Medical Mycology, 2016, 54, 757763

doi: 10.1093/mmy/myw016
Advance Access Publication Date: 26 April 2016
Original Article

Original Article

In vitro activity of new azoles luliconazole

and lanoconazole compared with ten other
antifungal drugs against clinical
dermatophyte isolates
Nesa Baghi1 , Tahereh Shokohi2 , Hamid Badali2 , Koichi Makimura3 ,
Ali Rezaei-Matehkolaei4 , Maryam Abdollahi5 , Mojtaba Didehdar1 ,
Iman Haghani2 and Mahdi Abastabar2,
1
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran, 2 Invasive Fungi
Research Center (IFRC), Department of Medical Mycology and Parasitology, School of Medicine, Mazan-
daran University of Medical Sciences, Sari, Iran, 3 Laboratory of Space and Environmental Medicine,
Graduate School of Medicine, Teikyo University, Japan; Asia International Institute of Infectious Dis-
eases Control, Teikyo University, Japan; Teikyo University Institute of Medical Mycology, Tokyo, Japan,
4
Department of Medical Mycology, School of Medicine, Infectious and Tropical Diseases Research Cen-
ter, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran and 5 Department of Microbiology
and Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

To whom correspondence should be addressed. Mahdi Abastabar, Ph.D., Assistant Professor of Medical Mycology,
Invasive Fungi Research Center, Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran
University of Medical Sciences, Sari, Iran. P.O. Box: 48175-1665, Sari, Iran. Tel: +98 9112111347;
E-mail: mabastabar@gmail.com
Received 28 September 2015; Revised 31 January 2016; Accepted 11 February 2016

Abstract
In vitro susceptibilities of 100 clinical dermatophyte isolates belonging to five species
from Iran toward lanoconazole and luliconazole were compared with ten other anti-
fungal agents including econazole, itraconazole, miconazole, fluconazole, griseofulvin,
butenafine, terbinafine, caspofungin, anidulafungin and tolnaftate. MIC and MEC val-
ues were analyzed according to CLSI M38-A2 document. The isolates were previously
identified to the species level using PCR-RFLP on ITS rDNA region. The range of lulicona-
zole and lanoconazole minimum inhibitory concentrations (MICs) was 0.0160.032 and
0.0631 g/ml, respectively for dermatophyte species. Luliconazole and lanoconazole re-
vealed potent activity against all dermatophyte isolates. Anidulafungin, caspofungin, and
luliconazole showed the best activity with the lowest geometric mean 0.01, 0.016, and
0.018 g/ml, respectively, followed by tolnaftate (0.06 g/ml), terbinafine (0.07 g/ml),
itraconazole (0.183 g/ml), butenafine (0.188 g/ml), econazole (0.20 g/ml), lanocona-
zole (0.24 g/ml), griseofulvin (1.28 g/ml), miconazole (2.34 g/ml) and fluconazole
(15.34 g/ml). The current study demonstrated luliconazole and lanoconazole displayed


