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Background. When the decision was made to prepare for a deliberate release of smallpox, the United States had ~15 million doses of Wyeth Dryvax vaccine, which was known to induce significant morbidity when used undiluted; Sanofi Pasteur, Inc., later identified ~85 million additional doses in storage. Methods. Eleven vaccine-dose groups, each with 30 vaccinia-naive subjects, were given diluted Dryvax vaccine or 1 of 2 lots of Sanofi Pasteur smallpox vaccine and were evaluated for vaccination success rates, morbidity, and immune responses. Results. Estimated doses of 106.6-108.2 pfu of virus/mL induced major reactions (or ‘takes’) in 93%-100% of subjects in each dose group. No differences in vaccination take rates, lesion size, erythema, and induration or in serum neutralizing-antibody response were detected between the groups. However, systemic reactogenicity and missed activities were significantly lower for the vaccine groups given doses of 106.6-107.2 pfu/mL than for those given doses of 107.6-108.2 pfu/mL. Conclusions. These findings support the use of a higher dilution of Wyeth Dryvax vaccine and Sanofi Pasteur smallpox vaccine, given that the resulting morbidity should be significantly lower without loss of vaccine effectiveness. A plan for use of higher dilutions would create an enormous stockpile of vaccine. [ABSTRACT FROM AUTHOR]

Provides information on a study that focused on the mechanisms of cefepime resistance among extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in Taiwan. Methodology of the study; Results and discussion on the study; Conclusions.

Background: Seasonal influenza results in significant morbidity and mortality worldwide, but the currently licensed inactivated vaccines generally have low vaccine efficacies and could be improved. In this phase 1 clinical trial, we compared seasonal influenza vaccine regimens with different priming strategies, prime-boost intervals, and administration routes to determine the impact of these variables on the resulting antibody response. Methods: Between August 17, 2012 and January 25, 2013, four sites enrolled healthy adults 18–70 years of age. Subjects were randomized to receive one of the following vaccination regimens: trivalent hemagglutinin (HA) DNA prime followed by trivalent inactivated influenza vaccine (IIV3) boost with a 3.5 month interval (DNA-IIV3), IIV3 prime followed by IIV3 boost with a 10 month interval (IIV3-IIV3), or concurrent DNA and IIV3 prime followed by IIV3 boost with a 10 month interval (DNA/IIV3-IIV3). Each regimen was additionally stratified by an IIV3 administration route of either intramuscular (IM) or intradermal (ID). DNA vaccines were administered by a needle-free jet injector (Biojector). Study objectives included evaluating the safety and tolerability of each regimen and measuring the antibody response by hemagglutination inhibition (HAI). Results: Three hundred and sixteen subjects enrolled. Local reactogenicity was mild to moderate in severity, with higher frequencies recorded following DNA vaccine administered by Biojector compared to IIV3 by either route (p <0.02 for pain, swelling, and redness) and following IIV3 by ID route compared to IM route (p <0.001 for swelling and redness). Systemic reactogenicity was similar between regimens. Though no overall differences were observed between regimens, the highest titers post boost were observed in the DNA-IIV3 group by ID route and in the IIV3-IIV3 group by IM route. Conclusions: All vaccination regimens were found to be safe and tolerable. While there were no overall differences between regimens, the DNA-IIV3 group by ID route, and the IIV3-IIV3 group by IM route, showed higher responses compared to the other same-route regimens. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed data for 195 respiratory infection patients who had positive Staphyloccocus aureus cultures and who were hospitalized in 2 hospitals in Iowa and Maryland, USA, during 2003-2009. Odds for death for patients who also had influenza-positive test results were >4 times higher than for those who had negative influenza test results. [ABSTRACT FROM AUTHOR]

