Browse
Submit Data
Databases
API
Help

Dataset Information

40 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Case Report: Echinocandin-Resistance Candida glabrata FKS Mutants From Patient Following Radical Cystoprostatectomy Due to Muscle-Invasive Bladder Cancer.

ABSTRACT: Invasive Candida glabrata infections are not common complications after radical cystoprostatectomy. Furthermore, resistance to echinocandins arising during the course of a patient's treatment is rarely recognised. We described a case of development of echinocandin resistance in a patient with muscle-invasive bladder cancer (pT2b N0 M0, high grade) diagnosis, subjected to radical cystoprostatectomy and exposed to echinocandins. A male patient with a previous surgical history after a traffic accident, who was operated on due to bladder cancer, underwent an episode of candidemia and mixed postoperative wound and urinary tract infection caused by C. glabrata and extended spectrum β-lactamase (ESBL)-producing Escherichia coli during hospital treatment. The patient was started on caspofungin. Repeat blood cultures showed clearance of the bloodstream infection; however, infection persisted at the surgical site. Resistance to echinocandins developed within 2 months from the day of initiation of therapy with caspofungin in the C. glabrata strain obtained from the surgical site. The isolates sequentially obtained during the patient's treatment demonstrated resistance to echinocandins due to the mutation in hotspot 1 FKS2. Although resistance to echinocandins is relatively rare, it should be considered in oncological patients with increased complexity of treatment and intestinal surgery.

SUBMITTER: Szymankiewicz M

PROVIDER: S-EPMC8714647 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Spontaneous Mutational Frequency and FKS Mutation Rates Vary by Echinocandin Agent against Candida glabrata.

Project description:Echinocandins are front-line agents for treatment of invasive candidiasis. There are no reported agent-specific differences in Candida mutational frequency of resistance or propensity to develop FKS mutations. The objective of this study was to measure spontaneous and FKS mutation rates among Candida glabrata strains. Twenty bloodstream isolates from patients with or without prior echinocandin exposure were included. Minimum inhibitory concentrations (MICs), minimum fungicidal concentrations (MFCs), and mutation prevention concentrations were higher for caspofungin than for anidulafungin (P < 0.0001) and micafungin (P < 0.0001). Mutational frequencies of resistance at 3× the baseline MIC were highest for caspofungin and lowest for micafungin. A total of 247 isolates were recovered at or above the MFC for caspofungin (n = 159), anidulafungin (n = 74), or micafungin (n = 14). Agent-specific MIC increases were noted for anidulafungin and caspofungin, but not micafungin. Thirty-three percent of isolates harbored hot spot mutations in FKS1 (n = 6) or FKS2 (n = 76). Mutations at the Ser629 (Fks1) or Ser663 (Fks2) loci were more common after selection with anidulafungin or micafungin than with caspofungin (P = 0.003). Four isolates demonstrated >4-fold increases in MICs without FKS hot spot mutations; three of these harbored Fks2 mutations upstream of hot spot 1. The final isolate was FKS1 and FKS2 wild-type, but the 50% inhibitory concentrations of caspofungin and micafungin were increased 2.7- and 8-fold, respectively. In conclusion, micafungin may be superior in vitro to the other agents in limiting the emergence of resistance among C. glabrata Caspofungin exposure may be most likely to promote resistance development. These data provide a foundation for future investigations of newly developed echinocandin agents.

| S-EPMC6325211 | biostudies-literature

FKS mutations and elevated echinocandin MIC values among Candida glabrata isolates from U.S. population-based surveillance.