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excellent activity against all dermatophyte isolates, although the majority of dermato-
phyte isolates showed low susceptibility to griseofulvin and very low to miconazole, and
fluconazole.
Key words: Dermatophytes, luliconazole, lanoconazole, in vitro antifungal susceptibility.
Introduction
Dermatophytes are a unique family of keratinophilic molds,
which cause cutaneous infections in humans and animals
and are classified in three anamorphic genera, that is, Tri-
chophyton, Microsporum, and Epidermophyton.1 More
than 40 species of dermatophytes have been identified, some
of which are among the most common agents of skin, hair,
and nail infections, worldwide.13 Trichophyton rubrum
and T. interdigitale are frequently isolated from different
clinical specimens. Other important species include Epi-
dermophyton floccosum, Trichophyton tonsurans, and Mi-
crosporum canis.13 Dermatophytosis affects millions of
people every year. Although this condition is not deemed
to be life-threatening, it reduces individuals quality of life
and imposes significant treatment costs on patients.13 Dif-
ferent types of dermatophytosis are usually treated with
systemic and/or topical formulations of two antifungal fam-
ilies, that is, allylamines and azoles. Oral use of itraconazole
and terbinafine is the treatment of choice for tinea unguium
as well as in case of severe, recalcitrant, or chronic infec-
tion which use of topical formulations is not reasonable
for the patients.1,4,5 Despite global reports on the resis-
tance of numerous Aspergillus and Candida isolates to var-
ious antifungal agents,6 intrinsic or acquired resistance is
considered rare in different dermatophyte species.7 There
is no evidence on dermatophyte resistance to antifungal
agents. Only recently, resistance of Trichophyton rubrum
isolates to terbinafine and their cross-resistance to different
squalene epoxidase inhibitors (i.e., tolnaftate, butenafine,
naftifine, and tolciclate) have been documented.8 In addi-
tion, over the past years, various researchers have reported
dermatophyte strains with high minimum inhibitory con-
centrations (MICs) for fluconazole.913 Despite the high
worldwide prevalence of dermatophytosis, antifungal sus-
ceptibility patterns of dermatophyte species have been
poorly evaluated. Luliconazole and lanoconazole are novel
imidazole antifungal agents, with broad-spectrum activi-
ties against medically important fungi such as Candida,
Malassezia, Aspergillus, and Trichophyton species.14 How-
ever, limited data are available on the in vitro susceptibility
profile of clinically important dermatophytes against luli-
conazole and lanoconazole, worldwide.
So, in the current study, we compared the in vitro activity
of lanoconazole (LAN) and luliconazole (LUL) with ten
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Medical Mycology, 2016, Vol. 54, No. 7
antifungal agents including econazole (ECO), itraconazole
(ITC), miconazole (MIC), fluconazole (FLC), griseofulvin
(GRI), butenafine (BUT), terbinafine (TER), caspofungin
(CAS), anidulafungin (ANI), tolnaftate (TOL), against 100
clinically strains of dermatophytes belonging to five species
(T. rubrum, T. interdigitale, E. floccosum, T. tonsurans,
and M. canis) isolated from patients in Iran.
Materials and methods
Fungal isolates
One hundred clinical isolates of dermatophyte belonging to
five species including T. interdigitale (n = 52), T. rubrum (n
= 29), T. tonsurans (n = 13), E. floccosum (n = 4), and M.
canis (n = 2) were obtained from the culture collection of
Invasive Fungi Research Center (IFRC), Mazandaran Uni-
versity of Medical Sciences, Sari, Iran. All isolates originated
from patients with dermatophytosis, which were recovered
from a variety of specimens including skin, nail, and hair
and have been identified previously based on both mor-
phological characteristics and restriction fragment length
polymorphism (RFLP).15,16
In vitro susceptibility testing
In vitro antifungal susceptibility testings were deter-
mined according to recommendations stated in the Clin-
ical and Laboratory Standards Institute (CLSI) M38-A2
documents.17 Fluconazole (Pfizer Central Research, Sand-
wich, United Kingdom), itraconazole, econazole, micona-
zole (Sigma-Aldrich Steinheim, Germany), luliconazole and
lanoconazole (Nihon Nohyaku Co. Ltd., Osaka, Japan),
terbinafine, butenafine, tolnaftate, griseofulvin (Sigma-
Aldrich, Steinheim, Germany), anidulafungin, caspofun-
gin (Pfizer Central Research, Sandwich, United Kingdom)
were obtained as reagent-grade powders from the respec-
tive manufacturers for preparation of the CLSI microdilu-
tion trays. Stock solutions of caspofungin and fluconazole
were prepared in water, while for other agents dimethyl
sulfoxide (DMSO) was administrated.
The antifungal drugs were diluted in the standard RPMI-
1640 medium (Sigma Chemical Co.) buffered to pH 7.0
with 0.165 M-morpholinepropanesulfonic acid (MOPS)
(Sigma) with L-glutamine without bicarbonate to yield
 Baghi et al.
two times their concentrations and dispensed into 96-well
microdilution trays with a final concentration of 0.016
16 g/ml for luliconazole, lanoconazole, tolnaftate, itra-
conazole, econazole, and miconazole; 0.06364 g/ml for
