In a significant development, the World Health Organization (WHO) has unveiled its latest roster of medically significant antimicrobials. Rolled out on February 8, the WHO’s List of Medically Important Antimicrobials introduces fresh classifications based on their pivotal role in human healthcare, susceptibility to antimicrobial resistance (AMR), and the potential repercussions of their misuse in non-human sectors, notably in animal farming.
This compilation aims to guide policymakers and regulators in making risk-conscious decisions to mitigate any adverse effects of antimicrobial application in animals on AMR in humans. Additionally, the WHO seeks to foster antimicrobial stewardship among veterinary practitioners and prescribers, while furnishing direction for national AMR steering committees and producers in the food animal sector.
“The menace of AMR persists as a paramount global public health challenge, being linked to the demise of nearly 5 million individuals worldwide in 2019,” affirmed the WHO in a statement. “The WHO MIA List is geared toward optimizing the usage of antimicrobial medications in both human and animal health domains.”
Nevertheless, the WHO’s list has drawn criticism. Dr. Patricia Gaunt, leading the AVMA Committee on Antimicrobials, opined that a broader One Health approach to prudent antimicrobial utilization, encompassing human, animal, and environmental facets, is imperative. “The WHO committee should recognize the interdependence of human health with animals and the environment, emphasizing the judicious use of antimicrobials across all sectors,” she remarked.
Revamped Antimicrobial Classifications
Initiated in 2005, the WHO’s compendium of critically important antimicrobials, formerly known as the WHO Critically Important Antimicrobial List for Human Medicine, has undergone periodic revisions. The latest update introduces three novel categories—”authorized for use in humans only,” “medically significant,” and “not medically significant”—to offer a more exhaustive framework for evaluating all antimicrobial classes.
The “authorized for use in humans only” category encompasses anti-pseudomonal penicillins, carbapenems, and third-, fourth-, and fifth-generation cephalosporins with beta-lactamase inhibitors.
Figure 1 from page 4 of the WHO MIA list: “Prioritization of antimicrobial classes in the WHO MIA list”
All classes of antimicrobials employed in human and animal contexts are classified in accordance with their significance in human medicine within the World Health Organization’s List of Medically Important Antimicrobials. This classification hinges on an assessment of the risks to human health stemming from potential AMR development associated with their use in animals.
The “medically important antimicrobials” category is further segmented into “highest priority critically important antimicrobials (HPCIA),” “critically important antimicrobials (CIA),” “highly important antimicrobials,” and “important antimicrobials.” The categorization of antimicrobials in this group is predicated on the WHO Model List of Essential Medicines and its Access, Watch, and Reserve (AWaRe) classification system.
Two primary criteria employed in categorizing a drug within the first two medically important antimicrobial categories revolve around whether the antimicrobial class constitutes the sole or one of the few available therapies for treating severe bacterial infections in humans, and whether it’s utilized to combat infections caused by bacteria potentially transmitted from non-human sources or harboring resistance genes from such sources.
Classes such as third- and fourth-generation cephalosporins, quinolones, and polymyxins are among those classified as HPCIA, while the CIA category includes aminoglycosides and macrolides.
Another noteworthy addition is the “authorized for use in animals only” category, encompassing antimicrobials where substantial evidence suggesting their usage could lead to resistance against medically significant antimicrobials is lacking.
Antimicrobial classes authorized solely for topical application were excluded unless they are frequently utilized in combating multidrug-resistant pathogens in humans.
This compilation was formulated in collaboration with the Food and Agriculture Organization (FAO), the United Nations Environment Programme (UNEP), and the World Organisation for Animal Health (WOAH, formerly known as the OIE), reflecting a joint endeavor to standardize and align related guidelines and lists crafted by these four entities.
Further efforts are underway to harmonize directives on the prudent use of antimicrobials across all four organizations (FAO, UNEP, WHO, and WOAH), alongside the WHO antimicrobial list and the WOAH roster of veterinary antimicrobial agents.
Implications for Veterinary Medicine
While the WHO professes support for antimicrobial utilization in animal health, certain recommendations in the list suggest otherwise, as per Dr. Gaunt, an associate professor specializing in aquatic animal health at Mississippi State University College of Veterinary Medicine.
For instance, the WHO list discourages the deployment of novel antibiotics in animal health, stipulating: “Any new antimicrobial class that is authorized only in humans will automatically be placed in the authorized for use in humans only category.” Dr. Gaunt highlights that if the Food and Drug Administration (FDA) were to endorse this recommendation, the development of new drugs for treating animal ailments could be dissuaded.
The restriction on access to novel antimicrobials in veterinary practice might engender recurrent utilization of existing ones, fostering the proliferation of resistant bacteria, contrary to the principles of judicious use, Dr. Gaunt elaborates. Furthermore, as scientific knowledge evolves, novel antimicrobials could furnish additional avenues for prevention, control, and treatment.
“However, under the WHO list, veterinarians would be deprived of these tools for use in food animals if regulatory agencies embrace this stance,” she asserts.
Dr. Gaunt also critiques the absence of definitions for terms such as “off-label” or “extralabel use” in the list.
“Do these terms exclusively encompass certain classes of medically important antimicrobials like the critically important ones? Are they applicable to unapproved applications of antimicrobials already sanctioned for use in a particular animal species?” she queries.
Another lingering concern pertains to whether the list might impinge upon a U.S. veterinarian’s ability to utilize antimicrobials under the Animal Medicinal Drug Use Clarification Act or Compliance Policy Guide 615.115 (Extralabel Use of Medicated Feeds for Minor Species), which permits veterinarians to employ a veterinary feed directive containing an approved antimicrobial in an extralabel manner in minor species.
Although nonbinding, the WHO’s list serves as a pivotal point of reference for policymakers and regulators in dictating antimicrobial usage.
“The regulation of antimicrobial utilization ought to adopt a risk- and science-based approach, a principle not evidently discernible in this document,” Dr. Gaunt concludes. “While this list may wield more influence in Europe, it could potentially sway U.S. regulatory bodies in their antimicrobial rankings, potentially curtailing veterinarians’ access to certain antimicrobials.”
