23
Nov
Fungal Resistance to Antimicrobial Pesticides Leads to Deadly Infection
(Beyond Pesticides, November 23, 2021) The U.S. Environmental Protection Agency (EPA) announced, in mid-October, a revision of its guidance on the evaluation of antimicrobial pesticides used against Candida auris (C. auris). This pathogen is a type of fungus (a yeast) that can cause serious infection, and can spread readily among patients and staff in hospitals and other congregate healthcare settings (such as nursing homes). C. auris has developed resistance to what used to be the therapeutic impacts of major antifungal medications. (Resistance is a major and growing problem in healthcare and in agriculture, with the latter exacerbating the former.) Another moving part in this unholy development of “chemical compounds no longer working” is EPA’s failure to assess the efficacy of any pesticides that are not used for public health purposes; for example, EPA evaluates the efficacy of only those antimicrobial compounds whose use patterns classify them as human-health-related. This failure to evaluate efficacy of all other pesticide products leaves many people in the dark about whether what they may be using actually works — never mind the potential risks associated with that use.
The antifungal medications that have been used for many years to treat Candida infections often no longer work for C. auris; some infections have shown resistance to all three types of antifungals available as treatments. Beyond Pesticides wrote, in 2019: “Echoing the development of resistance in bacteria, there have lately been resistant fungi showing up in hospitals and labs, adding to the already considerable worry in the medical community about how to treat people who contract infections caused by resistant pathogens. Matthew Fisher, Ph.D, a professor of fungal epidemiology at Imperial College London, has said, ‘It’s an enormous problem. We depend on being able to treat those patients with antifungals.’ Fungi, just like other organisms, adaptively exploit genetic mutations to defend against what would kill them — in this case, antifungal medications.”
The new guidance from EPA on C. auris offers recommendations for laboratory methods on producing and storing cultures of the drug-resistant pathogen, and evaluating the effectiveness of antimicrobial products intended to treat surfaces contaminated with it. To be clear, it is not all isolates (strains) of C. auris that have developed drug resistance — yet. Back in 2017, in consultation with The Centers for Disease Control and Prevention (CDC), EPA issued interim guidance for evaluating the efficacy of disinfectants used in hospitals against C. auris. Later on, lab data were generated (based on CDC’s tracking of clinical cases of multi–drug resistant C. auris isolates in the U.S.) as a basis for comparing the relative resistance of various isolates of C. auris to antimicrobial disinfectants.
The updated EPA guidance directs that manufacturers of any new products seeking registration should test for efficacy using a more-relevant strain of C. auris. Beyond Pesticides notes again the serious flaw in EPA’s practice: the agency leaves to the chemical industry the responsibility for testing its products for safety (and in this case, efficacy), and submitting related data as part of the registration application process. EPA’s Office of Pesticide Programs relies on industry-generated data to register and regulate pesticide products whose uses result in widespread public exposure.
Candida auris can be deadly; indeed, more than one in three patients with a serious C. auris infection of the blood, heart, or brain die from it, and nearly half of those who contract the infection die within 90 days. Immunocompromised people and infants are at high risk of lethality from these infections. C. auris is difficult to eradicate in patient surrounds, so healthcare settings are understandably concerned not only about the increasing inefficacy of antifungal medications, but also, about how to control the spread of C. auris once it has appeared in a patient and facility.
As recent research has noted, “Unfortunately, there are very few data available on the effectiveness of disinfectants against C. auris. Chlorine-based products appear to be the most effective for environmental surface disinfection. Other disinfectants, although less effective than chlorine-based products, may have a role as adjunctive disinfectants. A cleaning protocol will also need to be established as the use of disinfectants alone may not be sufficient for maximal decontamination of patient care areas. Furthermore, there are fewer data on the effectiveness of antiseptics against C. auris for patient decolonization and hand hygiene for healthcare personnel.”
As Beyond Pesticides wrote in its coverage of this growing problem, “One of the factors making this fungus so deadly is that it has developed resistance to existing antifungal medicines, with 90% of infections resistant to one drug, and 30% to two or more. As is true for resistant bacteria, culprits in C. auris’s development of resistance may be the overuse of antifungal medications in healthcare and overreliance on fungicides in agriculture.” The CDC calls C. auris “an emerging fungal pathogen,” with the incidence of infection having increased rapidly across many countries since it was first recognized in 2009 in Japan.
