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Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3
Published on: December 27, 2010
Multi-Locus Sequence Typing-Based Genetic Analysis, Antifungal Resistance, and Clinical Prognosis of Cryptococcus
Fang-Fang Dai1,2, Yan-Hua Yu1, Xin-Xin Lu2
1Department of Clinical Laboratory, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Abstract:
This study aimed to investigate the molecular epidemiological characteristics and drug sensitivity of Cryptococcus from HIV-infected patients and their relationship with patients' prognosis. Seventy-six strains were collected and identified to the species level by matrix-assisted laser desorption ionization-time of flight mass spectrometry, confirmed by internal transcribed spacer sequencing. Multi-locus sequence typing was used for the typing of Cryptococcus, and its antifungal susceptibility was tested using FUNGUS 3. The clinical outcomes of the patients were reviewed at 3-, 6-, 9-, and 12-month follow-ups. All strains were Cryptococcus neoformans var. grubii classified into seven sequence types (STs) dominated by ST5, ST31, and a new ST702 strain. The 6- and 9-month survival rates were highest for patients infected with ST31, ST32, and ST174. The antifungal resistant rates were 13.2%, 2.6%, and 1.4% for fluconazole, amphotericin B, and 5-fluorocytosine. Except itraconazole, the minimum inhibitory concentration (MIC) values and wild type (WT)/non-wild type (NWT) of Cryptococcus for antifungal drugs were not related to the clinical prognosis of HIV-infected patients with cryptococcal infection. ST5 was the main ST type, and the new ST702 type was found in a patient who died in a short period of time. Cryptococcus neoformans var. grubii had a relatively high antifungal drug resistance rate to fluconazole. The WT strain accounted for the highest proportions for 5-fluorocytosine, amphotericin B, fluconazole, voriconazole, and itraconazole. The MIC values of Cryptococcus for first-line antifungal drugs showed no relationship with clinical prognosis, implying that MIC values cannot be used to predict the clinical outcome of these patients.
Insights
Molecular epidemiology of Cryptococcus in HIV patients reveals drug resistance patterns. Specific sequence types (STs) correlate with survival, but drug sensitivity doesn't predict patient outcomes.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Molecular Epidemiology
Background:
- Cryptococcus infections pose a significant threat to HIV-infected individuals.
- Understanding the molecular characteristics and drug resistance of Cryptococcus is crucial for managing patient prognosis.
Purpose of the Study:
- To investigate the molecular epidemiology and antifungal drug susceptibility of Cryptococcus strains from HIV-infected patients.
- To determine the relationship between these characteristics and patient prognosis.
Main Methods:
- Seventy-six Cryptococcus strains were identified using MALDI-TOF MS and ITS sequencing.
- Multi-locus sequence typing (MLST) was performed for strain typing.
- Antifungal susceptibility testing was conducted using FUNGUS 3, and clinical outcomes were monitored over 12 months.
Main Results:
- All isolates were identified as Cryptococcus neoformans var. grubii, belonging to seven sequence types (STs), with ST5 being dominant.
- ST31, ST32, and ST174 were associated with higher 6- and 9-month survival rates.
- Fluconazole exhibited the highest resistance rate (13.2%), while amphotericin B and 5-fluorocytosine showed lower rates (2.6% and 1.4%).
- Minimum inhibitory concentration (MIC) values and wild type (WT)/non-wild type (NWT) status for most antifungals did not correlate with patient prognosis.
Conclusions:
- Cryptococcus neoformans var. grubii demonstrates notable resistance to fluconazole.
- While certain STs are linked to better survival, antifungal MIC values are not predictive of clinical outcomes in HIV-associated cryptococcosis.
- The emergence of new STs, like ST702, warrants further investigation due to potential links with poor prognosis.
