Immunosuppressed Patients with Clinically Diagnosed Invasive Fungal Infections: The Fungal Species Distribution, Antifungal Sensitivity and Associated Risk Factors in a Tertiary Hospital of Anhui Province

Abstract

Objective

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.

Keywords:

• invasive fungal infections
• immunosuppressed patients
• species distribution
• antifungal sensitivity
• risk factors
• treatment outcome

Abbreviations

IFI, invasive fungal infection; ERG3, sterol Δ^5,6-desaturase; ERG11, 14-ɑ-sterol demethylase; BALF, bronchoalveolar lavage fluid; MALDI-TOF MS, matrix-assisted laser desorption ionization-time of flight mass spectrometry; MIC, minimum inhibitory concentration; MIC₅₀ or MIC₉₀, MIC at which 50% or 90% of the isolates tested were inhibited; AMB, amphotericin B; 5-FC, 5-fluorocytosine; FLU, fluconazole; ITR, itraconazole; VOR, voriconazole; CAS, caspofungin; CLSI, Clinical and Laboratory Standards Institute; PCR, polymerase chain reaction; PB, peripheral blood; AF, ascitic fluid; DF, drainage fluid; HBV, hepatitis B virus; IL, interleukin.

Ethical Considerations

The study protocol was reviewed, approved by and carried out following the recommendations of the Ethics Committee of the First Affiliated Hospital of Anhui Medical University. Written informed consents were obtained from patients as per the Declaration of Helsinki.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All the authors declared no any competing interests.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (21604079) (JX), and the Natural Science Foundation of Anhui Province (1608085QH183) (JX).