OC-0074: A real time in vivo dosimeter integrated in the radiation protection disc for IORT breast treatment

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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

Analysis of the bias induced by voxel and unstructured mesh Monte Carlo models for the MCNP6 code in orthovoltage applications

The use of Monte Carlo methods for the set up of Treatment Planning Systems (TPS) in radiotherapy applications is a current standard. The most advanced modeling techniques aim at directly link the output of CT scans to a patient-specific model build up instead of standard phantoms and look-up tables. This link represents a critical step since even the most accurate segmentation and organ volume definition must be translated into a suitable input for the Monte Carlo code. During that step, the segmented volume is usually mapped on a regular geometrical lattice (voxels). A more sophisticated option appears to be a volume description based on an Unstructured Mesh (UM) geometry typical of current finite element codes. In this paper, we compared the two approaches analyzing the bias induced by the different choices. Starting from anonymous patient DICOM files coming from a CT scan, suitable segmentation and volume definition have been carried out and voxel and UM-based equivalent models for the Monte Carlo code MCNP6 have been built. Some computational phantoms, covering some significant portion of the human body (head and lower limb), have been used as a benchmark of the dose distribution obtained from X-ray sources commonly used in orthovoltage applications. The specific clinical application has been chosen because, despite being used on a growing number of patients and with multi-Gy doses, treatment planning is still based on poorly characterized dose mapping systems such as look-up tables or low-resolution computational phantoms for MC codes. Also, experimental measurements on phantom slabs irradiated by an X-ray source were carried out preliminarily to validate the simulated radiation source. As shown in the results, the UM computational phantoms (built through the Simpleware SCAN-IP\u2122 tool) can reduce the bias induced by the regularity of the classical cubic voxel geometry, give a more accurate description of volumes and complex surfaces and, thanks to an optimized discretization of the volumes, are also able to reduce the computational work. For the same UM models, various comparisons with different voxel sizes have been produced to investigate the dose distributions and evaluate the voxelization effects. The comparison shows a convergence pattern of the voxel model to the UM one. It has been possible to verify that the most significant bias occurs where the dose gradient is higher, along the beam borders and at tissue interfaces. The simulations showed that the UM can be really effective and reliable to compute the dose distributions within computational anthropomorphic phantoms obtained from the patient\u2019s CT scans

Comparison of sparfloxacin, temafloxacin, and ciprofloxacin for prophylaxis and treatment of experimental foreign-body infection by methicillin-resistant Staphylococcus aureus.

The prophylactic and therapeutic activities of three broad-spectrum fluoroquinolones were evaluated in two different experimental models of foreign-body infections caused by methicillin-resistant Staphylococcus aureus (MRSA) susceptible to quinolones. In a guinea pig model of prophylaxis, subcutaneously implanted tissue cages were infected at a > 90% rate by 10(2) CFU of MRSA in control animals. A single dose of 50 mg of ciprofloxacin per kg of body weight administered intraperitoneally 3 h before bacterial challenge was less effective than an equivalent regimen of either sparfloxacin or temafloxacin in decreasing the rate of experimental infection in tissue cages challenged with increasing inocula of MRSA. In a rat model evaluating the therapy of chronic tissue cage infection caused by MRSA, the efficacy of a 7-day high-dose (50-mg/kg twice-daily) regimen of sparfloxacin, temafloxacin, or ciprofloxacin was compared to that of vancomycin (50 mg/kg twice daily). Active levels of sparfloxacin, temfloxacin, or ciprofloxacin were continuously present in tissue cage fluid during therapy, exceeding their MBCs for MRSA by 6- to 20-fold. Either temafloxacin, sparfloxacin, or vancomycin was significantly (P < 0.01) more active than ciprofloxacin in decreasing the viable counts of MRSA in tissue cage fluids. The different activities of ciprofloxacin compared with those of the other two quinolones against chronic tissue cage infections caused by MRSA did not involve the selective emergence of quinolone-resistant mutants. Temafloxacin and ciprofloxacin, which showed the most prominent differences in their in vivo activities, however, exhibited similar bactericidal properties and pharmacokinetic parameters in the rat model. In conclusion, both temafloxacin and sparfloxacin were significantly more active than ciprofloxacin for the prophylaxis or treatment of experimental foreign-body infections caused by a quinolone-susceptible strain of MRSA