Tahereh Shokohi, et al.

S19

Original article

In vitro antifungal susceptibility of Candida species isolated from

oropharyngeal lesions of patients with cancer to some antifungal agents
Tahereh Shokohi, PhD1, 2*, Zainab Bandalizadeh, MSc1, Mohmmad Taghi Hedayati,
PhD1, 2, Sabah Mayahi, MSc1
1
Deptartment of Medical Mycology and Parasitology, Sari Medical School, Mazandaran
University of Medical Sciences, Sari, Iran
2
Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences,
Sari, Iran

How to cite this article:

Shokohi T, Bandalizadeh Z, Hedayati MT, Mayahi S. In vitro antifungal susceptibility of Candida species
isolated from oropharyngeal lesions of patients with cancer to some antifungal agents. Jundishapur J
Microbiol. 2011; 4(Supplement 1): S19-S26.

Received: July 2010 Accepted: October 2010

Abstract
Introduction and objective: Oropharyngeal candidiasis is a relatively common mycotic
infection in cancer patients. In vitro susceptibility of oropharyngeal Candida isolates can be
useful in selecting the appropriate treatment for the best therapeutic outcome. The aim of
this study was to evaluate the in vitro antifungal activity of Candida species against
antifungal agents.
Material and methods: In vitro activities of four antifungals were detected in 69 Candida
isolates recovered from cancer patients in four university hospitals using the microdilution
method described in the CLSI M27-A3 guideline.
Result: Only 12(17.4%) of Candida isolate were resistant to antifungal agents. Three
isolates (4.4% included C. albicans, C. glabrata, C. tropicalis, and C. pelliculosa) were
resistant to amphotericin B, 5(7.2% included two C. albicans, two C. glabrata, and one C.
kefyr) were itraconazole resistant. Two (2.9% include one C. albicans and one C. glabrata)
were fluconazole resistant. Caspofungin resistance was detected in two C. infanticola strains
which were reported as a clinical isolate for the first time. All Candida isolates (n=69) taken
together gave minimum inhibitory concentration (MIC90) value for amphotericin B,
fluconazole, itraconazole and caspofungin of 1, 0.25, 32 and 0.25g/ml, respectively. In
total, 18.7% of C. glabrata and 7.8% of C. albicans isolates were fully resistant to both
itraconazole and fluconazole.
Conclusion: Caspofungin had activity against oropharyngeal non- albicans Candida species
isolates, particularly against those with reduced susceptibility to amphotericin B,
fluconazole and itraconazole.
Keywords: Antifungals; In vitro susceptibility; Candida species; Oropharyngeal candidiasis

*Address for correspondence:

Dr. Tahereh Shokohi, Km 18 Khazar Abad Road, Sari Medical School, Mazandaran University of
Medical Sciences, Sari, Iran. PO. Box 48175-1665, Sari, Iran; Tel; +98151 3543087;
Fax: +98151 3543088; Email: Shokohi.tahereh@gmail.com
Jundishapur Journal of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran, Tel: +98611 3330074; Fax: +98611 3332036; URL: http://jjm.ajums.ac.ir; E-mail: editorial office: jjm@ajums.ac.ir
JJM. (2011); 4(Supplement 1): S19-S26.
Susceptibility of Candida antifungal agents S20

