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Antifungal susceptibility and multilocus sequence typing (MLST) of Cryptococcus neoformans complex from
Marla Jalene Alves1,2, Katia Santana Cruz3, Gleica Soyan Barbosa Alves4
1Laboratório de Diversidade Microbiana da Amazônia com importância para a Saúde, Instituto Leônidas e Maria Deane - FIOCRUZ, Manaus, Amazonas, Brazil.
Abstract:
Cryptococcus neoformans is primarily responsible for cases of cryptococcal meningitis in individuals with HIV/AIDS. This study evaluated the susceptibility of C. neoformans obtained from individuals with cryptococcal meningitis associated with HIV/AIDS in Manaus, Amazonas, Brazil, against the action of the antifungals amphotericin B, flucytosine, fluconazole, itraconazole and posaconazole and analyzed it using Multilocus Sequence Typing (MLST) in order to identify the Sequence Types (STs). We analyzed 30 isolates of C. neoformans, from 24 HIV/AIDS patients diagnosed with cryptococcosis from 2017 to 2019 in a reference hospital, in addition to 3 environmental isolates: 1 isolate obtained in the home of a patient and 2 isolates obtained from neighboring homes of patients. 86.6% (n = 26/30) of the clinical isolates were identified as C. neoformans VNI ST93, 6.6% (n = 2/30) as C. neoformans VNI ST5, 3.3% (n = 1/30) as C. neoformans VNI ST32 and 3.3% (n = 1/30) as C. neoformans VNB ST232. The environmental isolates were identified as C. neoformans VNI ST93 (n = 3/3). 96.6% (n = 29/30) isolates were sensitive to amphotericin B, though there was variation in the MIC. 60% (n = 18/30) presented a MIC above the proposed epidemiological cutoff values for one or more antifungals. All environmental isolates were sensitive to the tested antifungals. The MLST showed that there is an important relationship between C. neoformans VNI ST93 and individuals with HIV/AIDS, including in the environmental isolates analyzed. C. neoformans VNB ST232 was observed for the first time in Amazonas. Amphotericin B was proven to be the best drug, but fluconazole and posaconazole also showed relevant action.
Insights
Cryptococcus neoformans VNI ST93 is prevalent in HIV/AIDS patients in Brazil. Amphotericin B demonstrated the highest efficacy against C. neoformans isolates, with variations in antifungal susceptibility observed.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Cryptococcus neoformans is a significant cause of cryptococcal meningitis, particularly in individuals with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS).
- Understanding the antifungal susceptibility and genetic diversity of C. neoformans is crucial for effective treatment strategies.
Purpose of the Study:
- To evaluate the antifungal susceptibility of Cryptococcus neoformans isolates from HIV/AIDS patients in Manaus, Brazil.
- To identify the Sequence Types (STs) of these isolates using Multilocus Sequence Typing (MLST).
Main Methods:
- Analysis of 33 C. neoformans isolates (30 clinical, 3 environmental) from HIV/AIDS patients.
- Antifungal susceptibility testing against amphotericin B, flucytosine, fluconazole, itraconazole, and posaconazole.
- Multilocus Sequence Typing (MLST) for molecular characterization.
Main Results:
- Cryptococcus neoformans VNI ST93 was the predominant genotype (86.6% of clinical isolates).
- Most isolates (96.6%) were susceptible to amphotericin B, but 60% showed Minimum Inhibitory Concentrations (MICs) above epidemiological cutoff values for at least one antifungal.
- Cryptococcus neoformans VNB ST232 was identified for the first time in Amazonas.
Conclusions:
- A strong association exists between C. neoformans VNI ST93 and HIV/AIDS patients, extending to environmental isolates.
- Amphotericin B remains the most effective antifungal, with fluconazole and posaconazole also showing significant activity.
- Variations in antifungal susceptibility highlight the need for ongoing monitoring.
