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Hamouda et al., Sporicidal Activity of BCTP Nanoemulsion : with BCTP nancemulsion at final dilution of 1 : 10. These animals showed minimal skin lesions, with average area of 0.02 + 0.01 cm? (“98% reduction from lesions resulting from untreated infection with spores; P < .002). Histology of F indicated some inflammation; however, most cellular structures in epidermis and dermis were intact. All histopathology is shown at x4 magnification. Page 8 of 12 In vivo sporicidal activity. _B. cereus infection in experimental animals had been previously used as a model system for the study of anthrax and causes an illness similar to experimental anthrax [2, 9, 21 —24]. Two animal models of cutaneous B. cereus disease were developed to assess the in vivo sporicidal activity of BCTP. A suspension of 4 x 10’ B. cereus spores was mixed with saline or with BCTP at a final dilution of 1 : 10 and then immediately injected subcutaneously into the backs of CD-1 mice. Mice that were infected subcutaneously with B. cereus spores without BCTP developed severe edema in 6-8 h. This was followed by a gray, necrotic area surrounding the injection site at 18-24 h, with severe sloughing of the skin present by 48 h, leaving a dry, red-colored lesion (figure 6C, 6D). CD-1 mice injected with B. cereus spores premixed with BCTP never developed such a necrotic lesion, and edema and inflammation were minimal (figure 6E, 6F). The size of the necrotic lesion in BCTP-treated mice was “98% smaller than the necrotic lesion size in untreated mice (from 1.62 + 0.35 om? to 0.02 + 0.01 om?; P< .002). Similar results were observed with BCTP 401 diluted 1 : 10. In additional studies, a 1-cm skin wound was infected with 2.5 x 10’ B. cereus spores and then closed (figure 74, 7B). For some of the animals 1 h later, the wounds were irrigated with either BCTP diluted 1: 10 or saline to simulate postexposure decontamination, Irrigation of experimentally infected wounds with saline did not result in any apparent benefit (figure 7C, 7D). BCTP irrigation of wounds infected with B. cereus spores showed substantial benefit, resulting in a consistent 98% reduction in the lesion size (from 4.84 + 0.48 cm? to 0.06 + 0.03 cm?; P< .001; figure 7E, 7F). This reduction in lesion size _ ‘was accompanied by a 3-fold reduction in mortality (from 60% to 20%) compared with that in experimental animals receiving either no treatment or saline irrigation. Similar results were observed with BCTP 401 diluted 1 : 10. Figure 7. Gross and histologic photographs of animals with experimental wounds infected with Bacillus cereus spotes. A, B, mice with experimental wounds infected with 2.5 x 107 B. cereus spores but not treated. Histologic examination indicated extensive necrosis and marked inflammatory response. C, D, mice with wounds that were infected with 2.5 x 107 B. cereus spores and irrigated 1 h later with saline. By 48 h, large necrotic areas surrounded wounds, with average area of 4.86 + 0.48 cm. In addition, 60% of animals in this group died as result of infection. Histologic examination of these lesions indicated total necrosis of dermis and subdermis and large numbers of vegetative Bacillus organisms. E, F, mice with wounds infected with 2.5 x 107 B. cereus spores and irrigated 1 h later with 1 : 10 dilution of BCTP. There were small areas of necrosis adjacent to wounds (0.06 +: 0.03 cm), 98% reduction compared with animals receiving spores and saline irrigation (P < .001). In addition, only 20% of animals died from these wounds. Histologic examination of these lesions showed no evidence of vegetative Bacillus organisms and minimal disruption of epidermis. All histopathology is shown at x4 magnification. http://www.journals.uchicago.edu/JID/journal/issues/v180n6/990281/990281 text html 2/18/2005