Introduction use of antifungal therapies, requires an

Candida spp. and Candida albicans are part urgent need for laboratory support in the
of normal micro flora of oral cavity in 40% treatment of fungal infections including [1]
to 60% of healthy individuals. However, the rapid identification of fungal pathogens
they are also opportunistic pathogen in to the species level, and where appropriate
immunocompromised patients. They can [2] in vitro susceptibility testing of clinical
become aggressive, induce oropharyngeal isolates to guide the selection of antifungal
candidiasis (OPC), invade the digestive therapy [12]. In this study, an attempt has
tract and even lead to systemic infections been made to determine susceptibility
[1]. OPC is a relatively common mycotic pattern of four antifungal agents against the
infection in cancer patients undergoing Candida species isolated from patients with
radiotherapy and/or chemotherapy [2-5]. cancer.
Amphotericin B is the main therapy for
serious fungal infections for more than 40 Materials and methods
years. Infusion-related side effects and Fungal strains and culture conditions
dose-limiting nephrotoxicity associated Sixty nine strains of Candida species were
with its use prompted continuous search for isolated from orophareangeal lesions of
equally effective but less toxic alternatives. patients with cancer admitted in four
Azoles are safe and effective agents for the university hospitals of Mazandaran
treatment of oropharyngeal candidiasis and province. All patients gave written informed
have gradually replaced amphotericin B. consent and the study was approved by the
However, resistance to azoles is now ethics committee of research deputy of
becoming common. Several reports suggest Mazandaran university of Medical
that susceptibility rates of Candida spp. to Sciences. These strains were previously
triazole antifungal amongst cancer patients identified by phenotypic methods such as
have remained high with fluconazole germ tube formation in horse serum,
resistance restricted to C. krusei [6,7] and chlamydospore formation in Corn meal
C. glabrata [6-8]. Other investigators have agar-Tween 80 (Merck, Germany), colored
notified that C. albicans isolates from HIV colony morphology on CHROMagar
positive and cancer patients are resistant to Candida medium (CHROMagar Company,
fluconazole and itraconazole [9,10]. France), API 20C Aux (bioMerieux-France)
Newer antifungals, such as and genotypic methods such as sequencing
caspofungin, have a broader spectrum of D1/D2 region of LSU r DNA gene [13] and
activity that includes fluconazole resistant RFLP-PCR region of ITS1-5.8S-ITS2
Candida spp. and they are good substitutes rDNA region [14]. Stock cultures and
for amphotericin B that cannot be tolerated controls were grown on Sabouraud dextrose
by some patients. The use of this new agar (SDA, (Merck, Germany)), and were
option should therefore be considered for incubated at 35C for 24h.
the treatment of refractory oropharyngeal
candidiasis [11]. Although C. albicans is Antifungal agents
the most frequently implicated pathogen, The following agents were supplied as
other Candida species also may cause standard powders: Amphotricin B (Sigma-
infection. The emergence of antifungal Aldrich, USA), fluconazole (Sigma-
resistance within these causative yeasts, Aldrich, USA), itraconazole (Sigma-
especially in patients with recurrent Aldrich, USA), and caspofungin (Merck,
oropharyngeal infection or with long-term USA) and were dissolved in dissolved in
Jundishapur Journal of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran, Tel: +98611 3330074; Fax: +98611 3332036; URL: http://jjm.ajums.ac.ir; E-mail: editorial office: jjm@ajums.ac.ir
JJM. (2011); 4(Supplement 1): S19-S26.
Tahereh Shokohi, et al. S21

