Revisiting Species Distribution and Antifungal Susceptibility of Candida Bloodstream Isolates from Latin American Medical Centers.
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SUBMITTER: da Matta DA
PROVIDER: S-EPMC5715916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Candida bloodstream infections (CBI) are one of the most common nosocomial infections globally, and they account for a high mortality rate. The increasing global prevalence of drug-resistant Candida strains has also been posing a challenge to clinicians. In this study, we comprehensively evaluated the biofilm formation and production of hemolysin and proteinase of 63 CBI isolates derived from a hospital setting in Hong Kong as well as their antifungal susceptibility both in the presence and in the absence of human serum, using standard methodology. Candida albicans was the predominant species among the 63 CBI isolates collected, and non-albicans Candida species accounted for approximately one third of the isolates (36.5%). Of them, Candida tropicalis was the most common non-albicans Candida species. A high proportion (31.7%) of the CBI isolates (40% of C. albicans isolates, 10% of C. tropicalis isolates, 11% of C. parapsilosis isolates, and 100% of C. glabrata isolates) were found to be resistant to fluconazole. One of the isolates (C. tropicalis) was resistant to amphotericin B. A rising prevalence of drug-resistance CBI isolates in Hong Kong was observed with reference to a previous study. Notably, all non-albicans Candida species, showed increased hemolytic activity relative to C. albicans, whilst C. albicans, C. tropicalis, and C. parapsilosis exhibited proteinase activities. Majority of the isolates were capable of forming mature biofilms. Interestingly, the presence of serum distorted the yeast sensitivity to fluconazole, but not amphotericin B. Taken together, our findings demonstrate that CBI isolates of Candida have the potential to express to varying extent their virulence attributes (e.g., biofilm formation, hemolysin production, and proteinase activity) and these, together with perturbations in their antifungal sensitivity in the presence of serum, may contribute to treatment complication in candidemia. The effect of serum on antifungal activity warrants further investigations, as it has direct clinical relevance to the treatment outcome in subjects with candidemia.
| S-EPMC4767892 | biostudies-literature
Project description:Candida auris is a multidrug-resistant fungal pathogen that is endemic in South African hospitals. We tested bloodstream C. auris isolates that were submitted to a reference laboratory for national laboratory-based surveillance for candidemia in 2016 and 2017. We confirmed the species identification by phenotypic/molecular methods. We tested susceptibility to amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole, and flucytosine using broth microdilution and Etest methods. We interpreted MICs using tentative breakpoints. We sequenced the genomes of a subset of isolates and compared them to the C. auris B8441 reference strain. Of 400 C. auris isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (94%) to fluconazole alone (MICs of ≥32 µg/ml), 19 (6%) to fluconazole and amphotericin B (MICs of ≥2 µg/ml), and 1 (0.3%) to amphotericin B alone. Two (0.5%) isolates from a single patient were pan-resistant (resistant to fluconazole, amphotericin B, and echinocandins). Of 92 isolates selected for whole-genome sequencing, 77 clustered in clade III, including the pan-resistant isolates, 13 in clade I, and 2 in clade IV. Eighty-four of the isolates (91%) were resistant to at least one antifungal agent; both resistant and susceptible isolates had mutations. The common substitutions identified across the different clades were VF125AL, Y132F, K177R, N335S, and E343D in ERG11; N647T in MRR1; A651P, A657V, and S195G in TAC1b; S639P in FKS1HP1; and S58T in ERG3. Most South African C. auris isolates were resistant to azoles, although resistance to polyenes and echinocandins was less common. We observed mutations in resistance genes even in phenotypically susceptible isolates.
| S-EPMC8370198 | biostudies-literature
Project description:BackgroundThe incidence of candidemia is increasing in developing countries. Very little is known about the epidemiology of candidemia in Peru. The aim of this study is to describe the incidence, microbiology, clinical presentation and outcomes of Candida bloodstream infections in three Lima-Callao hospitals.MethodsCandida spp. isolates were identified prospectively at participant hospitals between November 2013 and January 2015. Susceptibility testing for amphotericin B, fluconazole, posaconazole, voriconazole and anidulafungin was performed using broth microdilution method. Clinical information was obtained from medical records and evaluated.ResultsWe collected information on 158 isolates and 157 patients. Median age of patients was 55.0 yrs., and 64.1% were males. Thirty-eight (24.2%) episodes of candidemia occurred in those <18 yrs. The frequency of non-Candida albicans was 72.1%. The most frequently recovered species were C. albicans (n = 44, 27.8%), C. parapsilosis (n = 40, 25.3%), C. tropicalis (n = 39, 24.7%) and C. glabrata (n = 15, 9.5%). Only four isolates were resistant to fluconazole, 86.7% (n = 137) were susceptible and 17 were susceptible-dose dependent. Decreased susceptibility to posaconazole was also observed in three isolates, and one to voriconazole. All isolates were susceptible to anidulafungin and amphotericin B. The most commonly associated co-morbid conditions were recent surgery (n = 61, 38.9%), mechanical ventilation (n = 60, 38.2%) and total parenteral nutrition (n = 57, 36.3%). The incidence of candidemia by center ranged between 1.01 and 2.63 cases per 1,000 admissions, with a global incidence of 2.04. Only 28.1% of cases received treatment within 72 hrs. of diagnosis. Overall, the 30-day survival was 60.4% (treated subjects, 67.4%; not-treated patients, 50.9%).ConclusionsWe found a very high proportion of non-albicans Candida species. Despite this, the decreased susceptibility/resistance to fluconazole was only 13.3% and not seen in the other antifungals. Overall, the incidence of candidemia mortality was high when compared to other international studies. It is possible, that the delay in initiating antifungal treatment contributed to the elevated mortality rate, in spite of low antifungal resistance.