S. aureus bacteremia (SAB) is a common condition with high rates of morbidity and mortality. Current methods used to diagnose SAB take at least a day, and often longer. Patients with suspected bacteremia must therefore be empirically treated, often unnecessarily, while assay results are pending. In this proof-of-concept study, we describe an inexpensive assay that detects SAB via the detection of micrococcal nuclease (an enzyme secreted by S. aureus) in patient plasma samples in less than three hours. In total, 17 patient plasma samples from culture-confirmed S. aureus bacteremic individuals were tested. 16 of these yielded greater nuclease assay signals than samples from uninfected controls or individuals with non-S. aureus bacteremia. These results suggest that a nuclease-detecting assay may enable the rapid and inexpensive diagnosis of SAB, which is expected to substantially reduce the mortality and morbidity that result from this condition. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant S. aureus (MRSA) pneumonia is associated with poor clinical outcomes. This study examined the association between microbial characteristics and poor outcomes among patients with methicillin-resistant Staphylococcus aureus pneumonia. Findings: This retrospective cohort study included 75 patients with MRSA pneumonia who were admitted to two large tertiary care medical centers during 2003-2010. Multivariable models were created using Cox proportional hazards regression and ordinal logistic regression to identify predictors of mortality or increased length of stay (LOS). None of the microbial characteristics (PFGE type, agr dysfunction, SCCmec type, and detection of PVL, ACME, and TSST-1) were significantly associated with 30-day mortality or post-infection hospital length of stay, after adjusting for gender, age, previous hospital admission within 12 months, previous MRSA infection or colonization, positive influenza test, Charlson Comorbidity Index score, and treatment (linezolid or vancomycin). Conclusion: Large prospective studies are needed to examine the impact of microbial characteristics on the risk of death and other adverse outcomes among patients with MRSA pneumonia. [ABSTRACT FROM AUTHOR]

Background. Children 6 through 35 months of age are recommended to receive half the dose of influenza vaccine compared with older children and adults. Methods. This was a 6-site, randomized 2:1, double-blind study comparing full-dose (0.5 mL) trivalent inactivated influenza vaccine (TIV) with half-dose (0.25 mL) TIV in children 6 through 35 months of age. Children previously immunized with influenza vaccine (primed cohort) received 1 dose, and those with no previous influenza immunizations (naive cohort) received 2 doses of TIV. Local and systemic adverse events were recorded. Sera were collected before immunization and 1 month after last dose of TIV. Hemagglutination inhibition antibody testing was performed. Results. Of the 243 subjects enrolled (32 primed, 211 naive), data for 232 were available for complete analysis. No significant differences in local or systemic reactions were observed. Few significant differences in immunogenicity to the 3 vaccine antigens were noted. The immune response to H1N1 was significantly higher in the full-dose group among primed subjects. In the naive cohort, the geometric mean titer for all 3 antigens after 2 doses of TIV were significantly higher in the 12 through 35 months compared with the 6 through 11 months age group. Conclusions. Our study confirms the safety of full-dose TIV given to children 6 through 35 months of age. An increase in antibody responses after full- versus half-dose TIV was not observed, except for H1N1 in the primed group. Larger studies are needed to clarify the potential for improved immunogenicity with higher vaccine doses. Recommending the same dose could simplify the production, storage, and administration of influenza vaccines. [ABSTRACT FROM AUTHOR]

We performed antimicrobial drug susceptibility testing and molecular typing on invasive methicillin-resistant Staphylococcus aureus (MRSA) isolates (n = 1,666) submitted to the University of Iowa Hygienic Laboratory during 1999-2006 as part of a statewide surveillance system. All USA300 and USA400 isolates were resistant to

This article discusses a study of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in Iowa. The study performed antimicrobial drug susceptibility testing on all isolates. It merged pulsed-field gel electrophoresis (PFGE) patterns and antimicrobial drug susceptibility test results with the demographic data. It showed that patients infected by MRSA were younger than those infected by other strains. The study also suggested that the incidence of invasive infections caused by MRSA increased artificially.

Invasive disease following methicillin-resistant Staphylococcus aureus (MRSA) detection is common, regardless of whether initial detection involves colonization or infection. We assessed the genetic relatedness of isolates obtained ⩾2 weeks apart representing either repeated infections or colonization-infection sets to determine if infections are likely to be caused by previously harbored strains. We found that MRSA infection following initial colonization or infection is caused by the same strain in most cases, suggesting that a single successful attempt at decolonization may prevent the majority of later infection. [ABSTRACT FROM AUTHOR]

