration / respiratory viruses S pneumoniae S aureus Legionella sp Gram-negative bacilli (GNB) H influenzae Adapted from: File TM. Community-acquired pneumonia. Lancet 2003;362:1991-2001. 2 †Healthcare-associated infections:9 Hospitalization within past 12 months Peritoneal/hemodialysis within 12 months Indwelling bladder/vascular device at home immediately prior to admission NOTE: long-term care facilities were not included in these criteria Morin and Hadler 2001 ‡Healthcare-associated bloodstream infection:10 Friedman et al 2002 Positive blood culture w/in 48 hours of admission with . . . Intravenous (IV) therapy/wound care at home in the past 30 days Hospital/hemodialysis (HD) clinic or IV chemotherapy in the past 30 days Hospitalized ≥ 2 days in the past 90 days Transfer from a nursing home or long-term care facility §Healthcare-associated bacteremia:11 Tacconelli et al 2004 Patients with MRSA in ≥ 1 blood culture within 24 hours of hospital admission with . . . IV therapy, chemotherapy, specialized nursing/wound care at home Ambulatory visit within past 30 days Chronic HD Hospitalized ≥ 2 days in past 6 months Nursing home or long-term care facility ψ Healthcare-associated pneumonia:2 ATS/IDSA Guidelines 2005 Hospitalization for 2 days or more in the preceding 90 days Residence in a nursing home or extended care facility Home infusion therapy (including antibiotics) Chronic dialysis within 30 days Home wound care Family member with multidrug-resistant pathogen Figure 1: The Origins of HCAP † This is largely considered the first definition of a healthcare-associated infection. The objective of the study was to determine the epidemiology of community-onset S. aureus bloodstream infections (BSIs) and the extent to which they are caused by MRSA. Three mutually exclusive cohorts were created; patients with “healthcareassociated infections” and patients “with underlying comorbidities” were more likely to have MRSA BSIs than patients “without underlying comorbidities” (MRSA rates as a % of S. aureus: 16% vs. 16% vs. 0%, respectively). ‡ Extrapolating from Morin and Hadler, Friedman and colleagues set out to further develop a classification scheme for BSIs that differentiated among community-acquired, healthcare-associated, and nosocomial infections. Results of their study led them to conclude that healthcare-associated BSIs are similar to nosocomial infections (e.g., pathogens and susceptibility patterns, mortality) and should be a separate category of infection. This definition is very similar to the definition in pneumonia set forth by the 2005 ATS/IDSA guidelines. § Tacconelli and colleagues performed a case-control study to further characterize patients found to have MRSA bacteremia within 24 hours of admission. All patients had healthcare-associated BSI risk factors (no “true” community-acquired MRSA BSIs). In the discussion, the authors emphasize the importance of using the “heathcare-associated” term when it applies to avoid confusion with any true community-acquired infections. ψ Historical healthcare-associated infection risk factors were applied to pneumonia in the 2005 ATS/IDSA guidelines for the management of HAP, VAP, and HCAP. 3 HCAP AS A DISTINCT CLINICAL ENTITY HCAP is a large, heterogeneous patient population with a poorly-defined conglomeration of risk factors that may increase the risk for infection with drug-resistant pathogens Risk Factor Hosp. in past 30d Hosp. in past 90d 1 2 3 4 5 Hosp. in past 12 months Transfer from other health facility Home infusion / IV therapy Chronic dialysis Family with MDR pathogen 8 1. Friedman et al 2002 2. ATS/IDSA Guidelines 2005 3. Kollef et al 2005 4. Carratalà et al 2007 5. Micek et al 2007 6. Shorr et al 2008 7. Venditti et al 2009 8. Shindo et al 2009 Home wound care 7 Hosp./surgery in past 180d Nursing home / ext. care facility 6 Attended hosp./HD clinic past 30d Regular clinic visits (HD, PD, infusions) IV chemotherapy past 30 days Immunocompromised state Figure 2: HCAP Definitions, By Study QUANTIFYING THE MAGNITUDE OF THE HCAP POPULATION Cohorts altered significantly by study site and selected HCAP inclusion criteria HCAP Kollef '05 CAP 30.8% 69.2% Micek '07 & Shorr '08 67.4% Carratala '07 32.6% 17.3% Venditti '09 82.7% 28.8% Shindo '09 71.2% 38.0% Average 62.0% 36.5% 0% 10% 20% 30% 63.9% 40% 50% 60% 70% 80% 90% 100% % HCAP of Community-Dwelling Adults Hospitalized for Pneumonia Figure 3: CAP vs. HCAP, By Study 4 Comparison of Etiology and Outcomes, HCAP vs. CAP 12 2005 Kollef et al – multicenter retrospective cohort analysis (U.S., 59 hospitals), 2002-03 Variable Pathogen (%, culture-positive) S. aureus [% MRSA] P. aeruginosa S. pneumoniae H. influenzae Hospital length of stay, days (mean ± SD) In-hospital mortality (%) 2007 46.7 [56.8] 25.3 5.5 5.8 8.8 ± 7.8 19.8 25.5 [34.8] 17.1 16.6 16.6 7.5 ± 7.2 10.0 <0.01 [<0.01] <0.01 <0.01 <0.01 <0.0001 <0.0001 HCAP (n=126) CAP (n=601) 27.8 11.9 2.4 1.6 2.4 [0] 32.5 10.4 ± 3.4 10.3 33.9 6.0 8.8 0.5 0 [0] 43.9 10.4 ± 4.7 4.3 P-value * = not provided 0.18 0.02 0.01 0.18* 0.005 0.02 0.94 0.007 HCAP (n=431) CAP (n=208) 44.5 [68.8] 10.4 25.5 4.2 0.2 Not provided 24.6 25.5 [47.1] 40.9 4.8 17.3 3.4 Not provided 9.1 P-value * = not provided 0.001* [0.001] <0.001 <0.001 <0.001 0.017 -<0.001 Venditti et al15 – multicenter prospective observational study (Italy, 55 hospitals), 2007 Variable [no pathogen data] Hosp. length of stay, days (mean, 95% CI) In-hospital mortality (%) 2009 P-value Micek et al14 – single-center retrospective cohort analysis (U.S.), 2003-05 Variable Pathogen, (%, culture-positive) S. aureus [% MRSA] S. pneumoniae P. aeruginosa H. influenzae Legionella sp Hospital Length of stay, days (mean ± SD) In-hospital mortality (%) 2009 CAP (n=2,221) Carratalà et al13 – single-center prospective observational analysis (Spain), 2001-04 Variable Pathogen, (%, culture-pos. and neg.) S. pneumoniae H. influenzae L. pneumophila P. aeruginosa S. aureus [% MRSA] No pathogen identified Hospital length of stay, days (mean ± SD) 30-day mortality (%) 2007 HCAP (n=988) HCAP (n=90) 18.7 (15.9-21.5) 17.8 CAP (n=49) 14.7 (13.4-15.9) 6.7 P-value <0.05 <0.05 Shindo et al16 – single-center retrospective observation study (Japan), 2005-07 Variable Pathogen, (%, culture-pos. and neg.) S. pneumoniae S. aureus [% MRSA] Pseudomonas sp Atypical pathogens No pathogen identified Previous antibiotics, past 90d (%) In-hospital mortality (%) HCAP (n=141) CAP (n=230) 13.5 9.9 [35.7] 5.7 0.7 45.4 63.1 21.3 19.1 6.1 [14.3] 1.7 7.0 52.6 20.9 7.4 P-value * = not provided 0.132* 0.235* [0.066]* 0.038* 0.004* 0.194* <0.001 <0.001 5 THE BIGGER ISSUE: HCAP or DRUG-RESISTANT PNEUMONIA? Shorr AF, Zilberberg MD, Micek ST, et al. Predictors of infection due to antibiotic-resistant bacteria by select risk 17 factors for health care-associated pneumonia. Arch Intern Med 2008;168(20):2205-10. 