Combinatory Effect of ALA-PDT and Itraconazole Treatment for Trichosporon asahii.

BACKGROUND AND OBJECTIVES: Trichosporiosis is an opportunistic infection that includes superficial infections, white piedra, hypersensitivity pneumonitis, and invasive trichosporonosis. The effect of antifungal agents against these infections is largely weakened by drug resistance and biofilms-related virulence. Photodynamic therapy (PDT) is a new therapeutic approach developed not only to combat cancerous lesions but also to treat infectious diseases such as fungal infections. However, there are few studies on the antimicrobial mechanism of 5-aminolevulinic acid PDT (ALA-PDT) in treating Trichosporon. In this work, we explored the possibility of combining ALA-PDT with an antifungal agent to enhance the therapeutic efficacy of Trichosporon asahii (T. asahii) in a clinical setting and in vitro. STUDY DESIGN/MATERIALS AND METHODS: The biofilms of T. asahii were constructed by a 96-well plate-based method in vitro. The planktonic and adherent T. asahii were exposed to different concentrations of photosensitizers and different light doses. After PDT treatment, counting colony-forming units and tetrazolium (XTT) reduction assay were used to estimate the antifungal efficacy. The minimal inhibitory concentration of itraconazole before and after PDT treatment was determined by the broth dilution method, and XTT viability assay was used to detect and evaluate the synergistic potential of ALA-PDT and itraconazole combinations in inhibiting biofilms. Scanning electron microscopy (SEM) was performed to assess the disruption of biofilms. RESULTS: Using combination therapy, we have successfully treated a patient who had a T. asahii skin infection. Further in vitro studies showed that the antifungal effect of ALA-PDT on planktonic and adherent T. asahii was dependent on the concentration of ALA and light dosages used. We also found that the sensitivity of both planktonic and biofilm cells to itraconazole were increased after ALA-PDT. Synergistic effect were observed for biofilms in ALA-PDT and itraconazole-combined treatment. The disruption of biofilms was confirmed by SEM, suggesting that ALA-PDT effectively damaged the biofilms and the destruction was further enhanced by ALA-PDT combination of antifungal agents. CONCLUSIONS: In conclusion, these data suggest that ALA-PDT could be an alternative strategy for controlling infections caused by Trichosporon. The combination therapy of ALA-PDT with itraconazole could result in increased elimination of planktonic cells and biofilms compared with single therapy. All these findings indicate that it could be a promising treatment against trichosporonosis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Study on the bacteriostatic action of Chinese herbal medicine on avian Trichosporon.

In this study, a strain of Trichosporon was isolated from white pseudomembranes and ulcers formed on mucous membranes of pigeon bursas and was identified through gene sequencing. Bacteriostatic actions of Acorus gramineus, Sophora flavescens, Polygonum hydropiper, and Chinese herbal mixture on this species were explored in vitro, and the minimum inhibitory concentration of herbal medicines against Trichosporon was determined through microdilution method. Therapeutic effects of herbal medicines on chickens infected by Trichosporon were studied, whose results showed that minimum inhibitory concentration of A. gramineus was 32 µg/µL, that of S. flavescens was 2 µg/µL, that of P. hydropiper was 120 µg/µL, and that of Chinese herbal mixture was 36 µg/µL. Antibacterial effects of S. flavescens were the best. In accordance with animal experiments, therapeutic effects of Chinese herbal medicines on infected chickens were better than those of fluconazole. The mortality rate of the Chinese herbal medicine treatment group was 33.33%, that of the fluconazole treatment group was 46.67%, and that of the Chinese medicine protection group was 23.33%. The longer the time of Chinese medicine treatments was, the better the treatment effects would be. Glutamic oxaloacetylase values of the serum and liver in the Chinese herbal medicine treatment group were both significantly lower than those of the nontreatment group. From the results, it can be seen that A. gramineus, S. flavescens, P. hydropiper, and Chinese herbal mixture have certain inhibitory effects on Trichosporon spp. Chinese herbal medicine protections in advance could reduce Trichosporon infections.

Trichosporon Asahii fungaemia in an immunocompetent polytrauma patient who received multiple antibiotics.

Trichosporon asahii is a yeast-like fungus that is emerging as an important cause of invasive infections in tertiary medical centres. A 58-year-old Chinese man with no known medical illnesses presented with liver lacerations and multiple fractures following an alleged 12-foot fall at a construction site. The gravity of his injuries and poor haemodynamic status necessitated an intensive care unit (ICU) admission, during which several febrile episodes were detected and multiple antibiotics were administered. After being in the ICU for at least two weeks, a urease-positive yeast was isolated from the patient's blood. The yeast formed dry, fuzzy and wrinkled white colonies on Sabouraud dextrose agar following prolonged incubation, and produced blastoconidia, true hyphae, pseudohyphae and arthroconidia on slide culture. It was identified biochemically by the ID 32 C kit as T. asahii. The yeast had elevated minimal inhibitory concentration (MIC) values to fluconazole, amphotericin B, flucytosine and all echinocandins tested. In view of this, the patient was treated with voriconazole and was successfully transferred to the general medical ward.

