scholarly journals High prevalence of Itraconazole Resistance among Candida parapsilosis isolated from Iran

2019 ◽  
Author(s):  
Fozieh Hassanmoghadam ◽  
Tahereh Shokohi ◽  
Mohammad Taghi Hedayati ◽  
Narges Aslani ◽  
Iman Haghani ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Inhibitory Concentration ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Sensu Stricto ◽  
Antifungal Drugs ◽  
High Prevalence ◽  
Invasive Infections ◽  
Prophylaxis Therapy

Background and Purpose: Candida parapsilosis isolates usually have a low minimum inhibitory concentration (MIC) against azoles. Although Candida parapsilosis isolates usually have low MICs against azoles, recent studies candida invasive infections due to azole resistant-C. parapsilosis isolates . Regarding this, the main aim of this study was to determine the susceptibility pattern of Iranian clinical C. parapsilosis against available azole antifungal drugs. Materials and Methods: This study was conducted on 105 previously-identified isolates of C. parapsilosis sensu stricto. For the purpose of the study, the isolates were subjected to antifungal susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), and two new azole drugs, namely luliconazole (LUZU) and lanoconazole (LZN). The broth microdilution reference method adopted in this study was according to the Clinical & Laboratory Standards Institute M27-A3 and M27-S4 documents. Results: According to the results, 89% (n=94) of C. parapsilosis isolates showed a MIC of ≥ 1 µg/ml, indicating resistance against ITZ. Multi-azole resistance was observed in 3.8% of the isolates. In addition, LUZU and LZN demonstrated the highest efficacy with the MIC50 values of 0.5 and 1 µg/ml, respectively. Conclusion: The majority of the isolates showed high MIC values against ITZ. This may have been associated with the long-term ITZ prophylaxis/therapy in patients infected with candidiasis. Hence, the adoption of an appropriate antifungal agent is a crucial step for starting the treatment.

scholarly journals Rapid Detection of Echinocandins Resistance by MALDI-TOF MS in Candida parapsilosis Complex

2020 ◽  
Vol 8 (1) ◽  
pp. 109
Author(s):  
Ana Emília M. Roberto ◽  
Danilo E. Xavier ◽  
Esteban E. Vidal ◽  
Cláudia Fernanda de L. Vidal ◽  
Rejane P. Neves ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Incubation Time ◽  
Candida Parapsilosis ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Sensu Stricto ◽  
Maldi Tof ◽  
Separation Parameter ◽  
Candida Parapsilosis Complex

Mass spectrometry by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) was used to identify and differentiate the pattern of susceptibility of clinical isolates of Candida parapsilosis complex. 17 C. parapsilosis sensu stricto, 2 C. orthopsilosis, and 1 C. metapsilosis strains were obtained from blood cultures, and three different inocula (103, 105, and 107 CFU/mL) were evaluated against three echinocandins at concentrations ranging from 0.03 to 16 µg/mL after incubation of 1 h, 2 h, and 3 h. Drug-free control was used. The spectra obtained at these concentrations were applied to generate composite correlation index (CCI) matrices for each yeast individually. After cross correlations and autocorrelations of each spectra with null (zero) and maximal (16) concentrations, the CCI was used as separation parameter among spectra. Incubation time and inoculum were critical factors to reach higher precision and reliability of this trial. With an incubation time of 3 h and inoculum of 107 CFU/mL, it was possible to determine the breakpoint of the clinical yeasts by MALDI-TOF that presented high agreement with the clinical laboratory standard institute (CLSI) reference method. Herein, we show that mass spectrometry using the MALDI-TOF technique is powerful when it exploits antifungal susceptibility testing assays.

scholarly journals The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex

2014 ◽  
Vol 63 (7) ◽  
pp. 936-944 ◽  
Author(s):  
Rossana de Aguiar Cordeiro ◽  
Ramila de Brito Macedo ◽  
Carlos Eduardo Cordeiro Teixeira ◽  
Francisca Jakelyne de Farias Marques ◽  
Tereza de Jesus Pinheiro Gomes Bandeira ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Calcineurin Inhibitor ◽  
Candida Parapsilosis ◽  
Antifungal Susceptibility ◽  
Inhibitory Effect ◽  
Sensu Stricto ◽  
Antifungal Drugs ◽  
Closely Related Species ◽  
Candida Orthopsilosis ◽  
Synergy Testing

