High dose trivalent influenza vaccine compared to standard dose vaccine in patients with rheumatoid arthritis receiving TNF-alpha inhibitor therapy and healthy controls: Results of the DMID 10-0076 randomized clinical trial.

INTRODUCTION: Subjects with rheumatoid arthritis (RA) receiving tumor necrosis factor-inhibiting (TNFi) therapies are at risk for severe influenza, and may respond less well to influenza vaccine. We examined the safety and immunogenicity of high dose influenza vaccine (HD) compared to standard dose vaccine (SD) in participants with RA receiving stable TNFi. METHODS: A randomized, double-blinded, Phase II study was conducted in adults with RA receiving TNFi, and healthy, gender and age-matched control subjects. Participants were immunized with HD (Sanofi Pasteur Fluzone High Dose [60 mcg × 3 strains]) or SD (Sanofi Pasteur Fluzone® [15 mcg × 3 strains]) intramuscularly (IM). A self-administered memory aid recorded temperature and systemic and local adverse events (AEs) for 8 days, and safety was evaluated and serum obtained to measure HAI activity on days 7, 21 and 180 days following vaccination. RESULTS: A greater proportion of RA subjects who received HD seroconverted at day 21 compared to SD, although this was not statistically significant. GMT antibody responses in RA subjects who received HD compared to SD were greater for all strains on day 21, and this was significant for H1N1. Seroconversion rates and GMT values were not different between RA subjects and control subjects. There were no safety concerns for HD or SD in RA subjects, and RA-related symptoms did not differ between SD and HD recipients by a RA-symptom questionnaire (RAPID 3). CONCLUSIONS: TNF-inhibitor therapy in people with RA did not appear to influence the immunogenicity of either SD or HD. Influenza seroconversion and GMT values were higher among RA subjects receiving HD compared to SD; however, differences were small and a larger study is needed to validate these findings. Given the apparent risk of increased influenza-related morbidity and mortality among immune compromised subjects, the higher GMT values generated by HD may be beneficial.

Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial.

BACKGROUND: Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs. METHODS: A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant. Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18-49 years. RESULTS: Two hundred and seventy subjects were enrolled. After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001). Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher. Vaccine + MF59 produced cross-reactive antibody responses against 4 heterologous H5N1 viruses. Excellent safety and tolerability were demonstrated. CONCLUSIONS: Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe. The feasibility of the point-of-use mixing should be studied further.

Multihospital surveillance of nosocomial methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, and Clostridium difficile: analysis of a 4-year data-sharing project, 1999-2002.

BACKGROUND: This study sought to establish a benchmark of resistant organism rates among a cohort of regional hospitals. METHODS: The Centers for Disease Control and Prevention (CDC) definitions were used to standardize the methodology for obtaining rates per 1000 patient days of nosocomial infection and colonization with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE), and nosocomial infection with Clostridium difficile (CDIF). Only newly acquired nosocomial cases were counted. Data were reported as individual hospital control charts and as cohorted aggregate data. VHA East Coast Infection Control Professionals from 32 hospitals in New Jersey and Pennsylvania were involved. RESULTS: Benchmarks were established with pooled mean rates for each cohort. During the observational period, a statistically significant downward trend was observed for VRE and MRSA (P = .02 and .0007, respectively), and an upward trend was observed for CDIF (P = .0256). CONCLUSION: Benchmarks were established to compare nosocomial MRSA, VRE, and CDIF rates. Although significant changes in rates were observed, no attempt was made to establish a causal relationship between infection control practices and observed rates. However, a secondary gain was achieved through sharing best practices.