Invasive Aspergillosis Due to Aspergillus Section Usti: A Multicenter Retrospective Study

Abstract

Background Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. Methods Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. Results Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively. Conclusions Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.

Clinical Relevance and Characteristics of Aspergillus calidoustus and Other Aspergillus Species of Section Usti

“…Actually, most cases of human infections that were attributed to A. ustus in the literature, were secondarily reassigned to a novel distinct species, A. calidoustus, which is able to grow at 37 • C [14]. Two other closely related species, A. pseudodeflectus and A. granulosus, are also thermotolerant at human body temperature and were also found to be able to cause invasive infections in humans [11,[15][16][17]. A. ustus sensu stricto was also isolated from a patient with aspergillosis localized to the skin and soft tissue [11].…”

“…Two other closely related species, A. pseudodeflectus and A. granulosus, are also thermotolerant at human body temperature and were also found to be able to cause invasive infections in humans [11,[15][16][17]. A. ustus sensu stricto was also isolated from a patient with aspergillosis localized to the skin and soft tissue [11]. Other non-thermotolerant species of section Usti that were isolated as colonizers or contaminants from clinical specimens include A. insuetus, A. puniceus and A. keveii [11].…”

“…A. ustus sensu stricto was also isolated from a patient with aspergillosis localized to the skin and soft tissue [11]. Other non-thermotolerant species of section Usti that were isolated as colonizers or contaminants from clinical specimens include A. insuetus, A. puniceus and A. keveii [11]. Table 1.…”

“…of section Usti are usually reliable for identification at the section level. However, species identification would require partial sequencing of the beta-tubulin (BenA) or calmodulin (CaM) genes, which is not routinely available in most diagnostic microbiology laboratories [11]. Standard sequencing methods targeting the internal transcribed spacer (ITS) or 26-28S rDNA are not reliable enough for identification beyond the section level.…”

“…A. ustus and related species were also frequently recovered from water-damaged buildings and from caves affected by human activities [8,9]. While the first case of IA due to Aspergillus of section Usti was described in 1974 [10], these infections have been increasingly reported in the literature since 2000 [11,12].…”