Subcutaneous Infection Associated with Trichosporon ovoides: A Case Report and Review of Literature.

Trichosporon species are opportunistic yeasts which can cause infections, especially in immunocompromised patients. This is a report of Trichosporon ovoides that caused subcutaneous infection in a patient with underlying ischemic heart disease. The identification of fungal isolate was confirmed by PCR sequencing of ITS and large subunit regions in rRNA gene. In vitro susceptibility study showed that the isolate was susceptible to amphotericin B, fluconazole and voriconazole, and resistant to caspofungin, anidulafungin and itraconazole. The lesion improved after treatment with oral fluconazole and topical miconazole.

Trichosporon inkin as an Emergent Pathogen in Patients With Severe Pemphigus.

IMPORTANCE: To our knowledge, these are the first reports of bloodstream infections by Trichosporon inkin in patients with pemphigus. OBSERVATIONS: Trichosporon inkin, a novel organism causing bloodstream infection, was detected in 2 patients with pemphigus. An elderly man with pemphigus foliaceus died despite treatment with liposomal amphotericin B, 3 mg/kg/d, and a young girl with pemphigus vulgaris responded to treatment with voriconazole, 8 mg/kg/d, for 24 days. One of the T inkin isolates had a minimal inhibitory concentration of 2 mg/L against amphotericin B, suggesting resistance to the drug. CONCLUSIONS AND RELEVANCE: Delayed suspicion of invasive infection by T inkin may result in a poor outcome in patients with severe forms of pemphigus. This opportunistic infection is highly refractory to conventional potent antifungal treatment.

Prompt diagnosis and effective treatment of Trichosporon asahii catheter-related infection in non-immunocompromised neurosurgical patient.

Trichosporon asahii is a rare but emerging fungal pathogen that causes severe and life-threatening infections with high mortality rate, mostly in immunocompromised patients. It could be easily misdiagnosed due to lack of awareness, especially when invasive or deep-seated infections occur in non-immunocompromised patients, and inadequately treated since the clinical failures and high minimum inhibitory concentrations to some antifungal agents have been described. We present a case of T. asahii catheter-related infection in 66-year-old comatose patient with polytrauma, who was not immunodeficient, but was receiving broad-spectrum antibiotics for a long period. Due to prompt diagnosis and treatment which included catheter replacement and voriconazole, the patient successfully recovered from this infection. The aims of this case report were to highlight the importance of recognizing this otherwise colonizing yeast as potentially dangerous pathogen in non-immunocompromised patients with a long-term antibiotic therapy, and to emphasize the importance of the right therapeutic choice due to its resistance to certain antifungal agents.

Emerging Trichosporon asahii in elderly patients: epidemiological and molecular analysis by the DiversiLab system.

Trichosporon asahii has been recognized as an emerging opportunistic agent for invasive infections, mainly in immunocompromised patients. Urinary tract infections by this pathogen may also occur, especially in patients with urinary obstruction or those undergoing vesical catheterization and antibiotic treatment. Many outbreaks of Trichosporon spp. have been detected after urinary catheter manipulations. We report the molecular-epidemiological characterization of T. asahii in our institution using the DiversiLab system for the molecular strain typing and compare three different methods for susceptibility testing. Our results present T. asahii as an emergent pathogen in elderly patients with urinary drainage devices that can be adequately treated with triazoles, with voriconazole being the most active. Broth dilution and Vitek 2 had good concordance, while Etest showed more discrepancies. In addition, the DiversiLab system for clonal strain typing may be a useful tool for fast and accurate management of nosocomial outbreaks.

Invasive Trichosporon infection in solid organ transplant patients: a report of two cases identified using IGS1 ribosomal DNA sequencing and a review of the literature.

Trichosporon species are rare etiologic agents of invasive fungal infection in solid organ transplant (SOT) recipients. We report 2 well-documented cases of Trichosporon inkin invasive infection in SOT patients. We also conducted a detailed literature review of Trichosporon species infections in this susceptible population. We gathered a total of 13 cases of Trichosporon species infections. Any type of organ transplantation can be complicated by Trichosporon infection. Bloodstream infections and disseminated infections were the most common clinical presentations. Liver recipients with bloodstream or disseminated infections had poor prognoses. Although the most common species was formerly called Trichosporon beigelii, this species name should no longer be used because of the changes in the taxonomy of this genus resulting from the advent of molecular approaches, which were also used to identify the strains isolated from our patients. Antifungal susceptibility testing highlights the possibility of multidrug resistance. Indeed, Trichosporon has to be considered in cases of breakthrough infection or treatment failure under echinocandins or amphotericin therapy. Voriconazole seems to be the best treatment option.