Comparison of two commercially available selective media to screen for vancomycin-resistant enterococci.

Campylobacter medium (CAMPY, Becton Dickinson [BD] Microbiology Systems, Cockeysville, MD) and Vancomycin Screen Agar (VSA, BD) were compared for their ability to screen for vancomycin-resistant Enterococcus (VRE) from primary plates. A microdilution minimal inhibitory concentration (MIC) assay (Pasco, BD) served as the reference vancomycin MIC. In the random sample of 200 enterococcal clinical isolates tested, the distribution of isolates was as follows: Enterococcus faecium, 113 (97 VRE); Enterococcus faecalis, 71(12 VRE); Enterococcus gallinarum, 10; and Enterococcus casseliflavus, 6. Of the 75 vancomycin-susceptible strains, none grew on CAMPY and 4 grew on VSA, whereas all 109 VRE isolates grew on both screen plates. Of the 16 strains with a Van C phenotype, ie, E. gallinarum and E. casseliflavus, 2 grew on CAMPY and 14 on VSA. Of the 899 clinical specimens plated onto both agars, 45 of 67 VRE were detected with both media, 20 were detected only with CAMPY and 2 were not detected by either screen plate. CAMPY compared with VSA as a primary plating medium was more sensitive and, when used to screen for VRE isolates from primary plates, was more specific for strains displaying Van A and B phenotypes.     

Induction of protective immunity against a Chlamydia trachomatis genital infection in three genetically distinct strains of mice

To establish the feasibility of inducing a protective immune response against a chlamydial genital infection in animals with different genetic backgrounds, groups of C3H/HeN (H-2k), BALB/c (H-2d) and C57BL/6 (H-2b) mice, were immunized intranasally with elementary bodies (EB) of the Chlamydia trachomatis mouse pneumonitis biovar. Following the intranasal immunization strong Chlamydia-specific humoral and cell-mediated immune (CMI) responses were detected in the three strains of mice. Eight weeks following immunization the animals were challenged with C. trachomatis in the genital tract. Vaginal cultures showed that the three strains of mice immunized with EB were significantly protected in comparison to the sham immunized animals. To determine the ability of this immunization protocol to protect against infertility six weeks after the genital challenge the animals were mated. Mice of the three strains immunized with EB showed significant protection as demonstrated by the number of animals that were fertile, and the number of embryos present in their uterine horns, in comparison to the sham immunized mice.     

Intra and Inter-Molecular Interactions Dictate the Aggregation State of Irinotecan Co-Encapsulated with Floxuridine Inside Liposomes

PURPOSE: The inter/intramolecular interactions between drugs (floxuridine, irinotecan) and excipients (copper gluconate, triethanolamine) in the dual-drug liposomal formulation CPX-1 were elucidated in order to identify the physicochemical properties that allow coordinated release of irinotecan and floxuridine and maintenance of the two agents at a fixed, synergistic 1:1 molar ratio. METHODS: Release of irinotecan and floxuridine from the liposomes was assessed using an in vitro-release assay. Fluorescence, Nuclear Magnetic Resonance spectroscopy (NMR) and UV-Vis were used to characterize the aggregation state of the drugs within the liposomes. RESULTS: Coordinated release of the drugs from liposomes was disrupted by removing copper gluconate. Approximately 45% of the total irinotecan was detectable in the copper-containing CPX-1 formulation by NMR, which decreased to 19% without copper present in the liposomal interior. Formation of higher order, NMR-silent aggregates was associated with slower and uncoordinated irinotecan release relative to floxuridine and loss of the synergistic drug/drug ratio. Solution spectroscopy and calorimetry revealed that while all formulation components were required to achieve the highest solubility of irinotecan, direct drug-excipient binding interactions were absent. CONCLUSIONS: Long-range interactions between irinotecan, floxuridine and excipients modulate the aggregation state of irinotecan, allowing for simultaneous release of both drugs from the liposomes.     

Role of matrix metalloproteinase-7 in the modulation of a Chlamydia trachomatis infection

To determine the role of matrix metalloproteinase-7 (MMP-7) in the pathogenesis of chlamydial infection, C57BL/6 wild-type (WT) and MMP-7 knockout (KO) mice were infected intravaginally with Chlamydia trachomatis mouse pneumonitis (MoPn). Over a period of 6 weeks postinfection, various organs were cultured for C. trachomatis. Other infected animals were mated to assess their fertility status. No significant differences were observed between WT and KO mice in the number of animals with positive vaginal cultures, length of time of C. trachomatis shedding, or the number of C. trachomatis inclusion-forming units (IFU) recovered from their genital tracts. Likewise, the number of animals with hydrosalpinx, and the fertility rates and the number of embryos per mouse, were similar in WT and KO mice. Cultures from the spleen, lungs, kidneys and large intestine yielded similar numbers of IFU from WT and KO mice. However, the number of C. trachomatis IFU recovered from the small intestine of KO mice was significantly higher than that recovered from the small intestine of WT mice at 2 weeks postinfection. Because MMP-7 KO mice are deficient in active intestinal alpha-defensins, the results suggest that these components play a role in regulating colonization of the gastrointestinal tract by Chlamydia. By contrast, MMP-7 is dispensable in the progression and resolution of the genital tract infection.