| S-EPMC5395148 | biostudies-literature
Project description:BACKGROUND:Antifungal resistance rates are increasing. We investigated the mechanisms of azole resistance of Candida spp. bloodstream isolates obtained from a surveillance study conducted between 2012 and 2015. METHODS:Twenty-six azole non-susceptible Candida spp. clinical isolates were investigated. Antifungal susceptibilities were determined using the Sensititre YeastOne® YO10 panel. The ERG11 gene was amplified and sequenced to identify amino acid polymorphisms, while real-time PCR was utilised to investigate the expression levels of ERG11, CDR1, CDR2 and MDR1. RESULTS:Azole cross-resistance was detected in all except two isolates. Amino acid substitutions (A114S, Y257H, E266D, and V488I) were observed in all four C. albicans tested. Of the 17 C. tropicalis isolates, eight (47%) had ERG11 substitutions, of which concurrent observation of Y132F and S154F was the most common. A novel substitution (I166S) was detected in two of the five C. glabrata isolates. Expression levels of the various genes differed between the species but CDR1 and CDR2 overexpression appeared to be more prominent in C. glabrata. CONCLUSIONS:There was interplay of various different mechanisms, including mechanisms which were not studied here, responsible for azole resistance in Candida spp in our study.
| S-EPMC6337757 | biostudies-literature
Project description:The most prevalent cause of nosocomial bloodstream infection (BSI) among non-C. albicans Candida species, Candida parapsilosis, may not only be resistant to azole antifungal agents but also disseminate to vulnerable patients. In this survey of BSIs occurring at a large Italian hospital between May 2014 and May 2019, C. parapsilosis accounted for 28.5% (241/844) of all Candida isolates causing BSI episodes. The majority of episodes (151/844) occurred in medical wards. Across the 5 yearly periods, the rates of azole non-susceptibility were 11.8% (4/34), 17.8% (8/45), 28.6% (12/42), 32.8% (19/58), and 17.7% (11/62), respectively, using the Sensititre YeastOne® method. Among azole non-susceptible isolates (54/241; 22.4%), 49 were available for further investigation. Using the CLSI reference method, all 49 isolates were resistant to fluconazole and, except one (susceptible dose-dependent), to voriconazole. Forty (81.6%) isolates harbored the Erg11p Y132F substitution and nine (18.4%) isolates the Y132F in combination with the Erg11p R398I substitution. According to their genotypes, as defined using a microsatellite analysis based on six short tandem repeat markers, 87.7% of isolates (43/49) grouped in two major clusters (II and III), whereas 4.1% of isolates (2/49) belonged to a separate cluster (I). Interestingly, all the isolates from cluster II harbored the Y132F substitution, and those from cluster III harbored both Y132F and R398I substitutions. Of 56 non-Italian isolates included as controls, two Indian isolates with the Y132F substitution had a genotype clearly differing from that of the isolates from clusters II and I. In conclusion, these findings show the dominance of clonal Y132F isolates in our hospital and suggest detection of the Y132F substitution as helpful tool to prevent transmission among hospitalized patients at risk of BSI.
| S-EPMC7261875 | biostudies-literature
Project description:Most population isolates examined to date were founded from a single ancestral population. Consequently, there is limited knowledge about the demographic history of admixed population isolates. Here we investigate genomic diversity of recently admixed population isolates from Costa Rica and Colombia and compare their diversity to a benchmark population isolate, the Finnish. These Latin American isolates originated during the 16th century from admixture between a few hundred European males and Amerindian females, with a limited contribution from African founders. We examine whole-genome sequence data from 449 individuals, ascertained as families to build mutigenerational pedigrees, with a mean sequencing depth of coverage of approximately 36×. We find that Latin American isolates have increased genetic diversity relative to the Finnish. However, there is an increase in the amount of identity by descent (IBD) segments in the Latin American isolates relative to the Finnish. The increase in IBD segments is likely a consequence of a very recent and severe population bottleneck during the founding of the admixed population isolates. Furthermore, the proportion of the genome that falls within a long run of homozygosity (ROH) in Costa Rican and Colombian individuals is significantly greater than that in the Finnish, suggesting more recent consanguinity in the Latin American isolates relative to that seen in the Finnish. Lastly, we find that recent consanguinity increased the number of deleterious variants found in the homozygous state, which is relevant if deleterious variants are recessive. Our study suggests that there is no single genetic signature of a population isolate.