fluconazole, 0.0088 g/ml for caspofungin, anidulafun-
gin, and griseofulvin, 0.0044 g/ml for butenafine and
terbinafine. Plates were stored at 70 C prior to use.
For adequate sporulation, all isolates were grown on
potato dextrose agar (PDA, Difco) or oatmeal agar (T.
rubrum) plates at 30 C for up to one week. Briefly, in-
oculum suspensions were performed under biosafety level
by covering the colonies with 1 ml of sterile saline solution
(0.85%), and preparing a suspension by slightly scraping
the surface of mature colonies with a loop or sterile swab.
Large particles in the cell suspensions were allowed to settle
for several minutes at room temperature and transferred to
a sterile syringe attached to a sterile filter holder with a ster-
ile filter (Whatman no. 40), filtered and collected in a sterile
tube. This procedure removed the majority of the hyphae,
producing an inoculum composed mainly of microconidia
and the cell suspension was transferred to sterile tubes and
adjusted spectrophotometrically at a 530 nm wavelength to
optical densities (ODs) that ranged from 65% to 70% trans-
mission. The final size of the stock inoculum suspensions of
the isolates tested ranged from 0.53 103 colony form-
ing units (CFU)/ml as determined by quantitative colony
counts on Sabouraud glucose agar (SGA, Difco). Microdi-
lution plates were incubated at 35 C for 96 h (plates with
insufficient growth were incubated for 120 h) and read vi-
sually to determine MICs and MECs value by comparison
of the growth in the wells containing the drug with the
drug-free control. Paecilomyces variotii (ATCC 22319),
Candida parapsilosis (ATCC 22019) and Candida krusei
(ATCC 6258) were chosen as quality controls to be used
with every new series of MICs plates. MIC range, geomet-
ric mean, MIC50 and MIC90 were analyzed. All tests were
performed in duplicate, and differences of the mean values
were determined by using ANOVA and Multiple Compar-
isons test with the statistical SPSS package (version 7.0). P
values of <0.05 were considered statistically significant.
Results
In the current study, MIC50 , MIC90 , geometric mean (GM),
and MIC ranges of 100 clinical isolates were determined.
Considering the limited number of M. canis and E. floc-
cosum isolates, MIC50 , MIC90, and GM MIC were not
calculated for these species. The in vitro antifungal sus-
ceptibility characteristics of 12 antifungal agents against
dermatophyte species are summarized in Table 1. MIC
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values of all dermatophyte isolates showed susceptibility
to antifungal agents, except for fluconazole. Based on the
findings, the activity level of fluconazole was significantly
lower than other tested drugs. MIC50 , MIC90 , and GM val-
ues of fluconazole against the tested dermatophyte isolates
were 16, 64, and 15.34 g/ml, respectively. Moreover, in
terms of MIC range a significant difference was observed be-
tween M. canis and T. interdigitale among the tested drugs
(P < 0.05).
Among all the tested isolates, M. canis was the most
susceptible isolate to antifungal agents, while T. interdigi-
tale exhibited the lowest susceptibility. The in vitro activ-
ity of luliconazole against all the isolates was more potent
than fluconazole, miconazole, griseofulvin, lanoconazole,
econazole, butenafine, itraconazole, terbinafine, and tolnaf-
tate and comparable with anidulafungin and caspofungin.
Overall, luliconazole, caspofungin, and anidulafungin were
more active against dermatophyte isolates, compared to
other tested agents. As presented in Table 1, MIC50 val-
ues for these agents were 0.016, 0.016, and 0.008 g/ml,
respectively. Based on the findings, the GM MIC values
of anidulafungin, caspofungin and luliconazole were obvi-
ously the lowest (0.010, 0.016, and 0.018 g/ml, respec-
tively). These values were almost similar to those reported
for tolnaftate (0.06 g/ml), terbinafine (0.07 g/ml), itra-
conazole (0.18 g/ml), butenafine (0.18 g/ml), econazole
(0.20 g/ml), and lanoconazole (0.24 g/ml). On the other
hand, the reported values were completely different from
griseofulvin (1.28 g/ml), miconazole (2.34 g/ml), and flu-
conazole (15.34 g/ml). In our study, more than 90% of T.
interdigitale isolates were susceptible to all agents, whereas
these isolates showed low sensitivity to miconazole and flu-
conazole with MIC90 values of 8 and 64 g/ml, respec-
tively. The MIC range was the narrowest for anidulafungin
and luliconazole (0.0080.016 and 0.0160.032 g/ml, re-
spectively) and the widest for miconazole and fluconazole
(0.258 and 264 g/ml, respectively).
Discussion
Evaluation of antifungal susceptibility patterns can provide
useful data on resistance patterns and probable challenges
of therapy, worldwide. Although dermatophyte species are
naturally sensitive to the majority of antifungal drugs, de-
tection of susceptibility and resistance profiles is of grave
significance due to the high prevalence of dermatophytosis,
multiple cases of treatment failure, and lack of interpre-
tive breakpoints.9,18 In the current study, we followed the
standard M38-A2 protocol by the Clinical and Laboratory
Standards Institute (CLSI) to determine the MIC values of
 760 Medical Mycology, 2016, Vol. 54, No. 7

