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1.  Staphylococcal Enterotoxin P Predicts Bacteremia in Hospitalized Patients Colonized With Methicillin-Resistant Staphylococcus aureus 
The Journal of Infectious Diseases  2013;209(4):571-577.
Background. Methicillin-resistant Staphylococcus aureus (MRSA) colonization predicts later infection, with both host and pathogen determinants of invasive disease.
Methods. This nested case-control study evaluates predictors of MRSA bacteremia in an 8–intensive care unit (ICU) prospective adult cohort from 1 September 2003 through 30 April 2005 with active MRSA surveillance and collection of ICU, post-ICU, and readmission MRSA isolates. We selected MRSA carriers who did (cases) and those who did not (controls) develop MRSA bacteremia. Generating assembled genome sequences, we evaluated 30 MRSA genes potentially associated with virulence and invasion. Using multivariable Cox proportional hazards regression, we assessed the association of these genes with MRSA bacteremia, controlling for host risk factors.
Results. We collected 1578 MRSA isolates from 520 patients. We analyzed host and pathogen factors for 33 cases and 121 controls. Predictors of MRSA bacteremia included a diagnosis of cancer, presence of a central venous catheter, hyperglycemia (glucose level, >200 mg/dL), and infection with a MRSA strain carrying the gene for staphylococcal enterotoxin P (sep). Receipt of an anti-MRSA medication had a significant protective effect.
Conclusions. In an analysis controlling for host factors, colonization with MRSA carrying sep increased the risk of MRSA bacteremia. Identification of risk-adjusted genetic determinants of virulence may help to improve prediction of invasive disease and suggest new targets for therapeutic intervention.
doi:10.1093/infdis/jit501
PMCID: PMC3903375  PMID: 24041793
Bacteremia; methicillin-resistant Staphylococcus aureus; epidemiology; hospital infections; microbial genetics
2.  Rapid detection of single bacteria in unprocessed blood using Integrated Comprehensive Droplet Digital Detection 
Nature Communications  2014;5:5427.
Blood stream infection or sepsis is a major health problem worldwide, with extremely high mortality, which is partly due to the inability to rapidly detect and identify bacteria in the early stages of infection. Here we present a new technology termed ‘Integrated Comprehensive Droplet Digital Detection’ (IC 3D) that can selectively detect bacteria directly from milliliters of diluted blood at single-cell sensitivity in a one-step, culture- and amplification-free process within 1.5–4 h. The IC 3D integrates real-time, DNAzyme-based sensors, droplet microencapsulation and a high-throughput 3D particle counter system. Using Escherichia coli as a target, we demonstrate that the IC 3D can provide absolute quantification of both stock and clinical isolates of E. coli in spiked blood within a broad range of extremely low concentration from 1 to 10,000 bacteria per ml with exceptional robustness and limit of detection in the single digit regime.
Early detection of blood stream infections is essential for providing effective treatments. Here the authors present a system integrating DNAzyme sensors, droplet microfluidics and a high-throughput 3D particle counter that can detect specific, single bacterial cells in blood within a few hours.
doi:10.1038/ncomms6427
PMCID: PMC4243214  PMID: 25391809
3.  Targeting TRPV3 for the Development of Novel Analgesics 
The open pain journal  2013;6(Spec Iss 1):119-126.
Decades of characterization of the transient receptor potential vanilloid subtype 1 (TRPV1) has led to the realization of its central role in thermosensation and pain perception. A large number of pharmaceutical companies have had interest in developing TPRV1 antagonists for the treatment of pain. The subsequent discovery of multiple other members of this TRPV family has not gone unnoticed. TRPV3 exhibits approximately 40% homology to TRPV1, and has common as well as distinct features from TRPV1 in channel physiology, expression and function. Here we review the current understanding of TRPV3 channel biology, activation, sensitization and the consequences of TRPV3 manipulation for thermosensation and nociception, as well as additional considerations regarding the expression of TRPV3 in the skin. We weigh in on the available evidence in the context of potential development of TRPV3 modulating agents as analgesics.
