Refractory and/or Relapsing Cryptococcosis Associated with Acquired Immune Deficiency Syndrome: Clinical Features, Genotype, and Virulence Factors of Cryptococcus spp. Isolates

Nascimento, Érika; Vitali, Lúcia Helena; Tonani, Ludmilla; Kress, Márcia Regina von Zeska; Takayanagui, Osvaldo Massaiti; Martínez, Roberto

doi:10.4269/ajtmh.15-0595

Cited by 11 publications

(10 citation statements)

References 38 publications

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“…Cryptococcus spp. isolates were previously identified by standard Clinical Mycology methods and also using the automated system Vitek ® 1 or Vitek ® 2 (bioMérieux, France) and by using molecular methods 8 . The yeasts were maintained in the laboratory by periodic culture in Sabouraud Dextrose Agar (SDA) medium at 25 °C.…”

Section: Methodsmentioning

confidence: 99%

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Cryptococcus neoformans and C. gattii isolates from both HIV-infected and uninfected patients: antifungal susceptibility and outcome of cryptococcal disease

Nascimento

Vitali

Kress

et al. 2017

Rev. Inst. Med. trop. S. Paulo

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One of the factors causing treatment failure in cryptococcosis is the resistance of Cryptococcus spp. to antifungal drugs, which has motivated the susceptibility assessment of isolates from patients with cryptococcosis, different clinical conditions and infections outcomes. Clinical isolates of Cryptococcus spp. from three different groups of patients were studied in the present investigation: 19 HIV-positive patients with relapsing and/or refractory meningitis (Group 1), 30 HIV-positive patients who experienced a single and limited episode of cryptococcosis (Group 2), and 19 HIV-negative patients with cryptococcosis (Group 3). Eighty C. neoformans var. grubii isolates and 7 C. gattii isolates were studied. The minimum inhibitory concentration (MIC) of amphotericin B, azole drugs and flucytosine was determined for Cryptococcus spp. by broth microdilution test and E-test. The MIC50 and MIC90 were 0.25 and 0.50 µg/mL for amphotericin B, 4.0 and 8.0 µg /mL for fluconazole, 0.06 and 0.25 µg/mL for itraconazole, 0.25 and 0.50 µg/mL for voriconazole, and 8.0 and 16.0 µg/mL for flucytosine, respectively. Amphotericin B and itraconazole showed higher MICs for C. neoformans var. grubii and C. gattii, respectively. The MICs of fluconazole and itraconazole obtained with the E-test were higher than those obtained with broth microdilution. Isolates from non-HIV coinfected were less sensitive to the azoles. There was no difference in the susceptibility of C. neoformans var. grubii isolates from patients with a favorable or unfavorable outcome or along the episodes of relapsing and/or refractory meningitis.

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Section: Methodsmentioning

confidence: 99%

“…In the present study, previously genotyped isolates 8 of C. neoformans var. grubii and C. gattii were used in order to assess antifungal drugs susceptibility by comparing the broth microdilution test with the E-test among the Cryptococcus species isolated from HIV-negative and HIV-positive, the latter group according to the outcome.…”

Section: Introductionmentioning

confidence: 94%

Cryptococcus neoformans and C. gattii isolates from both HIV-infected and uninfected patients: antifungal susceptibility and outcome of cryptococcal disease

Nascimento

Vitali

Kress

et al. 2017

Rev. Inst. Med. trop. S. Paulo

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“…Identification of Cryptococcus species through the amplification of the specific ITS region was performed using two universal primers ITS1 and ITS4 (ITS1: 5 -TCCGTAGGTGAACCTGCGG-3 and ITS4: 5 -TCCTCCGCTTATTGATATGC-3 ), as described previously (Nascimento et al, 2016). The PCR products were sequenced in both directions and were compared against those contained in the Centraalbureau voor Schimmelcultures (CBS) hosted at the Westerdijk Fungal Biodiversity Institute 1 .…”

Section: Internal Transcribed Spacer (Its) Sequencingmentioning

confidence: 99%

Microbiological, Epidemiological, and Clinical Characteristics of Patients With Cryptococcal Meningitis at a Tertiary Hospital in China: A 6-Year Retrospective Analysis

Zou

Yin

et al. 2020

Front. Microbiol.

