亀井 克彦

BACKGROUND: Gastrointestinal mucormycosis is a rapidly progressing and often fatal disease, predominantly affecting immunocompromised patients. Surgical intervention, in addition to antifungal therapy, is essential. Herein, we describe the successful management of appendiceal mucormycosis in a patient with acute promyelocytic leukemia through rapid surgical intervention and antifungal therapy. CASE PRESENTATION: A 29-year-old woman underwent autologous peripheral blood stem cell transplantation for acute promyelocytic leukemia (APL). Subsequently, her condition relapsed, and remission induction therapy was initiated. During the immunosuppressive period, she developed a fever and severe abdominal pain. Computed tomography revealed severe edema of the ileum, cecum, and ascending colon. Despite receiving multiple antibiotics, antivirals, and antifungals, her condition showed no improvement. Consequently, she underwent exploratory laparotomy, with no bowel perforation noted, revealing severe inflammation in the ileum, cecum, and ascending colon, as well as appendiceal necrosis. Appendectomy was performed, and histopathological analysis revealed hyphae in the vessels and layers of the appendiceal wall, suggestive of mucormycosis. The patient was diagnosed with appendiceal mucormycosis, and liposomal amphotericin B was administered. Subsequent monitoring showed no recurrence of mucormycosis. Genetic analysis of the resected tissue revealed Rhizopus microspores as the causative agent. CONCLUSIONS: Rapid surgical intervention and antifungal drug administration proved successful in managing appendiceal mucormycosis in a patient with APL. Early recognition and aggressive surgical intervention are imperative to improve outcomes in such patients.

Autosomal recessive CARD9 deficiency can underly deep and superficial fungal diseases. We identified two Japanese patients, suffering from superficial and invasive Candida albicans diseases, carrying biallelic variants of CARD9. Both patients, in addition to another Japanese and two Korean patients who were previously reported, carried the c.820dup CARD9 variant, either in the homozygous (two patients) or heterozygous (three patients) state. The other CARD9 alleles were c.104G > A, c.1534C > T and c.1558del. The c.820dup CARD9 variant has thus been reported, in the homozygous or heterozygous state, in patients originating from China, Japan, or South Korea. The Japanese, Korean, and Chinese patients share a 10 Kb haplotype encompassing the c.820dup CARD9 variant. This variant thus originates from a common ancestor, estimated to have lived less than 4,000 years ago. While phaeohyphomycosis caused by Phialophora spp. was common in the Chinese patients, none of the five patients in our study displayed Phialophora spp.-induced disease. This difference between Chinese and our patients probably results from environmental factors. (161/250).

Candida parapsilosis complex has recently received special attention due to naturally occurring FKS1 polymorphism associated with high minimal inhibitory concentrations for echinocandin and the increase of clonal outbreaks of strains resistant to commonly used antifungals such as fluconazole. Despite the previous fact, little is known about the genetic mechanism associated with echinocandin resistance. Therefore, the present study was designed to investigate the mechanism of acquired echinocandin resistance in C. parapsilosis complex strains. A total of 15 clinical C. parapsilosis complex isolates were sub-cultured for 30 days at a low concentration of micafungin at ½ the lowest MIC value of the tested isolates (0.12 µg/ml). After culturing, all the isolates were checked phenotypically for antifungal resistance and genotypically for echinocandin resistance by checking FKS1 gene hot spot one (HS1) and HS2 mutations. In vitro induction of echinocandin resistance confirmed the rapid development of resistance at low concentration micafungin, with no difference among C. parapsilosis, C. metapsilosis, and C. orthopsilosis in the resistance development. For the first time we identified different FKS1 HS1 and or HS2 mutations responsible for echinocandin resistance such as R658S and L1376F in C. parapsilosis, S656X, R658X, R658T, W1370X, X1371I, V1371X, and R1373X (corresponding to their location in C. parapsilosis) in C. metapsilosis, and L648F and R1366H in C. orthopsilosis. Our results are of significant concern, since the rapid development of resistance may occur clinically after short-term exposure to antifungals as recently described in other fungal species with the potential of untreatable infections.

We report the case of an 84-year-old man with a history of IgG4-related sclerosing cholangitis who was diagnosed with advanced esophageal cancer and underwent radiation and chemotherapy. An implantable central venous access port was placed for chemotherapy and total parenteral nutrition. The patient presented with a fever and received antimicrobial therapy for acute cholangitis but remained febrile, and subsequently, yeast was detected in the aerobic bottle of blood culture obtained from the central venous line. The yeast was identified as Wickerhamomyces anomalus. Liposomal amphotericin B was administered, and the central line access port was removed. After confirmation of negative blood cultures and 14 days post treatment, he underwent reinsertion of the central line access port. Due to persistent pain at the insertion site, fluconazole was added for an additional 14 days, and the patient was discharged and transferred to another hospital. Wickerhamomyces anomalus is a rare fungal infection with other synonyms including Pichia anomala, Hansenula anomala, and Candida pelliculosa. A literature review of 53 case reports of Wickerhamomyces anomalus, Pichia anomala, Hansenula anomala, and Candida pelliculosa was conducted, with a total of 211 cases reviewed. Fungemia was reported in 94% of cases, with central venous catheterization, parental feeding, low birth weight, and immunocompromised status identified as major risk factors. The majority of cases were pediatric, particularly neonatal, and there were reports of nosocomial infections causing outbreaks, with some cases involving the eye such as endophthalmitis or keratitis.

The identification of Aspergillus species has been performed mainly by morphological classification. In recent years, however, the revelation of the existence of cryptic species has required genetic analysis for accurate identification. The purpose of this study was to investigate five Aspergillus section Nigri strains isolated from a patient and the environment in a university hospital. Species identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry identified all five black Aspergillus strains as Aspergillus niger. However, calmodulin gene sequence analysis revealed that all five strains were cryptic species, four of which, including the clinical strain, were Aspergillus tubingensis. Hospital-acquired infection of the patient with the A. tubingensis strain introduced from the environment was suspected, but sequencing of six genes from four A. tubingensis strains revealed no environmental strain that completely matched the patient strain. The amount of in vitro biofilm formation of the four examples of the A. tubingensis strain was comparable to that of Aspergillus fumigatus. An extracellular matrix was observed by electron microscopy of the biofilm of the clinical strain. This study suggests that various types of biofilm-forming A. tubingensis exist in the hospital environment and that appropriate environmental management is required.