Antifungal Resistance Patterns in Molds Isolated from Wounds of Combat-Related Trauma Patients

Abstract

Background An outbreak of trauma-related invasive fungal infections (IFI) occurred in US service members injured in Afghanistan. Empiric treatment included voriconazole (VORI) and amphotericin (AMB) and aggressive surgical debridement. Antifungal susceptibilities (AS) and relation to outcomes are yet to be described.Methods Between 2009 and 2013, military trauma patients with initial unique and serial (>3 days after initial isolation) molds isolated from wounds and admitted to Brooke Army Medical Center as part of the Trauma Infectious Disease Outcomes Study were assessed. The AS to AMB, VORI, posaconazole (POSA), isavuconazole (ISA), itraconazole, and caspofungin were determined by broth microdilution with CLSI breakpoint interpretations for Aspergillus spp. and mucormycetes (MM).ResultsIncluded are 18 patients with 28 initial mold isolates with 72% of IFI diagnosed via histopathology. All patients were male with a median of eight operations. There was a median of 11 days post-injury to mold culture. Initial isolates were five Aspergillus spp., three MM, three Fusarium spp., and combinations of three Aspergillus and MM, two Aspergillus and Fusarium, one Aspergillus and Bipolaris, one MM and Fusarium. A. flavus (AFL) and A. fumigatus (AFU) were all susceptible to AMB and POSA and 25% of AFL were intermediate to VORI. Four A. terreus (AT) isolates had MICs to AMB of 0.25, 1, 2, and 4, and were susceptible to VORI. ISA MIC50 and 90 were one and two for Aspergillus spp. Fusarium spp. MICs were >16 for VORI, POSA, and ISA, with AMB MIC50/90 of two and three. Among MM isolates, 86% were susceptible to AMB and 29% to POSA, and ISA MIC50 and MIC90 were 8 and >16. Five patients had serial isolates. One with serial AFL and AFU received no antifungal therapy, one with AT was treated with VORI, AMB, and POSA, and one with AFL was treated with AMB with no new resistance. The patient with serial MM was treated with AMB and VORI and remained resistant to POSA, but susceptible to AMB. Serial A. elegans acquired new POSA and AMB resistance and ISA MIC increased from 4 to 16 after AMB and VORI exposure.Conclusion Antifungal exposure to AMB and VORI was not associated with new resistance within Aspergillus spp., but 50% of MM exposed to this combination developed POSA and AMB resistance. Despite resistance of Fusarium, it was not isolated on subsequent debridements.Disclosures All authors: No reported disclosures.