To determine whether poultry contact/consumption predicts colonization with antimicrobial-resistant Escherichia coli, 567 newly hospitalized patients and 100 vegetarians were assessed microbiologically and epidemiologically. Multivariable analysis showed that poultry contact/consumption, other dietary habits, and antimicrobial use did not significantly predict resistance. In contrast, foreign travel significantly predicted both trimethoprim-sulfamethoxazole resistance (prevalence ratio, 2.7 [95% confidence interval, 1.3-5.61) and "any resistance" (total population), whereas intensive-care-unit exposure predicted any resistance (hospital patients). Thus, most of the individual-level exposures—including poultry contact/consumption—that had been expected to be significant risk factors for infection with antimicrobial-resistant E. coli did not prove to be such. Other exposures, including household-, community-, and population-level effects, maybe more important. [ABSTRACT FROM AUTHOR]

The food supply, including poultry products, may transmit antimicrobial drug-resistant Escherichia coli to humans. To assess this hypothesis, 931 geographically and temporally matched E. coli isolates from human volunteers (hospital inpatients and healthy vegetarians) and commercial poultry products (conventionally raised or raised without antimicrobial drugs) were tested by PCR for phylogenetic group (A, B1, B2, D) and 60 virulence genes associated with extraintestinal pathogenic E. coli. Isolates resistant to trimethoprim-sulfamethoxazole, quinolones, and extended spectrum cephalosporins (n = 331) were compared with drug-susceptible isolates (n = 600) stratified by source. Phylogenetic and virulence markers of drug-susceptible human isolates differed considerably from those of human and poultry isolates. In contrast, drug-resistant human isolates were similar to poultry isolates, and drug-susceptible and drug-resistant poultry isolates were largely indistinguishable. Many drug-resistant human fecal E. coli isolates may originate from poultry, whereas drug-resistant poultry source E. coli isolates likely originate from susceptible poultry-source precursors. [ABSTRACT FROM AUTHOR]

Objective--To estimate the association between ceftiofur use and the isolation of Escherichia coli with reduced ceftriaxone susceptibility from fecal samples of dairy cow populations. Animals--1,266 dairy cows on 18 farms in Ohio. Procedures--Individual fecal samples from all cows in the study herds were tested for Escherichia coli with reduced ceftriaxone susceptibility. Herd antimicrobial use policy and antimicrobial treatment records were also obtained. Plasmid DNA from these isolates was tested for the presence of the AmpC β-lactamase gene (blaCMY-2). Minimum inhibitory concentrations to a standard panel of 16 antimicrobial drugs were determined by use of a broth microdilution system. Results--Herds for which ceftiofur use was reported were more likely to have cows from which reduced-susceptibility E coli was isolated than herds that did not report ceftiofur use (odds ratio, 25.0). However, at the individual cow level, no association was found between recent ceftiofur treatment and isolation of reduced-susceptibility E coli (adjusted odds ratio, 1.01). No observed linear relationship was found between the percentage of cows from which E coli with reduced ceftriaxone susceptibility was isolated and the percentage of cows in the herd recently treat ed with ceftiofur. Conclusions and Clinical Relevance--Our observation of a herd-level but not an individual cow-level association between ceftiofur use and isolation of E coli with reduced ceftriaxone susceptibility from fecal samples suggests that interventions to reduce the spread of antimicrobial resistance genes in agricultural animals will be most effective at the herd level. [ABSTRACT FROM AUTHOR]

In Escherichia coli infection, the implications of fluoroquinolone (FQ) and extended-spectrum cephalosporin plus cephamycin (AmpC) resistance for phylogenetic origin and virulence potential are undefined, as is the influence of ecological context on these associations. Accordingly, 106 E. coli isolates exhibiting FQ and/or AmpC resistance and 98 susceptible isolates were compared with regard to phylogenetic background and virulence profiles, stratified by host group (104 predominantly extraintestinal human isolates and 100 pre- dominantly intestinal cattle and swine isolates). Although resistant isolates exhibited significant shifts in phylogenetic distribution and virulence profiles, human and animal isolates exhibited different phylogenetic shifts, and only among human isolates did resistance predict reduced virulence. Evidence for similar strains being resistant versus susceptible was scant. The O15:K52:H1 clonal group and the closely related "clonal group A" featured prominently among resistant and susceptible human isolates, respectively. Thus, in E. coli, antibiotic resistance predicts phylogenetic background and virulence potential in a complex, context-dependent fashion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]