Widespread Lichtheimia Infection in a Patient with Extensive Burns: Opportunities for Novel Antifungal Agents

Abstract

The Mucorales fungi-formerly classified as the zygomycetes-are environmentally ubiquitous fungi, but generally rare causes of clinical infections. In the immunocompromised host, however, they can cause invasive, rapidly spreading infections that confer a high risk of morbidity and mortality, often despite surgical and antifungal therapy. Patients with extensive burn injuries are particularly susceptible to skin and soft-tissue infections with these organisms. Here, we present a case of Lichtheimia infection in a patient with extensive full-thickness burns that required significant and repeated surgical debridement successfully treated with isavuconazole and adjunctive topical amphotericin B washes. We also review the available literature on contemporary antifungal treatment for Lichtheimia species and related Mucorales fungi.

Necrotizing Mucormycosis of Wounds Following Combat Injuries, Natural Disasters, Burns, and Other Trauma

“…Development of new approaches for topical therapy, as well as discovery of novel antifungal agents with the potential for synergistic combinations with licensed compounds may improve therapeutic outcome, especially in eradicating residual fungi that are not removed by debridement or other surgical interventions [49,50]. Further study of the newer antifungal agents, such as posaconazole and isavuconazole, are merited [51]. Finally, the potential for novel tissue regenerative systems offers potential new approaches in management of the wounds associated with trauma-related mucormycosis.…”

Mucormycosis in Burn Patients

“…Three nosocomial outbreaks were reported: one in Belgium in 2005 and two in France in 2018 [13,14,15,16]. Lastly, 25 reports of individual cases were identified between 1990 and 2019, including publications from the USA ( n = 12, with three cases occurring in the Middle East (Afghanistan, Iraq) and one in Japan) [17,18,19,20,21,22,23,24,25,26,27,28], from Asia ( n = 6; two in China, three in India, one in Iran) [29,30,31,32,33,34], from Europe ( n = 3; in Czech Republic, Germany, and the U.K.) [35,36,37], from Australia ( n = 3) [3,38,39], and from Ecuador ( n = 1) [40]. The data from case series and outbreaks are summarized in Table 1.…”

“…Although posaconazole and isavuconazole can also be considered for the treatment of mucormycosis [42,43], only three reports of treatment with posaconazole and/or isavuconazole were identified in three patients, including two patients who underwent initial treatment with liposomal amphotericin B [14,33]. In the third patient, posaconazole was followed by isavuconazole and associated with local amphotericin B [27]. Surprisingly, one patient with low TBSA (4%–5%) who presented diabetes mellitus with hyperglycemia and was poorly controllable by high-dose insulin was successfully treated with voriconazole, which is known to lack meaningful in vitro activity against Mucorales [29].…”

Isavuconazole—Animal Data and Clinical Data

“…After exclusion of reports published in non-English language or in which clinical and therapeutic data were not available for the purpose of the present review, a total of 41 cases have been included. Clinical and demographic characteristics, details of the antifungal treatment, outcome and adverse effects reported on these patients are summarized in Table 2 [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Thirty-three out of 42 (78.5%) patients were male and the mean age was 52 years (range 20–79).…”