FIG 5.
Protective efficacy of postexposure treatment with MEDI4893* and/or linezolid (LZD). After intradermal infection with 2.7 × 109 CFU of the SF8300 wild-type strain, rabbits were randomized into one of the following four treatment groups: (i) a single dose of 30 mg/kg c-IgG intravenously at 2 h postinfection (11 rabbits), (ii) a single dose of 30 mg/kg MEDI4893* intravenously at 2 h postinfection (12 rabbits), (iii) four doses of 25 mg/kg linezolid (LZD) subcutaneously at 2, 10, 18, and 26 h postinfection (12 rabbits), and (iv) a single dose of 30 mg/kg MEDI4893* intravenously at 2 h postinfection and four doses of 25 mg/kg linezolid subcutaneously at 2, 10, 18, and 25 h postinfection (12 rabbits). (A) Dermonecrosis area on each day postinfection. Error bars indicate SEMs. Pairwise comparisons of the daily dermonecrosis area for rabbits treated with c-IgG versus linezolid (except on days 1 and 2), c-IgG versus MEDI4893*, c-IgG versus linezolid-MEDI4893*, and linezolid versus linezolid-MEDI4893* yielded multiplicity-adjusted P values of <0.05, whereas pairwise comparisons of the daily dermonecrosis area for rabbits treated with linezolid versus MEDI4893* and MEDI4893* versus linezolid-MEDI4893* yielded P values of >0.05 (see Table S5 in the supplemental material). (B) Bacterial burden of dermonecrotic ulceration harvested from rabbits euthanized on day 7 postinfection. Pairwise comparisons of the log10 number of CFU per gram for rabbits treated with c-IgG versus LZD, c-IgG versus MEDI4893*, c-IgG versus linezolid-MEDI4893*, and linezolid versus linezolid-MEDI4893* yielded P values of >0.05, whereas pairwise comparisons of the log10 number of CFU per gram for rabbits treated with linezolid versus MEDI4893* and MEDI4893* versus linezolid-MEDI4893* yielded P values of 0.028 and 0.043, respectively. (C) Representative gross images of dermonecrotic ulceration taken on day 7 postinfection.