14 Design Single-center retrospective review (same cohort as Micek et al 2007 ) Primary endpoint – presence of infection with a resistant pathogen o MRSA, P.aeruginosa, extended-spectrum β-lactamase-producing (ESBL) Klebsiella sp, and other non-fermenting gram-negative rods (GNRS) Population n=639 pts (HCAP, n=431; CAP, n=208) Resistant pathogen (45.2%) vs. no resistant pathogen (54.8%) see figure below Results Pathogen Distribution (not provided for HCAP and CAP individually) Resistant Pathogen No Resistant Pathogen MRSA: 54.3% S. pneumoniae: 37.1% P.aeruginosa: 41.5% ESBL Klebsiella sp/other nonfermenting GNRs: 16.3% HCAP definition specificity for resistant pathogen – 48.6% Four variables independently associated with a resistant pathogen (basis for scoring system) o OR 4.21 – recent hospitalization (4 points) o OR 2.75 – nursing home resident (3 points) o OR 2.11 – long-term hemodialysis (2 points) o OR 1.62 – ICU admission (1 point) Scoring system (out of 10 points) AUC under ROC curve = 0.75 (95% CI, 0.65-0.80) o Likelihood of Infection with a resistant pathogens Low-risk (<3 points): <20% Intermediate-risk (3-5 points): 55% High-risk (≥6 points): >75% Author’s As is, HCAP risk factors have limited value in predicting patients with resistant infections. Comments The use of simple of risk stratification tools can improve the likelihood of appropriate initial coverage without exposure to unnecessarily broad-spectrum agents. Resistant Pathogen No Resistant Pathogen 100% 80% 60% 40% 20% 0% Figure 4: Resistant Pathogens, By Risk Factor (Shorr et al 200817, all p<0.05) 6 INDIVIDUAL HCAP CRITERIA: WHAT IS THE RISK OF A RESISTANT PNEUMONIA PATHOGEN? Recent Hospitalization Proportion of the HCAP Cohort, By Study Study Previous Hospitalization 12 Kollef 2005 (HCAP, n=988) 13 Carratalà 2007 (HCAP, n=126) 14 17 Micek 2007 / Shorr 2008 (HCAP, n=431) 15 Venditti 2009 (HCAP, n=90) 16 Shindo 2009 (HCAP, n=141) Not provided Within 90 days: 55 (43.7%) Within 365 days: 402 (93.3%) Within 180 days: 384 (89.1%) Within 90 days: 297 (68.9%) Within 180 days: 72 (80.0%) Within 90 days: 55 (39.0%) Key Points One of the most prevalent HCAP risk factors – extremely heterogeneous group No published literature specifically on recent hospitalization Emphasis in literature on risk factors for drug-resistant pathogens o Previous hospitalization – consistently an identified risk factor In HCAP patients, primary pathogens of concern are MRSA and Pseudomonas sp Evidence for Pseudomonas and MRSA in community-dwelling patients (see below) Group Pseudomonas pneumonia MRSA pneumonia MRSA Colonization Publication Independent Risk Factors (OR, 95% CI) 18 Arancibia 2002 (n=559, CAP patients; n=60, Pseudomonas pneumonia) 19 Garcia-Vidal 2009 [abstract, ICAAC 2009] (n=4426, community-onset pneumonia; n=44, Pseudomonas pneumonia) 20 Lescure 2006 (n=198, MRSA case patients; n=198, MSSA control patients; 27.3% of infections in respiratory tract) 17 Shorr 2008 (n=639, CAP and HCAP patients; n=157, MRSA pneumonia) See Table 1, Appendix A Pulmonary comorbidity (5.8, 2.2-15.3) Previous hospital admission, 1 mo. (3.8, 1.8-8.3) COPD (5.5, 2.7-11.2) Prior use of steroids (3.9, 1.8-8.4) ICU admission (3.3, 1.4-8.1) Note: “Community-onset” not defined – may not have included patients with previous hospitalization. Prior hospitalization, past 3y (3.8, 1.8-7.9) Home nursing care (3.7, 2.0-6.7) Home care or hosp. for surgery, past 3y (3.1, 1.2-8.0) Referral [other hospital, nursing home] (2.3, 1.2-4.3) Age >65y (1.6, 1.1-2.5) Recent hospitalization, 3 mos. (2.35, 1.52-3.64) Nursing home resident (1.88, 1.21-2.90) ICU admission (1.75, 1.20-2.55) See Table 1, Appendix A The Bottom Line Previous hospitalization needs to be considered with the additional knowledge of reason for previous admission, duration of hospitalization, and receipt of antibiotic therapy, all of which may play a role in a patient’s risk for a drug-resistant pathogen. The search for drug-resistant pathogen-specific risk factors is complicated by issues of statistical power, selection bias, and limitations of the case-control study design. o For community-dwelling patients, there is limited evidence. 7 Residence in a Nursing Home / Long-Term Care Facility (LTCF) Size of Cohort Study Nursing Home / LTCF Patients 12 Kollef 2005 (HCAP, n=988) 13 Carratalà 2007 (HCAP, n=126) 14 17 Micek 2007 / Shorr 2008 (HCAP, n=431) 15 Venditti 2009 (HCAP, n=90) 16 Shindo 2009 (HCAP, n=141) 490 (49.6%) 32 (25.4%) 121 (28.1%) 6 (6.7%) 86 (61.0%) Key Points Nursing home-acquired pneumonia (NHAP): most evidence among the HCAP criteria Adults over age 85 are the fastest growing demographic in the U.S.21 Pneumonia second most common infection in nursing home residents22 o Highest mortality (15-60%) and common cause for hospital transfer22-24 Lack of standard “nursing home” definition major differences in scope of care25 NHAP is often managed in-house w/oral therapy (e.g., fluoroquinolones)22, 26 o Remember: HCAP focuses on hospitalized patients Evidence-based review of hospitalized NHAP publications containing pathogen data Lim WS, Macfarlane JT. A prospective comparison of nursing home acquired pneumonia with 27 community acquired pneumonia. Eur Respir J 2001;18:362-8. Design Single-center prospective cohort study (United Kingdom), 1998-2001 Population n=437 CAP patients; 40 (9%) admitted from nursing homes Excluded patients hospitalized in previous 10 days, HIV patients, and immunosuppressed patients (recent chemotherapy, recent daily corticosteroid therapy) For etiology, each NHAP “case” matched with 2 “control” CAP patients from 1998-1999 Characteristic NHAP (n=40) CAP (n=397) P-value Age, years 80.6 ± 9.6 65.5 ± 19.4 <0.001 Prior antibiotics 18 (45%) 145 (37%) 0.6 ECOG (1-4) 3±1 1.2 ± 1.2 <0.001 Barthel Index (0-20) 8.9 ± 6.7 17 ± 5.1 <0.001 PSI score 144 ± 26 90 ± 39 <0.001 Results Pathogen(s) were detected in 50 (77%) of 66 patients Pathogen NHAP (n=22) CAP (n=44) P-value (% cx-pos. and neg.) * = not provided S. pneumoniae 12 (55%) 19 (43%) 0.342* S. aureus 0 1 (2%) 0.481* H. influenzae 0 5 (11%) 0.104* Atypicals 4 (18%) 9 (20%) 0.860* No pathogen identified 7 (32%) 9 (20%) 0.287* Outcome NHAP (n=40) CAP (n=397) P-value LOS, days (survivors) 6 (median) 7 (median) -In-hospital mortality 21 (53%) 53 (13%) <0.001 No enteric gram-negative bacteria reported in either cohort Independent risk factor of mortality: functional status (ECOG) – OR 4.0, 95% CI, 1.3-12.0 Author’s Compared to CAP patients, NHAP patients have more severe disease but a similar Conclusions pathogen distribution. Choice of empiric antibiotics for hospitalized NHAP patients should not be any different than for older CAP patients. Functional status is the main factor in the higher mortality of NHAP patients. 