Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
This review critically examined culture-independent research exploring the effects of antimicrobial and heavy metal usage on the antimicrobial resistance (AMR) profiles known as the resistome of pigs. Emphasizing metagenomics and quantitative PCR (qPCR) methodologies, the article systematically searched and evaluated studies published between January 2000 and February 2022 that investigated how antimicrobial use (AMU) and heavy metal use (HMU), such as zinc oxide and copper, influence the prevalence, diversity, and persistence of antimicrobial resistance genes (ARGs) in pig production systems. The review also explored links between ARGs, mobile genetic elements (MGEs), the microbiome, and the virome, and assessed how factors like farm management, biosecurity, animal age, and environmental influences contribute to the development and dissemination of AMR on pig farms.
Who was reviewed?
The review synthesized findings from 28 original research studies that utilized culture-independent techniques (metagenomics or qPCR) to examine the porcine resistome in response to antimicrobial and heavy metal interventions. These studies included both randomized controlled trials and observational research, predominantly conducted in high-income countries such as the United States, various European nations, China, and Canada. The reviewed studies encompassed diverse pig populations—from neonates to fattening pigs—across commercial, research, and farm settings, with sample types ranging from feces and manure to environmental and slurry samples. The studies varied in experimental design, antimicrobial and heavy metal exposures, and analytical methods, but consistently addressed the association between AMU/HMU and AMR in pig production.
Most important findings
| Critical Points | Details |
|---|---|
| Positive Association Between AMU/HMU and AMR | Most studies demonstrated that both antimicrobial and heavy metal use (notably zinc and copper) were positively associated with increased abundance and diversity of resistance genes in pigs. |
| Cross-Resistance and Co-selection | Genes conferring resistance often co-occurred with mobile genetic elements and metal resistance genes, suggesting that use of heavy metals can co-select for antimicrobial resistance, compounding risk. |
| Microbiome, Age, and Environmental Factors | The resistome was strongly influenced by microbiome composition, animal age, and environmental exposures—indicating that AMR is shaped by a complex interplay of intrinsic and extrinsic factors. |
| Persistence Despite Withdrawal | Withdrawal or reduction of antimicrobials and heavy metals did not always result in decreased AMR, likely due to stable ARGs, environmental persistence, and ongoing exposure from external sources. |
| Methodological Insights | Metagenomics and qPCR offered complementary strengths; however, lack of standardization across studies in methods, reporting, and sampling limited direct comparability and synthesis. |
| Transmission Mechanisms | ARGs were frequently associated with MGEs, enabling horizontal gene transfer. The virome (bacteriophages) also played a role in ARG mobility, although its significance remains underexplored. |
| Regulatory Implications | Bans on prophylactic use of antimicrobials and zinc oxide in the EU were supported by evidence of their impact on AMR, but highlighted the need for tailored, context-specific farm-level interventions. |
Key implications
For heavy metal certification programs, the review underscores that zinc and copper usage are directly linked to increased AMR in pigs due to cross-resistance and co-selection mechanisms. Standardizing resistome analysis and integrating culture-independent surveillance are essential for effective regulation and risk assessment. The persistence of ARGs after intervention highlights the need for comprehensive, multifactorial management strategies beyond withdrawal alone.
Citation
Ekhlas D, Argüello H, Leonard FC, Manzanilla EG, Burgess CM. Insights on the effects of antimicrobial and heavy metal usage on the antimicrobial resistance profiles of pigs based on culture-independent studies. Vet Res. 2023;54(14). doi:10.1186/s13567-023-01143-3
