Efflux Pump Mediated Azole Resistance in Candida Albicans

NCT03659162 | Unknown

• 1 other identifier: xoxo
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Candida albicans is the major fungal pathogen causing infections in humans, ranging from superficial mucosal infection to systemic mycoses. In recent years, Candida infections have increased disproportionately as a result of the increased number of compromised host populations, such as patients with AIDS, diabetes and various cancers, and organ-transplant recipients. Severe oro-pharyngeal candidiasis afflicts many AIDS patients and is a significant infection in cancer patients being treated with chemotherapy and/or radiotherapy.

Conditions

Fungal Infection

Outcome Measures

Primary Outcomes (1)

• characterize the clinical Candida albicans strains isolated from neutropenic patients with Hematological Malignancies.

  isolation \& identification of of Candida albicans by culturing on Sabouraud's Dextrose Agar (SDA) and CHROM Agar Candida then determination of antifungal susceptibility testing by Disk Diffusion test and determination of MIC by broth microdilution method to identify resistant Candida albicans strains to decrease hazard to these high risk group of patients.

  3 months

Secondary Outcomes (3)

• Determination if Ibuprofen could elicit a reversal of fluconazole resistance by interference with efflux pump activity.

  2month

• Testing new NS-IDs other than Ibuprofen as efflux pump inhibitor

  3 months

• Uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen

  4 months

Study Arms (1)

neutropenic cancer patient recieving azoles .

neutropenic cancer patients that undergoing chemotherapy with prophylaxis with azoles and exhibit recurrent fungal infection so appropriate clinical specimen will taken for isolation \& identification of causative agent \& it's antimicrobial profile then identification of the mechanism of resistance by invitro technique then confirmed by real time pcr.

Drug: Azole Antifungal

Interventions

Azole Antifungal DRUG

oral gel \& injections

neutropenic cancer patient recieving azoles .

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

neutropenic patient with Hematological Malignancy receiving azoles

You may qualify if:

• Patients suffered from neutropenia. Patients with absolute neutrophiles count less than 500 cells / ml . 7 days or more from start of chemotherapy. Also neutropenic patients presented during relapse after first remission of hematological malignancies.
• Presence of resistance to at least one azole derivatives.

You may not qualify if:

• Patient who have contraindication to Azoles

Sponsors & Collaborators

• Assiut University: lead

Related Publications (10)

• Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001 May 1;29(9):e45. doi: 10.1093/nar/29.9.e45.

  PMID: 11328886 BACKGROUND

• Beck-Sague C, Jarvis WR. Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. National Nosocomial Infections Surveillance System. J Infect Dis. 1993 May;167(5):1247-51. doi: 10.1093/infdis/167.5.1247.

  PMID: 8486965 BACKGROUND

• Davies AN, Brailsford SR, Beighton D. Oral candidosis in patients with advanced cancer. Oral Oncol. 2006 Aug;42(7):698-702. doi: 10.1016/j.oraloncology.2005.11.010. Epub 2006 Mar 9.

  PMID: 16527512 BACKGROUND

• Soysa NS, Samaranayake LP, Ellepola AN. Antimicrobials as a contributory factor in oral candidosis--a brief overview. Oral Dis. 2008 Mar;14(2):138-43. doi: 10.1111/j.1601-0825.2006.01357.x.

  PMID: 18302673 BACKGROUND

• Shao PL, Huang LM, Hsueh PR. Recent advances and challenges in the treatment of invasive fungal infections. Int J Antimicrob Agents. 2007 Dec;30(6):487-95. doi: 10.1016/j.ijantimicag.2007.07.019. Epub 2007 Oct 24.

  PMID: 17961990 BACKGROUND

• Rogers PD, Barker KS. Genome-wide expression profile analysis reveals coordinately regulated genes associated with stepwise acquisition of azole resistance in Candida albicans clinical isolates. Antimicrob Agents Chemother. 2003 Apr;47(4):1220-7. doi: 10.1128/AAC.47.4.1220-1227.2003.

  PMID: 12654650 BACKGROUND

• Cannon RD, Lamping E, Holmes AR, Niimi K, Baret PV, Keniya MV, Tanabe K, Niimi M, Goffeau A, Monk BC. Efflux-mediated antifungal drug resistance. Clin Microbiol Rev. 2009 Apr;22(2):291-321, Table of Contents. doi: 10.1128/CMR.00051-08.

  PMID: 19366916 BACKGROUND

• Pina-Vaz C, Rodrigues AG, Costa-de-Oliveira S, Ricardo E, Mardh PA. Potent synergic effect between ibuprofen and azoles on Candida resulting from blockade of efflux pumps as determined by FUN-1 staining and flow cytometry. J Antimicrob Chemother. 2005 Oct;56(4):678-85. doi: 10.1093/jac/dki264. Epub 2005 Aug 22.

  PMID: 16115827 BACKGROUND

• Kotwal A, Biswas D, Sharma JP, Gupta A, Jindal P. An observational study on the epidemiological and mycological profile of Candidemia in ICU patients. Med Sci Monit. 2011 Nov;17(11):CR663-668. doi: 10.12659/msm.882053.

  PMID: 22037747 BACKGROUND

• Watamoto T, Samaranayake LP, Egusa H, Yatani H, Seneviratne CJ. Transcriptional regulation of drug-resistance genes in Candida albicans biofilms in response to antifungals. J Med Microbiol. 2011 Sep;60(Pt 9):1241-1247. doi: 10.1099/jmm.0.030692-0. Epub 2011 Apr 7.

  PMID: 21474609 BACKGROUND

MeSH Terms

Conditions

Mycoses

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Central Study Contacts

. Ehsan Abdelsabor Hassan, Professor

CONTACT

01114478527; dr_ehsan66@yahoo.com

Michael Nazmy Agban, Assistant Professor

CONTACT

01223961695; agbanmichael@aun.edu.eg

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: September 6, 2018
• Study Start: February 17, 2019
• Primary Completion: April 10, 2019
• Study Completion: July 24, 2019
• Last Updated: September 6, 2018

Record last verified: 2018-09