Burden of MRSA Colonization in Elderly Residents of Nursing Homes: A Systematic Review and Meta Analysis Monika Pogorzelska-Maziarz, MPH, PhD Thomas Jefferson University, Jefferson School of Nursing Philadelphia, PA
Long-term care facilities Institution that provide health care to people who are unable to manage independently in the community nursing homes rehabilitation facilities extended care facilities behaviour health, psychiatric, physical and mental challenges ~16,000 NH in the U.S. serving 1.6 million residents.
Consequences of HAI in LTCFs Between 1.6 and 3.8 million infections occur each year in LTCFs with nearly 388,000 deaths attributed to these infections Infections are the reason for 27 to 63 percent of all resident transfers to hospitals Cost is estimated to be between $673 million to $2 billion annually
The Alphabet Soup of Multidrug Resistant Organisms (MDROs) Methicillin-Resistant Staphylococcus aureus (MRSA ) Vancomycin-Resistant Enterococci (VRE) Multidrug Resistant Gram-Negative Rods (MDR- GNR) such as E. Coli, Klebsiella pneumoniae, Acinetobacter baumannii Clostridium difficile Just being a resident of a LTCF puts someone at high risk for being colonized or infected with a MDRO
Infection Control in NH Limited resources, overcrowding and vulnerable resident population Residents are not patients Focus of NH is comfort and dignity Shared spaces and group activities Frequent transfers back and forth between NHs and hospitals
Rationale for review Prevention of Nosocomial Infections and Cost Effectiveness in Nursing Home (PNICE-NH) Grant Limited data on overall estimates of MDRO infections in nursing homes 7
Research Objective To estimate the prevalence and/or incidence of colonization with MDRO in nursing homes Paucity of data on the overall burden of colonization in this setting 8
Methods o To establish clarity and standardized reporting of findings, the PRISMA checklist was used o PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement Developed by international group of experts 27-item checklist ensures standard method for transparent and complete reporting Increasingly being endorsed by and adhered to for journal submissions 9
Inclusion criteria Peer-reviewed and published in English from 2000 through August 2012 Reported original research in which investigators provide incidence or prevalence of MDRO colonization in nursing homes Specifically focused on elderly patients Exclusion criteria Outbreaks Long-term acute care hospitals and extended or LTC units within hospitals Nursing homes that are part of a hospital system Studies that identified colonization/infection through clinical cultures Studies primarily focusing on the molecular epidemiology or antibiotic susceptibility of organisms with no estimates of overall burden of infections 10
Selection and abstraction process Search conducted in Medline by primary reviewer Clostridium difficile /exp OR Vancomycin Resistance /exp OR Methicillin Resistant Staphylococcus aureus /exp OR Drug Resistance, Microbial /exp AND Nursing Homes /exp OR Long-Term Care /exp OR Skilled Nursing Facilities /exp Retrieved titles and abstract screened for potentially relevant studies that met the inclusion criteria Abstracts and full text of these potentially relevant studies reviewed by two secondary reviewers to confirm eligibility Reference lists of retrieved articles and relevant review articles assessed for additional studies 11
Data Extraction Descriptive Study Design Screening Methods Results Author Type of study Diagnostic Method Participation Rate Date of Publication Country Sample Size Multisite Description of NH(s) Eligibility Study period Sampling method Definitions Specified (if any) Specimen Sites Additional Info on Specimen collection Prevalence/ Incidence Risk Factors Presented Antibiotic Susceptability Data Quality Score 12
Quality appraisal Checklist adapted from a systematic review conducted by Dulon and colleagues 1. Outcome definition: Was a valid definition given of the outcome for the outcome for prevalence, colonization and infection? 2. Time unit: Was the endpoint calculated for a standardized time unit (daily, monthly, yearly)? 3. Target population: Was the target population specified by inclusion or eligibility criteria? 4. Participants: Was the number of included cases reported, e.g. by describing the numbers and reasons for non-participation? 5. Observer bias: Were sources of potential imprecision reported and/or have consequences been discussed? 6. Screening procedure: Were measures described that has been undertaken for standardization of screening measurements? Dulon, M., et al., MRSA prevalence in European healthcare settings: a review. BMC Infect Dis, 2011. 11: p. 138. 13
Methods: Meta Analysis Used a random effects meta analysis model to estimate a pooled prevalence of colonization across studies Assessed heterogeneity using Cochran Q and I² statistics Conducted sensitivity analyses to examine effect of potential sources of heterogeneity across studies according to study characteristics Data analysis conducted using Comprehensive Meta- Analysis (CMA) statistical software (Biostat, Inc).