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Cryptococcal meningitis, mainly caused by Cryptococcus neoformans/gattii species complexes, is a lethal infection in both immunosuppressive and immunocompetent populations. We characterized 110 Cryptococcus strains collected from Xiangya Hospital of Central South University in China during the 6-year study period between 2013 and 2018, and performed their antifungal susceptibility testing. Furthermore, the clinical features, laboratory and imaging data, treatment strategies and outcomes of the subjects were retrospectively analyzed. Of 110 Cryptococcus strains, C. neoformans species complexes accounted for 96.4% (106/110), including C. neoformans sensu stricto (VNI molecular type, 95.5%, 105/110) and Cryptococcus deneoformans (VNIV molecular type, 0.9%, 1/110), and Cryptococcus deuterogattii (VGII molecular type) accounted for 3.6% (4/110). The strains were further classified into 17 individual sequence types (STs) by using multilocus sequence typing (MLST). 89.1% (98/110) were represented by ST5; seven C. deuterogattii strains and one Cryptococcus deneoformans strain were assigned as ST7 and ST260, respectively. Antifungal minimal inhibitory concentrations above the epidemiological cutoff values (ECVs) were found mainly in C. neoformans species complexes strains (nine for amphotericin B, nine for fluconazole and seven for 5-fluorocytosine). Furthermore, 60.9% (67/110) of the subjects were male, and 40.0% (44/110) did not have underlying diseases. Hepatic diseases (hepatitis/HBV carrier status and cirrhosis) were the most common underlying health conditions (11.8%, 13/110), followed by autoimmune disorders (10.9%, 12/110) and chronic kidney disease (6.36%, 7/110). Only 4.5% (5/110) of the patients were HIV/AIDS positives. For clinical presentation, headache (77.3%, 85/110), fever (47.3%, 52/110), and stiff neck (40.9%, 45/110) were commonly observed. The mortality rate

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“…usually shows susceptibility to amphotericin B, azole drugs and flucytosine 13 . However, there are some cases of fungal persistence and disease relapse 14,15 . Additionally, resistance and non‐wild‐type phenotypes to antifungal drugs have been reported 16,17 …”

Section: Introductionmentioning

confidence: 99%

Molecular typing, in vitro susceptibility and virulence of Cryptococcus neoformans/Cryptococcus gattii species complex clinical isolates from south‐eastern Brazil

Barião

Tonani

Cocio

et al. 2020

Mycoses

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Summary Background Cryptococcus neoformans/ Cryptococcus gattii species complex is composed of encapsulated yeast species that are causative agents of cryptococcosis. The characterisation of pathogenic Cryptococcus species provides useful data for epidemiological studies as well as the clinical diagnosis and treatment of patients. Objectives This study aimed to characterise the epidemiology, antifungal susceptibility and virulence of 72 clinical strains isolated from cryptococcosis cases between 2012 and 2017 in a tertiary reference hospital in south‐eastern Brazil. Methods Species and molecular types were molecularly assessed by PCR and PCR‐restriction fragment length polymorphism (RFLP) of the URA5 gene. Antifungal susceptibility testing was performed according to the CLSI protocols. The virulence was studied in a Galleria mellonella infection model. Results The most frequently isolated strain was C. neoformans molecular type VNI (61/72; 84.7%), although C. neoformans molecular type VNII (3/72; 4.2%) was also isolated. Additionally, C. deuterogattii molecular type VGII (8/72; 11.1%) was present, but most frequently from non‐HIV‐infected patients. Non‐wild‐type phenotype to the antifungals was observed in 26.4% (19/72) of the C. neoformans and C. deuterogattii clinical isolates, and the latter demonstrated higher MIC to fluconazole and itraconazole than C. neoformans clinical isolates. Finally, the virulence of C. neoformans and C. deuterogattii clinical isolates was diverse in G mellonella larvae and uncorrelated with the virulence factors of melanin and capsule. Conclusions The assessment of the spread of cryptococcal species and molecular types as well as the pattern of corresponding antifungal susceptibility and virulence aids in surveil the emergence of resistant strains, ensuring more accurate management of the cryptococcal infection.

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Refractory and/or Relapsing Cryptococcosis Associated with Acquired Immune Deficiency Syndrome: Clinical Features, Genotype, and Virulence Factors of Cryptococcus spp. Isolates

Cited by 11 publications

References 38 publications

Cryptococcus neoformans and C. gattii isolates from both HIV-infected and uninfected patients: antifungal susceptibility and outcome of cryptococcal disease

Cryptococcus neoformans and C. gattii isolates from both HIV-infected and uninfected patients: antifungal susceptibility and outcome of cryptococcal disease

Microbiological, Epidemiological, and Clinical Characteristics of Patients With Cryptococcal Meningitis at a Tertiary Hospital in China: A 6-Year Retrospective Analysis

Molecular typing, in vitro susceptibility and virulence of Cryptococcus neoformans/Cryptococcus gattii species complex clinical isolates from south‐eastern Brazil

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