Aspergillus

Resistance
Antimicrobial resistance
▪ It happens when germs like bacteria and fungi develop the ability to
defeat the drugs designed to kill them.
▪ Antimicrobial resistance is emerging in one type of Aspergillus called
Aspergillus fumigatus (A. fumigatus), a common mold in the
environment and the leading cause of invasive mold infections in
people.
▪ Azole resistant A. fumigatus is o the watch list, a category of bacteria
that have caused few resistant infections in the United States to date
but have the potential to rapidly spread.
Aspergillus fumigatus (A.fumigatus)
 It’s a filamentous fungus that can be found in a variety of
environments including soil, compost, and decaying plant material;
however, in immunocompromised individuals, it can caused a disease
called aspergillosis which is a life threatening infection
Azole
 Triazole are core structure of several drugs and pharmaceutical agents
because it has antimicrobial, antiparasitic, and anti-inflammatory
properties.
 Triazole antifungal drugs, commonly known as Azoles, are the primary
treatment for aspergillosis.
 Widely used treatment both in clinical and agricultural settings which
is the most effective treatment to A. fumigatus.
Emergence globally and within the United States
 At medical centers in some parts of the world, an estimated 19% of A. fumigatus
infections are resistant to Azole antifungals.
 In a large U.S study, antimicrobial resistance was identified in up to 7% of
Aspergillus specimens from patients
 Azole resistant A. fumigatus infections are difficult to treat, and these patients are
up to 33% more likely to die than patients with infections that can be treated with
azoles.
The true burden of azole resistant aspergillosis in the United States is unknown and
few factors make it difficult to estimate:
 Aspergillosis is one of the leading missed diagnoses in intensive care units.
 Until recently, clinicians have had limited access to antifungal susceptibility
testing.
• An antifungal susceptibility testing is a methods which able to detect antifungal
resistance and to determine the best treatment for a specific fungus.
Azole resistance develops in the body and in the
environment
There are two ways that A. fumigatus can develop resistance to azoles.
 Inside the Body
• Strains of A. Fumigatus in people who take azole antifungals for a long
period of time can become resistant, and continue to cause infection.
 Outside the body
• Strains of A. fumigatus on decaying plants in the environment can be
exposed to azole compounds used as fungicides that are chemically
similar to azole antifungal medications. These strains develop
resistance to azoles.
Azole fungicide use
 Azole fungicides are used throughout the world to treat plant
infections, prevent crop loss, and increase production.
 Patients with azole resistant aspergillosis have been infected with A.
fumigatus strains with the same resistance gene markers (TR34/L98H
and TR46/Y121F/T298A) as resistant strains found in the environment
associated with agricultural azole fungicide use.
 Resistant Aspergillus infections are also found in people who have not
taken azole antifungals, further suggesting that the resistance is
partially driven by environmental sources.
 There are presence of multiple fungicide resistance alleles in
agricultural and clinical isolates that suggest that the unique genetics
of pan azole resistant clade enables the evolution of or the
persistence of antimicrobial resistance mutations
Preventing azole resistance
 The any use of antifungals can contribute to the development of
antimicrobial resistance.
 Ensuring appropriate use of azoles in human medicine, agriculture,
and industry will be essential to curbing the spread of antimicrobial
resistance.
 The agricultural community, phytologists, and federal partners should
work together to consider alternative ways to protect and treat crops.
 Integrated pest management (IPM) ia one strategy that has been
recognized by the World Health Organization (WHO) and the Food
and Agriculture Organization (FAO) to successfully reduce the need for
pesticide use and improve food quality and crops yields.