dimethyl sulfoxide (DMSO) (Sigma, USA) The minimum inhibitory concentration

to make stock solutions. (MIC) values for fluconazole, itraconazole,
and amphotericin B were compared to the
Antifungal susceptibility testing CLSI interpretative guideline on antifungal
Antifungal susceptibility testing of the susceptibility testing or based on CLSI
isolates was performed by micro broth standard protocol [15,16]. The fungal
dilution technique in accordance with growth is considered as resistant when
Clinical and Laboratory Standard institute 64g/ml of fluconazole is used, it is
(CLSI) guidelines M27-A3 and M27-S3 considered as susceptible dose dependent
[15,16]. All the testing was done in when16-32g/ml of fluconazole is used,
duplicates. The range of concentrations and is considered as susceptible when
tested was 0.125-64g/ml for fluconazole, 8g/ml used. The fungal growth is
0.015-8g/ml for caspofungin and 0.0313- considered as resistant when 1g/ml of
16g/ml for amphotericin B and itraconazole is used, it is considered as
itraconazole. susceptible dose dependent when 0.25-
Aliquots of 100l of each antifungal 0.5g/ml of itraconazole is used, and is
agent at a concentration two times the considered as susceptible when
targeted final concentration were dispensed 0.125g/ml used. The fungal growth is
in the wells of the sterile, disposable and considered as resistant when 2g/ml of
flat bottom 96 well microdilution plates. amphotericin B is used, and is considered as
Yeasts inoculum was prepared onto susceptible when <1g/ml used. The fungal
Sabouraud dextrose in sterile saline (0.85%) growth is considered as resistant when
after 24h of incubation, obtaining an initial 2g/ml of caspofungin is used, and is
concentration of 1 to 5106 cell/ml considered as susceptible when 2g/ml
(adjusted spectrophotometrically at 625nm used. The MICs endpoints were determined
to match the turbidity of a 0.5 Mc Farland with reading mirror.
standard). This inoculum was diluted in
RPMI 1640 medium with L-glutamine, Results
without sodium bicarbonate (Sigma, USA) A total of 69 oropharyngeal Candida
buffered with morpholine- propanesulfonic isolates from patient with cancer which
acid (Sigma-Aldrich, Germany) in order to were previously identified were included in
obtain a final concentration of 0.5103 to this study. The species distribution of
2.5103 cell/ml. Candida isolates were C. albicans (38,
A constant volume (100l) of the 55%), C. glabrata (16, 23.2%), C.
inoculum was added to each microdilution tropicalis (6, 8.7%), C. parapsilosis (1,
well containing 100l of the serial dilution 1.5%), C. krusei (2, 2.9%) and C.
of antifungal agents to reach final infanticola (2, 2.9%), C. kefyr (1, 1.5%), C.
concentrations. The microplates were pelliculosa (1, 1.5%), C. orthopsilosis (1,
incubated at 35C for 48h. Visible fungal 1.5%), C. terebra (1, 1.5%). These two C.
growth can be inhibited 100% by the infanticola strains were isolated from the
MIC100 of amphotericin B, whereas it can mouth of a two year-old boy and a 67 year-
be inhibited 50% by MICs50 of azoles and old man, both suffering from cancer,
caspofungin in relation to the drug-free identified with molecular tools.
growth control. In each test C. parapsilosis The comparative in vitro susceptib-
(ATCC 22019) and C. krusei (ATCC 6258) ilities of the yeast isolate to the antifungal
were used for quality control. agents were shown in Table 1. MICs for C.
Jundishapur Journal of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran, Tel: +98611 3330074; Fax: +98611 3332036; URL: http://jjm.ajums.ac.ir; E-mail: editorial office: jjm@ajums.ac.ir
JJM. (2011); 4(Supplement 1): S19-S26.
Susceptibility of Candida antifungal agents S22

parapsilosis (ATCC 22019) and C. krusei We found the widest range and the highest
(ATCC 6258) were within the expected MICs for fluconazole (range 0.063-64). The
ranges. Overall, 66(95.7%) of isolates were isolates of C. albicans and C. glabrata had
susceptible to amphotericin B (MIC1g/ high MICs for fluconazole. Caspofungin
ml). Three isolates (4.3% included C. and itraconazole demonstrated better in
albicans, C. glabrata, C. pelliculosa) were vitro activity than amphotericin B with
resistant to amphotericin B (MIC>1g /ml). MIC90 0.25g/ml, compared to 1g/ml for
Thirty three (47.8%) of the isolates were all Candida isolates. In our study, some rare
susceptible to itraconazole (MIC0.125g/ species that belong to C. pelliculosa, C.
ml), 31(44.9%) were susceptible dose krusei, C. orthopsilosis, C. parapsilosis, C.
dependent and 5(7.2%) were itraconazole kefyr, C. terebra, and C. Infanticola were
resistant (MIC1g /ml). Fifty four (78.2%) identified at the basis of the sequence
of the isolates were susceptible to analysis.
fluconazole (MIC8g/ml), 13(18.4%)
were susceptible dose dependent and Discussion
2(2.9%) were fluconazole resistant A variety of antifungal agents are now
(MIC64g/ ml). available for the treatment of oropharyngeal
All Candida isolates (n=69) taken candidiasis infections. Amphotericin B is
together gave MIC90 value for amphotericin used in the treatment of superficial and
B, fluconazole, itraconazole and systemic infections of hospitalized
caspofungin of 1, 32, 0. 25, and 0.25g/ml, individuals [17]. This study demonstrated
respectively. Only 12(17.4%) of Candida that C. albicans was the predominant
isolates (four of C. albicans, four of C. species of oropharyngeal candidiasis in
glabrata, one of C. pelliculosa, one of C. patients with cancer. Although C. albicans
kefyr and two of C. infanticola) were remain the most common pathogen in
resistant to antifungal agents. Only 2(2.9%) oropharyngeal candidiasis, non- albicans
and 3(4.3%) of the Candida isolates were species are increasingly associated with
resistant to caspofungin and amphotericin invasive candidiasis [18]. Although triazole
B, respectively. agents appear to be highly effective
In total, three of 16 C. glabrata isolates initially, the increase of resistance to them
(18.7%) and three of 38 C. albicans isolates has been reported [17,19].
(7.8%) were fully resistant to both Decreasing susceptibility to the first
itraconazole and fluconazole. However, generation azoles (fluconazole and
none of the C. tropicalis, C. parapsilosis, C itraconazole) due to the increasing
.krusei, C. orthopsilosis and C. terebra was incidence of colonization and infection with
resistant to these four antifungals. Overall, non- albicans Candida species, concerns
31(45%) of isolates were non-albicans have risen for newer antifungal drug. In the
Candida species which eight of them present study, overall resistance of all
(25.8%) were resistant and 19 of them Candida isolates to fluconazole was 2.9%,
(61.2%) were susceptible dose dependent to which is similar to that reported by other
antifungals. For all together non-albicans previous studies [20, 21]. The reason for the
Candida species (n=31) MIC90 values for low fluconazole resistance could be
amphotericin B, fluconazole, itraconazole explained by the fact that fluconazole was
and caspofungin of 1, 16, 0.5 and not prescribed to the most cancer patients as
0.125g/ml, respectively (not shown in a standard care in Iran.
table 1).
Jundishapur Journal of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran, Tel: +98611 3330074; Fax: +98611 3332036; URL: http://jjm.ajums.ac.ir; E-mail: editorial office: jjm@ajums.ac.ir
JJM. (2011); 4(Supplement 1): S19-S26.
Tahereh Shokohi, et al. S23

