Candida spp. are commonly a group of opportunistic dimorphic fungi, frequently causing diverse fungal infections in immunocompromised or immunosuppressant patients from mucosal disturbs (oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated infections (systemic candidiasis) with high morbidity and mortality. Importantly, several Candida species can be isolated from diseased individuals with digestive, neuropathic, respiratory, metabolic and autoimmune diseases. Due to increased resistance to conventional antifungal agents, the arsenal for antifungal purpose is in urgent need. Traditional Chinese Medicines (TCMs) are a huge treasury that can be used as promising candidates for antimycotic applications. In this review, we make a short survey of microbiological (morphology and virulence) and pathological (candidiasis and Candida related infections) features of and host immune response (innate and adaptive immunity) to Candida spp.. Based on the chemical structures and well-studied antifungal mechanisms, the monomers, extracts, decoctions, essential oils and other preparations of TCMs that are reported to have fair antifungal activities or immunomodulatory effects for anticandidal purpose are comprehensively reviewed. We also emphasize the importance of combination and drug pair of TCMs as useful anticandidal strategies, as well as network pharmacology and molecular docking as beneficial complements to current experimental approaches. This review construct a therapeutic module that can be helpful to guide in-future experimental and preclinical studies in the combat against fungal threats aroused by C. albicans and non-albicans Candida species.

Candidiasis is a common fungal infection caused by Candida species, with Candida albicans being the most prevalent. Resistance to azole drugs, commonly used to treat Candida infections, poses a significant challenge. Transcriptional activator candidate 1 (TAC1) gene has emerged as a key player in regulating drug resistance in C. albicans. This review explores the structure and function of the TAC1 gene and its role in azole resistance. This gene encodes a transcription factor that controls the expression of genes involved in drug resistance, such as efflux pump genes (CDR1, CDR2, and MDR1) and ERG11. Mutations in TAC1 can increase these genes\' expression and confer resistance to azoles. Various TAC1 gene mutations, mostly gain-of-function mutations, have been identified, which upregulate CDR1 and CDR2 expression, resulting in azole resistance. Understanding the mechanisms of azole resistance mediated by the TAC1 gene is crucial for the strategies in the effective antifungal development pipeline.

BACKGROUND: The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding.
METHODS: We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment.
CONCLUSIONS: The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population.

Extrapulmonary infections by Coccidioides spp., though rare, can occur via dissemination, affecting singular or multiple sites, including the skin and musculoskeletal system. Skeletal involvement often manifests as osteomyelitis, particularly in the axial skeleton. The present systematic review evaluates all documented cases of skeletal coccidioidomycosis to assess the diagnostic and treatment strategies alongside the outcomes, drawing insights from an analysis of 163 verified cases. A systematic review following PRISMA guidelines identified all studies reporting skeletal infections by Coccidioides spp. up to 2023 from the PubMed and Scopus databases. Eligible studies evaluated osteoarticular infections from Coccidioides spp. Data extraction included demographics, microbiological data, diagnostic methods, and treatment outcomes. Of the 501 initially identified records, a total of 163 patients from 69 studies met the inclusion criteria. Most cases were from the USA, predominantly males, while the median age of the population was 36 years. Diabetes mellitus was the common comorbidity (14.7%). C. immitis was the most prevalent pathogen. The spine and hand were common sites of infection (17.5% and 15.1%, respectively). Osteomyelitis by Coccidioides spp. was diagnosed, in most cases, by positive cultures (n = 68; 41.7%), while, in 49 (30.9%), both the histological examination and cultures yielded the fungus. Surgical debridement was performed in 80.9% of cases. A total of 118 (72.3%) patients were treated with monotherapy, while combination therapy with two or more antifungal agents was reported in 45 (17.7%). Amphotericin B (either liposomal or deoxycholate) was the most commonly given agent as monotherapy in 51 (31.2%) patients, while 30 (18.4%) patients received itraconazole as monotherapy. The rate of infection\'s resolution was higher in patients undergoing surgical debridement (79.5%), compared to those treated only with antifungal agents (51.6%, p = 0.003). Treatment outcomes showed complete resolution in 74.2% of patients, with a mortality rate of 9.2%. Coccidioidal osseous infections present diagnostic and therapeutic challenges. Surgical intervention is often necessary, complementing antifungal therapy. Vigilance for Coccidioides spp. infections, especially in regions with endemicity, is crucial, particularly when bacterial cultures yield negative results.

Cryptococcosis is a fungal infectious disease that enormously impacts human health worldwide. Cryptococcal meningitis is the most severe disease caused by the fungus Cryptococcus, and can lead to death, if left untreated. Many patients develop resistance and progress to death even after treatment. It requires a prolonged treatment course in people with AIDS. This narrative review provides an evidence-based summary of the current treatment modalities and future trial options, including newer ones, namely, 18B7, T-2307, VT-1598, AR12, manogepix, and miltefosine. This review also evaluated the management and empiric treatment of cryptococcus meningitis. The disease can easily evade diagnosis with subacute presentation. Despite the severity of the disease, treatment options for cryptococcosis remain limited, and more research is needed.