Candida parapsilosis complex comprises three closely related species, C. parapsilosis sensu stricto, Candida metapsilosis and Candida orthopsilosis. In the last decade, antifungal resistance to azoles and caspofungin among C. parapsilosis sensu lato strains has been considered a matter of concern worldwide. In the present study, we evaluated the synergistic potential of antifungals and the calcineurin inhibitor cyclosporin A (Cys) against planktonic and biofilms of C. parapsilosis complex from clinical sources. Susceptibility assays with amphotericin, fluconazole, voriconazole, caspofungin and Cys were performed by microdilution in accordance with Clinical and Laboratory Standards Institute guidelines. Synergy testing against planktonic cells of C. parapsilosis sensu lato strains was assessed by the chequerboard method. Combinations formed by antifungals with Cys were evaluated against mature biofilms in microtitre plates. No differences in the antifungal susceptibility pattern among species were observed, but C. parapsilosis sensu stricto strains were more susceptible to Cys than C. orthopsilosis and C. metapsilosis. Synergism between antifungals and Cys was observed in C. parapsilosis sensu lato strains. Combinations formed by antifungals and Cys were able to prevent biofilm formation and showed an inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. These results strengthen the potential of calcineurin inhibition as a promising approach to enhance the efficiency of antifungal drugs.

scholarly journals In Vitro Interaction between Isavuconazole and Tacrolimus, Cyclosporin A, or Sirolimus against Aspergillus Species

2020 ◽  
Vol 6 (3) ◽  
pp. 103 ◽  
Author(s):  
Patrick Schwarz ◽  
Eric Dannaoui
Keyword(s):  
Cyclosporin A ◽  
Aspergillus Terreus ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Common Species ◽  
Minimal Inhibitory Concentrations ◽  
In Vitro Interaction

The interaction of isavuconazole with immunosuppressors (tacrolimus, cyclosporin A, or sirolimus) against 30 Aspergillus isolates belonging to the most common species responsible for invasive aspergillosis in humans (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus) was evaluated in vitro by a microdilution checkerboard technique based on the EUCAST reference method for antifungal susceptibility testing. The interpretation of the results was performed based on the fractional inhibitory concentration index. The combination of isavuconazole with tacrolimus, cyclosporin A, or sirolimus, was synergistic for 56, 20, or 10% of the isolates, respectively. Interestingly synergy of the combination of isavuconazole with tacrolimus was also achieved for the majority of azole-resistant isolates of A. fumigatus, and for all A. niger isolates with isavuconazole minimal inhibitory concentrations ≥ 8 µg/mL. Antagonistic interactions were never observed for any combination tested.

scholarly journals Aspergillus calidoustus sp. nov., Causative Agent of Human Infections Previously Assigned to Aspergillus ustus

2008 ◽  
Vol 7 (4) ◽  
pp. 630-638 ◽  
Author(s):  
János Varga ◽  
Jos Houbraken ◽  
Henrich A. L. Van Der Lee ◽  
Paul E. Verweij ◽  
Robert A. Samson
Keyword(s):  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Protein Coding ◽  
Coding Regions ◽  
Aspergillus Ustus ◽  
Invasive Infections ◽  
Human Infections ◽  
Immunocompromised Hosts ◽  
A New Species

ABSTRACT Aspergillus ustus is a relatively rare human pathogen causing invasive infections in immunocompromised hosts. In this study isolates originating from clinical and other sources have been examined using molecular, morphological, and physiological approaches to clarify their species assignment. Phylogenetic analysis of partial β-tubulin, calmodulin, actin, and intergenic transcribed spacer sequences indicated that none of the clinical isolates recognized previously as A. ustus belongs to this species. All but two of these isolates formed a well-defined clade related to A. pseudodeflectus based on sequence analysis of protein-coding regions. Morphological and physiological examination of these isolates indicated that they are able to grow above 37°C, in contrast with A. ustus isolates, and give a positive Ehrlich reaction, in contrast with related species including A. granulosus, A. ustus, and A. pseudodeflectus. These isolates are proposed as a new species, A. calidoustus. Antifungal susceptibility testing showed that this species has decreased susceptibilities to several antifungal drugs. The triazoles are inactive in vitro, including the new azole posaconazole.

