Taliser R. Avery

Targeted versus Universal Decolonization to Prevent ICU Infection

BACKGROUND Both targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care-associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS We conducted a pragmatic, cluster-randomized trial. Hospitals were randomly assigned to one of three strategies, with all adult ICUs in a given hospital assigned to the same strategy. Group 1 implemented MRSA screening and isolation; group 2, targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and group 3, universal decolonization (i.e., no screening, and decolonization of all patients). Proportional-hazards models were used to assess differences in infection reductions across the study groups, with clustering according to hospital. RESULTS A total of 43 hospitals (including 74 ICUs and 74,256 patients during the intervention period) underwent randomization. In the intervention period versus the baseline period, modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation (crude rate, 3.2 vs. 3.4 isolates per 1000 days), 0.75 for targeted decolonization (3.2 vs. 4.3 isolates per 1000 days), and 0.63 for universal decolonization (2.1 vs. 3.4 isolates per 1000 days) (P=0.01 for test of all groups being equal). In the intervention versus baseline periods, hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 (crude rate, 4.1 vs. 4.2 infections per 1000 days), 0.78 (3.7 vs. 4.8 infections per 1000 days), and 0.56 (3.6 vs. 6.1 infections per 1000 days), respectively (P<0.001 for test of all groups being equal). Universal decolonization resulted in a significantly greater reduction in the rate of all bloodstream infections than either targeted decolonization or screening and isolation. One bloodstream infection was prevented per 54 patients who underwent decolonization. The reductions in rates of MRSA bloodstream infection were similar to those of all bloodstream infections, but the difference was not significant. Adverse events, which occurred in 7 patients, were mild and related to chlorhexidine. CONCLUSIONS In routine ICU practice, universal decolonization was more effective than targeted decolonization or screening and isolation in reducing rates of MRSA clinical isolates and bloodstream infection from any pathogen. (Funded by the Agency for Healthcare Research and the Centers for Disease Control and Prevention; REDUCE MRSA ClinicalTrials.gov number, NCT00980980).

Social Network Analysis of Patient Sharing Among Hospitals in Orange County, California

OBJECTIVES We applied social network analyses to determine how hospitals within Orange County, California, are interconnected by patient sharing, a system which may have numerous public health implications. METHODS Our analyses considered 2 general patient-sharing networks: uninterrupted patient sharing (UPS; i.e., direct interhospital transfers) and total patient sharing (TPS; i.e., all interhospital patient sharing, including patients with intervening nonhospital stays). We considered these networks at 3 thresholds of patient sharing: at least 1, at least 10, and at least 100 patients shared. RESULTS Geographically proximate hospitals were somewhat more likely to share patients, but many hospitals shared patients with distant hospitals. Number of patient admissions and percentage of cancer patients were associated with greater connectivity across the system. The TPS network revealed numerous connections not seen in the UPS network, meaning that direct transfers only accounted for a fraction of total patient sharing. CONCLUSIONS Our analysis demonstrated that Orange Countys 32 hospitals were highly and heterogeneously interconnected by patient sharing. Different hospital populations had different levels of influence over the patient-sharing network.

The Importance of Nursing Homes in the Spread of Methicillin-Resistant Staphylococcus aureus (MRSA) Among Hospitals

Background:Hospital infection control strategies and programs may not consider control of methicillin-resistant Staphylococcus aureus (MRSA) in nursing homes in a county. Methods:Using our Regional Healthcare Ecosystem Analyst, we augmented our existing agent-based model of all hospitals in Orange County (OC), California, by adding all nursing homes and then simulated MRSA outbreaks in various health care facilities. Results:The addition of nursing homes substantially changed MRSA transmission dynamics throughout the county. The presence of nursing homes substantially potentiated the effects of hospital outbreaks on other hospitals, leading to an average 46.2% (range, 3.3%–156.1%) relative increase above and beyond the impact when only hospitals are included for an outbreak in OC’s largest hospital. An outbreak in the largest hospital affected all other hospitals (average 2.1% relative prevalence increase) and the majority (∼90%) of nursing homes (average 3.2% relative increase) after 6 months. An outbreak in the largest nursing home had effects on multiple OC hospitals, increasing MRSA prevalence in directly connected hospitals by an average 0.3% and in hospitals not directly connected through patient transfers by an average 0.1% after 6 months. A nursing home outbreak also had some effect on MRSA prevalence in other nursing homes. Conclusions:Nursing homes, even those not connected by direct patient transfers, may be a vital component of a hospital’s infection control strategy. To achieve effective control, a hospital may want to better understand how regional nursing homes and hospitals are connected through both direct and indirect (with intervening stays at home) patient sharing.

Modeling the Spread of Methicillin-Resistant Staphylococcus aureus (MRSA) Outbreaks throughout the Hospitals in Orange County, California

BACKGROUND Since hospitals in a region often share patients, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in one hospital could affect other hospitals. METHODS Using extensive data collected from Orange County (OC), California, we developed a detailed agent-based model to represent patient movement among all OC hospitals. Experiments simulated MRSA outbreaks in various wards, institutions, and regions. Sensitivity analysis varied lengths of stay, intraward transmission coefficients (β), MRSA loss rate, probability of patient transfer or readmission, and time to readmission. RESULTS Each simulated outbreak eventually affected all of the hospitals in the network, with effects depending on the outbreak size and location. Increasing MRSA prevalence at a single hospital (from 5% to 15%) resulted in a 2.9% average increase in relative prevalence at all other hospitals (ranging from no effect to 46.4%). Single-hospital intensive care unit outbreaks (modeled increase from 5% to 15%) caused a 1.4% average relative increase in all other OC hospitals (ranging from no effect to 12.7%). CONCLUSION MRSA outbreaks may rarely be confined to a single hospital but instead may affect all of the hospitals in a region. This suggests that prevention and control strategies and policies should account for the interconnectedness of health care facilities.