Table 1. In vitro antifungal susceptibilities of 100 clinical isolates of dermatophytes against twelve antifungal agents.

Dermatophyte species Antifungal drug MIC range MIC50 MIC90 GM

T. interdigitale (n = 52) LAN 0.0630.5 0.25 0.25 0.17

LUL 0.0160.032 0.016 0.032 0.02
ECO 0.0310.5 0.5 0.5 0.30
ITC 0.0310.5 0.25 0.5 0.18
MIC 0.58 4 8 3.31
FLC 264 32 64 20.8
GRI 0.54 1 2 0.98
BUT 0.0311 0.25 1 0.26
TER 0.0080.125 0.063 0.25 0.071
CAS 0.0080.032 0.016 0.032 0.016
ANI 0.0080.016 0.008 0.016 0.010
TOL 0.0080.125 0.063 0.25 0.076
T. rubrum (n = 29) LAN 0.251 0.25 0.25 0.17
LUL 0.016 0.016 0.032 0.02
ECO 0.0310.5 0.5 0.5 0.30
ITC 0.0630.5 0.25 0.5 0.18
MIC 0.258 4 8 3.31
FLC 464 8 32 9.9
GRI 0.54 1 4 1.5
BUT 0.0310.5 0.25 0.5 0.10
TER 0.0080.25 0.063 0.25 0.06
CAS 0.0080.032 0.016 0.032 0.018
ANI 0.0080.016 0.008 0.016 0.010
TOL 0.0160.25 0.031 0.25 0.052
T. tonsurans (n = 13) LAN 0.250.5 0.25 0.5 0.34
LUL 0.016 0.016 0.016 0.016
ECO 0.0310.5 0.25 0.5 0.35
ITC 0.0630.5 0.125 0.25 0.16
MIC 0.258 2 8 2.10
FLC 832 16 32 15.16
GRI 14 4 4 3.06
BUT 0.0310.25 0.25 0.25 0.16
TER 0.0310.125 0.125 0.25 0.12
CAS 0.0080.016 0.008 0.016 0.010
ANI 0.008 0.008 0.008 0.008
TOL 0.0310.125 0.125 0.125 0.081
M. canis (n = 2) LAN 0.25
LUL 0.016
ECO 0.031
ITC 0.125
MIC 0.25
FLC 24
GRI 2
BUT 0.031
TER 0.125
CAS 0.016
ANI 0.008
TOL 0.031
E. floccosum (n = 4) LAN 0.250.5
LUL 0.016
ECO 0.25
ITC 0.125
MIC 48
FLC 832

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Table 1. Continued

Dermatophyte species Antifungal drug MIC range MIC50 MIC90 GM

GRI 0.51
BUT 0.5
TER 0.125
CAS 0.0080.016
ANI 0.008
TOL 0.0310.063
Total (N = 100) LAN 0.0631 0.25 0.5 0.18
LUL 0.0160.032 0.016 0.032 0.018
ECO 0.0310.5 0.25 0.5 0.018
ITC 0.0630.5 0.25 0.5 0.18
MIC 0.258 4 8 2.34
FLC 264 16 64 15.34
GRI 0.54 1 4 1.28
BUT 0.0310.5 0.25 0.5 0.18
TER 0.0160.25 0.125 0.25 0.07
CAS 0.0080.032 0.016 0.032 0.016
ANI 0.0080.016 0.008 0.016 0.010
TOL 0.0160.25 0.063 0.25 0.06

Notes: MIC50 concentration at which 50% of the isolates were inhibited, MIC90 concentration at which 90% of the isolates were inhibited, MEC minimum
effective concentrations. Abbreviations: LAN; lanoconazole, LUL; luliconazole, ECO; econazole, ITC; itraconazole, MIC; miconazole, FLC; fluconazole, GRI;
griseofulvin, BUT; butenafine, TER; terbinafine, CAS; caspofungin, ANI; anidulafungin, TOL; tolnaftate.