PMCID: PMC4182939  PMID: 25285178
4.  A Systematic Literature Review and Meta-analysis of Factors Associated with MRSA Colonization at Time of Hospital or ICU Admission 
Objective
Screening for methicillin-resistant Staphylococcus aureus (MRSA) in high-risk patients is a legislative mandate in nine U.S. states and has been adopted by many hospitals. Definitions of “high-risk” differ among hospitals and state laws. A systematic evaluation of factors associated with colonization is lacking. We performed a systematic review of the literature to assess factors associated with MRSA colonization at hospital admission.
Design
We searched MEDLINE from 1966–2012 for articles comparing MRSA colonized and non-colonized patients on hospital or ICU admission. Data were extracted using a standardized instrument. Meta-analyses were performed to identify factors associated with MRSA colonization.
Results
We reviewed 4,381 abstracts; twenty-nine manuscripts met inclusion criteria (n=76,913 patients). MRSA colonization at hospital admission was associated with recent prior hospitalization (OR=2.4 95%-CI=1.3–4.7;p<0.01), nursing home exposure (OR=3.8 95%-CI=2.3–6.3;p<0.01) and history of exposure to healthcare-associated pathogens (MRSA carriage OR=8.0 95%-CI =4.2–15.1, C. difficile infection OR=3.4 95%-CI=2.2–5.3, vancomycin-resistant Enterococci carriage OR=3.1 95%-CI=2.5–4.0;p<0.01 for all). Select comorbidities were associated with MRSA colonization (congestive heart failure, diabetes, pulmonary disease, immunosuppression and renal failure; p<0.01 for all), while others were not (HIV, cirrhosis, and malignancy). ICU admission was not associated with an increased risk of MRSA colonization (OR=1.1 95%-CI =0.6–1.8;p=0.87).
Conclusions
MRSA colonization on hospital admission was associated with healthcare contact, previous healthcare-associated pathogens, and select comorbid conditions. ICU admission was not associated with MRSA colonization although this is commonly used in state mandates for MRSA screening. Infection prevention programs utilizing targeted MRSA screening may consider our results to define patients likely to have MRSA colonization.
doi:10.1086/673157
PMCID: PMC3883507  PMID: 24018925
5.  Planned Analyses of the REDUCE MRSA Trial 
doi:10.1128/AAC.02792-13
PMCID: PMC4023732  PMID: 24643843
6.  Are nursing homes less likely to admit methicillin-resistant Staphylococcus aureus carriers? 
We surveyed administrators at 13 nursing homes in Orange County, CA, on their likelihood to admit methicillin-resistant Staphylococcus aureus (MRSA) carriers and assessed applicant characteristics associated with rejection. In multivariate models, denial of admission was associated with MRSA carriage (odds ratio, 2.7; P = .02) and receiving lower ratings for overall suitability for admission (odds ratio, 5.9; P < .001). Larger studies are needed to determine whether decolonization may remove barriers to accessing postdischarge care for MRSA carriers.
doi:10.1016/j.ajic.2013.07.015
PMCID: PMC4151248  PMID: 24388471
MRSA; Postdischarge care; Long-term care; Hospital discharge
7.  Predicting High Prevalence of Community Methicillin-Resistant Staphylococcus aureus Strains in Nursing Homes 
We assessed characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among residents of 22 nursing homes. Of MRSA-positive swabs, 25% (208/824) were positive for CA-MRSA. Median facility CA-MRSA percentage was 22% (range, 0%–44%). In multivariate models, carriage was associated with age less than 65 years (odds ratio, 1.2; P < .001) and Hispanic ethnicity (odds ratio, 1.2; P = .006). Interventions are needed to target CA-MRSA.
doi:10.1086/669519
PMCID: PMC4151251  PMID: 23388372
8.  Predictors of Hospitals with Endemic Community-Associated Methicillin-Resistant Staphylococcus aureus 
OBJECTIVE
We sought to identify hospital characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among inpatients.
DESIGN
Prospective cohort study.
SETTING
Orange County, California.
PARTICIPANTS
Thirty hospitals in a single county.
