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THE AZOLE MENACE: The dark side of azoles revealed
Joint Event on International Conference on Pathology and Infectious Diseases & 3rd International Conference on Pathology and Oncology Research
November 11-12, 2019 | Singapore
Sidharth Sonthalia
SKINNOCENCE: The Skin Clinic and Research Centre, India
Keynote : J Infectious Disease Med Microbiol
Abstract:
Background: The Epidemic of antifungal therapeutic
failures against superficial mycotic infections, especially
dermatophytosis is expanding at a rapid pace across South
Asia and beyond. Although the abuse of topical steroids,
inadequate dose/duration of therapy, and ignorance of
other important epidemiological and personal factors
are contributary, perhaps the strongest reason is the
AZOLE MENACE, relatively unknown and ill-understood
phenomenon. In this lecture, I shall dwell upon objectively
on how the indiscriminate use of azoles, in particular, oral
itraconazole is responsible for this regional epidemic that is
threatening to become a pandemic lest urgent rectification is
undertaken.
Unknown Facts Revealed: In this lecture some of the many
azole-related issues will be revealed with evidence-backed
data.
• Patients with tinea visiting a dermatologist are not naive,
rather polypharmacy-abused in more than 90% cases, having
received multiple antifungals especially oral itraconazole/
topical azoles.
• Oral itraconazole is often injudiciously prescribed by primary
care physicians in an inadequate dose/ duration or as multiple
intermittent/ prolonged courses.
The bioavailability/ serum levels of itraconazole are influenced
by at least 15+ inconsistent factors
• Around 54.3% Indians above the age of 45 years are on antacid
medications like PPI’s, resulting in reduced bioavailability of
itraconazole when co-administered. The effects of longer
acting PPI’s like esomeprazole may persist up to 4-5 days.
• Dependent on intake post meals and the effect of aerated
drinks.
• Serum levels affected by drug brand and pellet size.
• The sub-inhibitory concentrations of itraconazole achieved
in patient’s serum significantly increase the likelihood of
secondary azole resistance by selection pressure, since azoles
being fungistatic allow persistence of organisms.
• The selection pressure-induced secondary resistance resulting
from oral itraconazole is also seen to perpetuate pan-triazole and
partial terbinafine and amorolfine resistance. Ciclopirox olamine
is the only drug without a propensity to develop resistance.
• Itraconazole-resistant strains show high levels of crossresistance
to multiple triazoles including voriconazole and
posaconazole, and often to six triazole fungicides used
extensively in agriculture, qualifying for multi-triazole resistance).
• Azole-resistant fungi are more virulent because of the
differences in cell wall composition, increased filamentation
and adherence, and enhanced biofilm formation. Once
acquired, resistance is maintained even in the absence of drug.
• Primary azole resistance due to their widespread use as
agricultural fungicides, further adds to the azole menace.
This phenomenon, which started from the Netherlands and
rapidly engulfed majority of the European Union, has now
reached the shores of the Indian Ocean. As per the statistics
available from the website of Indian Ministry of Agriculture, in
the 4-year period from 2012 to 2016, there was an estimated
29.5% decrease and 34.2% increase in the consumption of
insecticides and fungicides respectively.
• The spreading azole resistance in superficial fungal infections
resulting in selection of a population of mutants that don’t
respond to any drug is likely to have graver ramifications in
invasive dermatophytosis in immunocompromised individuals.
Practical Guidelines to contain & reverse the epidemic:
• Majority of patients with complicated tinea (recurrent/
relapsed/recalcitrant/chronic) who visit dermatologists have
already taken multiple/prolonged courses of oral itraconazole,
rendering them resistant to any further course of itraconazole;
thus, they should not be given oral itraconazole.
• Resistance to terbinafine on the other hand, acquired
through a rare mechanism, is infrequent, shows restoration of susceptibility after drug removal and has not been reported to
confer cross-resistance to other antifungal agents.
• The dosing of oral TERBINAFINE should be as per body
weight, 6mg/kg/day and it should be given for a duration of 8
(minimum) to 12 weeks (preferred), taking into consideration
the dermatophytic involvement of vellus hair.
• For topical application, NO AZOLES should be used. Only
three anti-fungals seem fit for topical use in current scenario –
CICLOPIROX > TERBINAFINE > AMOROLFINE.
• Non-pharmaceutical means, such as low-dose UV-B therapy,
LLLT, apple cider vinegar and other herbal substances capable
of breaking the BIOFILM should be used as adjuvants.
Biography:
Sidharth Sonthalia is a Senior Consultant Dermatologist & Medical Director, SKINNOCENCE: The Skin Clinic & Research Center, Gurugram, India. He devotes his time equally to patients, active research (translational/clinical) and education of other Dermatologists and allied Specialists in novel and controversial subjects like Dermoscopy, Dermatopathology, Management of Resistant Fungal Infections, Psychodermatology PCOS etc., by organizing focused congresses and International Summits under the aegis of his initiative DermaSource India,. He has delivered more than 80 lectures as invited Guest Faculty at various International conferences organized by ASPCR, ICD, IPCC, CCD, WCD, WDC and DERMACONS. He is serving as the Founding Chair of the South Asian Alliance against Cutaneous Mycosis [SAARCUM], Secretary General of Asian Society of Pigment Cell research [ASPCR], Chief Founder & Secretary General of the Indian Society of Dermoscopy, Onychoscopy & Trichoscopy [ISODOT], He is a founding cochair of the Afro-Asian Dermoscopy Group [AADG].
E-mail: drsidharthsonthalia@gmail.com
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