Increasing Trends of Reduced Susceptibility to Antifungal Drugs Among Clinical<i>Candida glabrata</i>Isolates in Kuwait

Khan, Ziauddin; Ahmad, Suhail; Al‐Sweih, Noura; Mokaddas, Eiman; Al-Banwan, Khalifa; Al‐Obaid, Inaam; Alobaid, Khaled; Varghese, Soumya

doi:10.1089/mdr.2019.0437

Cited by 11 publications

(9 citation statements)

References 46 publications

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“…It seems that urinary tract and other non-sterile anatomic sites are favorable niches for the development of resistance in Candida spp. for echinocandins and amphotericin B [14,66,[68][69][70].…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of Candida Auris Outbreak in a Major Secondary-Care Hospital in Kuwait

Alfouzan

Ahmad

Dhar

et al. 2020

JoF

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The emerging, often multidrug-resistant Candida auris is increasingly being associated with outbreaks in healthcare facilities. Here we describe the molecular epidemiology of a C. auris outbreak during 18 months, which started in 2018 in the high dependency unit (HDU) of a secondary-care hospital in Kuwait. Demographic and clinical data for candidemia and colonized patients were prospectively recorded. Clinical and environmental isolates were subjected to phenotypic and molecular identification; antifungal susceptibility testing by broth microdilution method; PCR-sequencing of ERG11 and FKS1 for resistance mechanisms to triazoles and echinocandins, respectively; and molecular fingerprinting by short tandem repeat (STR) analyses. Seventy-one (17 candidemic and 54 colonized) patients including 26 with candiduria and seven environmental samples yielded C. auris. All isolates were identified as C. auris by Vitek2, MALDI-TOF MS, PCR amplification and/or PCR-sequencing of rDNA. Twelve candidemia and 26 colonized patients were admitted or exposed to HDU. Following outbreak recognition, an intensive screening program was instituted for new patients. Despite treatment of all candidemia and 36 colonized patients, 9 of 17 candidemia and 27 of 54 colonized patients died with an overall crude mortality rate of ~50%. Nearly all isolates were resistant to fluconazole and contained the Y132F mutation in ERG11 except one patient’s isolates, which were also distinct by STR typing. Only urine isolates from two patients developed echinocandin resistance with concomitant FKS1 mutations. The transmission of C. auris in this outbreak was linked to infected/colonized patients and the hospital environment. However, despite continuous surveillance and enforcement of infection control measures, sporadic new cases continued to occur, challenging the containment efforts.

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Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of Candida Auris Outbreak in a Major Secondary-Care Hospital in Kuwait

Alfouzan

Ahmad

Dhar

et al. 2020

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“…C. glabrata is among the most frequently isolated NACS from clinical specimens in Kuwait (17,18) (53) from China. The higher genetic diversity of C. glabrata from Kuwait, an Arabian Gulf country much smaller than Australia, Iran or Tanzania, is likely due to the large (nearly three times of Kuwaiti nationals) and highly diverse expatriate population (54,55).…”

Section: Discussionmentioning

confidence: 99%

“…Although Candida albicans is the most pathogenic and most frequently isolated species from clinical specimens, infections caused by non-albicans Candida species (NACS) have increased considerably in the last two decades and more than 50% of all Candida infections are now caused by NACS (5,13,16,17). Widespread use of azole antifungal drugs and improvements in diagnostic methods have likely contributed to the increased proportion of NACS infections in recent years (5,13,18). Candida glabrata, along with two other closely related species; Candida bracarensis and Candida nivariensis, now form part of the Nakaseomyces clade, and hence, have recently been transferred to a new genus, Nakaseomyces (19).…”

Section: Introductionmentioning

confidence: 99%

Molecular fingerprinting by multi-locus sequence typing identifies microevolution and nosocomial transmission of Candida glabrata in Kuwait