METHODS
We collected clinical MRSA isolates from inpatients in 30 of 31 hospitals in Orange County, California, from October 2008 through April 2010. We characterized isolates by spa typing to identify CA-MRSA strains. Using California’s mandatory hospitalization data set, we identified hospital-level predictors of CA-MRSA isolation.
RESULTS
CA-MRSA strains represented 1,033 (46%) of 2,246 of MRSA isolates. By hospital, the median percentage of CA-MRSA isolates was 46% (range, 14%–81%). In multivariate models, CA-MRSA isolation was associated with smaller hospitals (odds ratio [OR], 0.97, or 3% decreased odds of CA-MRSA isolation per 1,000 annual admissions; P < .001), hospitals with more Medicaid-insured patients (OR, 1.2; P = .002), and hospitals with more patients with low comorbidity scores (OR, 1.3; P < .001). Results were similar when restricted to isolates from patients with hospital-onset infection.
CONCLUSIONS
Among 30 hospitals, CA-MRSA comprised nearly half of MRSA isolates. There was substantial variability in CA-MRSA penetration across hospitals, with more CA-MRSA in smaller hospitals with healthier but socially disadvantaged patient populations. Additional research is needed to determine whether infection control strategies can be successful in targeting CA-MRSA influx.
doi:10.1086/670631
PMCID: PMC4151350  PMID: 23651888
9.  Use of family member-based supervision in the management of patients with hypertension in rural China 
Medication nonadherence is a major problem in the management of hypertension. The aim of this study was to develop a family member-based supportive therapy for patients with hypertension to provide an affordable way to access essential health services and to ensure adequate control of blood pressure. This study applied a mixed methods approach using qualitative and quantitative study designs in Yangzhong County, a rural area in the People’s Republic of China. Findings from indepth interviews demonstrated that the limited effects of traditional health education, a lack of professional advice regarding antihypertensive treatment, and age were related to a patient’s adherence with regular blood pressure measurement and taking medication. We also performed a quantitative study, selecting two villages in Yangzhong County as study sites. A total of 188 patients with hypertension were invited to participate in a 6-month family member-based intervention trial. The primary outcomes were the acceptability and feasibility of the intervention strategy. Secondary outcomes included medication adherence and changes in blood pressure. More than 75% of patients expressed a wish for external reminders, and 93.5% responded that they would accept the family member-based supervision. The patients preferred their spouse or a child as the supervisor. After the 6-month intervention, the proportion of patients with uncontrolled blood pressure decreased from 87.2% to 45.7%. This pilot study shows that external supervision by family members is acceptable and feasible for patients with hypertension; it also shows favorable effects with regard to improved treatment adherence and blood pressure control. Future randomized controlled trials with modified intervention measures are needed to validate this finding.
doi:10.2147/PPA.S66777
PMCID: PMC4125371  PMID: 25114514
hypertension; treatment; adherence; supervision; intervention
10.  Risk Factors for Glaucoma Suspicion in Healthy Young Asian and Caucasian Americans 
Journal of Ophthalmology  2014;2014:726760.
Purpose. To determine the prevalence of certain risk factors for glaucoma in a healthy, young population and to compare these risk factors between Asian Americans and Caucasians. Methods. 120 healthy graduate students (mean age 24.8 ± 3.0 years) underwent a comprehensive ophthalmic examination. Regression analyses controlling for age, sex, and refraction, comparing glaucoma risk factors in Asians (n = 54) and Caucasians (n = 41), were performed. Outcome variables included family history, intraocular pressure (IOP), spherical equivalent, central corneal thickness (CCT), mean deviation (MD) and pattern standard deviation (PSD), and disc and retinal nerve fiber layer (RNFL) parameters. Results. 61% of subjects were female; the mean spherical equivalent was −3.81 ± 3.2 D; and the mean axial length (AL) was 25.1 ± 1.7 mm. Regression analysis showed race affected spherical equivalent (P < 0.001), AL (P = 0.0073), IOP (P < 0.001), and cup to disc area ratio (CDAR) (P = 0.012). Family history, CCT, MD, and PSD did not vary between Asians and Caucasians (P > 0.05). In this study, we found Asian Americans, compared to Caucasians, had 2.95 ± 0.64 D greater myopia; greater IOP by 2.74 ± 0.62 mmHg; and larger CDAR by 0.12 ± 0.046. Conclusions. In our study population, young, healthy Asian Americans had greater myopia, IOP, and CDAR as compared to Caucasians, suggesting that racial variations can be important when diagnosing glaucoma.
