Invasive Candidiasis in Critically Ill Patients: A Prospective Cohort Study in Two Tertiary Care Centers

Al‐Dorzi, Hasan M.; Sakkijha, Hussam; Khan, Raymond; Aldabbagh, Tarek; Toledo, A.; Ntinika, Pendo; Johani, Sameera M. Al; Arabi, Yaseen M.

doi:10.1177/0885066618767835

Cited by 48 publications

(47 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As for the Arabian Peninsula, it has been recorded in Saudi Arabia that IC rates ranged from 1.55-1.65 cases per 1000 discharges to 26 cases per 1000 ICU admissions [39,48,49]. A retrospective study on IC among pediatric patients indicated a group of risk factors: prematurity in 37 (28.7%) of patients, low birth weight (32.6%), central venous catheter (45.7%), malignancy (16.3%), immunotherapy (15.5%), and ventilator support (46.5%) [50].…”

Section: Invasive Candidiasismentioning

confidence: 99%

Update on invasive fungal infections in the Middle Eastern and North African region

et al. 2020

View full text Add to dashboard Cite

In the recent years, the epidemiology of invasive fungal infections (IFIs) has changed worldwide. This is remarkably noticed with the significant increase in high-risk populations. Although surveillance of such infections is essential, data in the Middle Eastern and North African (MENA) region remain scarce. In this paper, we reviewed the existing data on the epidemiology of different IFIs in the MENA region. Epidemiological surveillance is crucial to guide optimal healthcare practices. This study can help to guide appropriate interventions and to implement antimicrobial stewardship and infection prevention and control programs in countries.

show abstract

Section: Invasive Candidiasismentioning

confidence: 99%

Update on invasive fungal infections in the Middle Eastern and North African region

et al. 2020

View full text Add to dashboard Cite

show abstract

“…3,4 Emergence of azole-and echinocandin-resistant C. albicans isolates is a significant concern because the number of systemic antifungal drugs available to fight C. albicans infections is limited. [5][6][7][8][9] Echinocandin resistance can occur through point mutations within hot-spot regions of FKS1 encoding the β-(1,3)-D-glucan synthase. 5,10 Azole resistance can occur through various mechanisms, such as alterations or overexpression of the drug target gene ERG11 (encoding the 14-α-lanosterol demethylase) or increased expression of genes encoding drug efflux transporters: CDR1, CDR2, or MDR1.…”

Section: Introductionmentioning

confidence: 99%

Large-scale genome mining allows identification of neutral polymorphisms and novel resistance mutations in genes involved in Candida albicans resistance to azoles and echinocandins

Sitterlé

Coste

Obadia

et al. 2020

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

Background The genome of Candida albicans displays significant polymorphism. Point mutations in genes involved in resistance to antifungals may either confer phenotypic resistance or be devoid of phenotypic consequences. Objectives To catalogue polymorphisms in azole and echinocandin resistance genes occurring in susceptible strains in order to rapidly pinpoint relevant mutations in resistant strains. Methods Genome sequences from 151 unrelated C. albicans strains susceptible to fluconazole and caspofungin were used to create a catalogue of non-synonymous polymorphisms in genes involved in resistance to azoles (ERG11, TAC1, MRR1 and UPC2) or echinocandins (FKS1). The potential of this catalogue to reveal putative resistance mutations was tested in 10 azole-resistant isolates, including 1 intermediate to caspofungin. Selected mutations were analysed by mutagenesis experiments or mutational prediction effect. Results In the susceptible strains, we identified 126 amino acid substitutions constituting the catalogue of phenotypically neutral polymorphisms. By excluding these neutral substitutions, we identified 22 additional substitutions in the 10 resistant strains. Among these substitutions, 10 had already been associated with resistance. The remaining 12 were in Tac1p (n = 6), Upc2p (n = 2) and Erg11p (n = 4). Four out of the six homozygous substitutions in Tac1p (H263Y, A790V, H839Y and P971S) conferred increases in azole MICs, while no effects were observed for those in Upc2p. Additionally, two homozygous substitutions (Y64H and P236S) had a predicted conformation effect on Erg11p. Conclusions By establishing a catalogue of neutral polymorphisms occurring in genes involved in resistance to antifungal drugs, we provide a useful resource for rapid identification of mutations possibly responsible for phenotypic resistance in C. albicans.

show abstract

“…The subset of invasive candidiasis patients enrolled in our study are representative of larger cohort studies (1,11,41). For example, the study participants carried the diagnosis of immunecompromising diseases, received immunosuppressive drugs, and frequently required central lines (11,41).…”

Section: Discussionmentioning

confidence: 99%

Neutrophils From Patients With Invasive Candidiasis Are Inhibited by Candida albicans Biofilms

et al. 2020

View full text Add to dashboard Cite

Invasive candidiasis frequently involves medical device placement. On the surfaces of these devices, Candida can form biofilms and proliferate in adherent layers of fungal cells surrounded by a protective extracellular matrix. Due in part to this extracellular matrix, biofilms resist host defenses and antifungal drugs. Previous work (using neutrophils from healthy donors) found that one mechanism employed to resist host defenses involves the inhibition of neutrophil extracellular traps (NET) formation. NETs contain nuclear DNA, as well as antimicrobial proteins that can ensnare pathogens too large or aggregated to be effectively killed by phagocytosis. Given that these neutrophil structures are anticipated to have activity against the large aggregates of C. albicans biofilms, understanding the role of this inhibition in patients could provide insight into new treatment strategies. However, prior work has not included patients. Here, we examine NET formation by neutrophils collected from patients with invasive candidiasis. When compared to neutrophils from healthy participants, we show that patient neutrophils exhibit a heightened background level of NET release and respond to a positive stimulus by producing 100% more NETs. However, despite these physiologic differences, patient neutrophil responses to C. albicans were similar to healthy neutrophils. For both groups, planktonic cells induce strong NET release and biofilms inhibit NET formation. These results show that a mechanism of immune evasion for fungal biofilms translates to the clinical setting.

show abstract

Invasive Candidiasis in Critically Ill Patients: A Prospective Cohort Study in Two Tertiary Care Centers

Abstract: NCT01490684; registered in ClinicalTrials.gov on February 11, 2012.

Cited by 48 publications

References 49 publications

Update on invasive fungal infections in the Middle Eastern and North African region

Update on invasive fungal infections in the Middle Eastern and North African region

Large-scale genome mining allows identification of neutral polymorphisms and novel resistance mutations in genes involved in Candida albicans resistance to azoles and echinocandins

Neutrophils From Patients With Invasive Candidiasis Are Inhibited by Candida albicans Biofilms

Contact Info

Product

Resources

About