Efficacy and Impact of Prophylactic Compared with Symptomatic Amoxicillin, Azithromycin, or Trimethoprim/Sulfamethoxazole Administration on Corynebacterium bovis Infection in NSG Mice (Mus musculus).

Infection with Corynebacterium bovis causes significant clinical disease in immunocompromised mice. The impact of antibiotics, administered prophylactically or symptomatically, on body weight, clinical condition, skin histopathology, and gut microbiota was assessed in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice infected with C. bovis. Mice were untreated (n = 5) or received oral amoxicillin, sulfamethoxazole/trimethoprim (TMS), or azithromycin a day prior to C. bovis exposure (n = 5/antibiotic) or after clinical signs developed (n = 5/antibiotic). Body weights and clinical scores were ascertained weekly. Mice were euthanized 24 weeks after infection, or earlier if humane endpoints were reached. Skin biopsies and fecal samples were collected at necropsy for histopathology scoring and gut flora characterization. Mice treated with amoxicillin had significant improvement in their clinical signs for the duration of treatment; however, 2 mice treated prophylactically experienced severe weight loss that necessitated euthanasia. Amoxicillin-treated mice had aberrant gut microbiota, including Clostridioides difficile colonization. In contrast, mice treated with TMS had no difference in their clinical scores, and their skin pathology was more severe, compared with untreated mice. There was no difference between symptomatic and prophylactic treatment. Clinical disease in azithromycin-treated mice improved for ∼5 weeks, but ultimately clinical disease recrudesced despite continuing therapy. Mice treated prophylactically with azithromycin experienced severe weight loss that necessitated euthanasia. Changes in the intestinal flora were not appreciated in mice treated with TMS or azithromycin as compared with untreated controls. While clinical signs of C. bovis infection in NSG mice improved when treated with amoxicillin, marked changes in the intestinal flora of these animals require careful consideration of both animal health and experimental outcomes before its use. TMS and azithromycin did not ameliorate C. bovis-associated disease, and their use as therapeutics for C. bovis is not recommended. Untreated C. bovis infection was not life-limiting for up to 24 weeks in NSG mice.