Evaluation of high-dose daptomycin for therapy of experimental Staphylococcus aureus foreign body infection

BACKGROUND: Daptomycin is a novel cyclic lipopeptide whose bactericidal activity is not affected by current antibiotic resistance mechanisms displayed by S. aureus clinical isolates. This study reports the therapeutic activity of high-dose daptomycin compared to standard regimens of oxacillin and vancomycin in a difficult-to-treat, rat tissue cage model of experimental therapy of chronic S. aureus foreign body infection. METHODS: The methicillin-susceptible S. aureus (MSSA) strain I20 is a clinical isolate from catheter-related sepsis. MICs, MBCs, and time-kill curves of each antibiotic were evaluated as recommended by NCCLS, including supplementation with physiological levels (50 mg/L) of Ca(2+ )for daptomycin. Two weeks after local infection of subcutaneously implanted tissue cages with MSSA I20, each animal received (i.p.) twice-daily doses of daptomycin, oxacillin, or vancomycin for 7 days, or was left untreated. The reductions of CFU counts in each treatment group were analysed by ANOVA and Newman-Keuls multiple comparisons procedures. RESULTS: The MICs and MBCs of daptomycin, oxacillin, or vancomycin for MSSA strain I20 were 0.5 and 1, 0.5 and 1, or 1 and 2 mg/L, respectively. In vitro elimination of strain I20 was more rapid with 8 mg/L of daptomycin compared to oxacillin or vancomycin. Twice-daily administered daptomycin (30 mg/kg), oxacillin (200 mg/kg), or vancomycin (50 mg/kg vancomycin) yielded bactericidal antibiotic levels in infected cage fluids throughout therapy. Before therapy, mean (± SEM) viable counts of strain I20 were 6.68 ± 0.10 log(10 )CFU/mL of cage fluid (n = 74). After 7 days of therapy, the mean (± SEM) reduction in viable counts of MSSA I20 was 2.62 (± 0.30) log(10 )CFU/mL in cages (n = 18) of daptomycin-treated rats, exceeding by >2-fold (P < 0.01) the viable count reductions of 0.92 (± 0.23; n = 19) and 0.96 (± 0.24; n = 18) log(10 )CFU/mL in cages of oxacillin-treated and vancomycin-treated rats, respectively. Viable counts in cage fluids of untreated animals increased by 0.48 (± 0.24; n = 19) log(10 )CFU/mL. CONCLUSION: The improved efficacy of the twice-daily regimen of daptomycin (30 mg/kg) compared to oxacillin (200 mg/kg) or vancomycin (50 mg/kg) may result from optimisation of its pharmacokinetic and bactericidal properties in infected cage fluids

Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography

Background: By allowing one to detect fluorescence beyond the retinal pigment epithelium, indocyanine green angiography (ICGA) has made it possible to analyse the choroidal vessels. Our aim was to characterize choroidal vasculitis in posterior uveitis using ICGA. Methods: Charts of active posterior uveitis patients with a specific diagnosis seen in the different centers participating in the study who had undergone dual fluorescein and ICG angiography were reviewed. The type of inflammatory involvement of the choroidal circulation at entry and the treatment response on follow-up angiograms were analysed. Results: A total of 129 patients were analysed. Choroidal vasculitis could be subdivided into two main patterns: (1) primary inflammatory choriocapillaropathy and (2) stromal inflammatory vasculopathy. The First pattern consisted of hypofluorescent areas up to the late phase of angiography characteristic for choriocapillaris non-perfusion and included entities such as multiple evanescent white dot syndrome (MEWDS), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), multifocal choroiditis (MC), ampiginous choroidopathy and serpiginous choroidopathy. The second pattern consisted of fuzzy indistinct appearance of vessels in the intermediate angiographic phase and diffuse choroidal hyperfluorescence in the late phase indicating inflammatory vasculopathy of larger choroidal vessels. This pattern was found in all cases of active Vogt-Koyanagi-Harada disease, ocular sarcoidosis and tuberculosis and birdshot chorioretinopathy. In Behcet's uveitis of recent onset, choriocapillaris perfusion delay and fuzzy choroidal vessels without diffuse late choroidal hyperfluorescence was found. In posterior scleritis, enlargement of vorticous veins was an additionnal ICGA sign. Stromal inflammatory vasculopathy always responded to anti-inflammatory therapy. A third group of patients with severe retinal or choroidal inflammation presented with associated secondary inflammatory choriocapillaropathy angiographically identical to the primary involvement. Conclusions: ICGA allowed the hitherto impossible characterization of inflammatory involvement of the choroidal vessels, showing either predominant inflammation of the choriocapillaris or predominant inflammation of the stromal choroidal vessels with or without secondary choriocapillaritis. ICGA will be indispensable for the correct evaluation and follow-up of posterior inflammation with suspected choroidal involvement