Antifungal Therapy and Management of Complications of Cryptococcosis due to Cryptococcus gattii

Chen, Sharon C.-A.; Korman, Tony M.; Slavin, Monica A; Marriott, Deborah; Bak, Narin; Currie, Bart J.; Hajkowicz, Krispin; Heath, Christopher H.; Kidd, Sarah; McBride, William J. H.; Meyer, Wieland; Murray, Ronan J.; Playford, Geoffrey; Sorrell, Tania C.

doi:10.1093/cid/cit341

Cited by 104 publications

(115 citation statements)

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“…Notably, in that study, median CD4 counts were higher than those in patients who did not develop IRIS (299). Unlike in HIV-positive patients, neither initial CSF cryptococcal antigen (CRAG) titers nor CSF leukocyte counts and protein levels differed from those in patients who did not develop IRIS (299,300). However, since patients with C. gattii who subsequently developed IRIS all presented with cryptococcomas in the brain, CSF parameters likely did not reflect the fungal load (or immune response) in this site.…”

Section: Immune Reconstitution Inflammatory Syndromementioning

confidence: 57%

“…No cases were reported for 10 HIV-negative Vietnamese patients with C. gattii meningitis (239). However, in an Australian study, IRIS occurred in 9.4% of patients, two-thirds of whom had no underlying immunocompromise, although one patient was postpartum (299). In that study, IRIS was diagnosed when symptoms or radiological features consistent with inflammation worsened or appeared following a clinical and/or microbiological response to anticryptococcal therapy, and cultures were negative.…”

Section: Immune Reconstitution Inflammatory Syndromementioning

confidence: 93%

“…In these patients, the development of IRIS is associated with immune reconstitution and typically presents with worsening of disease or recurrence in the same or new anatomical sites despite mycological evidence of effective antifungal therapy (reviewed in reference 298). IRIS has been described infrequently in association with C. gattii infection: occasional cases were reported in apparently healthy hosts in association with pregnancy and in immunocompromised individuals (216,217,241,299). No cases were reported for 10 HIV-negative Vietnamese patients with C. gattii meningitis (239).…”

Section: Immune Reconstitution Inflammatory Syndromementioning

confidence: 99%

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Cryptococcus gattii Infections

2014

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SUMMARY Understanding of the taxonomy and phylogeny of Cryptococcus gattii has been advanced by modern molecular techniques. C. gattii probably diverged from Cryptococcus neoformans between 16 million and 160 million years ago, depending on the dating methods applied, and maintains diversity by recombining in nature. South America is the likely source of the virulent C. gattii VGII molecular types that have emerged in North America. C. gattii shares major virulence determinants with C. neoformans , although genomic and transcriptomic studies revealed that despite similar genomes, the VGIIa and VGIIb subtypes employ very different transcriptional circuits and manifest differences in virulence phenotypes. Preliminary evidence suggests that C. gattii VGII causes severe lung disease and death without dissemination, whereas C. neoformans disseminates readily to the central nervous system (CNS) and causes death from meningoencephalitis. Overall, currently available data indicate that the C. gattii VGI, VGII, and VGIII molecular types more commonly affect nonimmunocompromised hosts, in contrast to VGIV. New, rapid, cheap diagnostic tests and imaging modalities are assisting early diagnosis and enabling better outcomes of cerebral cryptococcosis. Complications of CNS infection include increased intracranial pressure, severe neurological sequelae, and development of immune reconstitution syndrome, although the mortality rate is low. C. gattii VGII isolates may exhibit higher fluconazole MICs than other genotypes. Optimal therapeutic regimens are yet to be determined; in most cases, initial therapy with amphotericin B and 5-flucytosine is recommended.

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Section: Immune Reconstitution Inflammatory Syndromementioning

confidence: 57%

Section: Immune Reconstitution Inflammatory Syndromementioning

confidence: 93%

Section: Immune Reconstitution Inflammatory Syndromementioning

confidence: 99%

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Cryptococcus gattii Infections

2014

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“…After invading the lung tissue, hematogenous dissemination occurs with a predisposition for the central nervous system [23]. Meningitis and meningoencephalitis are the most common clinical manifestations in cases of cryptococcal meningitis caused by Cryptococcus spp, while C. gattii shows a propensity to cause cryptococcomas, focal CNS lesions and important neurological sequelae [14,15,23,24].…”

