Assessment of the Risk to Public Health due to Use of Antimicrobials in Pigs—An Example of Pleuromutilins in Denmark

Abstract

Antibiotic consumption in pigs can be optimized by developing treatment guidelines, which encourage veterinarians to use effective drugs with low probability of developing resistance of importance for human health. In Denmark, treatment guidelines for use in swine production are currently under review at the Danish Veterinary and Food Administration. Use of pleuromutilins in swine has previously been associated with a very low risk for human health. However, recent international data and sporadic findings of novel resistance genes suggest a change of risk. Consequently, a reassessment was undertaken inspired by a risk assessment framework developed by the European Medicines Agency. Livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (MRSA CC398) and enterococci were identified as relevant hazards. The release assessment showed that the probability of development of pleuromutilin resistance was high in MRSA CC398 (medium uncertainty) and low in enterococci (high uncertainty). A relatively small proportion of Danes has an occupational exposure to pigs, and foodborne transmission was only considered of relevance for enterococci, resulting in an altogether low exposure risk. The human consequences of infection with pleuromutilin-resistant MRSA CC398 or enterococci were assessed as low for the public in general but high for vulnerable groups such as hospitalized and immunocompromised persons. For MRSA CC398, the total risk was estimated as low (low uncertainty), among other due to the current guidelines on prevention of MRSA in place at Danish hospitals, which include screening of patients with daily contact to pigs on admittance. Moreover, MRSA CC398 has a medium human–human transmission potential. For enterococci, the total risk was estimated as low due to low prevalence of resistance, low probability of spread to humans, low virulence, but no screening of hospitalized patients, high ability of acquiring resistance genes, and a limited number of alternative antimicrobials (high uncertainty). This assessment reflects the current situation and should be repeated if pleuromutilin consumption increases substantially, resulting in increased prevalence of mobile, easily transmissible resistance mechanisms. Continuous monitoring of pleuromutilin resistance in selected human pathogens should therefore be considered. This also includes monitoring of linezolid resistance, since resistance mechanisms for pleuromutilins and oxazolidones are often coupled.

Veterinary Expert Opinion on Potential Drivers and Opportunities for Changing Antimicrobial Usage Practices in Livestock in Denmark, Portugal, and Switzerland

“…on production; (c) an antimicrobial consumption pattern in Portugal and Switzerland that could eventually mask the presence of these bacteria (e.g., use of pleuromutilins against swine dysentery will combat Lawsonia spp. too) ( 39 ); or (d) a higher occurrence of clinical cases of Lawsonia spp. in Denmark.…”

“…In another study, the implementation of treatment guidelines in Germany was followed by an increase in prudent AMU practices ( 59 ). In Denmark, treatment guidelines are in place for more than a decade, and in general the experience is that such guidelines help veterinarians to use the antimicrobials with highest effect on the infection and the lowest negative effect on resistance development ( 39 ).…”

Single Blinded Study on the Feasibility of Decontaminating LA-MRSA in Pig Compartments under Routine Conditions

“…In addition to the discussion about the role of antibiotics in animals, the level of risk for non-agriculturally associated persons ("normal" population) of consuming meat from such LA-MRSA-positive animal husbandry is discussed differently [10,11], as seen in an overview by [12].…”

Dose-dependent impact of oxytetracycline on the veal calf microbiome and resistome

“…Low doses of antibiotics can also be added to animal feed to promote growth, although this practice has been banned in the European Union since 2006 [1]. The use of antibiotics can lead to the selection of resistant strains in livestock, shedding in the food chain and posing a risk for food safety and human health [2]. Furthermore, resistant strains, along with residual antibiotics, antibiotic metabolites and antibiotic resistance genes, eventually can reach waters and soils [3].…”