12 antifungal agents against Iranian dermatophyte isolates.
To the best of our knowledge, this is the first study in which
the in vitro activity of seven antifungal agents, that is, bute-
nafine, tolnaftate, anidulafungin, caspofungin, econazole,
luliconazole, and lanoconazole, against Iranian clinical iso-
lates of dermatophyte was investigated. In a study by Adimi
et al. in Iran, itraconazole and terbinafine showed the lowest
MIC values, while fluconazole displayed the highest MIC
and GM values against 320 dermatophyte isolates.9 Also,
according to a study by Fernandez-Torres et al., itracona-
zole, ketoconazole, miconazole, clotrimazole, voriconazole,
terbinafine, and amphotericin B displayed excellent activi-
ties against 508 strains of 24 dermatophyte species, whereas
GM MIC for fluconazole was the highest.19 Similarly, in
our study, fluconazole showed the highest MIC, MIC50 ,
MIC90 , and GM values in comparison with other tested
agents. However, unlike the study by Fernandez-Torres et
al.19 and other previous research miconazole showed the
lowest activity.12 Econazole is among the most commonly
used topical formulations for dermatophytosis, although
it is not routinely applied in Iran.1 In contrast with flu-
conazole and miconazole, this azole showed good activ-
ity in the present study, with an MIC range of 0.031
0.5 g/ml. Nowadays, treatment of dermatophytosis is clas-
sically based on oral and/or topical formulations of ally-
lamines and azoles, especially terbinafine and itraconazole.1
In this study, all dermatophyte isolates were susceptible
to terbinafine with MIC90 and GM values of 0.25 and
0.07 g/ml, respectively. Previous studies by comparing
terbinafine and other agents against dermatophytes have
reported similar results.10,2022 However, Mukherjee et al.
described a T. rubrum isolate resistant to terbinafine with
an MIC value of > 4 g/ml.8
In various studies, the MICs of itraconazole against der-
matophyte species are almost similar to those reported in
the current study (0.0630.5 g/ml).10,14,19,20 However,
all the isolates in our study showed an MIC90 value of
0.5 g/ml, which was lower than MIC90 values reported
by Badali et al. and Adimi and colleagues.9,10 Based on
the present findings, butenafine, which is a benzylamine
derivative, showed potent activity against dermatophyte
isolates (MIC values ranging from 0.031 to 0.5 g/ml),
compared to commonly used drugs in Iran (i.e., griseoful-
vin, fluconazole, and miconazole). For many years, griseo-
fulvin has been the first-line antifungal agent for the treat-
ment of dermatophyte infections. However, in consistence
with previous studies, dermatophyte species exhibited very
low susceptibility to griseofulvin in the present study.1,23
In studies by Chadeganipour et al.23 and Adimi et al.9 in
Iran, the MIC90 values of griseofulvin against dermatophyte
strains were 8 and 256 g/ml, respectively. Interestingly, in
our study, differences were observed between MIC90 and
GM values of griseofulvin against T. rubrum and T. in-
terdigitale. On the other hand, Santos et al.24 and Barros
et al.25 reported no significant differences between T.
rubrum and T. interdigitale in terms of MIC values for