doi:10.1155/2014/726760
PMCID: PMC4130190  PMID: 25143829
11.  High Nasal Burden of Methicillin-Resistant Staphylococcus aureus Increases Risk of Invasive Disease 
Journal of Clinical Microbiology  2014;52(1):312-314.
In a retrospective cohort study of 1,140 patients harboring methicillin-resistant Staphylococcus aureus, the nasal burden was low in 31%, category 1+ to 2+ in 54%, and category 3+ to 4+ in 15%. There was a significant trend in infection risk with increasing nasal burden (P = 0.007). In multivariate models, high nasal burden remained significantly associated with invasive infection.
doi:10.1128/JCM.01606-13
PMCID: PMC3911445  PMID: 24153126
12.  The Economic Burden of Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) 
The economic impact of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) remains unclear. We developed an economic simulation model to quantify the costs associated with CA-MRSA infection from the societal and third-party payer perspectives. A single CA-MRSA case costs third-party payers $2,277 – $3,200 and society $7,070 – $20,489, depending on patient age. In the United States (US), CA-MRSA imposes an annual burden of $478 million - 2.2 billion on third-party payers and $1.4 billion - 13.8 billion on society, depending on the CA-MRSA definitions and incidences. The US jail system and Army may be experiencing annual total costs of $7 – 11 million ($6 – 10 million direct medical costs) and $15 – 36 million ($14 – 32 million), respectively. Hospitalization rates and mortality are important cost drivers. CA-MRSA confers a substantial economic burden to third-party payers and society, with CA-MRSA-attributable productivity losses being major contributors to the total societal economic burden. Although decreasing transmission and infection incidence would decrease costs, even if transmission were to continue at present levels, early identification and appropriate treatment of CA-MRSA infections before they progress could save considerable costs.
doi:10.1111/j.1469-0691.2012.03914.x
PMCID: PMC3463640  PMID: 22712729
Community; MRSA; Economics; Cost; CA-MRSA
13.  The Regional Healthcare Ecosystem Analyst (RHEA): a simulation modeling tool to assist infectious disease control in a health system 
Objective
As healthcare systems continue to expand and interconnect with each other through patient sharing, administrators, policy makers, infection control specialists, and other decision makers may have to take account of the entire healthcare ‘ecosystem’ in infection control.
Materials and methods
We developed a software tool, the Regional Healthcare Ecosystem Analyst (RHEA), that can accept user-inputted data to rapidly create a detailed agent-based simulation model (ABM) of the healthcare ecosystem (ie, all healthcare facilities, their adjoining community, and patient flow among the facilities) of any region to better understand the spread and control of infectious diseases.
Results
To demonstrate RHEA's capabilities, we fed extensive data from Orange County, California, USA, into RHEA to create an ABM of a healthcare ecosystem and simulate the spread and control of methicillin-resistant Staphylococcus aureus. Various experiments explored the effects of changing different parameters (eg, degree of transmission, length of stay, and bed capacity).
Discussion
Our model emphasizes how individual healthcare facilities are components of integrated and dynamic networks connected via patient movement and how occurrences in one healthcare facility may affect many other healthcare facilities.
Conclusions
A decision maker can utilize RHEA to generate a detailed ABM of any healthcare system of interest, which in turn can serve as a virtual laboratory to test different policies and interventions.
doi:10.1136/amiajnl-2012-001107
PMCID: PMC3715346  PMID: 23571848
Healthcare System; Hospitals; Patient Sharing; Infectious Diseases; Hospital Acquired Infections
14.  Confounding by indication affects antimicrobial risk factors for methicillin-resistant Staphylococcus aureus but not vancomycin-resistant enterococci acquisition 
Background
Observational studies rarely account for confounding by indication, whereby empiric antibiotics initiated for signs and symptoms of infection prior to the diagnosis of infection are then viewed as risk factors for infection. We evaluated whether confounding by indication impacts antimicrobial risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) acquisition.
