November 20, 2018 Liz Borkowski, MPH 0Comment

The public health community is well aware of the dangers posed by antibiotic-resistant bacteria, but many of us are less attuned to the problem of fungi resistant to antifungal compounds. In an in-depth piece for The Atlantic, journalist and antimicrobial-resistance expert Maryn McKenna traces resistant fungal infections from tulip fields to cancer wards.

A decade ago, researchers in the Netherlands sounded the alarm about aspergillus fumigatus, a soil-dwelling organism that breaks down decaying plant matter and is so ubiquitous that we’re all inhaling its spores on a daily basis. In patients with compromised immune systems, spores can settle in the lungs and cause invasive aspergillosis infections. McKenna notes that this infection is diagnosed in up to 10% of immunocompromised patients, and used to be deadly until triazole drugs (fluconazole, voriconazole, etc.) came onto the market in the 1990s and 2000s. Now, aspergillosis is becoming deadly again, because more of the infections are resistant to triazoles. Although some resistance is due to patients having been treated previously with antifungal compounds, researchers have identified agricultural use of azoles as the chief culprit.

This is a familiar story to those who, like McKenna, have been following the problem of antibiotic-resistant bacteria associated with routine use of antibiotics in livestock. But resistance to antifungal compounds hasn’t received nearly as much attention, even though the implications are also alarming. McKenna writes:

The Dutch government recognized that antibiotics are scarce and precious; there are only 12 classes of antibiotics—formulas that share the same core molecule— and no new class has entered the market since the 1980s. Antifungal drugs are even more scarce than antibiotics: There are only three classes of antifungal drugs, including the azoles. Yet the fact that medicine and agriculture are using the same antifungals has never provoked the same official concern that agriculture’s use of antibiotics did.

Here’s one possible reason. While the bacteria that cause illness in humans—Salmonella, Campylobacter, E. coli, and the like—are also found in animals, aspergillus fumigatus doesn’t affect plants. When flower growers use azoles, they are aiming for other fungi. Aspergillus is an accidental bystander, economically insignificant, hanging out in soil and in foliage that flowers shed.

With recognition of the problem coming later than it should have, quick action is essential to preserve the utility of antifungal compounds. In Environmental Microbiology, Anuradha Chowdhary and Jacques F. Meis explain what’s needed:

The overuse of antifungals needs to be limited or reduced both in human‐ and veterinary medicine, and agriculture via antifungal stewardship programmes in hospitals, animal husbandry and agriculture. The problem of AMR [antimicrobial resistance] is widespread all over the world and can only be managed with concerted efforts between medical doctors, veterinarians, scientists and plant pathologists through global monitoring of antifungal drug consumption not only in both human and animal medicine but also in the environment.

A general recommendation would be to use the azole compounds wisely and antifungal stewardship could help to achieve this goal. Azole fungicides represent an important group of compounds used for the control of fungal crop disease and for the preservation of a diversity of materials such as wood and coatings. In addition the medical triazoles are an important class of medicines for the management of aspergillus diseases. The ultimate aim would be to preserve this drug class for both applications and to reduce the risk of induction of resistant A. fumigatus at the same time. Antifungal stewardship programs are being implemented in hospitals and could also be promoted for applications outside medicine. Using similar molecules in the environment and in medicine is the basis of the resistance problems observed in Aspergillus diseases. Substitution of these fungicides by other molecules might reduce the risk of cross resistance and reduce the burden of resistant Aspergillus infections.

The findings underline the importance of One Health approaches to tackling azole resistance, which state that the health of people is connected to the health of animals and the environment. Multidisciplinary and intersectorial collaborative efforts are needed to counter the spread of antifungal resistance.

As CDC explains, One Health is a collaborative, multi-sectoral, and trans-disciplinary approach that “recognizes that the health of people is connected to the health of animals and the environment.” Adopting it will help us tackle this kind of public health threat more effectively.

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