Posaconazole

ABSTRACTTrichophyton species, the leading cause of dermatophytosis globally, are increasingly resistant to antifungal treatments, concerns about effective management strategies. In light of the absence of established resistance criteria for terbinafine and azoles, coupled with a dearth of research on resistance mechanisms in Trichophyton, antifungal susceptibility and drug resistance gene diversity were analyzed across 64 T. mentagrophytes, 65 T. interdigitale, and 2 T. indotineae isolates collected in China between 1999 and 2024 and 101 published T. indotineae strains. Analyses of the minimum inhibitory concentrations (MICs) of terbinafine, itraconazole, voriconazole, posaconazole, and isavuconazole revealed a concerning increase in T. indotineae with terbinafine resistance, including two novel isolates from China. Compared with T. interdigitale, T. mentagrophytes presented higher terbinafine MICs but similar azole susceptibility. Notably, 27 T. interdigitale isolates were classified as non-wild-type for terbinafine. Genetic diversity was analyzed for the SQLE, CYP51A and CYP51B gene. Specifically, T. indotineae isolates presented SQLE protein changes linked to terbinafine resistance. SQLE diversity was linked to terbinafine sensitivity, whereas alterations in CYP51A were associated with itraconazole sensitivity, with notable statistical significance evident across various protein isoforms. The relationship between protein diversity and drug sensitivity is presented in detail. Together, these findings highlight a growing prevalence of antibiotic resistance among Trichophyton and identify potential target genes for new therapies, underscoring the need for ongoing monitoring and offering directions for novel therapeutics.

To further standardize the diagnosis and treatment of invasive pulmonary fungal disease (IPFD) in China, particularly in non-immunosuppressed patients, and to enhance medical professionals' competence, the Infectious Diseases Group of Chinese Thoracic Society has organized experts to develop the Guidelines for the diagnosis and treatment of invasive pulmonary fungal disease (2025 Edition). These guidelines are based on the 2007 Chinese Expert Consensus on Pulmonary Mycosis and reference guidelines issued by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), integrating recent domestic and international research findings as well as clinical experience in China. The guideline development process incorporated feedback from multidisciplinary experts in pulmonology, infection, microbiology, laboratory testing, and neurology. The guidelines comprehensively cover eleven aspects of IPFD, including epidemiology, host factors, clinical and imaging features, diagnostic methods, hierarchical diagnostic criteria, therapeutic drugs, treatment regimens, immune reconstitution inflammatory syndrome, efficacy evaluation, common diagnostic and treatment issues, and rare pulmonary fungal diseases. Presented in a combined review-and-question format, the 2025 Edition provides sixteen evidence-based recommendations on key diagnostic and therapeutic issues, serving as a reference for Chinese medical practitioners.Recommendation 1: For allogeneic hematopoietic stem cell transplant recipients, lung transplant recipients, patients with severe granulocytopenia, and those at high risk of invasive pulmonary aspergillosis receiving high-dose immunosuppressive agents, prophylaxis should be given for at least 3 weeks until host factors have improved (evidence level: 2).Recommendation 2: For patients with persistent neutropenia and recurrent fever despite broad-spectrum antibacterial therapy, empirical antifungal therapy should be initiated and continued until the clinical condition stabilizes and the relevant microbiological and/or radiological findings have normalized (evidence level: 2).Recommendation 3: Bronchoscopy is recommended for the early diagnosis of clinically suspected invasive pulmonary aspergillosis, particularly in case of airway invasive aspergillosis (evidence level: 3).Recommendation 4: In addition to active antifungal therapy, bronchoscopic interventional procedures, including bronchoscopic injection and spraying of antifungal drugs, can be used for airway invasive aspergillosis. For massive hemoptysis, interventional treatments such as balloon occlusion under bronchoscopy and bronchial artery embolization can be considered (evidence level: 4).Recommendation 5: Inhalation of nebulized antifungal drugs is recommended for patients with invasive pulmonary aspergillosis combined with bronchial pulmonary aspergillosis when systemic antifungal treatment is not feasible, as well as for high-risk populations as prophylactic measure (evidence level: 3).Recommendation 6: For patients with severe, refractory, or treatment-failure invasive pulmonary aspergillosis, combination therapy with triazoles plus echinocandins and/or polyenes, or with echinocandins plus polyenes, is recommended. (evidence level: 4).Recommendation 7: A positive cryptococcal capsular polysaccharide antigen (CrAg) test indicates cryptococcal infection and is valuable for diagnostic purpose, but it should not be used to assess treatment efficacy or guide drug withdrawal (evidence level: 4).Recommendation 8: Lumbar puncture should be performed in patients with pulmonary cryptococcosis and neurological symptoms, high serum CrAg titres, or immunocompromised status (evidence level: 3).Recommendation 9: For patients with fluconazole resistance or treatment failure, the following: 1) Severe infection: induction therapy with L-AmB (3-6 mg·kg^-1·d^-1) and 5-FC (100 mg·kg^-1·d^-1) should continue for 4 weeks, followed by maintenance with fluconazole (800 mg/d) or voriconazole (evidence level: 2). 2) Mild to moderate infection or amphotericin B intolerance: voriconazole, posaconazole, or isaconazole should be used for 6-12 months (evidence level: 2). 3) If L-AmB is unavailable, consider 5-FC with fluconazole (800-1200 mg/d) (evidence level: 3).Recommendation 10: Combination antifungal therapy is not routinely recommended for pulmonary mucormycosis but can be used for severe infection or inadequate monotherapy response (evidence level: 4).Recommendation 11: Surgical treatment of pulmonary mucormycosis should include early evaluation, individualized decision-making, and multidisciplinary collaboration. Early surgical evaluation is crucial for localized lesions, whereas dynamic evaluation is needed for multiple lesions or high-risk patients (evidence level: 4).Recommendation 12: Patients with clinically diagnosed or confirmed pulmonary mucormycosis should be treated with local drug infusion via bronchoscopy (evidence level: 4).Recommendation 13: For patients with confirmed pulmonary mucormycosis who are scheduled for surgery or deemed inoperable, local debridement should be performed via bronchoscopy by an experienced team (evidence level: 4).Recommendation 14: Echinocandin treatment alone is not recommended for Pneumocystis pneumonia. Echinocandin combined with SMX-TMP is recommended for severe cases with respiratory failure. This combination is also recommended as second-line therapy when SMX-TMP use is limited by renal impairment (evidence level: 2).Recommendation 15: Consider echinocandin with other second-line agents if initial SMX-TMP treatment fails or in cases of patient intolerance or resistance (evidence level: 4).Recommendation 16: Use low-dose glucocorticoids early in severe pneumocystis pneumonia with hypoxemia but not in patients without hypoxemia (evidence level: 2).