In the present study, 5.4% of Candida species which was isolated from patients
albicans were resistant to itraconazole with allergic diseases [28]. C. orthopsilosis
which is accordant with those investigators isolates which are phenotypically similar to
which reported itraconazole resistance 4% C. parapsilosis has recently been
[22] and 7% [23] in advanced cancer and distinguished by molecular methods [29-
immunocompromised patients, respectively. 31]. This rare strain may be responsible for
In the present study 45% of isolates were infection and colonization in humans. In our
non-albicans Candida species which 19.4% study, in accordance with Tavanti et al. [29]
of them were resistant to amphotericin B, C. orthopsilosis isolate was found used to
itraconazole and fluconazole. Also in this be susceptible to all antifungals.
study 18.7% C. glabrata isolates were fully This report further highlights the
resistant to both itraconazole and presence of emerging pathogens that could
fluconazole. Almost similar results were not be identified reliably and support the
observed by Gonzales et al. [24] who requirement for careful mycological
showed 31.3% of C. glabrata bloodstream identification at the species level of
isolates were resistant to fluconazole, Candida isolates recovered from cancer
43.3% were resistant to itraconazole. patients, together with regular in vitro
Badiee et al. [25] also noted resistance to susceptibility testing to detect resistance to
fluconazole and itraconazole in some the azoles. These local surveillance studies
Candida species isolates from mucosal sites can help clinicians make treatment decision.
of HIV-positive patients in Shiraz, Iran. The data presented in this paper indicate
Caspofungin showed substantial that caspofungin and itraconazole are more
activity against isolates demonstrated in effective than either amphotericin B or
vitro resistance to fluconazole, itraconazole, fluconazole against all non- albicans
and amphotericin B. These results suggest Candida species isolated from the
that caspofungin activity against oropharynx of patients with cancer. Thus, in
oropharyngeal Candida isolates, such unresponsive case, caspofungin can be
particularly against those with reduced an alternative regime for managing
susceptibility to fluconazole and oropharyngeal candidiasis.
itraconazole. The results are similar to that
reported by Pfaller et al. [26] who Conclusion
compared caspofungin with fluconazole and These results suggest that caspofungin has
itraconazole against clinical isolates of activity against oropharyngeal non-
Candida spp., including fluconazole- albicans Candida species isolates,
resistant isolates. They also showed that particularly against those with reduced
caspofungin was as active as or more potent susceptibility to amphotericin B,
than either fluconazole or itraconazole fluconazole and itraconazole.
against all Candida spp. with the exception
of C. guilliermondii and C. famata. In our Acknowledgment
study there were no such Candida species We are grateful to the Vice-Chancellor of
between our isolates, but we demonstrated Research of Mazandaran University of
that caspofungin had no activity against C. Medical Sciences for financial support. We
infanticola. would like also thank Dr. Hamid Badali and
Candida infanticola is a rare species Dr. Kamyar Zomorodian for critical
that recently was isolated [27] from the ear assistance.
of an infant in Germany. C. terebra is a rare
Jundishapur Journal of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran, Tel: +98611 3330074; Fax: +98611 3332036; URL: http://jjm.ajums.ac.ir; E-mail: editorial office: jjm@ajums.ac.ir
JJM. (2011); 4(Supplement 1): S19-S26.
Susceptibility of Candida antifungal agents S24

