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

Abstract

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.

Minimum concentration of Amphotericin B in serum according to the formulation, dose, and daily or prolonged intermittent therapeutic regimen

“…When a daily L-AmB regimen was administered, the ratio of Cmax/MIC for the isolated fungi was higher in children with a full clinical response than in those with a partial response to antifungal treatment 20 . In the present study, the Cmin of patients treated daily with D-Amph and/or L-AmB was not associated with the outcome of patients with cryptococcal meningitis; this may be due to the high susceptibility to amphotericin B of the Cryptococcus isolated from cryptococcosis patients at the study center 21 . When a non-daily L-AmB regimem is employed, the Cmin may be more important for the outcome if there is a longer period between infusions.…”

The status of cryptococcosis in Latin America

“…to AmB Benaducci et al (2015) In vitro susceptibility testing of AmB for C. neoformans variety grubii AFLP1/VNI and C. gattii AFLP6/VGII by CLSI and flow cytometry Morales et al (2015) Heteroresistance to ITZ and changes in the morphology and virulence of C. gattii Ferreira et al (2015) Antifungal susceptibility of clinical C. deuterogattii (AFLP6/VGII) isolates from Southern Brazil Herkert et al (2016) Resistance to FCZ and changes on virulence and morphological aspects of C. neoformans and C. gattii Rossi et al (2016) Antifungal susceptibility testing and genotyping characterization of C. neoformans and C. gattii isolates from HIV-infected patients Figueiredo et al (2016) Evaluation of antifungal combination against Cryptococcus spp. Reichert-Lima et al (2016) C. neoformans and C. gattii isolates from both HIV-infected and uninfected patients: antifungal susceptibility and outcome of cryptococcal disease Nascimento et al (2017) FCZ non-susceptible C. neoformans . Use of LAmB in AIDS patient Santana et al (2017) FCZ levels in serum and cerebrospinal fluid Schiave et al (2018) Time-kill curves studies with AmB against C. neoformans / C .…”

“…Clinical and environmental data - The studies are presented in Table IV and the data is variable; hence, it is important to analyse each one of the articles’ data, separately ( Arechavala et al 2009 , Illnait-Zaragozí et al 2009 , Matos et al 2012 , Silva et al 2012 , Andrade-Silva et al 2013 , Teodoro et al 2013 , Figueiredo et al. 2016 , Herkert et al 2016 , Reichert-Lima et al 2016 , Nascimento et al 2017 ).…”

Caracterização molecular, susceptibilidade a antifúngicos e virulência de isolados clínicos de Cryptococcus spp

“…Além disso, em estudo realizado pelo nosso grupo de pesquisa com isolados clínicos de C. neoformans var. grubii e C. gattii foi observada SI para 5-FC (NASCIMENTO et al, 2017). Os dados de nosso trabalho não corroboram com os relatos na literatura, uma vez que todos os isolados clínicos C.…”

“…Resultado divergente foi relatado pelo nosso grupo de pesquisa que mostrou o não isolamento de Cryptococcus spp. resistentes à AMB(NASCIMENTO et al, 2017), revelando que os isolados clínicos de Cryptococcus spp. da região nordeste do estado de São Paulo são sensíveis à AMB.…”