A pilot clinical trial of a near-infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell trafficking.

Many vaccines require adjuvants to enhance immunogenicity, but there are few safe and effective intradermal (i.d.) adjuvants. Murine studies have validated the potency of laser illumination of skin as an adjuvant for i.d. vaccination with advantages over traditional adjuvants. We report a pilot clinical trial of low-power, continuous-wave, near-infrared laser adjuvant treatment, representing the first human trial of the safety, tolerability, and cutaneous immune cell trafficking changes produced by the laser adjuvant. In this trial we demonstrated a maximum tolerable energy dose of 300 J/cm2 to a spot on the lower back. The irradiated spot was biopsied 4 h later, as was a control spot. Paired biopsies were submitted for histomorphologic and immunohistochemical evaluation in a blinded fashion as well as quantitative PCR analysis for chemokines and cytokines. Similar to prior murine studies, highly significant reductions in CD1a+ Langerhans cells in the dermis and CD11c+ dermal dendritic cells were observed, corresponding to the increased migratory activity of these cells; changes in the epidermis were not significant. There was no evidence of skin damage. The laser adjuvant is a safe, well-tolerated adjuvant for i.d. vaccination in humans and results in significant cutaneous immune cell trafficking.-Gelfand, J. A., Nazarian, R. M., Kashiwagi, S., Brauns, T., Martin, B., Kimizuka, Y., Korek, S., Botvinick, E., Elkins, K., Thomas, L., Locascio, J., Parry, B., Kelly, K. M., Poznansky, M. C. A pilot clinical trial of a near-infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell trafficking.

Diversity of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from inpatients of 30 hospitals in Orange County, California.

There is a need for a regional assessment of the frequency and diversity of MRSA to determine major circulating clones and the extent to which community and healthcare MRSA reservoirs have mixed. We conducted a prospective cohort study of inpatients in Orange County, California, systematically collecting clinical MRSA isolates from 30 hospitals, to assess MRSA diversity and distribution. All isolates were characterized by spa typing, with selective PFGE and MLST to relate spa types with major MRSA clones. We collected 2,246 MRSA isolates from hospital inpatients. This translated to 91/10,000 inpatients with MRSA and an Orange County population estimate of MRSA inpatient clinical cultures of 86/100,000 people. spa type genetic diversity was heterogeneous between hospitals, and relatively high overall (72%). USA300 (t008/ST8), USA100 (t002/ST5) and a previously reported USA100 variant (t242/ST5) were the dominant clones across all Orange County hospitals, representing 83% of isolates. Fifteen hospitals isolated more t008 (USA300) isolates than t002/242 (USA100) isolates, and 12 hospitals isolated more t242 isolates than t002 isolates. The majority of isolates were imported into hospitals. Community-based infection control strategies may still be helpful in stemming the influx of traditionally community-associated strains, particularly USA300, into the healthcare setting.

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.

What is nosocomial? Large variation in hospital choice of numerators and denominators affects rates of hospital-onset methicillin-resistant Staphylococcus aureus.

We calculated hospital-onset methicillin-resistant Staphylococcus aureus (HO-MRSA) rates for Orange County, California, hospitals using survey and state data. Numerators were variably defined as HO-MRSA occurring more than 48 hours (37%), more than 2 days (30%), and more than 3 days (33%) postadmission. Survey-reported denominators differed from state-reported patient-days. Numerator and denominator choices substantially impacted HO-MRSA rates.

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

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.

Successful strategies for high participation in three regional healthcare surveys: an observational study.

BACKGROUND: Regional healthcare facility surveys to quantitatively assess nosocomial infection rates are important for confirming standardized data collection and assessing health outcomes in the era of mandatory reporting. This is particularly important for the assessment of infection control policies and healthcare associated infection rates among hospitals. However, the success of such surveys depends upon high participation and representativeness of respondents. METHODS: This descriptive paper provides methodologies that may have contributed to high participation in a series of administrative, infection control, and microbiology laboratory surveys of all 31 hospitals in a large southern California county. We also report 85% (N = 72) countywide participation in an administrative survey among nursing homes in this same area. RESULTS: Using in-person recruitment, 48% of hospitals and nursing homes were recruited within one quarter, with 75% recruited within three quarters. CONCLUSIONS: Potentially useful strategies for successful recruitment included in-person recruitment, partnership with the local public health department, assurance of anonymity when presenting survey results, and provision of staff labor for the completion of detailed survey tables on the rates of healthcare associated pathogens. Data collection assistance was provided for three-fourths of surveys. High compliance quantitative regional surveys require substantial recruitment time and study staff support for high participation.

Quantifying interhospital patient sharing as a mechanism for infectious disease spread.

BACKGROUND: Assessments of infectious disease spread in hospitals seldom account for interfacility patient sharing. This is particularly important for pathogens with prolonged incubation periods or carrier states. METHODS: We quantified patient sharing among all 32 hospitals in Orange County (OC), California, using hospital discharge data. Same-day transfers between hospitals were considered "direct" transfers, and events in which patients were shared between hospitals after an intervening stay at home or elsewhere were considered "indirect" patient-sharing events. We assessed the frequency of readmissions to another OC hospital within various time points from discharge and examined interhospital sharing of patients with Clostridium difficile infection. RESULTS: In 2005, OC hospitals had 319,918 admissions. Twenty-nine percent of patients were admitted at least twice, with a median interval between discharge and readmission of 53 days. Of the patients with 2 or more admissions, 75% were admitted to more than 1 hospital. Ninety-four percent of interhospital patient sharing occurred indirectly. When we used 10 shared patients as a measure of potential interhospital exposure, 6 (19%) of 32 hospitals "exposed" more than 50% of all OC hospitals within 6 months, and 17 (53%) exposed more than 50% within 12 months. Hospitals shared 1 or more patient with a median of 28 other hospitals. When we evaluated patients with C. difficile infection, 25% were readmitted within 12 weeks; 41% were readmitted to different hospitals, and less than 30% of these readmissions were direct transfers. CONCLUSIONS: In a large metropolitan county, interhospital patient sharing was a potential avenue for transmission of infectious agents. Indirect sharing with an intervening stay at home or elsewhere composed the bulk of potential exposures and occurred unbeknownst to hospitals.