Findings
We previously reported several predictors of MRSA and VRE acquisition in 967 intensive care unit (ICU) patients with no prior history of MRSA or VRE who had an initial negative screening culture followed by either a subsequent negative screening culture (controls) or positive screening or clinical culture (cases). Within and prior to this acquisition interval, we collected demographic, comorbidity, daily device and antibiotic utilization data. We now re-evaluate all antibiotics by medical record review for evidence of treatment for signs and symptoms ultimately attributable to MRSA or VRE. Generalized linear mixed models are used to assess variables associated with MRSA or VRE acquisition, accounting for clustering by ward. We find that exclusion of empiric antibiotics given for suspected infection affects 17% (113/661) of antibiotic prescriptions in 25% (60/244) of MRSA-positive patients but only 1% (5/491) of antibiotic prescriptions in 1% (3/227) of VRE-positive patients. In multivariate testing, fluoroquinolones are no longer associated with MRSA acquisition, and aminoglycosides are significantly protective (OR = 0.3, CI:0.1-0.7).
Conclusions
Neglecting treatment indication may cause common empiric antibiotics to appear spuriously associated with MRSA acquisition. This effect is absent for VRE, likely because empiric therapy is infrequent given the low prevalence of VRE.
doi:10.1186/2047-2994-3-19
PMCID: PMC4057914  PMID: 24932407
Antimicrobial predictors; MRSA; VRE; Confounding by indication
15.  Keeping the “Home” in Nursing Home 
JAMA internal medicine  2013;173(10):853-854.
doi:10.1001/jamainternmed.2013.330
PMCID: PMC3716459  PMID: 23589042
16.  Attributable healthcare utilization and cost of pneumonia due to drug-resistant streptococcus pneumonia: a cost analysis 
Background
The burden of disease due to S. pneumoniae (pneumococcus), particularly pneumonia, remains high despite the widespread use of vaccines. Drug resistant strains complicate clinical treatment and may increase costs. We estimated the annual burden and incremental costs attributable to antibiotic resistance in pneumococcal pneumonia.
Methods
We derived estimates of healthcare utilization and cost (in 2012 dollars) attributable to penicillin, erythromycin and fluoroquinolone resistance by taking the estimate of disease burden from a previously described decision tree model of pneumococcal pneumonia in the U.S. We analyzed model outputs assuming only the existence of susceptible strains and calculating the resulting differences in cost and utilization. We modeled the cost of resistance from delayed resolution of illness and the resulting additional health services.
Results
Our model estimated that non-susceptibility to penicillin, erythromycin and fluoroquinolones directly caused 32,398 additional outpatient visits and 19,336 hospitalizations for pneumococcal pneumonia. The incremental cost of antibiotic resistance was estimated to account for 4% ($91 million) of direct medical costs and 5% ($233 million) of total costs including work and productivity loss. Most of the incremental medical cost ($82 million) was related to hospitalizations resulting from erythromycin non-susceptibility. Among patients under age 18 years, erythromycin non-susceptibility was estimated to cause 17% of hospitalizations for pneumonia and $38 million in costs, or 39% of pneumococcal pneumonia costs attributable to resistance.
Conclusions
We estimate that antibiotic resistance in pneumococcal pneumonia leads to substantial healthcare utilization and cost, with more than one-third driven by macrolide resistance in children. With 5% of total pneumococcal costs directly attributable to resistance, strategies to reduce antibiotic resistance or improve antibiotic selection could lead to substantial savings.
doi:10.1186/2047-2994-3-16
PMCID: PMC4029811  PMID: 24851182
Streptococcus pneumoniae; Antibiotic resistance; Healthcare utilization; DRSP
17.  The Importance of Nursing Homes in the Spread of Methicillin-Resistant Staphylococcus aureus (MRSA) Among Hospitals 
Medical care  2013;51(3):205-215.