Table 1: The comparative In vitro susceptibilities of the Candida isolate from cancer patients to the
antifungal agents

Species (N/%) Antifungal MICg/ml R* SDD**

50% 90% Range N (%) N (%)
C .albicans Amphotricin B 0.5 1 0.125-2 1(2.6) -
(38/55) Itraconazole 0.25 0.5 0.03-2 2(5.4) 18(48.6)
Fluconazole 4 16 0.5-64 1(2.7) 6(15.7)
Caspofungin 0.063 0.125 0.015-0.25 - -
C. glabrata Amphotricin B 0.5 1 0.125-4 1(6.2) -
(16/23.2) Itraconazole 0.25 0.5 0.063-4 2(12.5) 10(62.5)
Fluconazole 2 16 1-64 1(6.2) 4(25)
Caspofungin 0.031 0.125 0.015-0.25 - -
C. tropicalis Amphotricin B 0.25 0.5 0.125-2 - -
(6/8.7) Itraconazole 0.125 0.25 0.063-0.5 - 1(16.6)
Fluconazole 1 4 0.25-16 - -
Caspofungin 0.063 0.5 0.031- 0.5 - -
C. parapsilosis Amphotricin B 0.25 0.5 0.25-0.5 - -
( 1/ 1.5) Itraconazole 0.125 0.25 0.125-0.25 - -
Fluconazole 4 8 4-8 - -
Caspofungin 0.25 0.25 0.25-0.5 - -
C. krusei Amphotricin B 0.25 0. 5 0.25-0.5 - -
(2/2.9) Itraconazole 0.063 0.125 0.063-0.125 - -
Fluconazole 1 2 1-2 - -
Caspofungin 0.125 0.25 0.125-0.25 - -
C. infanticola Amphotricin B 0.125 0.125 0.125 - -
(2/2.9) Itraconazole 0.5 0.5 0.5 - 2(100)
Fluconazole 4 8 4-8 - -
Caspofungin 4 4 4 2(100)
C. orthopsilosis Amphotricin B 0.25 - -
(1/1.5) Itraconazole 0.125 - -
Fluconazole 16 - 1(1.5)
Caspofungin 0.5 - -
C. pelliculosa Amphotricin B 2 1(1.5) -
(1/1.5) Itraconazole 0.125 - -
Fluconazole 32 - 1(1.5)
Caspofungin 1 -
C. kefyr Amphotricin B 0.5 - -
(1/1.5) Itraconazole 2 1(1.5) -
Fluconazole 16 -
Caspofungin 1 -
C. terebra Amphotricin B 0.25 - -
(1/1.5) Itraconazole 0.125 - -
Fluconazole 16 - -
Caspofungin 0.5 - -
All Candida Amphotricin B 0.5 1 0.125-2 3(4.4) -
(69/100) Itraconazole 0.125 0.25 0.03-4 5(7.2) 31(44.9)
Fluconazole 4 32 0.063-64 2(2.9) 13(18.4)
Caspofungin 0.125 0.25 0.015-4 2(2.9) -
C. parapsilosis Amphotricin B 1 1 1
(ATCC 22019) Itraconazole 0.5 0.5 1
Fluconazole 2 4 0.5
Caspofungin 1 1 1
C. krusei Amphotricin B 1 2 1-2
(ATCC 6258) Itraconazole 0.5 1 0.5-1
Fluconazole 32 68 32-68
Caspofungin 0.5 0.5 0.5