scholarly journals Candida parapsilosis: from Genes to the Bedside

2019 ◽  
Vol 32 (2) ◽  
Author(s):  
Renáta Tóth ◽  
Jozef Nosek ◽  
Héctor M. Mora-Montes ◽  
Toni Gabaldon ◽  
Joseph M. Bliss ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Candida Parapsilosis ◽  
Molecular Genetic ◽  
Antifungal Susceptibility ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Host Responses ◽  
Content Type ◽  
Antifungal Drug Resistance ◽  
Geographical Regions

SUMMARYPatients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal nosocomial infection. Over recent decades, the combined prevalence of non-albicans Candidaspecies outrankedCandida albicansinfections in several geographical regions worldwide, highlighting the need to understand their pathobiology in order to develop effective treatment and to prevent future outbreaks.Candida parapsilosisis the second or third most frequently isolatedCandidaspecies from patients. Besides being highly prevalent, its biology differs markedly from that ofC. albicans, which may be associated withC. parapsilosis’ increased incidence. Differences in virulence, regulatory and antifungal drug resistance mechanisms, and the patient groups at risk indicate that conclusions drawn fromC. albicanspathobiology cannot be simply extrapolated toC. parapsilosis. Such species-specific characteristics may also influence their recognition and elimination by the host and the efficacy of antifungal drugs. Due to the availability of high-throughput, state-of-the-art experimental tools and molecular genetic methods adapted toC. parapsilosis, genome and transcriptome studies are now available that greatly contribute to our understanding of what makes this species a threat. In this review, we summarize 10 years of findings onC. parapsilosispathogenesis, including the species’ genetic properties, transcriptome studies, host responses, and molecular mechanisms of virulence. Antifungal susceptibility studies and clinician perspectives are discussed. We also present regional incidence reports in order to provide an updated worldwide epidemiology summary.

scholarly journals Regional Differences in Antifungal Susceptibility of the Prevalent Dermatophyte Trichophyton rubrum

2020 ◽  
Vol 186 (1) ◽  
pp. 53-70
Author(s):  
Y. Jiang ◽  
W. Luo ◽  
P. E. Verweij ◽  
Y. Song ◽  
B. Zhang ◽  
...  
Keyword(s):  
Trichophyton Rubrum ◽  
Antifungal Susceptibility ◽  
Sensu Stricto ◽  
Antifungal Drugs ◽  
Primary Therapy ◽  
In Vitro Susceptibility ◽  
Minimal Inhibitory Concentrations ◽  
Upper Limits ◽  
In Vitro Susceptibility Testing

AbstractIn vitro susceptibility testing for Trichophyton rubrum has shown resistance to terbinafine, azoles and amorolfine, locally, but epidemiological cutoffs are not available. In order to assess the appropriateness of current first-line antifungal treatment for T. rubrum in China, we characterized antifungal susceptibility patterns of Chinese T. rubrum strains to nine antifungals and also described the upper limits of wild-type (WT) minimal inhibitory concentrations (MIC) (UL-WT) based on our study and another six studies published during the last decades. Sixty-two clinical isolates originating from seven provinces in China were identified as T. rubrum sensu stricto; all Chinese strains showed low MICs to eight out of nine antifungal drugs. Terbinafine (TBF) showed the lowest MICs of all antifungal classes tested in both the Chinese and global groups, with a 97.5% UL-WT MIC-value of 0.03 mg/L. No non-WT isolates were observed for TBF in China, but were reported in 18.5% of the global group. Our study indicated that TBF was still the most active drug for Chinese T. rubrum isolates, and all strains were within the WT-population. TBF therefore remains recommended for primary therapy to dermatophytosis caused by T. rubrum in China now, but regular surveillance of dermatophytes and antifungal susceptibility is recommended.

scholarly journals Epidemiology and Antifungal Susceptibility of BloodstreamCandidaIsolates in Quebec: Report on 453 Cases between 2003 and 2005

2008 ◽  
Vol 19 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Guy St-Germain ◽  
Michel Laverdière ◽  
René Pelletier ◽  
Pierre René ◽  
Anne-Marie Bourgault ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Population Based ◽  
Intravascular Catheter ◽  
Fluconazole Resistant ◽  
Candida Lusitaniae

