Validation of a Novel Murine Wound Model of Acinetobacter baumannii Infection

Patients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which include A. baumannii (the ESKAPE pathogens are En-terococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). As new therapies are being developed to counter A. baumannii infections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine woundmodel in which a diminutive inoculum of a clini-cally relevant, multidrug-resistant A. baumannii isolate can proliferate, form biofilms, and be effectively treated with antibiot-ics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and quali-tative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA commu-nity profiling, histopathology, peptide nucleic acid-fluorescence in situ hybridization, and scanning electron microscopy assess-ment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treate