Effect of Antimicrobial Prophylaxis on Corynebacterium bovis Infection and the Skin Microbiome of Immunodeficient Mice.

Corynebacterium bovis is an opportunistic pathogen of the skin of immunodeficient mice and is sensitive to oral antibiotics that reach therapeutic blood concentrations. However, prophylactic antibiotics are considered to be ineffective at preventing C. bovis infection. In addition, the effect of C. bovis on the skin microbiome (SM) of common immunodeficient mouse strains has yet to be characterized. Consequently, we evaluated whether oral prophylactic antibiotics prevent C. bovis infection after inoculation. An infectious dose of C. bovis was applied to the skin of Hsd:Athymic Nude (nude) and NOD. Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Mice were then housed individually and assigned randomly to receive either untreated drinking water (Cb+Abx-group) or prophylactic amoxicillin-clavulanic acid in the drinking water (0.375 mg/mL) for 14 d (Cb+Abx+group). A third treatment group of each mouse strain was uninoculated and untreated (Cb-Abx-group). Mice from all groups were serially sampled by using dermal swabs to monitor C. bovis infection via quantitative real-time PCR and the SM via 16S rRNA sequence analysis. Fourteen days of prophylactic antibiotics prevented the perpetuation of C. bovis skin infection in both strains. Only the combination of C. bovis inoculation and oral antibiotics (Cb+Abx+) significantly affected the SM of NSG mice at day 14; this effect resolved by the end of the study (day 70). In mice that did not receive antibiotics, C. bovis significantly altered the SM of nude mice but not NSG mice at days 14 and 70. These findings demonstrate the potential benefit of prophylactic antibiotics for prevention of C. bovis infection. However, indirect effect of antibiotics on commensal bacteria and potential effects on xenograft models must be considered.

Antimicrobial Susceptibility of Corynebacterium bovis Isolates from Immunodeficient Rodents.

Corynebacterium bovis, the causative agent of hyperkeratotic dermatitis in immunodeficient mice, is a significant problem in preclinical oncology research. Infection results in lifelong skin colonization and a decrease in successful engraftment of patient-derived xenograft tumor models. The use of antimicrobial agents for C. bovis is controversial in light of reports of poor efficacy and the possibility of selection for resistant strains. The purpose of this study was to describe the antimicrobial susceptibilities of C. bovis isolates obtained exclusively from immunodeficient rodents in order to aid in antimicrobial dose determination. Between 1995 and 2018, 15 isolates were collected from 11 research institutions across the United States. Antimicrobial susceptibility testing was performed for 24 antimicrobials commonly used against gram-positive bacteria. Our results provide an updated understanding of the susceptibility profiles of rodent C. bovis isolates, indicating little variability between geographically and temporally distant isolates. These results will facilitate appropriate antimicrobial use to prevent and treat C. bovis infections in immunodeficient rodents.