We reported a 31-year-old man who received renal transplantation for more than 2 years. He was admitted to our hospital on 9 March 2022 due to intermittent diarrhea accompanied by leukopenia for more than 1 month. The patient successively developed high fever, cough, anemia, weight loss, gastrointestinal bleeding, and liver function impairment. Computed tomography (CT) revealed a slight inflammation in the lower lobes of both lungs, enlargement of the lymph nodes in the retroperitoneal and the root of mesenteric areas, and hepatosplenomegaly. Talaromyces marneffei was detected by metagenomics next-generation sequencing (mNGS) in blood and bronchoalveolar lavage fluid, and the pathogen was subsequently verified by blood culture. After endoscopic hemostatic therapy and antifungal therapy with voriconazole and amphotericin B cholesteryl sulfate complex, the patient was successfully discharged. Oral voriconazole was given regularly after discharge. Diarrhea, fever, enlargement of the lymph nodes, and endoscopic evidence of erosion may indicate intestinal T. marneffei infection. Although the mortality of T. marneffei infection after renal transplantation is very high, timely and effective antifungal therapy with amphotericin B cholesteryl sulfate complex is still expected to improve its prognosis.

UNASSIGNED: To summarize the clinical characteristics, treatment and outcomes of transplant recipients infected with Talaromyces marneffei (TM).
UNASSIGNED: A retrospective analysis was performed on 2 patients with Talaromycosis marneffei (TSM) and transplants at the First Affiliated Hospital of Guangxi Medical University, and a systematic literature review was conducted simultaneously.
UNASSIGNED: This article reported two patients after kidney transplantation who developed fever, cough within 3-4 months. Their haemoglobin was decreased. Their chest computed tomography (CT) showed nodules. TM was detected in their blood or bronchoalveolar lavage fluid samples by next-generation sequencing (NGS). After antifungal treatment with voriconazole (VOR), one patient worsened, the other patient died. A total of 21 patients with TSM after transplants were reported in the literature review. Fourteen underwent kidney transplantation, 4 underwent liver transplantation, 2 underwent lung transplantation, and 1 underwent bone marrow transplantation. The median time from initiating the postoperative immunosuppressive therapy to the onset of symptoms or disease changes was 18 (0.5-140) months. Among them, 9 patients developed fever, 7 patients developed cough or expectoration and 4 patients developed dyspnoea. Haemoglobin was decreased in 10 patients. Pulmonary nodules were found in 7 patients. Among the 21 patients, 7 were diagnosed by positive culture, 6 by biopsy, 5 by culture and biopsy. Of the 21 patients, 13 patients improved by antifungal therapy, 8 patients worsened or died. Seven patients who received amphotericin B followed by itraconazole (ITR) therapy all improved. Regarding the use of immunosuppressants in 12 patients, 9 patients had to discontinue or reduce their medications (6 patients improved, 3 patients worsened or died).
UNASSIGNED: Patients with TSM after transplant often have disseminated infections, involving the respiratory, hematopoietic and so on. Fever, cough, decreased haemoglobin and pulmonary nodules often occur approximately 18 months after surgery. The combined applications of culture, biopsy, NGS are helpful for an early diagnosis. Antifungal therapy with amphotericin B followed by itraconazole is recommended, and the dosage of the immunosuppressant should be adjusted timely.

Objectives/Hypothesis: To perform a systematic review and meta-analysis to compare the efficacy of and complications associated with antifungal drugs and traditional antiseptic medication for the treatment of otomycosis. Data Sources: The PubMed, EMBASE, GeenMedical, Cochrane Library, CBM, CNKI, VIP and other databases were searched from January 1991 to January 2021. Methods: The systematic literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) and non-randomized studies (case-control, cohort, and case series) were included to assess the topical use of antifungal drugs and traditional antiseptic medication in patients with otomycosis. The research subjects were patients who were clinically diagnosed with otomycosis and whose external auditory canal secretions were positive for fungi. Funnel plots were used to detect bias, and the Q test was used to assess heterogeneity. The random-effects model was used for meta-analysis. The t-test was used to assess significance. Results: Of the 324 non-duplicate studies screened, 16 studies met the criteria for full-text review, and 7 were included in the meta-analysis. Four studies reported recovery conditions (P = 0.01). Six common complications after medication use were compared, and there were no significant differences. The authors further conducted subgroup analysis according to complications. The differences in the rates of ear distension (P = 0.007), earache (P = 0.03) and tinnitus (P = 0.003) were statistically significant. Conclusion: The results of this meta-analysis and literature review showed that antifungal drugs and traditional antiseptic medication were effective in relieving symptoms in patients with otomycosis, and the two treatments were associated with different complications. Otolaryngologists have the option to use one medication or a combination of two drugs on the basis of the condition. Future research in this area should include RCTs with long-term follow-up to guide the development of otomycosis guidelines to overcome some of the weaknesses found in the literature. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero.

Due to the increasing numbers of fungal infections and the emergence of drug-resistant fungi, optimization and standardization of diagnostic methods for the measurement of antifungal susceptibility are ongoing. The M27-A4 document by the US Clinical and Laboratory Standards Institute (CLSI) is presently used for the interpretation of minimum inhibitory concentrations of major opportunistic yeast species as measured by broth microdilution testing in many countries. Although microdilution is considered a benchmark for reproducible and accurate results, increased testing capacity, and limited human bias, the method is often inaccessible to routine clinical laboratories and researchers, especially in low-income countries. Furthermore, several studies suggest that there are still a considerable number of factors that make the estimation of in vitro activity of antifungal agents challenging. This review article summarizes the limitations of the M27-A4 standard which, despite the advances and improvements obtained by the standardization of antimicrobial resistance testing methods by CLSI, still persist.

Precision dosing for many antifungal drugs is now recommended. Saliva sampling is considered as a non-invasive alternative to plasma sampling for therapeutic drug monitoring (TDM). However, there are currently no clinically validated saliva models available. The aim of this study is firstly, to conduct a systematic review to evaluate the evidence supporting saliva-based TDM for azoles, echinocandins, amphotericin B, and flucytosine. The second aim is to develop a saliva population pharmacokinetic (PK) model for eligible drugs, based on the evidence. Databases were searched up to July 2019 on PubMed® and Embase®, and 14 studies were included in the systematic review for fluconazole, voriconazole, itraconazole, and ketoconazole. No studies were identified for isavuconazole, posaconazole, flucytosine, amphotericin B, caspofungin, micafungin, or anidulafungin. Fluconazole and voriconazole demonstrated a good saliva penetration with an average S/P ratio of 1.21 (± 0.31) for fluconazole and 0.56 (± 0.18) for voriconazole, both with strong correlation (r = 0.89-0.98). Based on the evidence for TDM and available data, population PK analysis was performed on voriconazole using Nonlinear Mixed Effects Modeling (NONMEM 7.4). 137 voriconazole plasma and saliva concentrations from 11 patients (10 adults, 1 child) were obtained from the authors of the included study. Voriconazole pharmacokinetics was best described by one-compartment PK model with first-order absorption, parameterized by clearance of 4.56 L/h (36.9% CV), volume of distribution of 60.7 L, absorption rate constant of 0.858 (fixed), and bioavailability of 0.849. Kinetics of the voriconazole distribution from plasma to saliva was identical to the plasma kinetics, but the extent of distribution was lower, modeled by a scale factor of 0.5 (4% CV). A proportional error model best accounted for the residual variability. The visual and simulation-based model diagnostics confirmed a good predictive performance of the saliva model. The developed saliva model provides a promising framework to facilitate saliva-based precision dosing of voriconazole.