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Since the nosocomial fungal infections increasingly emerge, we extensively investigated the fungal species stratification and antifungal sensitivity profiles, clinical characteristics and associated risk factors of immunosuppressed patients with clinically diagnosed invasive fungal infections (IFIs) in a tertiary hospital of Anhui province. Methods: In total, 112 subjects with immunosuppressive state were enrolled from a comprehensive tertiary hospital in Central China between July 2019 and December 2021. Eight-one fungal isolates were clinically recovered by fungus-culturing approaches. The identifications were conducted through a mass spectrometry detecting platform. The susceptibilities to antifungals were tested using the broth micro-dilution method, and the possible antifungal azole-resistance mechanism in specific Candida species was availably explored by sequencing. Patient medical profiles were accessed via the digitized retrieval system of hospital, from which clinical outcomes and multiple risk factors for immunosuppressed patients with clinically diagnosed IFIs were explicitly documented for evaluation. Results: Candida species predominated in clinically diagnosed IFIs of immunosuppressed patients (accounting for 88.88%), followed by Trichosporon and Aspergillus species (6.17% and 4.94%, respectively). The source types of specimen were primarily comprised of urine (41.98%), respiratory samples (33.33%) and peripheral blood (9.88%). Frequently isolated Candida and Trichosporon species exhibited a high level of in vitro sensitivity for amphotericin B and 5-fluorocytosine, whereas a substantial portion of Candida species including C. glabrata, C. parapsilosis complex and C. tropicalis, and Trichosporon species showed lowered sensitivity patterns toward itraconazole, fluconazole and voriconazole at different levels. Specifically, gene mutations of ERG11 were identified in azole-resistant C. tropicalis. Distinct risk factors were analyzed to be highly associated with the clinically diagnosed IFI incidence, mainly including hospitalization duration, surgical procedures, immunosuppressive treatments, underlying diseases and other conditions. Conclusion: Candida, Trichosporon and Aspergillus species were the top three pathogenic fungal agents causing clinically diagnosed IFIs in immunosuppressed patients. The attenuated sensitivity to azoles in Candida and Trichosporon species needs close surveillance, and ERG11 polymorphism might contribute to azole resistance in specific Candida species. Multiple featured risk factors for immunosuppressed patients developing clinically diagnosed IFIs require further consideration during clinical practice.

Objective Invasive infections due to Candida spp. have unique epidemiology, strain distribution, antimicrobial susceptibility, and clinical features. This study aimed to compare and evaluate these characteristic variables between invasive Candida infection and colonization of critically ill patients in local China to potentially improve differential diagnosis and therapy. Methods A total of 193 critically ill patients were recruited and followed up for the study, and 133 Candida isolates were obtained from invasive Candida -infected or -colonized subjects. The strains were identified to species level through matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry, assisted by DNA sequencing. Candida susceptibility to common antifungals, including azoles, was determined by microbroth ATB Fungus 3 methodology. Azole resistance–related gene sequencing and homologous 3D-structure modeling were employed. Patient demographics and clinical risk factors were documented and comparatively analyzed from the hospital information-management system. Results Non– C. albicans Candida (56%) principally caused invasive Candida infections, while C. albicans (55.17%) contributed more to Candida colonization in critically ill patients. Additional risk factors exerted significant impact on both Candida cohorts, primarily including invasive interventions, cancers, and concurrent infections in common. Most colonized Candida spp. harbored relatively higher sensitivity to azoles. ERG11 gene mutations of T348A and A1309G, A395T and C461T, and a novel G1193T to our knowledge were identified in azole-resistant C. albicans , C. tropicalis , and C. parapsilosis respectively, and their corresponding homologous 3D-structure modeling was putatively achieved. Conclusion Distinct epidemiological and clinical characteristics existed between invasive Candida infection and colonization in critically ill patients. Multiple risk factors significantly involved both the Candida cohorts. Colonized Candida exhibited generally higher azole sensitivity than invasively infectious counterparts. ERG11 point mutations had mechanistically potential ties with local Candida resistance to azoles.

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