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 (RHEA), 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 healthcare 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 six 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 via patient transfers by an average 0.1% after six 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 via both direct and indirect (with intervening stays at home) patient sharing.
doi:10.1097/MLR.0b013e3182836dc2
PMCID: PMC3687037  PMID: 23358388
MRSA; Outbreak; Long-term Care; Nursing Homes; Hospitals
18.  Quantifying The Impact of Extra-Nasal Testing Body Sites for MRSA Colonization at the Time of Hospital or Intensive Care Unit Admission 
Objective
Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of healthcare-associated infections. Recent legislative mandates require nares screening for MRSA at hospital and ICU admission in many states. However, MRSA colonization at extra-nasal sites is increasingly recognized. We conducted a systematic review of the literature to identify the yield of extra-nasal testing for MRSA.
Design
We searched MEDLINE from January 1966 through January 2012 for articles comparing nasal and extra-nasal screening for MRSA colonization. Studies were categorized by population tested, specifically those admitted to ICUs, and those admitted to hospitals with a high prevalence (≥6%) or low prevalence (<6%) of MRSA carriers. Data were extracted using a standardized instrument.
Results
We reviewed 4,381 abstracts and 735 manuscripts. Twenty-three manuscripts met criteria for analysis (n=39,479 patients). Extra-nasal MRSA screening increased yield by approximately one-third over nares alone. The yield was similar upon ICU admission (weighted average 33%, range 9%–69%), and hospital admission in high (weighted average 37%, range 9–86%) and low prevalence (weighted average 50%, range 0–150%) populations. Comparing individual extra nasal sites, testing the oropharynx increased MRSA detection by 21% over nares alone; rectum by 20%; wounds by 17%; and axilla by 7%.
Conclusions
Extra-nasal MRSA screening at hospital or ICU admission in adults will increase MRSA detection by one-third compared to nares screening alone. Findings were consistent among subpopulations examined. Extra-nasal testing may be a valuable strategy for outbreak control or in settings of persistent disease, particularly when combined with decolonization or enhanced infection prevention protocols.
doi:10.1086/669095
PMCID: PMC3894230  PMID: 23295562
19.  Modeling the regional spread and control of vancomycin-resistant enterococci 
American journal of infection control  2013;41(8):10.1016/j.ajic.2013.01.013.
Background
Because patients can remain colonized with vancomycin-resistant enterococci (VRE) for long periods of time, VRE may spread from one health care facility to another.
Methods
Using the Regional Healthcare Ecosystem Analyst, an agent-based model of patient flow among all Orange County, California, hospitals and communities, we quantified the degree and speed at which changes in VRE colonization prevalence in a hospital may affect prevalence in other Orange County hospitals.
Results
A sustained 10% increase in VRE colonization prevalence in any 1 hospital caused a 2.8% (none to 62%) average relative increase in VRE prevalence in all other hospitals. Effects took from 1.5 to >10 years to fully manifest. Larger hospitals tended to have greater affect on other hospitals.
Conclusions
When monitoring and controlling VRE, decision makers may want to account for regional effects. Knowing a hospital’s connections with other health care facilities via patient sharing can help determine which hospitals to include in a surveillance or control program.
doi:10.1016/j.ajic.2013.01.013
PMCID: PMC3836830  PMID: 23896284
Vancomycin-resistant Enterococcus; Hospitals; Health care-associated infections; Modeling; Simulation
20.  Diversity of Methicillin-Resistant Staphylococcus aureus Strains Isolated from Residents of 26 Nursing Homes in Orange County, California 
Journal of Clinical Microbiology  2013;51(11):3788-3795.
