Comparison of immune response to the influenza vaccine in obese and nonobese healthcare workers.

OBJECTIVE: To determine whether there is a difference in antibody titers and functionality after receipt of the influenza vaccine for obese versus nonobese healthcare workers (HCW). DESIGN: Prospective observational study. SETTING: Tertiary medical center. PARTICIPANTS: Healthcare workers. METHODS Baseline influenza antibody titers for obese and nonobese HCW were recorded during the hospital's 2011 annual influenza vaccination day and follow-up antibody titers were measured 4 weeks later. Antibodies were measured using the hemagglutination inhibition assay and functionality was measured using the micro-neutralization method. RESULTS: Of 200 initial HCWs, 190 completed the study (97 obese and 93 nonobese). Seroprotection after immunization was not significantly different for nonobese compared with obese HCW for each strain (influenza A [H1N1], 99% and 99%; influenza A [H3N2], 100% and 99%; and influenza B, 67% and 71%, respectively) All geometric mean titers measured by micro-neutralization showed statistically significant increases in activity. In comparison, there was no difference in the 4-fold increase in H1N1 or B titers. There was a significant difference in the 4-fold increase of H3N2 titers between the nonobese and obese HCWs (82/93 [88%] vs 64/97 [66%], P=.003) In an ad hoc analysis we found that obese HCWs had a statistically greater number of 4-fold decreases in titers with H1N1 and H3N2. CONCLUSIONS: There was no significant difference in protection from influenza between obese and nonobese HCWs after immunization.

Left knee prosthesis-related Mycobacterium goodii infection.

Non-tuberculous mycobacteria are increasingly being recognized as important human pathogens. We present the case of a 44-year-old non-diabetic male who underwent left total knee arthroplasty for degenerative arthritis after trauma. He developed left knee swelling and progressively worsening pain over the next 4 weeks. He was referred for treatment using whirlpool baths and developed a blister at the surgical incision site. Repeated aspirations of the left knee failed to show any growth of organism on routine cultures. He finally underwent explantation of the left knee prosthesis with antimicrobial spacer placement 4 months later. Cultures of three different intra-operative specimens turned positive for Mycobacterium goodii. This infection was successfully treated with combination oral antimicrobials for 6 months. The patient underwent revision left knee arthroplasty subsequently and was symptom-free until his last follow-up visit 1 year later. This patient highlights the importance of testing for mycobacteria in prosthesis-related infections with previously negative routine bacterial cultures.

Candida endophthalmitis: focus on current and future antifungal treatment options.

Candida endophthalmitis is a sight-threatening manifestation of disseminated candidiasis. The occurrence of endogenous candida endophthalmitis in patients with candidemia has ranged from 0-45% in the published literature. In critically ill patients, it has even been associated with increased mortality. In recent years, use of newer antifungal therapies for invasive candidiasis has increased given the rise in infections with non-albicans species of Candida. To identify current practices of the management of endogenous candida endophthalmitis and relevant antifungal drug research in this disease state, we conducted a MEDLINE search (1967-2006) and bibliographic search of the English-language literature. Treatments for candida endophthalmitis have not been evaluated through well-designed, well-powered clinical trials. Data have mainly been presented in case reports, case series, animal studies, pharmacokinetic studies, and as small subsets of larger trials. Traditional systemic therapies have been amphotericin B with or without flucytosine or fluconazole. Cure rates with antifungal drugs alone appear to be much higher in patients with chorioretinitis than in endophthalmitis with vitreal involvement. Pars plana vitrectomy with or without intravitreal amphotericin B injections has been advocated particularly for patients with moderate-to-severe vitritis and substantial vision loss. Information on new antifungal agents for endophthalmitis is limited, despite increasing use in patients with candidemia. Voriconazole may be a particularly attractive agent to consider for infections with fluconazole-resistant, voriconazole-susceptible strains. The current patchwork of animal studies and small patient reports provide clinicians with some insight into the role of newer agents in the treatment of candida endophthalmitis. In general, it appears that chorioretinitis infections can be more readily cured with most systemic antifungal agents, whereas more aggressive treatment, often including vitrectomy with or without intra-vitreal antifungal administration, is needed for patients with endophthalmitis with vitritis.

Association of hemochromatosis with infectious diseases: expanding spectrum.

Withholding iron from potential pathogens is a host defense strategy. There is evidence that iron overload per se compromises the ability of phagocytes to kill microorganisms. Several hypotheses exist to explain the association of hemochromatosis with infection. A combination of mechanisms likely contributes to the increase in susceptibility to infection in these patients. A review of the current literature delineating various pathogens to which patients with hemochromatosis are potentially susceptible, and recent advances in the understanding of the association of hemochromatosis with infection, are discussed.

Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers.

STUDY OBJECTIVE: To determine whether daily high-dose vitamin C alters the steady-state pharmacokinetics of indinavir, a protease inhibitor indicated for treatment of the human immunodeficiency virus type 1. DESIGN: Prospective, open-label, longitudinal, two-period time series. SETTING: University medical center. SUBJECTS: Seven healthy volunteers. INTERVENTION: Indinavir 800 mg every 8 hours was given to subjects for four doses on days 1 and 2. Plasma samples were then collected for indinavir pharmacokinetic determination. After a 7-day washout period, subjects were given vitamin C 1000 mg/day for 7 days. Beginning on day 6 of vitamin C administration, indinavir 800 mg every 8 hours was restarted for four doses. Plasma was then collected from subjects to determine indinavir pharmacokinetics. All subjects were given a vitamin C content-controlled diet for 1 week before the study began and throughout the study period. MEASUREMENTS AND MAIN RESULTS: Steady-state plasma samples were collected before dosing (0 hr) and 0.5, 1, 2, 3, 4, and 5 hours after dosing to determine indinavir pharmacokinetics. Parameters of interest were maximum plasma concentration (C max ), time to C max , area under the plasma concentration-time curve from 0-5 hours after the dose (AUC 0-5 ), an extrapolated 8-hour AUC (AUC 0-8 ), trough (minimum) plasma concentration (C min ), and oral clearance. Mean steady-state indinavir C max was significantly reduced (20%) after 7 days of vitamin C administration (10.3 +/- 1.5 vs 8.2 +/- 2.9 microg/ml, p=0.04). The corresponding mean AUC 0-8 was also significantly decreased (14%; 26.4 +/- 7.2 vs 22.7 +/- 8.1 microg*hr/ml, p=0.05). Although not statistically significant, the mean indinavir C min was 32% lower in the presence of vitamin C (0.27 +/- 0.17 C vs 0.18 +/- 0.08 microg/ml, p=0.09). Indinavir oral clearance and half-life were not significantly different. CONCLUSION: Concomitant administration of high doses of vitamin C can reduce steady-state indinavir plasma concentrations. Subtherapeutic concentrations of antiretroviral agents have been associated with viral resistance and regimen failure, but the clinical significance of our findings remains to be established.

Computerized antimicrobial decision support: an offline evaluation of a database-driven empiric antimicrobial guidance program in hospitalized patients with a bloodstream infection.

INTRODUCTION: We developed a computerized antimicrobial guidance program based on the last 5 years of our laboratory culture data augmented by expert infectious disease logic. The program is designed to assist physicians with the targeting of empiric antimicrobials for hospitalized patients by tracking pathogenic bacteria and their evolving antimicrobial resistance profiles. Costs, toxicities, and environmental impact of antimicrobial use also influence the final recommendations. We undertook the following analysis to verify its potential safety and efficacy in hospitalized patients with a bloodstream infection. METHODS: We retrospectively enrolled all inpatients with a positive blood culture for a previously undetermined pathogen during the first 6 months of 2002 and determined the empiric therapy initiated within the 12h before and after the time of culture. Antimicrobial recommendations from the microbiologic decision support tool were then determined by matching specimen (blood), hospital unit, community- versus hospital-acquired category, age category, and gender. Generated antimicrobial recommendations were tailored to patient allergies, age category, and presence of pregnancy, lactation, or hepatic impairment. RESULTS: The microbiology laboratory recorded 226 unique patient/pathogen blood cultures during the study period. Physicians initiated effective empiric therapy in 150 of the 226 cases, for an effectiveness rate of 66%. The computer-guided therapy was effective in 195 of the 226 cases for a rate of 86%. A contingency table analysis showed 55 cases where the computer recommendation was effective but the physicians' selection was not, and eight cases where the physicians' antimicrobials were effective but the computer's were not (P < 0.0001). DISCUSSION: For patients with a bloodstream infection, we found that our computer-guided statistically-derived antimicrobial therapy would potentially improve the rate of effectiveness of empirically chosen antimicrobials.

Computerized antimicrobial decision support for hospitalized patients with a bloodstream infection.

We developed a computerized antimicrobial decision support program founded on our local bacterial susceptibility data. In a retrospective analysis of patients with a bloodstream infection, we compared the actual antimicrobials prescribed to the antimicrobials recommended by the program. We found the computer-guided therapy to be clinically and statistically more effective than the therapy initiated by the physicians. We conclude that computerized decision support can improve the targeting of empiric antimicrobial therapy.