Jundishapur Journal of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran, Tel: +98611 3330074; Fax: +98611 3332036; URL: http://jjm.ajums.ac.ir; E-mail: editorial office: jjm@ajums.ac.ir
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Tahereh Shokohi, et al. S25

References 11) Garbino J. Caspofungin-a new therapeutic

1) Fidel Jr PL, Wozniak KL. Superficial option for oropharyngeal candidiasis. Clin
candidiasis. In: Collier L, Balows A, Microbiol Infect. 2004; 10: 187-9.
Sussman M, Ajello L, Hay RJ, (eds), 12) Lewis RE, Fothergill AW. Antifungal
Topley & Wilson's microbiology and agents. In: Hospentha DR, Rinaldi MG
microbial infections. Vol 4, Medical (eds), Diagnosis and treatment of human
mycology. 10th ed. UK, ASM Press, 2005; mycoses. USA, Humana Press Inc, 2008;
255-72. 105-36.
2) Bodey GP. Candidiasis in cancer patients. 13) Fatahi M, Shokohi T, Hashemi Sooteh MB,
Am J Med. 1984; 77: 13-9. et al. Molecular identification of Candida
3) Mooney MA, Thomas I, Sirois D. Oral albicans Isolated from the oncology
candidiasis. Int J Dermatol. 1995; 34: 759- patients at four university hospitals in
65. Mazandaran province (2005-6). J
4) Epstein JB, Polsky B. Oropharyngeal Mazandaran Uni Med Sci. 2008; 17: 1-11.
candidiasis: a review of its clinical 14) Shokohi T, Hashemi Soteh MB, Pouri ZS,
spectrum and current therapies. Clin Ther. Hedayati MT, Mayahi S. Identification of
1998; 20: 40-57. Candida species using PCR-RFLP in cancer
5) Peterson DE. Oral candidiasis. Clin Geriatr patients in Iran. Indian J Med Microbiol.
Med. 1992; 8: 513-27. 2010; 28: 147-51.
6) Hoban DJ, Zhanel GG, Karlowsky JA. In 15) Clinical and laboratory standard institute
vitro susceptibilities of Candida and (2008). Reference method for broth dilution
Cryptococcus neoformans isolates from antifungal susceptibility testing of yeasts;
blood cultures of neutropenic patients. approved standard- third edition M27-A3,
Antimicrob Agents Chemother. 1999; 43: 2008. National Committee for Clinical
1463-4. Laboratory Standards, Wayne,
7) Girmenia C, Tuccinardi C, Santilli S, et al. Pennsylvania, USA.
In vitro activity of fluconazole and 16) Clinical and laboratory standard institute
voriconazole against isolates of Candida reference method for broth dilution
albicans from patients with haematological antifungal susceptibility testing of yeasts;
malignancies. J Antimicrob Chemother. approved standard- third edition M27-S3,
2000; 46: 479-83. 2008. National Committee for Clinical
8) Kennedy HF, Shankland GS, Bagg J, Laboratory Standards, Wayne,
Chalmers EA, Gibson BE, Williams CL. Pennsylvania, USA.
Fluconazole and itraconazole susceptibil- 17) Ellepola AN, Samaranayake LP. Oral
ities of Candida spp. isolated from candidal infections and antimycotics. Crit
oropharyngeal specimens and blood Rev Oral Biol Med. 2000; 11: 172-98.
cultures of paediatric haematology/oncol- 18) Diekema DJ, Messer SA, Brueggemann
ogy patients. Mycoses. 2006; 49: 457-62. AB, et al. Epidemiology of candidemia: 3-
9) Antoniadou A, Torres HA, Lewis RE, et al. year results from the emerging infections
Candidemia in a tertiary care cancer center: and the epidemiology of Iowa organisms
in vitro susceptibility and its association study. J Clin Microbiol. 2002; 40: 1298-
with outcome of initial antifungal therapy. 302.
Medicine (Baltimore). 2003; 82: 309-21. 19) Pfaller MA, Diekema DJ. Epidemiology of
10) Ruhnke M, Eigler A, Tennagen I, Geiseler invasive candidiasis: a persistent public
B, Engelmann E, Traumann M. Emergence health problem. Clin Microbiol Rev. 2007;
of fluconazole-resistant strains of Candida 20: 133-63.
albicans in patients with recurrent 20) Hamza OJ, Matee MI, Moshi MJ, et al.
oropharyngeal candidose and human Species distribution and in vitro antifungal
immunodeficiency virus infection. J Clin susceptibility of oral yeast isolates from
Microbiol. 1994; 32: 2092-8. Tanzanian HIV-infected patients with
primary and recurrent oropharyngeal
Jundishapur Journal of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran, Tel: +98611 3330074; Fax: +98611 3332036; URL: http://jjm.ajums.ac.ir; E-mail: editorial office: jjm@ajums.ac.ir
JJM. (2011); 4(Supplement 1): S19-S26.
Susceptibility of Candida antifungal agents S26