Nursing homes represent a unique and important methicillin-resistant Staphylococcus aureus (MRSA) reservoir. Not only are strains imported from hospitals and the community, strains can be transported back into these settings from nursing homes. Since MRSA bacteria are prevalent in nursing homes and yet relatively poorly studied in this setting, a multicenter, regional assessment of the frequency and diversity of MRSA in the nursing home reservoir was carried out and compared to that of the MRSA from hospitals in the same region. The prospective study collected MRSA from nasal swabbing of residents of 26 nursing homes in Orange County, California, and characterized each isolate by spa typing. A total of 837 MRSA isolates were collected from the nursing homes. Estimates of admission prevalence and point prevalence of MRSA were 16% and 26%, respectively. The spa type genetic diversity was heterogeneous between nursing homes and significantly higher overall (77%) than the diversity in Orange County hospitals (72%). MRSA burden in nursing homes appears largely due to importation from hospitals. As seen in Orange County hospitals, USA300 (sequence type 8 [ST8]/t008), USA100 (ST5/t002), and a USA100 variant (ST5/t242) were the dominant MRSA clones in Orange County nursing homes, representing 83% of all isolates, although the USA100 variant was predominant in nursing homes, whereas USA300 was predominant in hospitals. Control strategies tailored to the complex problem of MRSA transmission and infection in nursing homes are needed in order to minimize the impact of this unique reservoir on the overall regional MRSA burden.
doi:10.1128/JCM.01708-13
PMCID: PMC3889768  PMID: 24025901
21.  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.
doi:10.1086/669091
PMCID: PMC3763186  PMID: 23295561
22.  Simulation Shows Hospitals That Cooperate On Infection Control Obtain Better Results Than Hospitals Acting Alone 
Health affairs (Project Hope)  2012;31(10):2295-2303.
Efforts to control life-threatening infections, such as with methicillin-resistant Staphylococcus aureus (MRSA), can be complicated when patients are transferred from one hospital to another. Using a detailed computer simulation model of all hospitals in Orange County, California, we explored the effects when combinations of hospitals tested all patients at admission for MRSA and adopted procedures to limit transmission among patients who tested positive. Called “contact isolation,” these procedures specify precautions for health care workers interacting with an infected patient, such as wearing gloves and gowns. Our simulation demonstrated that each hospital’s decision to test for MRSA and implement contact isolation procedures could affect the MRSA prevalence in all other hospitals. Thus, our study makes the case that further cooperation among hospitals—which is already reflected in a few limited collaborative infection control efforts under way—could help individual hospitals achieve better infection control than they could achieve on their own.
doi:10.1377/hlthaff.2011.0992
PMCID: PMC3763190  PMID: 23048111
23.  Trends in Antibiotic Use in Massachusetts Children, 2000–2009 
Pediatrics  2012;130(1):15-22.
OBJECTIVE:
Antibiotic use rates have declined dramatically since the 1990s. We aimed to determine if, when, and at what level the decline in antibiotic-dispensing rates ended and which diagnoses contributed to the trends.
METHODS:
Antibiotic dispensings and diagnoses were obtained from 2 health insurers for 3- to <72-month-olds in 16 Massachusetts communities from 2000 to 2009. Population-based antibiotic-dispensing rates per person-year (p-y) were determined according to year (September–August) for 3 age groups. Fit statistics were used to identify the most likely year for a change in trend. Rates for the first and last years were compared according to antibiotic category and associated diagnosis.
RESULTS:
From 2000–2001 to 2008–2009, the antibiotic-dispensing rate for 3- to <24-month-olds decreased 24% (2.3–1.8 antibiotic dispensings per p-y); for 24- to <48-month-olds, it decreased 18% (1.6–1.3 antibiotic dispensings per p-y); and for 48- to <72-month-olds, it decreased 20% (1.4–1.1 antibiotic dispensings per p-y). For 3- to <48-month-olds, rates declined until 2004–2005 and remained stable thereafter; the downward trend for 48- to <72-month-olds ended earlier in 2001–2002. Among 3- to <24-month-olds, first-line penicillin use declined 26%. For otitis media, the dispensing rate decreased 14% and the diagnosis rate declined 9%, whereas the treatment fraction was stable at 63%.