8 El Solh AA, Sikka P, Ramadan F, Davies J. Etiology of severe pneumonia in the very elderly. Am J Respir 28 Crit Care Med 2001;163:645-51. Design Multi-center prospective cohort study (2 hospitals); June 1996 – September 1999 Population n=104 pts >75 years of age with severe CAP and NHAP (all mechanically-ventilated) Excluded if transferred to ICU after 24h of initial admission, recent hospitalization (30d) Patients assigned Activities of Daily Living (ADL) score as marker of functional status ADL scores from 6 (best) to 18 (worst); divided into 3 arbitrary classes o ADL I – 6-8 points; ADL II – 9-13 points; ADL III – 14-18 points Results Microbial etiology determined in 55 (53%) patients *“n” per cohort not provided+ Variable Nursing Home (n=47) Home (n=57) P-value Pathogens (% cx-pos. and neg.) S. pneumoniae 4 (9%) 8 (14%) 0.380* S. aureus 14 (29%) 4 (7%) 0.002* o % MRSA 3 (21%) 0 0.053* P. aeruginosa 2 (4%) 1 (2%) 0.448* L. pneumonphila 0 5 (9%) 0.037* APACHE II score 28.4 ± 5.7 25.8 ± 5.4 0.04 In-hospital mortality 27 (57.4%) 30 (52.6%) 0.8 Poor functional status associated with higher rates of: o S. aureus: ADL III (56%) vs. ADL I (9%), p=0.0034 o GNB and P. aeruginosa: ADL III (39%) vs. ADL I (17%), p=0.16 Independent predictors of hospital mortality (multivariable regression) were multilobar involvement, septic shock, 24-h urine output, and inadequate antimicrobial therapy o In this patient group, no impact of functional status on mortality Author’s Respiratory pathogens differ based on residence prior to admission. Conclusions Functional status may factor into pneumonia due to S. aureus and Pseudomonas. El Solh AA, Pietrantoni C, Bhat A, et al. Indicators of potentially drug-resistant bacteria in severe 29 nursing-home acquired pneumonia. Clin Infect Dis 2004;39:474-80. Design Single-center ICU retrospective cohort study (12-bed ICU, average 650 admissions/yr) Derived from a prospective database – patient data collected between 1998-2003 Population n=135 mechanically-ventilated patients from a long-term care facility o Excluded if transferred to ICU >48h after admission, hospitalized >48 hours in previous 6 months, immunocompromised, or receiving antibiotic therapy within 72h of enrollment Utilized 2 cohorts (derivation cohort, n=88; validation cohort, n=47) to derive and validate a classification tree that predicts the risk of a drug-resistant pathogen Results In both cohorts, patients with pneumonia secondary to drug-resistant pathogens had: o Higher ADL scores (higher=↑ dependence) [p<0.05] o Higher Charlson Index scores (higher=↑ risk of 1-year mortality) [p<0.05] o Higher rates of previous antibiotic use [p<0.001] Microbial etiology determined for 93 (68%) of 135 patients Gram-Positive Cocci (% culture-positive) Gram-Negative Bacilli (% culture-positive) S. pneumoniae: 25 (25.3%) P. aeruginosa: 9 (9.1%) MRSA: 20 (20.2%) E. coli: 9 (9.1%) MSSA: 11 (11.1%) K. pneumoniae: 6 (6.1%) Stratifying patients by previous antibiotic exposure and a cut-off ADL score of 12.5, the classification tree selected patients with drug-resistant pathogens with sensitivities of 100% and 100% and specificities of 53.5% and 69.4% in the derivation and validation cohorts, respectively. Author’s Functional status and previous antibiotic use are predictors of pneumonias due to drugConclusions resistant pathogens and may be considered when choosing therapy for severe NHAP. 9 Martínez-Moragόn E, Garcia Ferrer L, Serra Sanchos B, et al. Community-acquired pneumonia among the elderly: differences between patients living at home and in nursing homes. Arch Bronconeumol 30 2004;140(12):547-52. Design Single-center prospective cohort study (Spain), 2002-2003 Population n=91 CAP pts; all patients >65 years old; 25/91 (27.5%) admitted from nursing homes Excluded patients hospitalized in prior 10 days or w/o primary diagnosis of pneumonia Results Microbiologic diagnosis, n=22 (24%) nursing home, n=6 (24%); home, n=16 (24%) Variable Nursing Home (n=25) Home (n=66) P-value Age, years 82 ± 4 73 ± 5 0.0001 ECOG score 2.09 ± 0.9 0.93 ± 11 0.0001 Karnofsky Index 51 ±17 78 ± 23 0.0001 Barthel Index 19 ± 33 77 ± 35 0.0001 PSI score 134 ± 26 95 ± 28 0.0001 Pathogen (n) - S. pneumoniae 2 4 S. aureus 3 4 Enteric GNB 1 0 Atypicals 0 5 LOS, days 8 ± 7.87 8.54 ± 4.97 NS In-hospital mortality, n (%) 7 (28%) 3 (4.5%) 0.005 Univariable analysis: age, residence, Barthel Index, respiratory rate, hemoglobin, urea, creatinine, arterial pH, and PSI score associated with mortality (all p<0.05) 2 Stepwise linear regression only predictor of mortality was serum urea (adj. r =0.452) Author’s High mortality rate of nursing home patients consistent with other published data. Conclusions Pneumonia etiology was similar between CAP patients from home and nursing homes. Given their prognosis value, general condition scales should be standardized. Kothe H, Bauer T, Marre R, et al. Outcome of community-acquired pneumonia: influence of age, 31 residence status and antimicrobial treatment. Eur Respir J 2008;32:139-46. Design Prospective observational study; consecutive CAP patients, March 2003 – October 2005 Data from the CAPNETZ group [based in Germany: >670 practitioners, >30 hospitals] Population n=2,647; 74.8% hospitalized, 25.2% outpatient Excluded patients with acquisition of pneumonia after admission, immunosuppression Microbial etiology determined in 539 (20.4%) of cases Subgroup analysis performed for those ≥65 in nursing homes *i.e., NHAP patients+ Results Multivariable model (elderly patients): age, CURB score, residence status [nursing home], cerebrovascular/chronic liver disease, and treatment failure predictive of death Subgroup analysis: n=1,349 patients ≥65; 15.2% resided in a nursing home Variable NHAP (n=205) Home (n=1,144) P-value Age, years 82.3 ± 7.9 76.1 ± 7.0 <0.001 CURB score 1.52 ± 1.01 0.93 ± 0.83 <0.001 Pathogens (% cx-pos. and neg.) GNB 18.8% 5.5% 0.02 S. aureus 2.3% 1.0% NS P. aeruginosa 1.0% 0.3% NS Change in treatment Ineffective 14.1% 11.2% 0.233 Resistance 2.0% 1.6% 0.560 30-day mortality 28.8% 6.9% <0.001 Author’s Age and residence in a nursing home are associated with 30-day mortality after Conclusions controlling for comorbid conditions and disease severity. Mortality was significantly higher in nursing home patients despite similar rates of drugresistant pathogens and ineffective antibiotic therapy. 10 Maruyama T, Niederman MS, Kobayashi T, et al. A prospective comparison of nursing home-acquired 32 pneumonia with hospital-acquired pneumonia in non-intubated elderly. Respir Med 2008;102:1287-95. Design Single-center prospective cohort study (Japan), June 2004 – May 2005 Population n=108 patients; HAP, n=33; NHAP, n=75 Excluded early-onset HAP/NHAP, hemodialysis, malignant disease, immunosuppression Variable HAP (n=33) NHAP (n=75) P-value Age, years 79.0 ± 7.2 87.3 ± 8.9 <0.0001 ECOG, grade 1-4 3.4 ± 0.5 3.0 ± 0.5 <0.0001 Prior antibiotics 14 (42.4%) 26 (34.7%) 0.4419 CURB-65 2.54 ± 1.37 1.95 ± 1.03 0.0343 ICU admission 4 (12.1%) 6 (8.0%) 0.483* Results Pneumonia etiology; microbiologic diagnosis in 26 (78.8%) HAP pts; 54 (72%) NHAP pts Variable HAP (n=33) NHAP (n=75) P-value Pathogen S. pneumoniae 4 (12.1%) 25 (33.3%) 0.031 S. aureus 9 (27.2%) 3 (4.0%) 0.006 P. aeruginosa 4 (12.1%) 3 (4.0%) 0.075 Atypicals 10 (30.3%) 28 (37.3%) 0.730 Presence of MDR pathogen 8 (24.2%) 7 (9.3%) 0.036* In-hospital mortality 17 (51.5%) 28 (37.3%) 0.0213 Results of logistic regression determined ECOG status to be an indicator of prognosis in all patients and a subgroup of only NHAP patients. Author’s Causative pathogens and outcomes differ for elderly non-intubated patients Conclusions hospitalized for the treatment of pneumonia. Findings