There are very few published data describing and quantifying consumption of AAIs (AGPs) in commercial feeds in poultry farming systems in low-and middle income countries (LMICs) (4). Our findings complement existing data on antimicrobials administered to chicken flocks (mainly through water) (~792 mg/kg) in the Mekong Delta region of Vietnam (24). Consumption of in-feed antimicrobials over the life of the flock (~85 mg/kg), therefore represents ~10% of total chicken AMU. These figures are consistent with previous estimates (77-95 mg/kg) (17, 18).
This study is based on data from a large cohort study aiming at reducing AMU in chicken production in the Mekong Delta of Vietnam (25). The study is representative since the selection of farms was random. Even though our data came from an intervention study, our advice to farmers was focused on reducing AMU as medicine (both prophylaxis and therapeutic), and did not include any advice on feed. We did not find any difference between flocks allocated to the intervention compared with the baseline phase (data not shown).
A major concern is the relatively high number of products that did not comply with Vietnamese regulations. Bacitracin, banned in feed rations in Vietnam since May 2016 (21), was the second most common AAI found. More worryingly, 6/35 (17%) antimicrobial-containing feeds included AAIs in concentrations above those permitted by the Vietnamese authorities. For example, the colistin concentration in all feed products examined was 3-5 times greater than that permitted by the Government. Non-authorised antimicrobials (avilamycin, flavomycin, oxytetracyline) were also found in some chicken feeds. This raises concerns regarding compliance of commercial feed mills with regulations, and casts doubts over the effective enforcement of the planned bans (23). An additional challenge is the ambiguous labelling with regards to AAI in about a third of the rations investigated.
Recent studies have reported a high prevalence of colistin resistance encoded by mcr-1 in chicken flocks in the area (18, 26). This antimicrobial, classified as highly critically important by WHO (27), was listed in 5% feeds examined (brooder feeds) and it was estimated that on average, flocks consumed 5mg/kg (about 3% of total in feed AMU). This is a modest amount compared with the reported magnitude of AMU through water administration (42mg/kg). However it is of concern that in our study cohort farms tended to use these feeds towards the end of the production cycle with high drug concentration. This resulted in long elimination profile of antimicrobials, therefore posing a risk of residues in poultry meat (28).
Quantitatively, chlortetracycline, bacitracin and enramycin were the AAIs most consumed through commercial feeds. These results are not dissimilar to previous extrapolations from a retail survey (17). Tetracyclines were also the most consumed antimicrobial consumed by flocks through water (24). Tetracyclines is also the antimicrobial class against which resistance among Escherichia coli and non-typhoidal Salmonella strains in the Mekong Delta is highest (29, 30, 31, 32). Bacitracin use has been shown to promote resistance among Clostridium perfringens isolates from chickens (33-35). With regards to enramycin, there is little information on its impact on AMR. A Japanese study that investigated Enterococcus faecium isolates from chicken flocks found no evidence of resistance against enramycin (36), although the study presented no enramycin use data.
The inclusion of AGPs in animal feeds and its impact on human health have been the subject of intense debate since the ban of AGP in animal production in Europe (37, 38). A major concern prior to the ban on AGPs in Europe was the widespread inclusion of avoparcin (a glycopeptide) in animal feeds, which was identified as a source of vancomycin resistance among zoonotic Enterococcus faecium bacteria (39). In contrast, other studies have indicated that the use of enramycin and bacitracin as AGPs involves no risk to human health (40, 41). The association between AGPs in animal feeds and human health is beyond the scope of this study.
The finding that AAIs in feed were consumed in some of our study flocks during the latter weeks of the production cycle is of concern given the potential for residues in chicken meat. A recent survey showed that 8.4% of chicken meat samples in Vietnam contained antimicrobials residues, with tetracyclines being the most common residue detected (42).
Much of the debate on AMU in animals has often been framed around the issue AGPs. Unfortunately, accurate data on total amounts of AGPs consumed globally are lacking. In Great Britain, in 2001 (5 years before the 2006 EU ban), growth promoters represented only 11.6% of 371 tonnes of antimicrobial active ingredients used in animal production (43). We believe that AGPs still represent a considerable fraction of total AMU globally, although the quantities have been decreasing over recent years, since more and more countries have phased out their use. A recent OIE survey reports that AGPs were used in 23% countries surveyed in 2018, compared with 51% countries in 2012 (44, 45). A review of the data of the impact of AGP from 1950 to 2010 on farm productivity indicate that productivity gains due to AGP in feeds decreased over the years, suggesting that any potential positive effects are of greater magnitude in low-biosecurity production systems (46). Indeed, recent studies in industrial broiler production systems have identified that AGPs had an overall negative impact on flock productivity (47, 48). In the non-industrial chicken production systems included in this study, AGPs in feeds represented a small fraction of total AMU. It is conceivable that even if APGs resulted in marginal productivity gains, these would be offset by the high mortality rates due to disease observed in the area (49). However, data from Vietnam suggest that consumption of AGPs in pig production is of considerable greater magnitude than in chickens (17), and therefore the outcomes of AGPs reductions in this species are more uncertain.