CONCLUSIONS:
The downward trend in antibiotic dispensings to young children in these communities ended by 2004–2005. This trend was driven by a declining otitis media diagnosis rate. Continued monitoring of population-based dispensing rates will support efforts to avoid returning to previous levels of antibiotic overuse.
doi:10.1542/peds.2011-3137
PMCID: PMC3382917  PMID: 22732172
antibiotic use; managed care programs; otitis media
24.  Chlorhexidine and Mupirocin Susceptibilities of Methicillin-Resistant Staphylococcus aureus from Colonized Nursing Home Residents 
Chlorhexidine and mupirocin are used in health care facilities to eradicate methicillin-resistant Staphylococcus aureus (MRSA) carriage. The objective of this study was to assess the frequency of chlorhexidine and mupirocin resistance in isolates from nares carriers in multiple nursing homes and to examine characteristics associated with resistance. Nasal swab samples were collected from approximately 100 new admissions and 100 current residents in 26 nursing homes in Orange County, CA, from October 2008 to May 2011. MRSA isolates were tested for susceptibility by using broth microdilution, disk diffusion, and Etest; for genetic relatedness using pulsed-field gel electrophoresis; and for qac gene carriage by PCR. Characteristics of the nursing homes and their residents were collected from the Medicare Minimum Data Set and Long-Term Care Focus. A total of 829 MRSA isolates were obtained from swabbing 3,806 residents in 26 nursing homes. All isolates had a chlorhexidine MIC of ≤4 μg/ml. Five (0.6%) isolates harbored the qacA and/or qacB gene loci. Mupirocin resistance was identified in 101 (12%) isolates, with 78 (9%) isolates exhibiting high-level mupirocin resistance (HLMR). HLMR rates per facility ranged from 0 to 31%. None of the isolates with HLMR displayed qacA or qacB, while two isolates carried qacA and exhibited low-level mupirocin resistance. Detection of HLMR was associated with having a multidrug-resistant MRSA isolate (odds ratio [OR], 2.69; P = 0.004), a history of MRSA (OR, 2.34; P < 0.001), and dependency in activities of daily living (OR, 1.25; P = 0.004). In some facilities, HLMR was found in nearly one-third of MRSA isolates. These findings may have implications for the increasingly widespread practice of MRSA decolonization using intranasal mupirocin.
doi:10.1128/AAC.01623-12
PMCID: PMC3535956  PMID: 23147721
25.  Methicillin-Resistant Staphylococcus aureus (MRSA) Burden in Nursing Homes is Associated with Environmental Contamination of Common Areas 
Background
Variation in MRSA prevalence across nursing homes is poorly understood. Differences in environmental cleaning may be one source of variable MRSA burden.
Design
Prospective study of environmental contamination and cleaning quality.
Setting/Participants
10 California nursing homes.
Measurements
We categorized nursing homes into two groups based upon high and low differences in MRSA point prevalence and admission prevalence (delta prevalence) from nares screenings of nursing home residents. We evaluated environmental cleaning and infection control practices by (a) culturing common area objects for MRSA, (b) assessing removal of intentionally-applied marks visible only under ultraviolet light (c) administering surveys on infection control and cleaning.
Results
Overall, 16% (78/500) of objects were MRSA-positive, and 22% (129/577) of UV-visible marks were removed. A higher proportion of MRSA-positive objects was found in the high vs. low nursing home groups (19% vs. 10%, p=0.005). Infection control and cleaning policies varied, including the frequency of common room cleaning (mean 2.5 times daily, range 1–3) and time spent cleaning per room (mean 18 min, range 7–45). In multivariate models, MRSA-positive objects were associated with high delta prevalence nursing homes (OR=2.8, p=0.005), facilities spending less time cleaning each room (OR = 2.9, p<0.001) and facilities where common rooms were cleaned less frequently (OR =1.5, p=0.01).
Conclusions
We found substantial variation in MRSA environmental contamination, infection control practices, and cleaning quality. MRSA environmental contamination was associated with larger differences between MRSA point and admission prevalence, less frequent common room cleaning, and less time spent cleaning per room. This suggests that modifying cleaning practices may reduce both MRSA environmental contamination and burden among nursing homes.
doi:10.1111/j.1532-5415.2012.03978.x
PMCID: PMC3376013  PMID: 22670708
Methicillin-resistant Staphylococcus aureus (MRSA); environmental contamination; cleaning quality; infection control; long term care facility

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