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 762
griseofulvin. On the contrary, the present study indicated
that T. interdigitale was more sensitive to griseofulvin,
compared to T. rubrum. Another surprising finding of
our study was the complete similarity between tolnaftate
and terbinafine (Table 1). In this regard, Favre et al.26
reported that all terbinafine-sensitive isolates were also
susceptible to tolnaftate. Similarly, in a previous study,
terbinafine-resistant isolates of T. rubrum were completely
cross-resistant to some classes of squalene epoxidase in-
hibitors such as tolnaftate.8 Echinocandins generally exhibit
fungistatic and fungicidal activities against Aspergillus and
Candida species, respectively.27 The in vitro susceptibility
profile of dermatophytes to these agents has not been ex-
tensively evaluated, except in studies by Badali et al.10 and
Bao and colleagues.28
In agreement with previous studies, two agents, that
is, anidulafungin and caspofungin demonstrated potent ac-
tivities against dermatophyte isolates. The MIC50 , MIC90 ,
and GM values reported in the study by Badali et al.10
were similar to the values reported in the present study.
Also, these values were notably lower than those reported
for other tested agents, with the exception of lulicona-
zole, terbinafine, and tolnaftate. As mentioned earlier, three
agents including luliconazole, caspofungin, and anidulafun-
gin showed the best activities against dermatophyte iso-
lates; terbinafine and tolnaftate also showed similar effects.
Luliconazole, which is an optically related compound of
lanoconazole, is an imidazole antifungal agent, recently ap-
proved by the US Food and Drug Administration (FDA)
for the treatment of some types of dermatophytosis.14 The
MIC90 values of luliconazole against Trichophyton species
in studies by Wiederhold et al.22 and Koga et al.29 (0.0005
and 0.002 g/ml, respectively) were lower than the present
study (0.018 g/ml). Interestingly, MIC50 of luliconazole
against all the dermatophyte isolates in our study was simi-
lar to MIC50 values of two agents, that is, lanoconazole and
anidulafungin. In summary, the current study demonstrated
that luliconazole and lanoconazole were active against all
dermatophyte isolates; however, luliconazole was more po-
tent than lanoconazole. Also, other used antifungal agents
displayed excellent activities, although the majority of der-
matophyte isolates exhibited low susceptibility to griseoful-
vin and very low susceptibility to miconazole and flucona-
zole.
Acknowledgements
This study was financially supported by grant number 997, with eth-
ical code IR.MAZUMS.REC.93-997 from Invasive Fungi Research
Center (IFRC), Faculty of Medicine, Mazandaran University of Med-
ical Sciences, Sari, Iran.
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Medical Mycology, 2016, Vol. 54, No. 7
Declaration of Interest
The authors report no conflicts of interest. The authors alone are
responsible for the content and the writing of the paper.
References
1. Gupta AK, Cooper EA. Update in antifungal ther-
apy of dermatophytosis. Mycopathologia 2008; 166:
353367.
2. Abastabar M, Mirhendi H, Rezaei-Matehkolaei A et al. Re-
striction analysis of -tubulin gene for differentiation of the
common pathogenic dermatophytes. J Clin Lab Anal 2014; 28:
9196.
3. Chimelli PAV, Sofiatti AdA, Nunes RS et al. Dermatophyte
agents in the city of Sao Paulo, from 1992 to 2002. Rev Inst
Med Trop Sao Paulo 2003; 45: 259263.
4. Osborne CS, Leitner I, Favre B et al. Amino acid substitution in
Trichophyton rubrum squalene epoxidase associated with resis-
tance to terbinafine. Antimicrob Agents Chemother 2005; 49:
28402844.
5. Succi IB, Bernardes-Engemann AR, Orofino-Costa R. Intermit-
tent therapy with terbinafine and nail abrasion for dermato-
phyte toe onychomycosis: a pilot study. Mycoses 2013; 56:
327332.
6. Nabili M, Shokohi T, Moazeni M et al. http://www.ncbi.
nlm.nih.gov/pubmed/27008655 High Prevalence of Clinical
and Environmental Triazole Resistant Aspergillus fumigatus
in Iran: Is It a Challenging Issue?. J Med Microbiol. doi:
10.1099/jmm.0.000255.
7. Martinez-Rossi NM, Peres NT, Rossi A. Antifungal resistance
mechanisms in dermatophytes. Mycopathologia 2008; 166:
369383.
8. Mukherjee PK, Leidich SD, Isham N et al. Clinical Trichophy-