candidiasis. BMC Microbiol. 2008; 12; 8: 157 fluconazole-resistant isolates.

135. Antimicrob Agents Chemother. 2003; 47:
21) Kuriyama T, Williams DW, Bagg J, Coulter 1068-71.
WA, Ready D, Lewis MA. In vitro 27) Kurtzman C. New anamorphic yeast
susceptibility of oral Candida to seven species: Candida infanticola sp. nov.,
antifungal agents. Oral Microbiol Immunol. Candida polysorbophila sp. nov., Candida
2005; 20: 349-53. transvaalensis sp. nov. and Trigonopsis
22) Bagg J, Sweeney MP, Lewis MA, et al. californica sp. nov. Antonie van
High prevalence of non-albicans yeasts and Leeuwenhoek. 2007; 92: 221-31.
detection of antifungal resistance in the 28) Arzumanyan VG, Semenov BF. Drug
flora of patients with advanced cancer. sensitivity of Candida yeast isolated from
Palliat Med. 2003; 17: 477-81. patients with allergic diseases. Bulletin Exp
23) Badiee P, Alborzi A, Shakiba E, Ziyaeyan Biol Med. 2001; 131: 346-9.
M, Rasuli M. Molecular identification and 29) Tavanti A, Hensgens LA, Ghelardi E,
in vitro susceptibility of Candida albicans Campa M, Senesi S. Genotyping of
and C. dubliniensis isolated from Candida orthopsilosis clinical isolates by
immunocompromised patients. Iranian Red amplification fragment length
Crescent Med J. 2009; 11: 391-7. polymorphism reveals genetic diversity
24) Gonzalez G M, Elizondo M, Ayala J. among independent isolates and strain
Trends in species distribution and maintenance within patients. J Clin
susceptibility of bloodstream isolates of Microbiol. 2007; 45: 1455-62.
Candida collected in Monterrey, Mexico, to 30) Asadzadeh M, Ahmad S, Al-Sweih N, Khan
seven antifungal agents: results of a 3-year ZU. Rapid molecular differentiation and
(2004 to 2007) surveillance study. J Clin genotypic heterogeneity among Candida
Microbiol. 2008; 46: 2902-5. parapsilosis and Candida orthopsilosis
25) Badiee P, Alborzi A, Davarpanah MA, strains isolated from clinical specimens in
Shakiba E. Distributions and antifungal Kuwait. J Med Microbiol. 2009; 58: 745-
susceptibility of Candida species from 52.
Mucosal sites in HIV positive patients. Arch 31) Mirhendi H, Bruun B, Schnheyder HC, et
Iran Med. 2010; 13: 282-7. al. Molecular screening for Candida
26) Pfaller MA, Diekema DJ, Messer SA, orthopsilosis and Candida metapsilosis
Hollis RJ, Jones RN. In vitro activities of among Danish Candida parapsilosis group
caspofungin compared with those of blood culture isolates: proposal of a new
fluconazole and itraconazole against 3,959 RFLP profile for differentiation. J Med
clinical isolates of Candida spp., including Microbiol. 2010; 59: 414-20.

Jundishapur Journal of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran, Tel: +98611 3330074; Fax: +98611 3332036; URL: http://jjm.ajums.ac.ir; E-mail: editorial office: jjm@ajums.ac.ir
JJM. (2011); 4(Supplement 1): S19-S26.