Beyond Pesticides has previously called attention to the role of EPA in the issue of inefficacy of pesticide compounds (which include fungicides, antimicrobials, insecticides, herbicides, rodenticides, parasiticides, and others). The agency has a decades-long poor track record on this front. Back in 1990, the EPA Office of the GAO (U.S. Government Accountability Office) issued recommendations, based on its review of EPA’s regulation of disinfectants, in a document titled “Disinfectants: EPA Lacks Assurance They Work.” Since then, EPA has begun to evaluate — sometimes — the efficacy of disinfectants and antimicrobial compounds through its Antimicrobial Performance Evaluation Program. Yet, even here, the scope of its review is narrow because EPA classifies disinfectants into three categories — hospital disinfectants, broad-spectrum (general) disinfectants, and limited disinfectants — and requires only that hospital disinfectants must have demonstrated efficacy against only two qualifying bacteria — Pseudomonas aeruginosa and Staphylococcus aureus.
As for all the other pesticide compounds in use in a variety of settings, EPA essentially neither requests nor requires efficacy data in its registration of any that are used for non–public health purposes. (In addition, although required by law to weigh pesticide risks and benefits, EPA rarely has the data to make that determination). Thus, for nearly all pesticides used in agriculture, around homes and buildings, and on landscapes, decisions about whether a compound even works on the target pest or pathogen — and therefore, whether the risks inherent in its use can be deemed “worth it” — are left to consumers, farmers, and healthcare organizations to figure out. This is, obviously, a problem.
EPA’s position on this is that the marketplace (somehow) determines efficacy. Given that most healthcare professionals, farmers, and consumers do not have at hand the information with which to make such a decision, nor the ability to do laboratory efficacy evaluations, they are left to make decisions without benefit of full information about a pesticide product. This is especially nonsensical because resistance to pesticides builds over relatively short periods of time, meaning that without benefit of accurate, independent evaluation of efficacy, people are applying toxic compounds that may not even “work.”
Farmers may discover product inefficacy when they see infestations of weeds or insects among their crops — because the pests are no longer controlled by the herbicides or insecticides the farm has been purchasing and using, often for some years. [This is the resistance issue about which Beyond Pesticides has written often — see here, here, and here.] If a conventionally operated, chemical-intensive farm enterprise, which is typically very dependent on pesticides for pest control, discovers after a crop loss that a pesticide did not work, the results can be economically devastating.
Further, EPA’s implicit contention that the marketplace can be the arbiter of efficacy is implausible, at best. How can “the marketplace” determine relative benefits (based on efficacy and risks) — and thus, guide farmers’ and consumers’ and health professionals’ decisions — when lack of efficacy is discovered after the fact? That is some serious “cart before the horse” logic.
This lack of information on efficacy can have dire consequences that could be avoided if EPA were to conduct efficacy reviews to determine whether pesticides work over time. In agriculture, in part because the agrichemical industry has successfully indoctrinated producers into the “chemical controls” approach, EPA’s failure to do such reviews often results, downstream, in farmers seeking (very often granted) “emergency exemptions” to use unregistered pesticides (which may be in the registration pipeline), or those that are intended for other purposes.
There is often a “throw whatever you have at it” attitude in these “emergency” situations — which Beyond Pesticides regards as the “chickens of chemical control coming inevitably home to roost.” Agrichemical industry response to the development of resistance has largely been to promote use of yet another pesticide or herbicide for the problem, or to “double down” with paired pesticide compounds, or to roll out yet another herbicide-plus-GE-seed combination to try to stave off the pest. (This has been particularly true in the case of developing resistance to glyphosate-based herbicides.) But this entropic “resistance and response” dynamic is a unidirectional progression along an increasingly poisonous and unsustainable path.
Fraught as it is with negative impacts on human and environmental health, including the mounting resistance issues, chemically intensive agriculture should be understood as a sign of the ineffectiveness of conventional, chemical approaches to pest control. Adoption of organic agricultural practices can diminish the resistance problem, potentially helping to preserve important antibiotic and antifungal medicines for treatment of human infection. But EPA abdicates its responsibility “to protect human health and the environment” when it fails to address the issue of efficacy of pesticide products, causing downstream health, economic, and environmental harms. Beyond Pesticides recommends that EPA Administrator Michael Regan and officials in the Office of Pesticide Programs address this wide gap in agency function.
Sources: https://www.epa.gov/pesticides/epa-revises-guidance-ensure-effectiveness-antimicrobial-pesticides-against-candida-auris and https://www.jdsupra.com/legalnews/epa-announces-revisions-to-guidance-to-5506501/
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
