Molecular typing and in vitro resistance of Cryptococcus neoformans clinical isolates obtained in Germany between 2011 and 2017

Selb, Regina; Fuchs, Vidmante; Graf, Barbara; Hamprecht, Axel; Hogardt, Michael; Sedlacek, Ludwig; Schwarz, Roman; Idelevich, Evgeny A.; Becker, Sören L.; Held, Jürgen; Küpper-Tetzel, Claus P.; McCormick-Smith, Ilka; Heckmann, Daniela; Gerkrath, Jasmin; Han, Chang-Ok; Wilmes, Dunja; Rickerts, Volker

doi:10.1016/j.ijmm.2019.151336

Cited by 20 publications

(15 citation statements)

References 32 publications

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“…Our results are in line with most of Cryptococcus spp. isolates since the emergence of HIV, which are mostly wild‐type to AMB 13,17,33,34,36,37 . Therefore, the majority of C. neoformans VNI isolates are currently wild‐type concerning AMB.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…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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“…However, in pathological conditions, including acquired immunodeficiency syndrome (AIDS), tuberculosis, diabetes mellitus, and cancer, or under increased physiological stress, such as during organ transplantation, corticosteroid administration, and chemotherapy [6,7], the risk of developing fungal infections-related ailments is highly increased [8]. Among the infectious fungal species, Aspergillus spp., Candida spp., Cryptococcus spp., and Pneumocystis jirovecii are the causative agents of major mycoses in humans [9,10]. In addition, the incidence of infections caused by Zygomycetes, Fusarium, and Scedosporium has been rising [11,12].…”

Section: Introductionmentioning

confidence: 99%

Antifungal Agents in Agriculture: Friends and Foes of Public Health

et al. 2019

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Fungal diseases have been underestimated worldwide but constitute a substantial threat to several plant and animal species as well as to public health. The increase in the global population has entailed an increase in the demand for agriculture in recent decades. Accordingly, there has been worldwide pressure to find means to improve the quality and productivity of agricultural crops. Antifungal agents have been widely used as an alternative for managing fungal diseases affecting several crops. However, the unregulated use of antifungals can jeopardize public health. Application of fungicides in agriculture should be under strict regulation to ensure the toxicological safety of commercialized foods. This review discusses the use of antifungals in agriculture worldwide, the need to develop new antifungals, and improvement of regulations regarding antifungal use.

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“…27,36,37 For example, based on the same AFST method and ECV, a recent study in Germany showed no non-wild type isolate to AMB among 102 C. neoformans/VNI strains isolated in the present days. 38 Moreover, the most comprehensive cryptococcal AFST study with strains collected from six laboratories during 2010-2012, 39 VNI, VGI, and VGII strains showed only 2.8% (28/1002 strains), 0.8% (2/259 strains), and 0.2% (1/ 470 strains) non-wild type rate. The difference in antifungal susceptibility pattern between pre-HIV and HIV pandemic might be explained by the fact that ECV was developed mainly from strains collected from HIV pandemic.…”

Section: Discussionmentioning

confidence: 98%

<p><em>Cryptococcus neoformans/gattii</em> Species Complexes from Pre-HIV Pandemic Era Contain Unusually High Rate of Non-Wild-Type Isolates for Amphotericin B</p>

Pharkjaksu

Chongtrakool

Chayakulkeeree

et al. 2020

IDR

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Introduction: The Cryptococcus neoformans/gattii species complexes are a leading cause of fatality among HIV-infected patients. Despite the unavailability of clinical breakpoints (CBPs) for antifungal agents, epidemiological cutoff values (ECVs) were recently proposed, and non-wild-type isolates for polyenes and azoles are being increasingly reported. However, the distributions of the susceptibility patterns for pre-HIV-era isolates have not been studied. Methods: We determined the in vitro antifungal susceptibility patterns of 233 Cryptococcus isolates, collected at the National Institutes of Health, USA, in pre-HIV pandemic era, to study minimum inhibitory concentrations (MICs) to the important drugs for cryptococcosis and to compare the results with strain genotypes. Amphotericin B susceptibility was compared to published ECV of C. neoformans. Results: The 233 Cryptococcus strains consisted of 89.7% C. neoformans species complex and 10.3% C. gattii species complex. Most were from clinical sources (189, 81.1%), and the major molecular type was VNI (146, 62.7%). The highest geometric mean (GM) was observed for fluconazole (GM = 0.96 µg/mL) while the lowest was for itraconazole (GM = 0.10 µg/mL). MICs to fluconazole in C. gattii species complex were significantly higher than C. neoformans species complex (p < 0.001). Moreover, C. neoformans/VNI strains showed significantly higher MICs than others such as C. neoformans/VNII to fluconazole (p < 0.0001) and C. deneoformans/VNIV to amphotericin B (p = 0.022) and fluconazole (p = 0.008). In our collection of 167 clinical C. neoformans species complex strains, 85 (50.9%), 24 (14.4%), and 3 (1.8%) strains had an amphotericin B (AMB)-MIC of 1, 2, and 4 µg/mL, respectively. The high percentage (66.9%, 79/118 strains) of non-wild-type clinical C. neoformans VNI strains, using an AMB-ECV of 0.5 µg/mL, was found. Moreover, 25 of 28 (89.3%) C. neoformans VNI strains from environmental and veterinary sources also had AMB-MICs above 0.5 µg/mL. In general, there was no significant difference in GM AMB-MIC of the clinical strains isolated from patients with (35 patients) and without (78 patients) prior AMB treatment (0.85 vs 0.76; p = 0.624). GM MIC of the environmental strains was not significantly different from that of the prior AMB-treatment strains (0.98 vs 0.76, p = 0.159) and the post-AMB-treatment strains (0.98 vs 0.85, p = 0.488). Conclusion: The high rate of non-wild-type among these otherwise naive isolates to amphotericin B is unexpected. Confirmation with more strains from a later era is needed.

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Molecular typing and in vitro resistance of Cryptococcus neoformans clinical isolates obtained in Germany between 2011 and 2017

Cited by 20 publications

References 32 publications

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

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

Antifungal Agents in Agriculture: Friends and Foes of Public Health

<p><em>Cryptococcus neoformans/gattii</em> Species Complexes from Pre-HIV Pandemic Era Contain Unusually High Rate of Non-Wild-Type Isolates for Amphotericin B</p>

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