Identification 317 records identified through MEDLINE database search Flow diagram Screening Eligibility 297 records screened after duplicates removed 131 full text articles assessed for eligibility 15 full text articles assessed per hand searching reference lists Inclusion 41 studies selected for inclusion in systematic review 90 full-text articles removed 29 studies included in meta analysis 15
Characteristics of 41 Included Studies Geography 8 U.S. 24 Europe (5 Germany, 4 UK, 4 Ireland, 3 Belgium, 2 Italy, 1 each in Finland, France, Slovenia, Spain, Sweden, The Netherlands) 3 Australia & New Zealand 6 Asia Setting & Sample size: 9 single site (42 270 participants) 32 multi site (79 3236 participants, 2-69 facilities) 16
Individual components of quality scores of included studies Yes No? Screening Procedure 11 28 2 Bias 23 18 Participants 26 8 7 Target Population 35 1 5 Time Unit 34 7 Outcome definition 39 2
Focus of studies Organism under study Number of studies MRSA 29 (25) MDR GNBs 10 (5) VRE 7 (2) C. difficile 4 (3) H. influenzae 1 Multiple organisms 5 Numbers in parentheses present number of studies focusing exclusively on that given organism 18
Characteristics of MRSA studies (n = 29) 26 (90%) of studies used a cross-sectional design 3 were series cross-sectional Sampling 4 random sample 1 convenience sample 1 with no information 1 combination 22 all eligible/consenting residents Specimen Sites 12 (41%) collected nasal cultures only 17 (59%) collected cultures from multiple sites 19
MRSA studies in the US (n = 5) Author Multisite Participation Rate Prevalence Mody, 2007 Yes (14 NH) Pop-Vicas, 2008 Reynolds, 2008 O Fallon, 2009 80% 55% (55/100) in device group 29% (29/100) in control group No 53% 28% (24/84) Yes (10 NH) Fisch, 2012 Yes (15 SNFs) Not provided 31%, range 7-52% No 95% 11% (18/161) 37% 63% (52/82) Prevalence of MRSA colonization ranged from 11-63% 20
MRSA studies in Europe (n = 20) 20 cross-sectional, 1 RCT Country # of studies Prevalence Belgium 3 5%, 20%, 26% Finland 1 1% Germany 4 0%, 1%, 8%, 8% Ireland 2 9%, 23% Italy 2 8%, 19% Slovenia 1 9% Spain 1 34% Sweden 1 0% The Netherlands 1 0.4% UK 4 8%, 17%, 20%, 22%, 21
Estimated pooled prevalence of MRSA Statistics for each study Study name Subgroup within study Event rate Lower limit Upper limit p-value Event rate and 95% CI Ho et al., 2007 Asia 0.028 0.020 0.041 0.000 Karabay, 2006 Asia 0.051 0.019 0.127 0.000 Mendelson, 2003 Asia 0.063 0.039 0.099 0.000 Schwaber, 2011 Asia 0.141 0.099 0.198 0.000 Pooled Result (Asia) 0.061 0.026 0.136 0.000 Baldwin, 2009 Europe 0.240 0.216 0.266 0.000 Baldwin, 2010 Europe 0.170 0.146 0.198 0.000 Barr, 2007 Europe 0.220 0.191 0.251 