Project description:Candida glabrata is the second leading cause of candidemia in the United States. Its high-level resistance to triazole antifungal drugs has led to the increased use of the echinocandin class of antifungal agents for primary therapy of these infections. We monitored C. glabrata bloodstream isolates from a population-based surveillance study for elevated echinocandin MIC values (MICs of ?0.25 ?g/ml). From the 490 C. glabrata isolates that were screened, we identified 16 isolates with an elevated MIC value (2.9% of isolates from Atlanta and 2.0% of isolates from Baltimore) for one or more of the echinocandin drugs caspofungin, anidulafungin, and micafungin. All of the isolates with elevated MIC values had a mutation in the previously identified hot spot 1 of either the glucan synthase FKS1 (n = 2) or FKS2 (n = 14) gene. No mutations were detected in hot spot 2 of either FKS1 or FKS2. The predominant mutation was mutation of FKS2-encoded serine 663 to proline (S663P), found in 10 of the isolates with elevated echinocandin MICs. Two of the mutations, R631G for FKS1 and R665G for FKS2, have not been reported previously for C. glabrata. Multilocus sequence typing indicated that the predominance of the S663P mutation was not due to the clonal spread of a single sequence type. With a rising number of echinocandin therapy failures reported, it is important to continue to monitor rates of elevated echinocandin MIC values and the associated mutations.

| S-EPMC2981257 | biostudies-literature

Set of classical PCRs for detection of mutations in Candida glabrata FKS genes linked with echinocandin resistance.

Project description:Clinical echinocandin resistance among Candida glabrata strains is increasing, especially in the United States. Antifungal susceptibility testing is considered mandatory to guide therapeutic decisions. However, these methodologies are not routinely performed in the hospital setting due to their complexity and the time needed to obtain reliable results. Echinocandin failure in C. glabrata is linked exclusively to Fks1p and Fks2p amino acid substitutions, and detection of such substitutions would serve as a surrogate marker to identify resistant isolates. In this work, we report an inexpensive, simple, and quick classical PCR set able to objectively detect the most common mechanisms of echinocandin resistance in C. glabrata within 4 h. The usefulness of this assay was assessed using a blind collection of 50 C. glabrata strains, including 16 FKS1 and/or FKS2 mutants.

| S-EPMC4097693 | biostudies-literature

Novel FKS mutations associated with echinocandin resistance in Candida species.

Project description:We studied three clinical isolates of Candida spp. (one C. tropicalis isolate and two C. glabrata isolates) from patients with invasive candidiasis. The first isolate emerged during echinocandin treatment, while the others emerged after the same treatment. These strains harbored an amino acid substitution in Fksp never linked before with reduced echinocandin susceptibility in C. tropicalis or in C. glabrata. The molecular mechanism of reduced susceptibility was confirmed using a 1,3-beta-D-glucan synthase inhibition assay.

| S-EPMC2863628 | biostudies-literature

Detection of Echinocandin-Resistant Candida glabrata in Blood Cultures Spiked with Different Percentages of FKS2 Mutants.

Project description:Infections caused by the coexistence of Candida glabrata echinocandin-resistant and echinocandin-susceptible cells may be possible, and the detection of FKS mutants when the proportions of FKS mutants are underrepresented poses a problem. We assessed the role of EUCAST and methods directly performed on positive blood cultures-Etest (ETDIR) and anidulafungin-containing agar plate assays-for detecting resistance in C. glabrata isolates containing different amounts of echinocandin-susceptible and -resistant Candida glabrata isolates. We studied 10 pairs of C. glabrata isolates involving parental echinocandin-susceptible isolates and isogenic echinocandin-resistant FKS mutant isolates. Three inocula per pair (1 × 103 to 5 × 103, 1 × 102 to 5 × 102, and 10 to 50 CFU/ml) spanning suspensions with different amounts of susceptible/resistant isolates (9/1, 5/5, and 1/9 proportions for each the three inocula) were prepared. The suspensions were spiked in Bactec bottles and incubated until they were positive, and the three methods were compared. The EUCAST method showed echinocandin resistance when the bottles were spiked with susceptible/resistant isolates at 5/5 and 1/9 proportions; the results for the suspensions with a 9/1 proportion of susceptible/resistant isolates were susceptible for three pairs. We observed with the ETDIR resistance to both echinocandins in all pairs (resistance to micafungin and anidulafungin; MICs, ≥0.064 mg/liter and ≥0.125 mg/liter, respectively) and a double ring of growth inhibition in two pairs. The anidulafungin-containing plates showed fungal growth in the 90 spiked blood cultures at 48 h. Testing of echinocandin susceptibility with the ETDIR directly on the positive blood culture bottles is a reliable and rapid method to detect echinocandin resistance in C. glabrata On the other hand, resistance can be missed with the EUCAST method when resistant isolates are underrepresented.

| S-EPMC6395934 | biostudies-literature

Recurrent episodes of Candidemia due to <i>Candida glabrata, Candida tropicalis</i> and <i>Candida albicans</i> with acquired echinocandin resistance.