The Potential Regional Impact of Contact Precaution Use in Nursing Homes to Control Methicillin-Resistant Staphylococcus aureus

OBJECTIVE Implementation of contact precautions in nursing homes to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission could cost time and effort and may have wide-ranging effects throughout multiple health facilities. Computational modeling could forecast the potential effects and guide policy making. DESIGN Our multihospital computational agent-based model, Regional Healthcare Ecosystem Analyst (RHEA). SETTING All hospitals and nursing homes in Orange County, California. METHODS Our simulation model compared the following 3 contact precaution strategies: (1) no contact precautions applied to any nursing home residents, (2) contact precautions applied to those with clinically apparent MRSA infections, and (3) contact precautions applied to all known MRSA carriers as determined by MRSA screening performed by hospitals. RESULTS Our model demonstrated that contact precautions for patients with clinically apparent MRSA infections in nursing homes resulted in a median 0.4% (range, 0%-1.6%) relative decrease in MRSA prevalence in nursing homes (with 50% adherence) but had no effect on hospital MRSA prevalence, even 5 years after initiation. Implementation of contact precautions (with 50% adherence) in nursing homes for all known MRSA carriers was associated with a median 14.2% (range, 2.1%-21.8%) relative decrease in MRSA prevalence in nursing homes and a 2.3% decrease (range, 0%-7.1%) in hospitals 1 year after implementation. Benefits accrued over time and increased with increasing compliance. CONCLUSIONS Our modeling study demonstrated the substantial benefits of extending contact precautions in nursing homes from just those residents with clinically apparent infection to all MRSA carriers, which suggests the benefits of hospitals and nursing homes sharing and coordinating information on MRSA surveillance and carriage status.

Cost Savings of Universal Decolonization to Prevent Intensive Care Unit Infection: Implications of the REDUCE MRSA Trial

OBJECTIVE To estimate and compare the impact on healthcare costs of 3 alternative strategies for reducing bloodstream infections in the intensive care unit (ICU): methicillin-resistant Staphylococcus aureus (MRSA) nares screening and isolation, targeted decolonization (ie, screening, isolation, and decolonization of MRSA carriers or infections), and universal decolonization (ie, no screening and decolonization of all ICU patients). DESIGN Cost analysis using decision modeling. METHODS We developed a decision-analysis model to estimate the health care costs of targeted decolonization and universal decolonization strategies compared with a strategy of MRSA nares screening and isolation. Effectiveness estimates were derived from a recent randomized trial of the 3 strategies, and cost estimates were derived from the literature. RESULTS In the base case, universal decolonization was the dominant strategy and was estimated to have both lower intervention costs and lower total ICU costs than either screening and isolation or targeted decolonization. Compared with screening and isolation, universal decolonization was estimated to save

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial

171,000 and prevent 9 additional bloodstream infections for every 1,000 ICU admissions. The dominance of universal decolonization persisted under a wide range of cost and effectiveness assumptions. CONCLUSIONS A strategy of universal decolonization for patients admitted to the ICU would both reduce bloodstream infections and likely reduce healthcare costs compared with strategies of MRSA nares screening and isolation or screening and isolation coupled with targeted decolonization.

Long-Term Care Facilities: Important Participants of the Acute Care Facility Social Network?

ABSTRACT Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB. At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution.

Patient sharing and population genetic structure of methicillin-resistant Staphylococcus aureus

Background Acute care facilities are connected via patient sharing, forming a network. However, patient sharing extends beyond this immediate network to include sharing with long-term care facilities. The extent of long-term care facility patient sharing on the acute care facility network is unknown. The objective of this study was to characterize and determine the extent and pattern of patient transfers to, from, and between long-term care facilities on the network of acute care facilities in a large metropolitan county. Methods/Principal Findings We applied social network constructs principles, measures, and frameworks to all 2007 annual adult and pediatric patient transfers among the healthcare facilities in Orange County, California, using data from surveys and several datasets. We evaluated general network and centrality measures as well as individual ego measures and further constructed sociograms. Our results show that over the course of a year, 66 of 72 long-term care facilities directly sent and 67 directly received patients from other long-term care facilities. Long-term care facilities added 1,524 ties between the acute care facilities when ties represented at least one patient transfer. Geodesic distance did not closely correlate with the geographic distance among facilities. Conclusions/Significance This study demonstrates the extent to which long-term care facilities are connected to the acute care facility patient sharing network. Many long-term care facilities were connected by patient transfers and further added many connections to the acute care facility network. This suggests that policy-makers and health officials should account for patient sharing with and among long-term care facilities as well as those among acute care facilities when evaluating policies and interventions.

Drug safety data mining with a tree‐based scan statistic

Rates of hospital-acquired infections, specifically methicillin-resistant Staphylococcus aureus (MRSA), are increasingly being used as indicators for quality of hospital hygiene. There has been much effort on understanding the transmission process at the hospital level; however, interhospital population-based transmission remains poorly defined. We evaluated whether the proportion of shared patients between hospitals was correlated with genetic similarity of MRSA strains from those hospitals. Using data collected from 30 of 32 hospitals in Orange County, California, multivariate linear regression showed that for each twofold increase in the proportion of patients shared between 2 hospitals, there was a 7.7% reduction in genetic heterogeneity between the hospitals’ MRSA populations (permutation P value = 0.0356). Pairs of hospitals that both served adults had more similar MRSA populations than pairs including a pediatric hospital. These findings suggest that concerted efforts among hospitals that share large numbers of patients may be synergistic to prevent MRSA transmission.