BACKGROUND: Between May 2003 and April 2005, a population-based surveillance ofCandidabloodstream infections was conducted in Quebec. A total of 453 episodes of candidemia (464 yeast isolates) from 54 participating hospitals were studied.RESULTS: The annual incidence rate was three per 100,000 population. Global hospital mortality was 38%. The most common predisposing factors were the presence of an intravascular catheter (80%), use of antibacterial therapy (67%), stay in an intensive care unit (49%), use of parenteral nutrition (32%) and intra-abdominal surgery (31%). Fluconazole alone or in association with other antifungals was used for treatment in over 80% of cases.Candida albicanscomprised 62% of isolates, followed byCandida glabrata(17%),Candida parapsilosis(9%),Candida tropicalis(5%),Candida lusitaniae(3%) andCandida krusei(3%). Of the 288C albicansisolates, seven (2%) were resistant to flucytosine, one to fluconazole and none to itraconazole or voriconazole. Of the 75 non-C albicansspecies isolates with reduced susceptibility to fluconazole (minimum inhibitory concentration [MIC] 16 μg/mL or greater), none were susceptible to itraconazole (MIC 0.12 mg/L or lower), whereas 71 (95%) were susceptible to voriconazole (MIC 1 μg/mL or lower). However, only five of 12 (42%) fluconazole-resistant isolates were susceptible to voriconazole. Posaconazole, ravuconazole and caspofungin displayed a broad spectrum of activity against these isolates, with MICs of 1 mg/L or lower in 56%, 92% and 100% of isolates, respectively. Overall, a correlation (r2>0.87) was observed among increasing fluconazole MICs and the geometric mean MICs of itraconazole, voriconazole, posaconazole and ravuconazole.CONCLUSIONS: These surveillance results when compared with those of the 1993 to 1995 survey confirm little variation in the distribution of species causing invasiveCandidainfection over a 10-year period in Quebec, as well as the continuous excellent overall in vitro activity of fluconazole.

scholarly journals Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center

2021 ◽  
Vol 7 (4) ◽  
pp. 259 ◽  
Author(s):  
Danilo Y. Thomaz ◽  
João N. de Almeida ◽  
Odeli N. E. Sejas ◽  
Gilda M. B. Del Negro ◽  
Gabrielle O. M. H. Carvalho ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Candida Parapsilosis ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Blood Cultures ◽  
Environmental Niche ◽  
Referral Center ◽  
Major Cluster ◽  
Environmental Decontamination

Clonal outbreaks due to azole-resistant Candida parapsilosis (ARCP) isolates have been reported in numerous studies, but the environmental niche of such isolates has yet to be defined. Herein, we aimed to identify the environmental niche of ARCP isolates causing unremitting clonal outbreaks in an adult ICU from a Brazilian cancer referral center. C. parapsilosis sensu stricto isolates recovered from blood cultures, pericatheter skins, healthcare workers (HCW), and nosocomial surfaces were genotyped by multilocus microsatellite typing (MLMT). Antifungal susceptibility testing was performed by the EUCAST (European Committee for Antimicrobial Susceptibility Testing) broth microdilution reference method and ERG11 was sequenced to determine the azole resistance mechanism. Approximately 68% of isolates were fluconazole-resistant (76/112), including pericatheter skins (3/3, 100%), blood cultures (63/70, 90%), nosocomial surfaces (6/11, 54.5%), and HCW’s hands (4/28, 14.2%). MLMT revealed five clusters: the major cluster contained 88.2% of ARCP isolates (67/76) collected from blood (57/70), bed (2/2), pericatheter skin (2/3), from carts (3/7), and HCW’s hands (3/27). ARCP isolates were associated with a higher 30 day crude mortality rate (63.8%) than non-ARCP ones (20%, p = 0.008), and resisted two environmental decontamination attempts using quaternary ammonium. This study for the first time identified ARCP isolates harboring the Erg11-Y132F mutation from nosocomial surfaces and HCW’s hands, which were genetically identical to ARCP blood isolates. Therefore, it is likely that persisting clonal outbreak due to ARCP isolates was fueled by environmental sources. The resistance of Y132F ARCP isolates to disinfectants, and their potential association with a high mortality rate, warrant vigilant source control using effective environmental decontamination.

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