Biofilms are microbial communities, embedded in a polymeric matrix, growing attached to a surface. Nearly all device-associated infections involve growth in the biofilm life style. Biofilm communities have characteristic architecture and distinct phenotypic properties. The most clinically important phenotype involves extraordinary resistance to antimicrobial therapy, making biofilm infections very difficulty to cure without device removal. The current studies examine drug resistance in Candida albicans biofilms. Similar to previous reports, we observed marked fluconazole and amphotericin B resistance in a C. albicans biofilm both in vitro and in vivo. We identified biofilm-associated cell wall architectural changes and increased -1,3 glucan content in C. albicans cell walls from a biofilm compared to planktonic organisms. Elevated -1,3 glucan levels were also found in the surrounding biofilm milieu and as part of the matrix both from in vitro and in vivo biofilm models. We thus investigated the possible contribution of -glucans to antimicrobial resistance in Candida albicans biofilms. Initial studies examined the ability of cell wall and cell supernatant from biofilm and planktonic C. albicans to bind fluconazole. The cell walls from both environmental conditions bound fluconazole; however, four-to fivefold more compound was bound to the biofilm cell walls. Culture supernatant from the biofilm, but not planktonic cells, bound a measurable amount of this antifungal agent. We next investigated the effect of enzymatic modification of -1,3 glucans on biofilm cell viability and the susceptibility of biofilm cells to fluconazole and amphotericin B. We observed a dose-dependent killing of in vitro biofilm cells in the presence of three different -glucanase preparations. These same concentrations had no impact on planktonic cell viability. -1,3 Glucanase markedly enhanced the activity of both fluconazole and amphotericin B. These observations were corroborated with an in vivo biofilm model. Exogenous biofilm matrix and commercial -1,3 glucan reduced the activity of fluconazole against planktonic C. albicans in vitro. In sum, the current investigation identified glucan changes associated with C. albicans biofilm cells, demonstrated preferential binding of these biofilm cell components to antifungals, and showed a positive impact of the modification of biofilm -1,3 glucans on drug susceptibility. These results provide indirect evidence suggesting a role for glucans in biofilm resistance and present a strong rationale for further molecular dissection of this resistance mechanism to identify new drug targets to treat biofilm infections.
We used Centers for Disease Control and Prevention HIV Counseling and Testing System data from 2007 to determine the percentage and characteristics of persons newly identified as HIV-positive in US correctional facilities. The newly identified HIV positivity was 0.7%, and 30% of detainees newly identified with HIV were categorized as having low-risk heterosexual contact or no acknowledged risk. Correctional facilities should provide detainees with routine opt-out HIV testing, unless the prevalence of previously undiagnosed HIV infection has been documented to be less than 0.1%.
Objective. We determined the demographic and HIV test characteristics of tests conducted in CDC-funded sexually transmitted disease (STD) clinics with provision of test results and posttest counseling.Methods. We used CDC's HIV Counseling and Testing System data from 2007 for the 24 U.S. health departments that reported test-level data from STD clinics. We calculated and analyzed newly identified HIV positivity and the percentage of tests with provision of test results and posttest counseling (provision of posttest counseling), by demographic and HIV-related characteristics.
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