0.000 Burgnaro, 2009 Europe 0.078 0.058 0.104 0.000 Cretnik, 2005 Europe 0.110 0.060 0.192 0.000 Daeschlein, 2006 Europe 0.001 0.000 0.016 0.000 Denis, 2009 Europe 0.199 0.185 0.214 0.000 Greenland, 2011 Europe 0.000 0.000 0.006 0.000 Hoefnagels-Schermans, 2002 Europe 0.009 0.042 0.058 0.000 Kerttula, 2007 Europe 0.049 0.002 0.037 0.000 Lasseter, 2010 Europe 0.079 0.062 0.100 0.000 Manzur, 2008 Europe 0.168 0.149 0.188 0.000 Monaco, 2009 Europe 0.193 0.124 0.289 0.000 Olofsson, 2012 Europe 0.002 0.000 0.038 0.000 O Sullivan 2000 Europe 0.206 0.175 0.241 0.000 Pfingsten-Wurzburg, 2011 Europe 0.076 0.065 0.089 0.000 Raab, 2006 Europe 0.076 0.046 0.122 0.000 Smith, 2008 Europe 0.198 0.184 0.212 0.000 Suetens, 2007 Europe 0.047 0.040 0.055 0.000 Von Baum, 2002 Europe 0.011 0.008 0.015 0.000 Pooled Result (Europe) 0.086 0.062 0.118 0.000 Fisch, 2012 US 0.634 0.525 0.731 0.016 Mody, 2007 US 0.420 0.354 0.490 0.024 O Fallon, 2009 US 0.112 0.072 0.170 0.000 Pop-Vicas, 2008 US 0.286 0.199 0.391 0.000 Reynolds, 2009 US 0.310 0.282 0.339 0.000 Pooled Result (US) 0.331 0.216 0.472 0.019 Pooled Result (All studies) 0.119 0.092 0.152 0.000 Prevalence (rectangles), 95% CI (lines), pooled prevalence (diamonds) I² = 98.2, P-value 0.001
Sensitivity Analysis of MRSA Prevalence Variable Study Quality High Poor Specimen Sites Nares only Multiple sites Subject Participation Rates (%) 0-50 51-75 76-100 Rate missing Number of studies 1 3 3 1 1 -- 2 1 Asia Europe United States Prevalence 95% CI Number of Prevalence 95% CI Number Prevalence (%) studies (%) of studies (%) 5.1 6.4 8.3 2.8* 2.8 9.4 6.3* 1.9-12.7 2.3-16.4 4.2-15.8 2.0-4.1 2.0-4.1 3.4-23.5 3.9-9.9 10 10 7 13 2 4 7 7 10.1 8.0 10.5 8.0 0.7 16.5 6.2 9.9 6.9-14.5 4.5-13.9 6.5-16.5 5.1-12.4 0.0-57.3 9.7-26.5 2.6-13.8 6.1-15.5 3 2 1 4 1 1 2 1 30.8 35.9 31.0 33.6 63.4 28.6 23.4 31.0* 95% CI 9.1-66.5 26.0-47.2 28.2-33.9 16.2-56.8 52.5-73.1 19.9-39.1 5.2-62.9 28.2-33.9 *MRSA prevalence significantly varies within geographic region (p<0.05) by variable
Conclusions The burden of MRSA in NH is substantial Prevalence of colonization varied greatly Differences in prevalence across geographic regions Methodological differences between studies Standardization of surveillance methods and outcomes is needed to allow for comparisons between different studies
Limitations Potential for publication bias Only included studies published in English in peerreviewed literature Search of only one database using keywords Excluded studies based on clinical isolates
Acknowledgements Supported by the National Institute of Nursing Research (R01 NR013687) Columbia University team (Dr. Elaine Larson, Kimberly Alvarez, Dr. Arlene Smaldone)