Fungal keratitis represents a potentially sight-threatening infection associated with poor prognosis, as well as financial burden. Novel diagnostic methods include polymerase-chain-reaction (PCR)-based approaches, metagenomic deep sequences, in vivo confocal microscopy, and antifungal susceptibility testing. The ideal therapeutic approaches and outcomes have been widely discussed in recent times, with early therapy being of the utmost importance for the preservation of visual acuity, minimizing corneal damage and reducing the scar size. However, combination therapy can be more efficacious compared to monotherapy. Understanding the pathogenesis, early diagnosis, and prevention strategies can be of great importance. In this narrative, we discuss the recent progress that may aid our understanding of the diagnosis, treatment, and prevention of mycotic keratitis.

Hormographiella aspergillata is a rare and emerging cause of invasive mould infections in patients with haematological malignancies, with a mortality rate of approximately 70%. Here, we present the first reported case of suspected disseminated H. aspergillata infection in China. The patient experienced a second relapse of acute myeloid leukaemia and developed neutropenia, fever, discrepant blood pressure between limbs, and cutaneous lesions limited to the left upper extremity. Since lung tissue biopsy was not feasible, metagenomic next-generation sequencing (mNGS) and panfungal polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid and blood samples were performed, which indicated probable H. aspergillata pulmonary infection. Histopathology of cutaneous lesions revealed numerous fungal hyphae within dermal blood vessels. mNGS of a skin biopsy sample identified H. aspergillata sequences, and the fungi was subsequently recovered from fungal culture, proving cutaneous H. aspergillata infection. Despite combined antifungal therapy, the patient died owing to disease progression. Additionally, 22 previously reported cases of invasive H. aspergillata infection were reviewed in patients with haematological malignancies. Thus, mNGS is a powerful diagnostic tool for the early and effective detection of invasive H. aspergillata infections, with the advantage of sequencing all potential pathogens, and providing results within 24 h.

UNASSIGNED: Hepatosplenic candidiasis is a rare but severe complication in immunocompromised patients undergoing chemotherapy. Antifungal agents are widely accepted as the first choices for therapy. However, resistance to or side-effect of antifungal agents may comxpromise its efficiency. Splenectomy has also been rarely performed as treatment for this disease.
UNASSIGNED: We present two cases of splenectomy for treating hepatosplenic candidiasis after failure of the initial drug therapy. Literatures on splenectomy as treatment for hepatosplenic candidiasis were searched in Pubmed and summarized.
UNASSIGNED: Two leukemia patients developed hepatosplenic candidiasis after received chemotherapy for their primary diseases. Various antifungal agents including amphotericin B were all demonstrated failure to cure fever and the Candida abscesses due to resistance or intractable side-effect. Laparoscopic splenectomy were finally performed and resolved the candidiasis successfully. A total of 12 splenectomy cases for treating hepatosplenic candidiasis had been previously reported in literature. All the cases showed either resistance or unimproved to initial antifungal therapies. Splenectomy provided salvage therapeutic value in all cases.
UNASSIGNED: Splenectomy has therapeutic effect and may change the traditional concept in most surgeons. The present study may expand an alternative strategy in clinical practice guideline for the management of hepatosplenic candidiasis.

(1) Background: Although invasive fungal infections are a major cause of neonatal morbidity and mortality, data on the incidence and outcomes of localized abscesses in solid organs due to fungal infections are scarce. The aim of this study was to consolidate evidence and enhance our understanding on neonatal liver abscesses due to invasive fungal infections. (2) Methods: An electronic search of the PubMed and Scopus databases was conducted, considering studies that evaluated fungal liver abscesses in the neonatal population. Data on the epidemiology, clinical course, treatment, and outcome of these infections were integrated in our study. (3) Results: Overall, 10 studies were included presenting data on 19 cases of neonatal fungal liver abscesses. Candida spp. were the most common causative pathogens (94.7%). Premature neonates constituted the majority of cases (93%), while umbilical venous catheter placement, broad spectrum antibiotics, and prolonged parenteral nutrition administration were identified as other common predisposing factors. Diagnosis was established primarily by abdominal ultrasonography. Medical therapy with antifungal agents was the mainstay of treatment, with Amphotericin B being the most common agent (47%). Abscess drainage was required in four cases (21%). Eradication of the infection was achieved in the majority of cases (80%). (4) Conclusions: Even though fungal liver abscess is a rare entity in the neonatal population, clinicians should keep it in mind in small, premature infants who fail to respond to conventional treatment for sepsis, particularly if an indwelling catheter is in situ. A high index of suspicion is necessary in order to achieve a timely diagnosis and the initiation of the appropriate treatment.

UNASSIGNED: Skeletal involvement of Cryptococcus neoformans is rare and normally associated with disseminated cryptococcosis or potential predisposing factors. Here, we report an atypical case of osteoarticular cryptococcosis in an immunocompetent patient.
UNASSIGNED: We report a case of cryptococcal osteomyelitis in a 45-year-old female who presented with swelling and pain in the left inner thigh. After a biopsy of the pubic bone and surrounding soft tissue, the pathological results and bacterial culture of the biopsy tissue confirmed Cryptococcus neoformans infection. After draining the pus by aspiration and administering oral fluconazole (400 mg/d) treatment, the patient\'s symptoms disappeared.
UNASSIGNED: Cryptococcus neoformans is a rare etiology of infection of the entire pubis, and oral fluconazole and pus aspiration could benefit some cryptococcal osteomyelitis patients with soft-tissue cryptococcal infection.