| S-EPMC6218714 | biostudies-literature
Project description: Not available
| S-EPMC7920659 | biostudies-literature
Project description:Azole-resistant Candida tropicalis has emerged in Asia in the context of its trailing nature, defined by residual growth above minimum inhibitory concentrations (MICs). However, limited investigations in C. tropicalis have focused on the difference of genotypes and molecular mechanisms between these two traits. Sixty-four non-duplicated C. tropicalis bloodstream isolates collected in 2017 were evaluated for azole MICs by the EUCAST E.def 7.3.1 method, diploid sequence type (DST) by multilocus sequencing typing, and sequences and expression levels of genes encoding ERG11, its transcription factor, UPC2, and efflux pumps (CDR1, CDR2 and MDR1). Isavuconazole showed the highest in vitro activity and trailing against C. tropicalis, followed by voriconazole and fluconazole (geometric mean [GM] MIC, 0.008, 0.090, 1.163 mg/L, respectively; trailing GM, 27.4%, 20.8% and 19.5%, respectively; both overall p < 0.001). Fourteen (21.9%) isolates were non-WT to fluconazole/voriconazole, 12 of which were non-WT to isavuconazole and clustered in clonal complex (CC) 3. Twenty-five (39.1%) isolates were high trailing WT, including all CC2 isolates (44.0%) (containing DST140 and DST98). All azole non-WT isolates carried the ERG11 mutations A395T/W and/or C461T/Y, and most carried the UPC2 mutation T503C/Y. These mutations were not identified in low and high trailing WT isolates. Azole non-WT and high trailing WT isolates exhibited the highest expression levels of ERG11 and MDR1, 3.91- and 2.30-fold, respectively (both overall p < 0.01). Azole resistance and trailing are phenotypically and genotypically different in C. tropicalis. Interference with azole binding and MDR1 up-regulation confer azole resistance and trailing, respectively.
| S-EPMC8396981 | biostudies-literature
Project description:BackgroundIncreasing numbers of immunocompromised patients have resulted in greater incidence of invasive fungal infections with high mortality. Candida albicans infections dominate, but during the last decade, Candida glabrata has become the second highest cause of candidemia in the United States and Northern Europe. Reliable and early diagnosis, together with appropriate choice of antifungal treatment, is needed to combat these challenging infections.ObjectivesTo confirm the identity of 183 Candida glabrata isolates from different human body sites using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and VITEK(®)2, and to analyze isolate protein profiles and antifungal susceptibility. The minimum inhibitory concentration (MIC) of seven antifungal drugs was determined for the isolates to elucidate susceptibility.DesignA total of 183 C. glabrata isolates obtained between 2002 and 2012 from Norwegian health-care units were analyzed. For species verification and differentiation, biochemical characterization (VITEK(®)2) and mass spectrometry (MALDI-TOF) were used. MIC determination for seven antifungal drugs was undertaken using E-tests(®).ResultsUsing VITEK(®)2, 92.9% of isolates were identified as C. glabrata, while all isolates (100%) were identified as C. glabrata using MALDI-TOF. Variation in protein spectra occurred for all identified C. glabrata isolates. The majority of isolates had low MICs to amphotericin B (≤1 mg/L for 99.5%) and anidulafungin (≤0.06 mg/L for 98.9%). For fluconazole, 18% of isolates had MICs >32 mg/L and 82% had MICs in the range ≥0.016 mg/L to ≤32 mg/L.ConclusionsProtein profiles and antifungal susceptibility characteristics of the C. glabrata isolates were diverse. Clustering of protein profiles indicated that many azole resistant isolates were closely related. In most cases, isolates had highest susceptibility to amphotericin B and anidulafungin. The results confirmed previous observations of high MICs to fluconazole and flucytosine. MALDI-TOF was more definitive than VITEK(®)2 for C. glabrata identification.
| S-EPMC4748091 | biostudies-literature
Project description:Background and Objectives:Identification of yeasts provides helpful information for appropriate administration of anti-fungal treatments; however, few reports from the Vietnam have been published. This study has been performed to find the prevalence of Candida blood stream isolates from patients in two hospitals in Vietnam. Materials and Methods:Candida spp. were isolated from blood cultures in two hospitals, Vietnam between May 2013 and May 2015. Participating hospitals were 103 Military Hospital, Ha Noi city (550 beds) and Cho Ray Hospital, Ho Chi Minh city (1800 beds). All the bloodstream isolates were identified to species level by the germ tube test and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, unknown isolates were subjected to PCR sequencing. Results:A total of 93 Candida isolates were isolated from blood cultures during the study period. The results of this study showed that C. tropicalis (n = 47, 50.54%) was the most common agent, followed by Candida albicans/dubliniensis (n = 18, 19.35%), C. parapsilosis (n = 16, 17.20%), C. glabrata (n = 6, 6.45%), C. mesorugosa (n = 5, 5.38%) and C. krusei (n = 1, 1.08%), respectively. Conclusion:The frequency of the non-albicans Candida species in blood is increasing, especially C. tropicalis. Additional investigations should be made to clarify the epidemiological profile of invasive Candida bloodstream in Vietnam.
| S-EPMC6635319 | biostudies-literature