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

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.

Combination therapy for mucormycosis: why, what, and how?

The high mortality rate of mucormycosis with currently available monotherapy, particularly in hematology patients, has stimulated interest in studying novel combinations of antifungal agents to determine whether superior outcomes might be achieved. Combination lipid polyene-echinocandin therapy is the most promising of such regimens based on safety profile, the availability of parenteral formulations of echinocandins, their synergy in murine models of mucormycosis, and observational clinical data that are concordant. Other options include combination lipid polyene plus deferasirox or posaconazole therapy. Definitive, randomized, placebo-controlled phase III clinical trials are needed to determine whether combination therapy with any of these options is superior to monotherapy. Until such studies are conducted, clinicians will continue to be placed in the unacceptable position of not knowing if and when to administer combination therapy. Such a state of confusion may lead to undertreatment if combination therapy is indeed superior but is not used and, conversely, may lead to unacceptable toxicity and cost to patients if combination therapy is not superior but is used. It is critical that sponsors step forward with funding to conduct these clinical trials to determine whether outcomes from these devastating infections can be improved.

Acute Invasive Fungal Rhinosinusitis in Immunocompromised Patients: Role of an Early Diagnosis.

Objective The aims of the present study were to evaluate the clinical significance of the delay for surgical treatment and the prognostic value of other clinical, pathologic, and microbiological variables among hematologic patients affected by acute invasive fungal rhinosinusitis (AIFRS). Furthermore, we propose our early diagnosis and treatment protocol, reporting its 10-year results. Study Design Monocentric retrospective analysis. Setting The study was conducted from 2001 to 2017 at the University Hospital of Bologna, Italy. Subjects and Methods The impact of time to treatment and clinical, pathologic, and microbiological variables were analyzed among patients with histologically and microbiologically proven AIFRS. The outcomes of patients treated before the introduction of the early diagnosis protocol were compared with those treated afterward. Results Nineteen patients affected by AIFRS were eligible for the study. Treatment delay >4 days ( P = .002), infection caused by Mucorales ( P = .015), and extension of the disease were negative prognostic variables ( P = .017). The application of our protocol significantly reduced the delay for diagnosis and appropriate treatment by an average of 7.3 days ( P = .02). Conclusion The promptness of the diagnosis and surgical treatment may play a significant role in the management of AIFRS, as it appears to be significantly associated with the disease outcome. Our protocol may help to reduce the time required for diagnosis of high-risk hematologic patients.

Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin.

We hypothesized that the cell wall inhibitor micafungin (MICA) induces apoptosis in both MICA-susceptible (MICA-S) and MICA-non-susceptible (MICA-NS) Candida parapsilosis. Antifungal activity and apoptosis were analyzed in MICA-S and MICA-NS C. parapsilosis strains following exposure to micafungin for 3 h at 37°C in RPMI 1640 medium. Apoptosis was characterized by detecting phosphatidylserine externalization (PS), plasma membrane integrity, reactive oxygen species (ROS) generation, mitochondrial membrane potential changes, adenosine triphosphate (ATP) release, and caspase-like activity. Apoptosis was detected in MICA exposed (0.25 to 1 mg/L) susceptible C. parapsilosis strains and was associated with apoptosis of 20-52% of analyzed cells versus only 5-30% of apoptosis in MICA-NS cells exposed to micafungin (0.5 to 2 mg/L; P = 0.001). The MICA antifungal activity was correlated with apoptotic cells showing increased dihydrorhodamine-123 staining (indicating ROS production), Rh-123 staining (decreased mitochondrial membrane potential), elevated ATP, and increased metacaspase activity. In conclusion, MICA is pro-apoptotic in MICA-S cells, but still exerts apoptotic effects in MICA -NS C. parapsilosis.