Section: Introductionmentioning

confidence: 99%

Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil

Favalessa

Paula

Dutra

et al. 2014

J Infect Dev Ctries

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Introduction: Cryptococcosis is a systemic fungal infection that affects humans and animals, mainly due to Cryptococcus neoformans and Cryptococcus gattii. Following the epidemic of acquired immunodeficiency syndrome (AIDS), fungal infections by C. neoformans have become more common among immunocompromised patients. Cryptococcus gattii has primarily been isolated as a primary pathogen in healthy hosts and occurs endemically in northern and northeastern Brazil. We to perform genotypic characterization and determine the in vitro susceptibility profile to antifungal drugs of the Cryptococcus species complex isolated from HIV-positive and HIV-negative patients attended at university hospitals in Cuiabá, MT, in the Midwestern region of Brazil. Methodology: Micromorphological features, chemotyping with canavanine-glycine-bromothymol blue (CGB) agar and genotyping by URA5-RFLP were used to identify the species. The antifungal drugs tested were amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole. Minimum inhibitory concentrations (MICs) were determined according to the CLSI methodology M27-A3. Results: Analysis of samples yelded C. neoformans AFLP1/VNI (17/27, 63.0%) and C. gattii AFLP6/VGII (10/27, 37.0%). The MICs ranges for the antifungal drugs were: amphotericin B (0.5-1 mg/L), fluconazole (1-16 mg/L), flucytosine (1-16 mg/L), itraconazole (0.25-0.12 mg/L) and voriconazole (0.06-0.5 mg/L). Isolates of C. neoformans AFLP1/VNI were predominant in patients with HIV/AIDS, and C. gattii VGII in HIV-negative patients. The genotypes identified were susceptible to the antifungal drugs tested. Conclusion: It is worth emphasizing that AFLP6/VGII is a predominant genotype affecting HIV-negative individuals in Cuiabá. These findings serve as a guide concerning the molecular epidemiology of C. neoformans and C. gattii in the State of Mato Grosso.

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“…These organisms usually produce a polysaccharide capsule that acts as an important virulence factor against the host's defenses (2). Besides its epidemiological importance, species differentiation in this genus has major clinical relevance since patients with central nervous system (CNS) infection by C. gattii have a higher risk of neurological complications, need a more prolonged course of induction antifungal therapy, and have poorer prognoses than those with C. neoformans infections (3,4).…”

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confidence: 99%

Does the Capsule Interfere with Performance of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Identification of Cryptococcus neoformans and Cryptococcus gattii?

et al. 2016

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We described the impact of the capsule size for Cryptococcus neoformans and Cryptococcus gattii identification at the species level by Bruker matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). After experimental capsule size modulation, we observed that reducing the capsule size resulted in improved identification by Bruker MALDI-TOF MS across all of the reference strains analyzed. Cryptococcus neoformans and Cryptococcus gattii are relevant species among the pathogenic basidiomycetous yeasts responsible for infection in humans (1). These organisms usually produce a polysaccharide capsule that acts as an important virulence factor against the host's defenses (2). Besides its epidemiological importance, species differentiation in this genus has major clinical relevance since patients with central nervous system (CNS) infection by C. gattii have a higher risk of neurological complications, need a more prolonged course of induction antifungal therapy, and have poorer prognoses than those with C. neoformans infections (3, 4).Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been shown to be a precise technology for Cryptococcus species identification (ID), replacing conventional and time-consuming phenotypic methods and providing an alternative to expensive and labor-intensive molecular techniques (5, 6). However, during routine practice in our clinical microbiology laboratory, we observed that some Cryptococcus isolates with prominent capsule sizes had low discriminatory ID when using Bruker MALDI-TOF MS analysis. These isolates required the application of old phenotypic methods, which delayed the release of the final result. This led us to investigate the impact of cryptococcal capsule size in correct species ID by Bruker MALDI-TOF MS analysis.For this purpose, reference strains of the eight genotypes of C. neoformans and C. gattii, WM148 (serotype A, VNI), WM626 (serotype A, VNII), WM 628 (serotype AD, VNIII), WM629 (serotype D, VNIV), WM179 (serotype B, VGI), WM178 (serotype B, VGII), WM161 (serotype B, VGIII), and WM779 (serotype C, VGIV), were subjected to capsule size modulation according to previously described methods (7,8). Briefly, 2 ml of capsule growth-inducing medium (CGIM) (Sabouraud dextrose broth [BD, Franklin Lakes, NJ, USA] diluted 10 times with sterile water, pH 7.3) containing 2 ϫ 10 6 yeast cells was incubated at 37°C with shaking. In an attempt to increase the variability in capsule size, all strains were subjected to a prolonged incubation in CGIM (up to 28 days) and were evaluated simultaneously on days 2, 3, 7, 14, 21, and 28, giving a total of 48 capsule size measurements (six replicates for each strain of the two Cryptococcus species). Next, yeast cells collected from the CGIM were submitted to a progressive capsule reduction protocol with four consecutive initial seedings in Sabouraud dextrose agar (SDA; BD) and two more seedings in the capsule-reducing medium (CRM) (SDA plus 2.9% NaCl). Dur...

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Antifungal Therapy and Management of Complications of Cryptococcosis due to Cryptococcus gattii

Abstract: Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.

Cited by 104 publications

References 28 publications

Cryptococcus gattii Infections

Cryptococcus gattii Infections

Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil

Does the Capsule Interfere with Performance of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Identification of Cryptococcus neoformans and Cryptococcus gattii?

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