A Novel, Reverse-Phase-Shifting, Thermoreversible Foaming Hydrogel Containing Antibiotics for the Treatment of...

More than one-third of patients with a combat injury evacuated to the United States have wound-related infections during their initial hospitalization, with prevention of such infections an ongoing battlefield challenge. Use of a reverse-phase-shifting thermoreversible foaming hydrogel containing vancomycin and tobramycin (HA) is one possible solution to this problem.

This study compared HA to the hydrogel vehicle without antibiotics (HV) and control (i.e., no intervention). Bilateral, 5 cm diameter, full-thickness wounds were created in 12 male swine (∼50 kg, Sus scrofa). These wounds were then inoculated with Staphylococcus aureus and Pseudomonas aeruginosa. Ten minutes after inoculation, the wounds were treated with HA, HV, or no intervention. This treatment was reapplied daily for a total of 7 days. Blood samples were drawn at baseline, 1 h after initial administration, and on days 1, 3, and 7. After 7 days, the animals were humanely euthanized and the wounds were swabbed or biopsied for microbiological analysis and culture. Full-thickness tissue specimens were subsequently collected for blinded histopathological evaluation of wound healing and bacterial growth.Institutional Animal Care and Use Committee and the U.S. Army's Animal Care and Use Review Office approvals were received prior to initiation of animal experiments.

Bacterial growth and histopathology analyses of cutaneous and skeletal muscle biopsies at the end of the study showed less severe and/or less frequent intralesional bacterial and neutrophilic inflammation in the HA group compared to the HV and control groups. The HV and control groups were comparable, showing no significant differences in treatment effects. Statistical significance was observed in reduced bacterial infiltration when comparing the HA group with both the control and HV groups. Neither vancomycin nor tobramycin was detected systemically in any plasma sample at all time points, with a lower limit of quantification of 50 ng/mL for both antibiotics.

Histopathology demonstrated significantly lower bacterial growth in the HA versus control (P = 1.4e-4) and HV (P = 3.2e-4) groups. It also showed statistically significant differences in other secondary outcomes for wound healing (e.g., neutrophilic infiltrate, fibroplasia, edema) between HA versus HV, as well as HA versus control, in both skin and muscle. In this porcine model of infected traumatic soft tissue injury, HA demonstrated significant benefits, and further research and development to explore its use in a range of settings is justified.