do not support treating NHAP patients the same as late-onset HAP patients, as outlined in the 2005 ATS/IDSA pneumonia guidelines. Attridge RT, Frei CR. Etiology and outcomes for pneumonia patients admitted from skilled-nursing facilities (SNFs): implications for empiric antibiotic therapy. In: Meeting guide and abstracts of the 2009 ACCP/ESCP International Congress on Clinical Pharmacy (Orlando). Lenexa, Kansas: American College of 24 Clinical Pharmacy, 2009:257-8. Design Multicenter retrospective cohort study (U.S.), 1996-2006 Data from the CDC National Hospital Discharge Survey (NHDS) Population n=5,477,504 patients (weighted data); SNF patients, n=130,081 (2.4%) Pneumonia diagnosis and pathogen data extracted from ICD-9-CM codes Results Culture-positive patients: SNF vs. home, 15.4% vs. 12.7%, p<0.0001 Variable SNF (n=130,081) Home (n=5,477,504) P-value Age, years (mean) 80.1 70.2 <0.0001 Pathogen (cx-positive) S. aureus (%) 44.8 22.0 <0.0001 P. aeruginosa (%) 22.1 14.4 <0.0001 S. pneumoniae (%) 5.6 20.7 <0.0001 H. influenzae (%) 1.4 7.1 <0.0001 LOS ≥7 days (%) 40 28 <0.0001 Death, at discharge (%) 13 5 <0.0001 No data available on antibiotic therapy or drug-resistance (e.g., S. aureus resistance) Author’s Conclusions Compared to patients admitted from home, SNF patients present with different bacterial pathogens, utilize more healthcare resources, and suffer increased mortality. These results support the inclusion of SNF patients in the HCAP population and are similar to other recent U.S. data on pneumonia in SNF patients (Kollef et al 2005). 11 El Solh AAA, Akinnusi ME, Alfarah Z, Patel A. Effect of antibiotic guidelines on outcomes of hospitalized 33 patients with nursing home-acquired pneumonia. J Am Geriatr Soc 2009;57:1030-5. Design Retrospective cohort study (3 northeastern U.S. hospitals), January 2006 – August 2008 Compared time to clinical stability (TTCS), time to switch therapy (TTST), length of hospital stay (LOS), and mortality in hospitalized NHAP patients when treated according to the 2003 CAP or the 2005 HCAP guidelines Population n=337; consecutive adult patients admitted to hospital with principal diagnosis of pneumonia and residence in a nursing home Excluded patients with HIV, previous hospitalization (30 days), ICU admission, outside hospital transfer, active chemotherapy, or those receiving more than 1 dose of antibiotics prior to ER presentation Variable 2003 CAP (n=258) 2005 HCAP (n=76) P-value Age, years 73.5 ± 13.8 76.7 ± 13.1 0.08 ADL score, median 14 (11-16) 14.5 (11-17) 0.32 PSI score, mean 127 ± 31 135 ± 35 0.11 Results Clinical endpoints, based on guideline-concordant treatment Outcome 2003 CAP (n=258) 2005 HCAP (n=76) P-value TTCS, days 3.6 ± 0.7 3.9 ± 0.8 0.38 TTST, days 4.1 ± 1.6 5.8 ± 2.2 <0.001 LOS, days 5.7 ± 1.7 6.9 ± 2.8 <0.001 Hospital mortality 34 (13.2%) 13 (17.1%) 0.49 30-day mortality 39 (15.1%) 17 (22.4%) 0.19 Author’s Treatment of hospitalized NHAP patients according to either the 2003 CAP guidelines or Conclusions the 2005 HCAP guidelines led to comparable outcomes in time to clinical stability and mortality. The Bottom Line There are wide variations among the NHAP evidence in study populations, disease severity, functional status, and pathogen distribution. Functional status may play an important role in both: o Mortality27, 34 o Risk of a drug-resistant pathogen28, 29, 35-37 Initial evidence suggests that guideline-concordant CAP and HCAP therapy have comparable outcomes in NHAP patients. Chronic Hemodialysis Size of Cohort Study Dialysis Patients 12 Kollef 2005 (HCAP, n=988) 13 Carratalà 2007 (HCAP, n=126) 14 17 Micek 2007 / Shorr 2008 (HCAP, n=431) 15 Venditti 2009 (HCAP, n=90) 16 Shindo 2009 (HCAP, n=141) Not provided 40 (31.7%) 43 (10.0%) 3 (3.3%) 10 (7.1%) 12 From: U.S. Renal Data System, USRDS 2009 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2009. Figure 5: Infectious-disease related admissions (per 1,000 patient years) [dialysis patients] Key Points Infections in hemodialysis patients – 2nd most common cause of death38 Infectious disease mortality rates (2004-2006 combined data) in dialysis patients38 o Septicemia 19.5 deaths/1,000 patient-years (72% of infectious deaths) o Pulmonary infection 4.4 deaths/1,000 patient-years (16% of inf. deaths) Pulmonary infectious mortality 14- to 16-fold higher than general population39 Evidence-based review of pneumonia etiology in dialysis patients Slinin Y, Foley RN, Collins AJ. Clinical epidemiology of pneumonia in hemodialysis patients: the USRDS 40 waves 1, 3, and 4 study. Kidney Int 2006;70:1135-41. Design Retrospective cohort study (Waves 1, 3, and 4 Dialysis Morbidity & Mortality Study set) Random sample: 1 of every 5 US dialysis pts alive on 12/31/1993 (>1300 dialysis units) Population n=10,635 linked to Medicare claims to identify hospitalizations with pneumonia mean age: 60.3 years mean duration of ESRD: 3.8 years Pneumococcal vaccination: 8.7% in 5-years preceding study Influenza vaccination: 31.6% in 4 months preceding study Results Average follow-up interval: 3.3 years 28.9% of population hospitalized with pneumonia o Primary discharge diagnosis: 57.1% of hospitalizations involving pneumonia Organism identified in 18.2% of cases Gram-negative vs. gram-positive bacteria (% overall): 11.1% vs. 4.8%, respectively Gram-negatives (%overall, % cx-positive) Gram-positives (% overall, % cx-positive) P. aeruginosa: 2.8% (15.4%) S. pneumoniae: 3.4% (26.4%) K. pneumoniae: 1.6% (8.8%) Other Streptococcus: 1.0% (5.5%) H. influenzae: 1.5% (8.2%) Staphylococcus sp: 0.4% (2.2%) In-hospital mortality: 384 (12.4%) died with pneumonia diagnosis o 134 (4.3%) – primary discharge diagnosis o 250 (8.1%) – secondary discharge diagnosis Author’s There was a noteworthy burden of disease and associated mortality. The mortality rate Comments of 12.4% is similar to the 11% in-hospital mortality rate found in a study of the general 41 U.S. Medicare population. Pneumonia was identified through administrative claims, meaning that a substantial number of pneumonias may have occurred after admission for another serious illness. o This may affect the spectrum of pathogens and the ability to show a direct causal link between pneumonia and death. 