Project description:Mixed fungal infection and acquired echinocandin resistance of Candida spp. remain infrequent. In this study we have reported the case of a patient hospitalized for tuberculosis who experienced multiple infections due to three common Candida species (C. albicans, C. glabrata, C. tropicalis). Furthermore, consecutive isolates from blood cultures and heart valve were found resistant to azoles (C. tropicalis) and to echinocandin with either novel (C. tropicalis) or previously described (C. albicans) missense mutations in the Fks gene.

| S-EPMC5155041 | biostudies-literature

Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility.

Project description:A recognized hotspot for mutations conferring reduced echinocandin susceptibility (RES) is residue S645 of Candida albicans Gsc1(Fks1). We report that the mutation F641Y is associated with RES in a C. albicans isolate. The analogous Fks2 residue is mutated F to V in a Candida glabrata RES isolate; the introduction of this mutation into susceptible C. glabrata confirmed its role in RES. Y641-equivalent Fks residues were identified in intrinsically RES Fusarium species and Candida guilliermondii.

| S-EPMC1538661 | biostudies-literature

Emerging echinocandin-resistant Candida albicans and glabrata in Switzerland.

Project description:Echinocandins represent the first-line therapy of candidemia. Echinocandin resistance among Candida spp. is mainly due to acquired FKS mutations. In this study, we report the emergence of FKS-mutant Candida albicans/glabrata in Switzerland and provide the microbiological and clinical characteristics of 9 candidemic episodes. All patients were previously exposed to echinocandins (median 26 days; range 15-77). Five patients received initial echinocandin therapy with persistent candidemia in 4 of them. Overall mortality was 33%.

| S-EPMC7518979 | biostudies-literature

Clinical characteristics of the first cases of invasive candidiasis in China due to pan-echinocandin-resistant Candida tropicalis and Candida glabrata isolates with delineation of their resistance mechanisms.

Project description:Echinocandin antifungal agents have become the first-line therapy for invasive candidiasis (IC) in many countries. Despite their increasing use, resistance to this class of drug is, overall, still uncommon. Here, we report two patients from the People's Republic of China with IC, one with infection caused by pan-echinocandin-resistant Candida tropicalis and the other by pan-echinocandin-resistant Candida glabrata. We also describe the mechanisms of drug resistance of these isolates. The echinocandin-resistant C. glabrata isolate was cultured from ascitic fluid of a 46-year-old male patient with intra-abdominal IC developing after surgery in 2012. This patient had had no prior antifungal exposure. The echinocandin-resistant C. tropicalis isolate was cultured from chest drainage fluid of a 60-year-old female patient with severe coronary disease and lung infection. Prior to culture and identification of the isolate, the patient had received micafungin treatment for 19 days. Both isolates were cross-resistant to micafungin, anidulafungin, and caspofungin, with minimum inhibitory concentration values of ≥2 µg/mL. The amino acid substitution E655K was found adjacent to the FKS2 HS1 region of the C. glabrata isolate, while the substitution S80P were found in the FKS1 HS1 region of the C. tropicalis isolate. This report highlights the emergence of echinocandin resistance in two important non-albicans Candida species. Although the overall prevalence of echinocandin resistance is low in the People's Republic of China, monitoring of antifungal susceptibility trends in all Candida species is warranted.

| S-EPMC5790075 | biostudies-literature

Breakthrough invasive Candida glabrata in patients on micafungin: a novel FKS gene conversion correlated with sequential elevation of MIC.

Project description:Candida glabrata strains sequentially isolated from blood developed resistance to micafungin (MICs from <0.015 to 4 μg/ml). A novel mutation identified in micafungin-resistant strains at bp 262 of FKS2 (containing a deletion of F659 [F659del]) was inserted into the homologous region in FKS1.

| S-EPMC4097732 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data