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Journal of Infectious Diseases and Medical Microbiology | Volume 3
J Infectious Disease Med Microbiol
| Volume 3
November 11-12, 2019 | Singapore
International Conference on
3
rd
International Conference on
Pathology and Infectious Diseases
Pathology and Oncology Research
Joint Event
&
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
•Around54.3%Indiansabovetheageof45yearsareonantacid
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.
• Theselectionpressure-inducedsecondaryresistanceresulting
fromoralitraconazoleisalsoseentoperpetuatepan-triazoleand
partialterbinafineandamorolfineresistance.Ciclopiroxolamine
is the only drug without a propensity to develop resistance.
• Itraconazole-resistant strains show high levels of cross-
resistance to multiple triazoles including voriconazole and
posaconazole, and often to six triazole fungicides used
extensivelyinagriculture,qualifyingformulti-triazoleresistance).
• 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 ismaintainedeven in the absenceof 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 IndianMinistry 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
invasivedermatophytosisinimmunocompromisedindividuals.
Practical Guidelines to contain & reverse the epidemic:
• Majority of patients with complicated tinea (recurrent/
relapsed/recalcitrant/chronic) who visit dermatologists have
already takenmultiple/prolonged courses of oral itraconazole,
rendering themresistant 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
Sidharth Sonthalia
SKINNOCENCE: The Skin Clinic and Research Centre, India
THE AZOLE MENACE: The dark side of azoles revealed