13 Guo H, Liu J, Collins AJ, Foley RN. Pneumonia in incident dialysis patients – the United States Renal Data 42 System. Nephrol Dial Transplant 2008;23:680-6. Design Retrospective cohort study using the Renal Beneficiary Utilization System files and the CMS Institutional Inpatient Analytic Files Population n=289,210 patients initiating maintenance dialysis (use of dialysis for 90 days) between 1996-2001; followed until the end of 2003 Medicare claims used to define pneumonia and cardiovascular events Mean age: 63.8 years Hemodialysis: 90.4%; peritoneal dialysis: 9.6% Results Out- and inpatient pneumonia assessed – 42% of pneumonia patients hospitalized Within one year of dialysis, 60,610 patients (21.0%) developed pneumonia o Overall event rate: 27.9/100 patient-years o Hospitalized for treatment: 11.8/100 patient-years o ↑ rates in hemo- vs. peritoneal dialysis (29.0 vs. 18.2/100 patient-years) Organism identified in 15.6% of cases: 4.01% gram-negative, 4.73% gram-positive Gram-Negatives (% of culture-positive) Gram-Positives (% of culture-positive) P. aeruginosa: 1.19% (7.6%) S. pneumoniae: 2.56% (16.4%) K. pneumoniae: 1.06% (6.8%) Staphylococcus sp: 1.73% (11.1%) H. influenzae: 0.47% (3.0%) Other Streptococcus: 0.43% (2.8%) E. coli: 0.23% (1.5%) Author’s The disease burden and mortality of pneumonia in dialysis patients should encourage Comments practitioners to ensure preventative measures in patients (vaccinations). Pneumonia was identified through administrative claims, meaning that a substantial number of pneumonias may have occurred after admission for another serious illness. o This may affect the spectrum of pathogens and the ability to show a direct causal link between pneumonia and death. D’Agata et al 200043 – hospital-acquired infections among chronic hemodialysis patients Single-center matched case-control study of dialysis and non-dialysis patients N=47 nosocomial infections (from 578 dialysis patient admissions) Most common infection site/type: 1) urinary tract; 2) bloodstream; 3) pneumonia Dialysis patients with identified pneumonia pathogen, n=5 too small to consider What about MRSA? No studies of pneumonia in dialysis provide information on S. aureus resistance Dialysis patients higher risk of invasive MRSA infection vs. general population44 o 2005 data – 45.2/1,000 vs. 0.2-0.4/1,000, dialysis vs. general pop., respectively Surveillance data from the Active Bacterial Core (ABC) system (2005 data)44 o Dialysis patients 15.6% of invasive MRSA infections (813/5,287 isolates) MRSA colonization rates in dialysis patients – variable, ranging from 2-22%45-48 The Bottom Line Considering the frequency of pneumonia and its associated mortality in dialysis patients, there is little data regarding epidemiology, risk factors, and pathogens. Bacterial etiology is crudely-defined with no information on MRSA, making it difficult to make any meaningful conclusions that might influence therapy. As HCAP criteria, dialysis seems to be included more by convention than evidence. 14 Home Healthcare Size of cohort Study Home Healthcare Patients 12 Kollef 2005 (HCAP, n=988) 13 Carratalà 2007 (HCAP, n=126) 14 17 Micek 2007 / Shorr 2008 (HCAP, n=431) 15 Venditti 2009 (HCAP, n=90) 16 Shindo 2009 (HCAP, n=141) Not included 18 (14.3%) Not included Not included 3 (2.1%) Key Points Home healthcare includes processes such as the receipt of home intravenous therapy, home wound care, or specialized nursing care (e.g., catheter changes) No epidemiological data specifically on pneumonia risk factors/pathogens/outcomes Evidence-based review – one study of MRSA infections in home nursing care patients Lescure F, Locher G, Eveillard M, et al. Community-acquired infection with healthcare-associated methicillin-resistant Staphylococcus aureus: the role of home nursing care. Infect Control Hosp 20 Epidemiol 2006;27(11):1213-18. Design Single-center prospective case-control study (France), April 2002 – July 2003 Population n=396 cases, n=198; controls, n=198; included patients with positive sample for S. aureus w/in 48h of admission (cases = MRSA infection; controls = MSSA infection) Sites of infection 1) skin/soft tissue (38.5%), 2) respiratory tract (27.3%), 3) urinary tract (17.2%), 4) blood (9.8%), 5) other (7.2%) Results Characteristic Cases (n=175) Controls (n=173) P-value Age, years; mean ± SD 67 ± 18 57 ± 20 <0.001 Prior hospitalization, 3y (%) 85.1 67.6 <0.001 Home nursing care, 3y (%) 65.1 42.2 <0.001 Nursing procedures, 3y (mean ± SD) 192 ± 302 102 ± 2332 0.002 Healthcare worker in family (%) 8.1 7.0 0.70 Transfer from another facility (%) 24.6 11.6 0.002 Antibiotic use, 6 mos. (%) 52.6 42.8 0.07 Positive relationship between home nursing procedures and MRSA infection Independent risk factors for MRSA infection on hospital admission (OR, 95% CI) o Prior hospitalization (3.8, 1.8-7.9) o Home nursing care (3.7, 2.0-6.7) o Home care or hosp. for surgery, past 3y (3.1, 1.2-8.0) o Referral [other hospital, nursing home] (2.3, 1.2-4.3) o Age >65y (1.6, 1.1-2.5) Author’s Recognized risk factors (prior hosp, nursing home) are confirmed for MRSA in this study. Comments Presence and duration of home nursing care are associated with S. aureus resistance; indirect contact with healthcare workers (e.g., a family member) is not. Infection control procedures (e.g., hand washing) should be reinforced among community healthcare workers. The Bottom Line Home healthcare accounts for a small subset of the studied HCAP cohorts, and there is little information on its epidemiology in pneumonia. Limited evidence demonstrates an association between home healthcare and the risk of MRSA infection/carriage, potentially related to the number of procedures by and/or carriage among community healthcare worker.20, 49 15 Immunosuppression Size of cohort Study Kollef 2005 (HCAP, n=988) Carratalà 2007 (HCAP, n=126) Micek 2007 / Shorr 2008 (HCAP, n=431) Venditti 2009 (HCAP, n=90) Shindo 2009 (HCAP, n=141) Immunosuppressed Patients Not included Not included 169 (39.2%) Not included Not included Diverse group of patients in HCAP studies14, 17 includes: Seropositivity for human immunodeficiency virus (HIV) Radiation or chemotherapy for underlying malignancy within 6 months Receipt of either solid organ transplant or bone marrow transplant Daily administration of corticosteroids (≥5mg/day of prednisone or equivalent) Use of other immunosuppressive agent (e.g., cyclosporine) Acquired immune deficiency disorders Seropositivity for HIV Increased incidence of bacterial pneumonia among HIV-positive patients50 o HIV pts vs. non-HIV pts, 5.5 vs. 0.9 episodes per 100 person-years (p<0.001) Similar to non-HIV patients with regards to most common pathogens and treatment o S. pneumoniae and Haemophilus sp. are most common51-58 o Treatment in accordance with 2007 ATS/IDSA CAP guidelines58 In contrast to non-HIV population, increased incidence of pneumonia due to community-acquired P. aeruginosa and S. aureus54, 56, 59-61 o Pseudomonas pneumonia: 2-18% in HIV-infected patients51, 53-56, 59, 60, 62, 63 Often associated with low CD4 count51, 54, 60, 61, 63 o Lack of data on MRSA pneumonia in HIV-infected patients Active Malignancy / Chemotherapy Multiple groups within this population: o Host factors: non-neutropenic vs. neutropenic w/o fever vs. febrile neutropenia o Disease factors: type of malignancy, active/recent chemotherapy Where is the data?25 o No evidence in non-neutropenic cancer patients on the potential effect of chemotherapy, increased healthcare contact, or simply cancer itself on pneumonia epidemiology Reasonable to treat as CAP according to 2007 ATS/IDSA guidelines 1, 64 o Febrile neutropenia – treat according to established National Comprehensive Cancer Network (NCCN) guidelines64 Pseudomonas coverage recommended65, 66 16 The Bottom Line Immunosuppression is not part of the HCAP criteria set forth by the ATS/IDSA in the 2005 HCAP/HAP/VAP guidelines; however, it has been included as HCAP criteria in some studies. Two of the