JOAO NOBREGA DE ALMEIDA JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
4 resultados
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- Global guideline for the diagnosis and management of rare yeast infections: an initiative of the ECMM in cooperation with ISHAM and ASM(2021) CHEN, Sharon C-A; PERFECT, John; COLOMBO, Arnaldo L.; CORNELY, Oliver A.; GROLL, Andreas H.; SEIDEL, Danila; ALBUS, Kerstin; ALMEDIA JR., Joao Nobrega de; GARCIA-EFFRON, Guillermo; GILROY, Nicole; LASS-FLOERL, Cornelia; OSTROSKY-ZEICHNER, Luis; PAGANO, Livio; PAPP, Tamas; RAUTEMAA-RICHARDSON, Riina; SALMANTON-GARCIA, Jon; SPEC, Andrej; STEINMANN, Joerg; ARIKAN-AKDAGLI, Sevtap; ARENZ, Dorothee E.; SPRUTE, Rosanne; DURAN-GRAEFF, Luisa; FREIBERGER, Tomas; GIRMENIA, Corrado; HARRIS, Michelle; KANJ, Souha S.; ROUDBARY, Maryam; LORTHOLARY, Olivier; MELETIADIS, Joseph; SEGAL, Esther; TUON, Felipe Francisco; WIEDERHOLD, Nathan; BICANIC, Tihana; CHANDER, Jagdish; CHEN, Yee-Chun; HSUEH, Po-Ren; IP, Margaret; MUNOZ, Patricia; SPRIET, Isabel; TEMFACK, Elvis; THOMPSON, Luis; TORTORANO, Anna Maria; VELEGRAKI, Aristea; GOVENDER, Nelesh P.Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections.
- Multidrug-resistant Trichosporon species: underestimated fungal pathogens posing imminent threats in clinical settings(2021) ARASTEHFAR, Amir; ALMEIDA JUNIOR, Joao N. de; PERLIN, David S.; ILKIT, Macit; BOEKHOUT, Teun; COLOMBO, Arnaldo LopesSpecies of Trichosporon and related genera are widely used in biotechnology and, hence, many species have their genome sequenced. Importantly, yeasts of the genus Trichosporon have been increasingly identified as a cause of life-threatening invasive trichosporonosis (IT) in humans and are associated with an exceptionally high mortality rate. Trichosporon spp. are intrinsically resistant to frontline antifungal agents, which accounts for numerous reports of therapeutic failure when echinocandins are used to treat IT. Moreover, these fungi have low sensitivity to polyenes and azoles and, therefore, are potentially regarded as multidrug-resistant pathogens. However, despite the clinical importance of Trichosporon spp., our understanding of their antifungal resistance mechanisms is quite limited. Furthermore, antifungal susceptibility testing is not standardized, and there is a lack of interpretive epidemiological cut-off values for minimal inhibitory concentrations to distinguish non-wild type Trichosporon isolates. The route of infection remains obscure and detailed clinical and environmental studies are required to determine whether the Trichosporon infections are endogenous or exogenous in nature. Although our knowledge on effective IT treatments is rather limited and future randomized clinical trials are required to identify the best antifungal agent, the current paradigm advocates the use of voriconazole, removal of central venous catheters and recovery from neutropenia.
- Determinants of fluconazole resistance and the efficacy of fluconazole and milbemycin oxim combination against Candida parapsilosis clinical isolates from Brazil and Turkey(2022) DANESHNIA, Farnaz; POLAT, Suleyha Hilmioglu; ILKIT, Macit; SHOR, Erika; ALMEIDA, Joao Nobrega de; FAVARELLO, Larissa M.; COLOMBO, Arnaldo Lopes; ARASTEHFAR, Amir; PERLIN, David S.Fluconazole-resistant Candida parapsilosis (FLZR-CP) outbreaks are a growing public health concern and have been reported in numerous countries. Patients infected with FLZR-CP isolates show fluconazole therapeutic failure and have a significantly increased mortality rate. Because fluconazole is the most widely used antifungal agent in most regions with outbreaks, it is paramount to restore its antifungal activity. Milbemycin oxim (MOX), a well-known canine endectocide, is a potent efflux pump inhibitor that significantly potentiates the activity of fluconazole against FLZR C. glabrata and C. albicans. However, the FLZ-MOX combination has not been tested against FLZR-CP isolates, nor is it known whether MOX may also potentiate the activity of echinocandins, a different class of antifungal drugs. Furthermore, the extent of involvement of efflux pumps CDR1 and MDR1 and ergosterol biosynthesis enzyme ERG11 and their link with gain-of-function (GOF) mutations in their transcription regulators (TAC1, MRR1, and UPC2) are poorly characterized among FLZR-CP isolates. We analyzed 25 C. parapsilosis isolates collected from outbreaks in Turkey and Brazil by determining the expression levels of CDR1, MDR1, and ERG11, examining the presence of potential GOF mutations in their transcriptional regulators, and assessing the antifungal activity of FLZ-MOX and micafungin-MOX against FLZR and multidrug-resistant (MDR) C. parapsilosis isolates. ERG11 was found to be universally induced by fluconazole in all isolates, while expression of MDR1 was unchanged. Whereas mutations in MRR1 and UPC2 were not detected, CDR1 was overexpressed in three Brazilian FLZR-CP isolates, which also carried a novel TAC1(L518F) mutation. Of these three isolates, one showed increased basal expression of CDR1, while the other two overexpressed CDR1 only in the presence of fluconazole. Interestingly, MOX showed promising antifungal activity against FLZR isolates, reducing the FLZ MIC 8- to 32-fold. However, the MOX and micafungin combination did not exert activity against an MDR C. parapsilosis isolate. Collectively, our study documents that the mechanisms underpinning FLZR are region specific, where ERG11 mutations were the sole mechanism of FLZR in Turkish FLZR-CP isolates, while simultaneous overexpression of CDR1 was observed in some Brazilian counterparts. Moreover, MOX and fluconazole showed potent synergistic activity, while the MOX-micafungin combination showed no synergy.
- Clonal Candidemia Outbreak by Candida parapsilosis Carrying Y132F in Turkey: Evolution of a Persisting Challenge(2021) ARASTEHFAR, Amir; HILMIOGLU-POLAT, Suleyha; DANESHNIA, Farnaz; PAN, Weihua; HAFEZ, Ahmed; FANG, Wenjie; LIAO, Wanqing; SAHBUDAK-BAL, Zumrut; METIN, Dilek Yesim; ALMEIDA JUNIOR, Joao N. de; ILKIT, Macit; PERLIN, David S.; LASS-FLOERL, CorneliaAs the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019-2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019-2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.