Comparison of Difference Between Fluconazole and Silver Nanoparticles in Antimicrobial Effect on Fluconazole-Resistant Candida Albicans Strains

AUTHORS

Shadi Alimehr 1 , Hamide Shekari Ebrahim Abad 2 , Ahmadreza Shahverdi 3 , Jamal Hashemi 1 , Kamyar Zomorodian 4 , Maryam Moazeni 5 , Sahar Vosoghian 2 , Sassan Rezaie 1 , *

1 Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran

2 Pediatric Infections Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran

3 Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, IR Iran

4 Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran

5 Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IR Iran

How to Cite: Alimehr S, Shekari Ebrahim Abad H, Shahverdi A, Hashemi J, Zomorodian K, et al. Comparison of Difference Between Fluconazole and Silver Nanoparticles in Antimicrobial Effect on Fluconazole-Resistant Candida Albicans Strains, Arch Pediatr Infect Dis. 2015 ; 3(2):e21481. doi: 10.5812/pedinfect.21481.

ARTICLE INFORMATION

Archives of Pediatric Infectious Diseases: 3 (2); e21481
Published Online: April 15, 2015
Article Type: Research Article
Received: June 23, 2014
Revised: December 3, 2014
Accepted: January 28, 2015
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Abstract

Background: Opportunistic fungi cause fungal infections. Whereas some microorganisms are resistant to chemical drugs, scientists are looking for new natural and inorganic antimicrobial agents. The recent research on metal nanoparticles showed that silver nanoparticles (nanosilver) exhibits lower toxicity to mammalian cells and higher toxicity to microorganisms.

Objectives: This study aimed to compare the difference between antimicrobial effect of nanosilver and some antibiotic agents on Candidaalbicans.

Materials and Methods: We studied effect of fluconazole, nanosilver, and their combination on 20 fluconazole-resistant C. albicans from two centers and one standard sample (ATCC10261) by minimal inhibitory concentration (MIC) method.

Results: Result of fungi static and fungicidal activities of nanosilver plus fluconazole on fluconazole-resistant C. albicans showed better inhibitory effect on the growth of standard C. albicans when MIC of fluconazole (8 µg/mL) combined with MIC of Nanosilver (0.0625 µg/mL).

Conclusions: Totally, our results showed nanosilver caused an increase of at least nine-fold in inhibitory effect of fluconazole.

Keywords

Fluconazole Silver Nanoparticles Candida albicans

Copyright © 2015, Pediartric Infections Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

1. Background

In recent years, morbidity and mortality are increased significantly by severe fungal infections (1). Candida species have been one of the most common pathogens responsible for fungal infections, which cause hospital-acquired sepsis with annually mortality rate of up to 40% (2). Opportunistic fungi cause fungal infections, especially in vulnerable people with special conditions such as pregnancy or HIV-positive and immune-compromised patients who need intensive treatment with broad-spectrum antibiotics (3-5). Nowadays most of the available effective antifungal agents are based on polyenes (amphotericin B), echinocandins (caspofungin, micafungin, and anidulafungin) and triazoles (fluconazole, itraconazole, voriconazole, and posaconazole) (6, 7). However, scientists are looking for new natural and inorganic antimicrobial agents (8, 9). The recent research on metal nanoparticles showed that silver nanoparticles (nanosilvers) have received special attention as a possible antimicrobial agent (10-16). Since ancient times, silver has been used widely to treat infections and has strong inhibitory effects as well as a broad spectrum of antimicrobial activities against microorganisms, which has been thoroughly investigated (1, 9, 15, 17). This toxicity effect on bacteria has been investigated for more than 60 years (16) and in comparison to other metals, silver exhibits lower toxicity to mammalian cells and higher toxicity to microorganisms (18). Nanosilver exerts antimicrobial effects through interacting with main components of microorganisms including DNA (19), microbial proteins (20), and cell wall (20, 21); moreover, nanosilver produces reactive oxygen species (ROS) (21). The accumulation of intracellular ROS is as an important regulator for starting early apoptosis phase (22). Subsequently, increasing level of intracellular ROS lead to initiation of mitochondrial fragmentation (23).

2. Objectives

Regarding comparison of difference between antimicrobial effect of nanosilver and some antibiotic agents on Candida albicans, we compared the effect of nanosilver with fluconazole and their combination on collected fluconazole-resistant and fluconazole-sensitive C.albicans.

4. Results

Result of fungi static and fungicidal activities of fluconazole against C. albicans showed: 1) The MIC of fluconazole concentration for standard sample was 16 µg/mL (Table 1). 2) The growth of 20 fluconazole-resistant C. albicans was inhibited at MICs > 512 µg/mL (Table 1).

Result of fungi static and fungicidal activities of nanosilver against C. albicans showed: 1) The MIC of nanosilver for standard sample was 4 µg/mL. (Table 2). 2) The MICs of nanosilver for 20 resistant C. albicans were 2 µg/mL (58%) and 4 µg/mL (42%).

Result of fungi static and fungicidal activities of nanosilver plus fluconazole (8 µg/mL) on C. albicans showed: 1) the combination had better inhibitory effect on the growth of standard C. albicans when MIC of fluconazole (8 µg/mL) was combined with MIC of Nanosilver (0.0625 µg/mL) (Table 3). 2) Results on 20 resistant C. albicans showed there are several MIC of nanosilver: 40% of resistant C. albicans samples grew on 0.25 µg/mL, 11% on 0.0625 µg/mL, 22% on 0.03125 µg/mL, and 27% had no growth on 0.03125 (Table 3).

Table 1. The Growths of Standard and Fluconazole-Resistant Candida albicans on Difference Fluconazole Concentrations
VariablesFluconazole Concentrations, µg/mL
0.51248163264128256512
ResistantCandida albicans samples+++++++++++
Standard sample+++++------
Table 2. The Growths of Standard Sample and Fluconazole-Resistant Candida albicans on Difference Nanosilver Concentrations
VariablesNanosilver Concentrations, µg/mL
0.51248163264
58% of resistantCandida albicans samples +-------
42% of resistant Candida albicans samples ++------
Standard sample+++-----
Table 3. The Growth of Standard and Fluconazole-resistant Candida albicans on Difference Nanosilver Concentrations Combined with 8 µg/mL Fluconazole
VariablesNanosilver Concentrations (0.5-0.0625 µg/mL) Plus 8 µg/mL of Fluconazole
0.0156250.031250.06250.1250.25
22% of resistant Candida albicans samples ++---
11% of resistant Candidaalbicans samples +++--
40% of resistant Candida albicans samples +++++
27% of resistant Candida albicans samples +----
Standard sample+----

Footnote

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