groups, HIV-positive patients and patients with active malignancies, are diverse groups within themselves. Disease-specific characteristics (e.g., CD4 count in HIV, febrile neutropenia in cancer) should be considered before making treatment decisions. REFINING THE HCAP CRITERIA Based on the available evidence, should ________ be part of the HCAP criteria? Previous hospitalization Previous 3 months Previous 6 months Previous 12 months Residence in a nursing home / long-term care facility: Poor functional status Chronic hemodialysis Home healthcare Immunosuppression: HIV seropositivity Active malignancy / chemotherapy *ICU admission *Prior antibiotic therapy (any) Broad-spectrum antibiotic therapy, 3 months Yes No Unclear X X X X X X X X X X X X X X * Not covered explicitly in presentation – extrapolated from data. The BIRP Criteria – Patients at high risk for drug-resistant pneumonia: Broad-spectrum antibiotic therapy, 3 months Intensive care unit (ICU) admission Residence in a nursing home/LTCF and poor functional status Prior hospitalization, 3 months 17 CONCLUSIONS The current evidence in HCAP is limited; however, these data have influenced practice guidelines and have major implications for empiric antibiotic therapy. Current HCAP criteria are broad and may be imprecise in predicting the risk of an infection with a drug-resistant pathogen. Aside from nursing home-acquired pneumonia, evidence is scarce for pneumonia patients with each individual risk factor. Evidence that further defines the relationship between treatment strategies and outcomes is essential to improve the care of HCAP patients. The difficulty of refining the HCAP criteria is in making the criteria simple yet specific enough that a clinician can gather the required information and develop an appropriate treatment plan in a timely manner. 18 ABBREVIATIONS ACCP: American College of Clinical Pharmacy ADL: Activities of daily living APACHE: Acute Physiologic and Chronic Health Evaluation ATS: American Thoracic Society CAP: Community-acquired pneumonia CDC: Centers for Disease Control and Prevention COPD: Chronic obstructive pulmonary disease CURB: Confusion – urea – respiration – blood pressure ECOG: Eastern Cooperative Oncology Group ESBL: Extended-spectrum beta-lactamase ESCP: European Society of Clinical Pharmacy GNR: Gram-negative rod GNB: Gram-negative bacilli HAP: Hospital-acquired pneumonia HD: Hemodialysis HIV: Human Immunodeficiency Virus ICAAC: International Conference on Antimicrobial Agents and Chemotherapy IDSA: Infectious Diseases Society of America LOS: Length of stay MDR: Multi-drug resistant MRSA: Methicillin-resistant Staphylococcus aureus NHAP: Nursing home-acquired pneumonia PD: Peritoneal dialysis PDR: Potentially drug resistant PSI: Pneumonia Severity Index TTCS: Time to clinical stability TTST: Time to switch therapy USRDS: United States Renal Data System WHO: World Health Organization 19 APPENDIX A: RISK FACTORS FOR MRSA COLONIZATION Table 1: Previous Hospitalization as a Risk Factor for MRSA Colonization, by Study Study Warshawsky 2000 (n=331) 68 Hori 2002 (n=342) Hidron 2005 (n=726) Outcome Measure Independent Risk Factors (OR, 95% CI) Colonization (nares, groin); Infection (urinary tract, surgical wound, skin ulcer, lower resp tract) Inpatient or outpatient contact with healthcare facility: Previous month: 90.6% Previous 3 months: 96.7% Previous 6 months: 97.0% Previous 12 months: 98.2% *Note: Logistic regression not performed. Exposure to ciprofloxacin (17.06, 2.91- 99.90) Exposure to ampicillin (4.10, 1.28-13.14) Prior hospitalization, 1 mo. (1.82, 0.62-5.38) [p=0.278] HIV (+) w/o antibiotics in past 3 mos. (13.81, 4.34-43.04) Hospitalization, past year (4.01, 1.97-8.15) Skin or soft-tissue infection at admission (3.40, 1.46-7.90) HIV (-) w/anitibiotic use in past 3 mos. (2.46, 1.20-5.03) Alternative housing (2.03, 0.97-4.27) Recent hospitalization, 3 mos. (5.4, 1.53-19.03) Gastrointestinal diseases (2.74, 1.32-5.70) LTCF admission, past year (6.47, 1.97-21.18) Hospitalization, past year (4.06, 1.13-14.61) Mean age (1.04, 1.00-1.08) Malignancy (6.4, 2.5-16.4) ≥3 antibiotic treatments, 12 mos. (4.0 (1.7-9.9) Recent hospitalization, 12 mos. (2.2, 1.0-4.4) Presence of household members <age 7 (2.24, 1.53-3.29) Antibiotic use, past year (2.05, 1.35-3.11) Hospitalization, past year (1.46, p=0.3609) Colonization; Nasal swabs 69 Colonization; Nasal swab 70 Lu 2005 (n=2,231) 71 Casas 2007 (n=1,127) Brugnaro 2009 (n=551) Wang 2009 (n=3,098) 67 73 Colonization; Nasal swab Colonization; Nasal swab 72 Colonization (long-term care patients); Nasal swab Colonization with MRSA or MSSA; Nasal swab 20 APPENDIX B: MEASURES OF FUNCTIONAL STATUS Table 1: Eastern Cooperative Oncology Group (ECOG) Performance Status74 Grade 0 1 2 3 4 5 ECOG Fully active Able to carry on all pre-disease performance without restriction Restricted in physically strenuous activity Ambulatory and able to carry out work of a light or sedentary nature (light house work, office work) Ambulatory and capable of all self-care Unable to carry out any work activities Up and about more than 50% of waking hours Capable of only limited self-care Confined to bed or chair >50% of waking hours Completely disabled Cannot carry on any self-care Totally confined to bed or chair Dead Table 2: The Barthel Index (BI)75 Activity Feeding Bathing Grooming Dressing Bowels Bladder Toilet Use Transfers (Bed to Chair) Mobility (level surfaces) Stairs Score 0 5 10 0 5 0 5 0 5 10 0 5 10 0 5 10 0 5 10 0 5 10 15 0 5 10 15 0 5 10 Index Description Unable Needs help cutting, spreading butter, etc., or requires modified diet Independent Dependent Independent (or in shower) Needs help with personal care Independent face/hair/teeth/shaving (implements provided) Dependent Needs help but can do about half unaided Independent (including buttons, zips, laces, etc.) Incontinent (or needs to be given enemas) Occasional accident Continent Incontinent, or catheterized and unable to manage alone Occasional accident Continent Dependent Needs some help, but can do something alone Independent (on and off, dressing, wiping) Dependent Major help (one or two people, physical), can sit Minor help (verbal or physical) Independent Immobile or <50 yards Wheelchair independent, including corners, >50 yards Walks with help of one person (verbal or physical) >50 yards Independent (but may use any aid; for example, stick) >50 yards Unable Needs help (verbal, physical, carrying aid) Independent 21 Table 3: Karnofsky Performance Status76, 77 Definition Scale Able to carry on normal activity and to work. No special care is needed. 100 Normal; no complaints; no evidence of disease. 90 Able to carry on normal activity; minor signs or symptoms of disease. Normal activity with effort; some signs or symptoms of disease. 80 Unable to work. Able to live at home, care for most personal needs. A varying amount of assistance is needed. Unable to care for self. Requires equivalent of institutional or hospital care. Disease may be progressing rapidly. 