ton rubrum strain exhibiting primary resistance to terbinafine.
Antimicrob Agents Chemother 2003; 47: 8286.
9. Adimi P, Hashemi SJ, Mahmoudi M et al. In vitro activity of
10 antifungal agents against 320 dermatophyte strains using
microdilution method in Tehran. Iran J Pharm Res 2013; 12:
537.
10. Badali H, Mohammadi R, Mashedi O et al. In vitro suscepti-
bility patterns of clinically important Trichophyton and Epider-
mophyton species against nine antifungal drugs. Mycoses 2015;
58: 303307.
11. Keyvan P, Leila B, Zahra R et al. In vitro activity of six antifungal
drugs against clinically important dermatophytes. Jundishapur J
Microbiol 2009; 2: 158163.
12. Perea S, Fothergill AW, Sutton DA et al. Comparison of
in vitro activities of voriconazole and five established anti-
fungal agents against different species of dermatophytes us-
ing a broth macrodilution method. J Clin Microbiol 2001; 39:
385388.
13. Santos D, Hamdan J. In vitro activities of four antifungal drugs
against Trichophyton rubrum isolates exhibiting resistance to
fluconazole. Mycoses 2007; 50: 286289.
14. Khanna D, Bharti S. Luliconazole for the treatment of fun-
gal infections: an evidence-based review. Core Evid 2014;
9: 113.
 Baghi et al.
15. Rezaei-Matehkolaei A, Makimura K, Shidfar MR et al. Use of
single-enzyme PCR-restriction digestion barcode targeting the
internal transcribed spacers (ITS rDNA) to identify dermato-
phyte species. Iranian J Publ Health 2012; 41: 8294.
16. Mohammadi R, Abastabar M, Mirhendi H et al. Use of restric-
tion fragment length polymorphism to rapidly identify dermato-
phyte species related to dermatophytosis. Jundishapur J Micro-
biol 2015; 8: e17296.
17. CLSI. Reference method for broth dilution antifungal suscepti-
bility testing of yeasts; approved standard3rd ed. CLSI doc-
ument M27-A3.Clinical and Laboratory Standards Institute,
Wayne, PA.
18. Abastabar M, Rezaei-Matehkolaei A, Shidfar MR et al. A molec-
ular epidemiological survey of clinically important dermato-
phytes in Iran based on specific RFLP profiles of Beta-tubulin
gene. Iran J Public Health 2013; 42: 10491057.
19. Fernandez-Torres B, Carrillo A, Martin E et al. In vitro activ-
ities of 10 antifungal drugs against 508 dermatophyte strains.
Antimicrob Agents Chemother 2001; 45: 25242528.
20. Irimie M, Tataru A, Oanta A et al. In vitro susceptibility of der-
matophytes isolated from patients with end-stage renal disease:
a casecontrol study. Mycoses 2014; 57: 129134.
21. Silva L, Oliveira D, Silva B et al. Identification and antifungal
susceptibility of fungi isolated from dermatomycoses. J Eur Acad
Dermatol Venereol 2014; 28: 633640.
22. Wiederhold NP, Fothergill AW, McCarthy DI et al. Luliconazole
demonstrates potent in vitro activity against dermatophytes re-
Downloaded from https://academic.oup.com/mmy/article-abstract/54/7/757/2222549/In-vitro-activity-of-new-azoles-luliconazole-and
by guest
on 03 October 2017
763
covered from patients with onychomycosis. Antimicrob Agents
Chemother 2014; 58: 35533555.
23. Chadeganipour M, Nilipour S, Havaei A. In vitro evaluation
of griseofulvin against clinical isolates of dermatophytes from
Isfahan. Mycoses 2004; 47: 503507.
24. Santos D, Hamdan J. In vitro antifungal oral drug and drug-
combination activity against onychomycosis causative dermato-
phytes. Med Mycol 2006; 44: 357362.
25. da Silva Barros ME, de Assis Santos D, Hamdan JS. Evaluation of
susceptibility of Trichophyton mentagrophytes and Trichophy-
ton rubrum clinical isolates to antifungal drugs using a modified
CLSI microdilution method (M38-A). J Med Microbiol 2007;
56: 514518.
26. Favre B, Hofbauer B, Hildering K-S et al. Comparison of in vitro
activities of 17 antifungal drugs against a panel of 20 dermato-
phytes by using a microdilution assay. J Clin Microbiol 2003;
41: 48174819.
27. Canton E, Peman J, Hervas D et al. Examination of the in vitro
fungicidal activity of echinocandins against Candida lusitaniae
by timekilling methods. J Antimicrob Chemother 2013; 68:
864868.
28. Bao Y-q, Wan Z, Li R-y. In vitro antifungal activity of micafun-
gin and caspofungin against dermatophytes isolated from China.
Mycopathologia 2013; 175: 141145.
29. Koga H, Nanjoh Y, Makimura K et al. In vitro antifungal activ-
ities of luliconazole, a new topical imidazole. Med Mycol 2009;
47: 640647.