Asadzadeh,

Ahmad,

Al-Sweih

et al. 2023

Front. Public Health

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BackgroundsCandida glabrata is a frequently isolated non-albicans Candida species and invasive C. glabrata infections in older patients are associated with high mortality rates. Opportunistic Candida infections in critically ill patients may be either endogenous or nosocomial in origin and this distinction is critical for effective intervention strategies. This study performed multi-locus sequence typing (MLST) to study genotypic relatedness among clinical C. glabrata isolates in Kuwait.MethodsCandida glabrata isolates (n = 91) cultured from 91 patients were analyzed by MLST. Repeat isolates (n = 16) from 9 patients were also used. Antifungal susceptibility testing for fluconazole, voriconazole, caspofungin and amphotericin B (AMB) was determined by Etest. Genetic relatedness was determined by constructing phylogenetic tree and minimum spanning tree by using BioNumerics software.ResultsResistance to fluconazole, voriconazole and AMB was detected in 7, 2 and 10 C. glabrata isolates, respectively. MLST identified 28 sequence types (STs), including 12 new STs. ST46 (n = 33), ST3 (n = 8), ST7 (n = 6) and ST55 (n = 6) were prevalent in ≥4 hospitals. Repeat isolates obtained from same or different site yielded identical ST. No association of ST46 with source of isolation or resistance to antifungals was apparent. Microevolution and cross-transmission of infection was indicated in two hospitals that yielded majority (57 of 91, 67%) of C. glabrata.ConclusionOur data suggest that C. glabrata undergoes microevolution in hospital environment and can be nosocomially transmitted to other susceptible patients. Thus, proper infection control practices during routine procedures on C. glabrata-infected patients may prevent transmission of this pathogen to other hospitalized patients.

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“…strains with acquired resistance to this antifungal in prolonged treatments has been noted [1,7]. The mechanisms of resistance may be related to an increase in the efflux of the drug, genetic or quantitative alterations in ergosterol and the creation of alternative pathways for the production of ergosterol [8,9]. Thus, due to the low number of available drugs and the increase in resistance to these drugs, it is necessary to develop new molecules with antifungal activity or drugs that can be used in association with classic antifungals, thus increasing their time of use and reducing the development of resistance [10,11].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action

Silva

Sá

Santos

et al. 2022

Journal of Medical Microbiology

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Introduction. Candida spp. are commensal fungal pathogens of humans, but when there is an imbalance in the microbiota, or weak host immunity, these yeasts can become pathogenic, generating high medical costs. Gap Statement. With the increase in resistance to conventional antifungals, the development of new therapeutic strategies is necessary. This study evaluated the in vitro antifungal activity of chlorogenic acid against fluconazole-resistant strains of Candida spp. Mechanism of action through flow cytometry and in silico analyses, as well as molecular docking assays with ALS3 and SAP5, important proteins in the pathogenesis of Candida albicans associated with the adhesion process and biofilm formation. Results. The chlorogenic acid showed in vitro antifungal activity against the strains tested, causing reduced cell viability, increased potential for mitochondrial depolarization and production of reactive oxygen species, DNA fragmentation and phosphatidylserine externalization, indicating an apoptotic process. Concerning the analysis through docking, the complexes formed between chlorogenic acid and the targets Thymidylate Kinase, CYP51, 1Yeast Cytochrome BC1 Complex e Exo-B-(1,3)-glucanase demonstrated more favourable binding energy. In addition, chlorogenic acid presented significant interactions with the ALS3 active site residues of C. albicans, important in the adhesion process and resistance to fluconazole. Regarding molecular docking with SAP5, no significant interactions were found between chlorogenic acid and the active site of the enzyme. Conclusion. We concluded that chlorogenic acid has potential use as an adjuvant in antifungal therapies, due to its anti-Candida activity and ability to interact with important drug targets.

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Increasing Trends of Reduced Susceptibility to Antifungal Drugs Among ClinicalCandida glabrataIsolates in Kuwait

Cited by 11 publications

References 46 publications

Molecular Epidemiology of Candida Auris Outbreak in a Major Secondary-Care Hospital in Kuwait

Molecular Epidemiology of Candida Auris Outbreak in a Major Secondary-Care Hospital in Kuwait

Molecular fingerprinting by multi-locus sequence typing identifies microevolution and nosocomial transmission of Candida glabrata in Kuwait

Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action

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