70 Index Description 50 Cares for self. Unable to carry on normal activity or do active work. Requires occasional assistance, but is able to care for most of his needs. Requires considerable assistance and frequent medical care. 40 Disable; requires special care and assistance. 30 10 Severely disabled; hospitalization indicated although death not imminent. Very sick; hospitalization necessary; active supportive treatment necessary. Moribund; fatal processes progressing rapidly. 0 Dead. 60 20 Table 4: Activities of Daily Living (ADL) score (from New York State Dept of Health)28, 78 Area of Activity Eating Toileting Feeding Bathing Mobility Continence Score 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 Index Description Fully independent Partially independent Completely dependent Fully independent Partially independent Completely dependent Fully independent Partially independent Completely dependent Fully independent Partially independent Completely dependent Fully independent Partially independent Completely dependent Fully independent Partially independent Completely dependent ADL Class (Score): ADL I (6-8); ADL II (9-13); ADL III (14-18) 22 REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27-72. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388-416. World Health Organization 2008. The global burden of disease: 2004 update. (Accessed November 12, 2008, at http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/index.html.) Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: final data for 2005. Natl Vital Stat Rep 2008;56:1-120. DeFrances CJ, Lucas CA, Buie VC, Golosinskiy A. 2006 National Hospital Discharge Survey. Natl Health Stat Report 2008:1-20. Mandell LA. Spectrum of microbial etiology of community-acquired pneumonia in hospitalized patients: implications for selection of the population for enrollment in clinical trials. Clin Infect Dis 2008;47 Suppl 3:S189-92. Bratzler DW, Ma A, Nsa W. Initial antibiotic selection and patient outcomes: observations from the National Pneumonia Project. Clin Infect Dis 2008;47 Suppl 3:S193-201. File TM. Community-acquired pneumonia. Lancet 2003;362:1991-2001. Morin CA, Hadler JL. Population-based incidence and characteristics of community-onset Staphylococcus aureus infections with bacteremia in 4 metropolitan Connecticut areas, 1998. J Infect Dis 2001;184:1029-34. Friedman ND, Kaye KS, Stout JE, et al. Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 2002;137:791-7. Tacconelli E, Venkataraman L, De Girolami PC, EM D'Agata. Methicillin-resistant Staphylococcus aureus bacteraemia diagnosed at hospital admission: distinguishing between community-acquired versus healthcare-associated strains. J Antimicrob Chemother 2004;53:474-9. Kollef MH, Shorr A, Tabak YP, et al. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005;128:3854-62. Carratala J, Mykietiuk A, Fernandez-Sabe N, et al. Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med 2007;167:1393-9. Micek ST, Kollef KE, Reichley RM, et al. Health care-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother 2007;51:3568-73. Venditti M, Falcone M, Corrao S, et al. Outcomes of patients hospitalized with community-acquired, health careassociated, and hospital-acquired pneumonia. Ann Intern Med 2009;150:19-26. Shindo Y, Sato S, Maruyama E, et al. Health-care-associated pneumonia among hospitalized patients in a Japanese community hospital. Chest 2009;135:633-40. Shorr AF, Zilberberg MD, Micek ST, Kollef MH. Prediction of infection due to antibiotic-resistant bacteria by select risk factors for health care-associated pneumonia. Arch Intern Med 2008;168:2205-10. Arancibia F, Bauer TT, Ewig S, et al. Community-acquired pneumonia due to gram-negative bacteria and Pseudomonas aeruginosa: incidence, risk, and prognosis. Arch Intern Med 2002;162:1849-58. Garcia-Vidal C, Falguera M, Viasus D, et al. Risk factors and outcome of community-onset Pseudomonas aeruginosa pneumonia. In: Final program for the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (San Franscisco). Washington, DC: American Society of Microbiology, 2009:63. Lescure FX, Locher G, Eveillard M, et al. community-acquired infection with healthcare-associated methicillin-resistant Staphylococcus aureus: the role of home nursing care. Infect Control Hosp Epidemiol 2006;27:1213-8. The Elderly Population. U.S. Census Bureau, Population Division, 2008. (Accessed May 29, 2009, at http://www.census.gov/population/www/pop-profile/elderpop.html.) Mylotte JM. Nursing home-acquired pneumonia: update on treatment options. Drugs Aging 2006;23:377-90. Muder RR. Pneumonia in residents of long-term care facilities: epidemiology, etiology, management, and prevention. Am J Med 1998;105:319-30. Attridge RT, Frei CR. Etiology and outcomes for pneumonia patients admitted from skilled-nursing facilities (SNFs): implications for empiric antibiotic therapy. In: Meeting guide and abstracts of the 2009 ACCP/ESCP International Congress on Clinical Pharmacy (Orlando). Lenexa, Kansas: American College of Clinical Pharmacy, 2009:257-8. Poch DS, Ost DE. What are the important risk factors for healthcare-associated pneumonia? Semin Respir Crit Care Med 2009;30:26-35. Loeb M, Carusone SC, Goeree R, et al. Effect of a clinical pathway to reduce hospitalizations in nursing home residents with pneumonia: a randomized controlled trial. JAMA 2006;295:2503-10. Lim WS, Macfarlane JT. A prospective comparison of nursing home acquired pneumonia with community acquired pneumonia. Eur Respir J 2001;18:362-8. El-Solh AA, Sikka P, Ramadan F, Davies J. Etiology of severe pneumonia in the very elderly. Am J Respir Crit Care Med 2001;163:645-51. El Solh AA, Pietrantoni C, Bhat A, Bhora M, Berbary E. Indicators of potentially drug-resistant bacteria in severe nursing home-acquired pneumonia. Clin Infect Dis 2004;39:474-80. 23 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. Martinez-Moragon E, Garcia-Ferrer L, Serra-Sanchis B, et al. Community-acquired pneumonia among the elderly: differences between patients living at home and in nursing homes. Arch Bronconeumol 2004;40:547-52. Kothe H, Bauer T, Marre R, et al. Outcome of community-acquired pneumonia: influence of age, residence status and antimicrobial treatment. Eur Respir J 2008;32:139-46. Maruyama T, Niederman MS, Kobayashi T, et al. A prospective comparison of nursing home-acquired pneumonia with hospital-acquired pneumonia in non-intubated elderly. Respir Med 2008;102:1287-95. El Solh AA, Akinnusi ME, Alfarah Z, Patel A. Effect of antibiotic guidelines on outcomes of hospitalized patients with nursing home-acquired pneumonia. J Am Geriatr Soc 2009;57:1030-5. Marrie TJ, Wu L. Factors influencing in-hospital mortality in community-acquired pneumonia: a prospective study of patients not initially admitted to the ICU. Chest 2005;127:1260-70. Trick WE, Weinstein RA, DeMarais PL, et al. Colonization of skilled-care facility residents with antimicrobial-resistant pathogens. J Am Geriatr Soc 2001;49:270-6. Wiener J, Quinn JP, Bradford PA, et al. Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. JAMA 1999;281:517-23. El Solh AA, Aquilina AT, Dhillon RS, et al. Impact of invasive strategy on management of antimicrobial treatment failure in institutionalized older people with severe pneumonia. Am J Respir Crit Care Med 2002;166:1038-43. U.S. Renal Data System (USRDS). USRDS 2009 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2009. Sarnak MJ, Jaber BL. Pulmonary infectious mortality among patients with end-stage renal disease. Chest 2001;120:1883-7. Slinin, Foley RN, Collins AJ. Clinical epidemiology of pneumonia in hemodialysis patients: the USRDS waves 1, 3, and 4 study. Kidney Int 2006;70:1135-41. Kaplan V, Clermont G, Griffin MF, et al. Pneumonia: still the old man's friend? Arch Intern Med 2003;163:317-23. Guo, Liu J, Collins AJ, Foley RN. Pneumonia in incident dialysis patients--the United States Renal Data System. Nephrol Dial Transplant 2008;23:680-6. D'Agata EM, Mount DB, Thayer V, Schaffner W. Hospital-acquired infections among chronic hemodialysis patients. Am J Kidney Dis 2000;35:1083-8. Invasive methicillin-resistant Staphylococcus aureus infections among dialysis patients--United States, 2005. MMWR Morb Mortal Wkly Rep 2007;56:197-9. Lu, Tsai JC, Chiu YW, et al. Methicillin-resistant Staphylococcus aureus carriage, infection and transmission in dialysis patients, healthcare workers and their family members. Nephrol Dial Transplant 2008;23:1659-65. Pop-Vicas A, Strom J, Stanley K, D'Agata EM. Multidrug-resistant gram-negative bacteria among patients who require chronic hemodialysis. Clin J Am Soc Nephrol 2008;3:752-8. Hadley AC, Karchmer TB, Russell GB, et al. The prevalence of resistant bacterial colonization in chronic hemodialysis patients. Am J Nephrol 2007;27:352-9. Johnson LB, Jose J, Yousif F, et al. Prevalence of colonization with community-associated methicillin-resistant Staphylococcus aureus among end-stage renal disease patients and healthcare workers. Infect Control Hosp Epidemiol 2009;30:4-8. Troillet N, Carmeli Y, Samore MH, et al. Carriage of methicillin-resistant Staphylococcus aureus at hospital admission. Infect Control Hosp Epidemiol 1998;19:181-5. Hirschtick RE, Glassroth J, Jordan MC, et al. Bacterial pneumonia in persons infected with the human immunodeficiency virus. N Engl J Med 1995;333:845-51. Curran A, Falco V, Crespo M, et al. Bacterial pneumonia in HIV-infected patients: use of the pneumonia severity index and impact of current management on incidence, aetiology and outcome. HIV Med 2008;9:609-15. Attridge RT, Frei CR. Comparison of pneumonia etiology among HIV and non-HIV patients admitted to United States Hospitals. In: Final program for the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (San Franscisco). Washington, DC: American Society of Microbiology, 2009:103. Rimland D, Navin TR, Lennox JL, et al. Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection. AIDS 2002;16:85-95. Park DR, Sherbin VL, Goodman MS, et al. The etiology of community-acquired pneumonia at an urban public hospital: influence of human immunodeficiency virus infection and initial severity of illness. J Infect Dis 2001;184:268-77. Falco V, Fernandez de Sevilla T, Alegre J, et al. Bacterial pneumonia in HIV-infected patients: a prospective study of 68 episodes. Eur Respir J 1994;7:235-9. Baril L, Astagneau P, Nguyen J, et al. Pyogenic bacterial pneumonia in human immunodeficiency virus-infected inpatients: a clinical, radiological, microbiological, and epidemiological study. Clin Infect Dis 1998;26:964-71. Polsky B, Gold JW, Whimbey E, et al. Bacterial pneumonia in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1986;104:38-41. Kaplan JE, Benson C, Holmes KH, et al. Guidelines for prevention and treatment of opportunistic infections in HIVinfected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009;58:1-207. 24 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. Cordero E, Pachon J, Rivero A, et al. Community-acquired bacterial pneumonia in human immunodeficiency virusinfected patients: validation of severity criteria. Am J Respir Crit Care Med 2000;162:2063-8. Afessa B, Green B. Bacterial pneumonia in hospitalized patients with HIV infection: the pulmonary complications, ICU support, and prognostic factors of hospitalized patients with HIV (PIP) study. Chest 2000;117:1017-22. Schuster MG, Norris AH. Community-acquired Pseudomonas aeruginosa pneumonia in patients with HIV infection. AIDS 1994;8:1437-41. Burack JH, Hahn JA, Saint-Maurice D, Jacobson MA. Microbiology of community-acquired bacterial pneumonia in persons with and at risk for human immunodeficiency virus type 1 infection: implications for rational empiric antibiotic therapy. Arch Intern Med 1994;154:2589-96. Miller RF, Foley NM, Kessel D, Jeffrey AA. Community acquired lobar pneumonia in patients with HIV infection and AIDS. Thorax 1994;49:367-8. Segal BH, Freifeld AG, Baden LR, et al. Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw 2008;6:122-74. Sickles EA, Young VM, Greene WH, Wiernik PH. Pneumonia in acute leukemia. Ann Intern Med 1973;79:528-34. Carratala J, Roson B, Fernandez-Sevilla A, et al. Bacteremic pneumonia in neutropenic patients with cancer: causes, empirical antibiotic therapy, and outcome. Arch Intern Med 1998;158:868-72. Warshawsky B, Hussain Z, Gregson DB, et al. Hospital- and community-based surveillance of methicillin-resistant Staphylococcus aureus: previous hospitalization is the major risk factor. Infect Control Hosp Epidemiol 2000;21:724-7. Hori S, Sunley R, Tami A, Grundmann H. The Nottingham Staphylococcus aureus population study: prevalence of MRSA among the elderly in a university hospital. J Hosp Infect 2002;50:25-9. Hidron AI, Kourbatova EV, Halvosa JS, et al. Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: emergence of community-associated MRSA nasal carriage. Clin Infect Dis 2005;41:159-66. Lu PL, Chin LC, Peng CF, et al. Risk factors and molecular analysis of community methicillin-resistant Staphylococcus aureus carriage. J Clin Microbiol 2005;43:132-9. Casas I, Sopena N, Esteve M, et al. Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus carriage at hospital admission. Infect Control Hosp Epidemiol 2007;28:1314-7. Brugnaro P, Fedeli U, Pellizzer G, et al. Clustering and risk factors of methicillin-resistant Staphylococcus aureus carriage in two Italian long-term care facilities. Infection 2009;37:216-21. Wang JT, Liao CH, Fang CT, et al. Prevalence of and risk factors for colonization by methicillin-resistant Staphylococcus aureus among adults in community settings in Taiwan. J Clin Microbiol 2009;47:2957-63. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-55. Mahoney FI, Barthel D. Functional evaluation: the Barthel Index. Md State Med J 1965;14:56-61. Karnofsky DA, Abelman WH, Craner LF. The use of nitrogen mustards in palliative treatment of carcinoma. Cancer 1948;1:634-56. Verger E, Salamero M, Conill C. Can Karnofsky performance status be transformed to the Eastern Cooperative Oncology Group scoring scale and vice versa? Eur J Cancer 1992;28A:1328-30. New York State Department of Health. Hospital and Community Patient Review Instrument. Albany, NY: Department of Health;1989. DOH-694. 25
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