9. Dual administration of liposomal amphotericin B and a broad-spectrum triazole is recommended as the first-line antifungal agents. Among triazoles, clinical experience has been primarily with voriconazole. Many of the wounds incurred by combat casualties grow more than one mold.32 Furthermore, prescribe broad-spectrum antibiotics covering both gram-positive and gram-negative organisms (e.g., vancomycin and meropenem)are prescribed as fungal-infected wounds frequently also have bacterial growth

Initial studies have shown that combat IFI wound cultures growing order Mucorales will have a second non-Mucorales fungus present 30% of the time. Aspergillus species is more difficult to grow than order Mucorales but should be suspected and empirically treated initially as it has been shown to be virulent in this patient population.40 Therefore, dual use of a broad-spectrum triazole and liposomal amphotericin B is suggested for wounds infected with either or both of these fungi. If long-term treatment is required, the antifungal medications should be targeted based on culture results.

10. Isavuconazole is a triazole agent available in IV and oral formulations with mold activity including against mucormycosis. Isavuconazole has not been studied in randomized controlled trials but in one multicenter open-label single-arm study, isavuconazole demonstrated similar efficacy to amphotericin B formulations in an external matched control group.40

11. Particular attention should be given to aggressive debridement of non-viable tissue at each debridement procedure. The extent of necrosis and appearance of the wound before and after completion of the operation should be documented in the operative note. Appendix B shows a standardized operative note for wound description to be used for patients at increased risk for IFI. Whenever a significant amount of necrotic tissue is debrided, repeat debridement should be performed in 24 hours or less.

As aggressive surgical debridement of all necrotic and infected tissue remains the mainstay of treatment for IFI, surgical exploration and debridement should continue at least every 24 hours until cessation of necrosis occurs. Wound coverage and closure should not occur until after the wound is clean, contracting, and granulating.

12. If angioinvasive fungal elements or fungal elements among tissue are reported on histopathology, or if cultures are positive in the setting of recurrent necrosis, initiate (or continue) treatment with systemic antifungal medications. Treatment will require close consultation with infectious disease; however, as a general guideline, stop systemic antifungal medications if the wound remains clean/viable for two weeks and if the patient remains clinically stable. If the patient has a fungal infection in more than one body region (e.g., extremity/pelvis, abdomen, and chest), long-term treatment may be indicated.