31. An estimation of total antimicrobial usage in humans and animals in Vietnam
Abstract: The accurate assessment of antimicrobial use (AMU) requires relating quantities of active ingredients (AAIs) with population denominators. These data can be used to prioritize potential sources of selective pressure for antimicrobial resistance and to establish reduction targets. Here, we estimated AMU in Vietnam (human population 93.4 M in 2015), and compared it with European Union (EU) data (population 511.5 M in 2014). We extrapolated AMU data on each key animal species and humans from different published sources to calculate overall AMU (in
tonnes) in Vietnam. We then compared these data with published statistics on AMU in the European Union (EU). A total of 3838 t of antimicrobials were used in Vietnam, of which 2751 (71.7%) corresponded to animal use, and the remainder (1086 t; 28.3%) to human AMU. This equates to 261.7 mg and 247.3 mg per kg of human and animal biomass, compared with 122.0 mg and 151.5 mg in the EU. The greatest quantities of antimicrobials (in decreasing order) were used in pigs (41.7% of total use), humans (28.3%), aquaculture (21.9%) and chickens (4.8%). Combined
AMU in other species accounted for < 1.5%. These results are approximate and highlight the need to conduct targeted surveys to improve country-level estimates of AMU.
32. Carriage of the zoonotic organism Streptococcus suis in chicken flocks in Vietnam
Streptococcus suis infections are an emerging zoonotic agent causing severe disease in humans and a major pig pathogen worldwide. We investigated the colonization of S. suis in healthy chickens in different flocks (n = 59) as well as in‐contact pigs in farms with S. suis‐positive chickens (n = 44) in the Mekong Delta of Vietnam. Streptococcus suis was isolated from 20 (33.9%) chicken flocks and from all pigs investigated. Chicken isolates formed a distinct genotypic cluster compared with pig and human strains, although two chicken isolates (10%) clustered with pig isolates. Chicken isolates had unusually high levels of resistance against tetracycline (100%), clindamycin (100%) and erythromycin (95%); and intermediate resistance against penicillin (35%) and ceftriaxone (15%). Our findings suggest that chickens may potentially represent a source of S. suis infection to in‐contact humans and pigs.
33. Characterizing Antimicrobial Resistance in Chicken Pathogens: A Step towards Improved Antimicrobial Stewardship in Poultry Production in Vietnam
In the Mekong Delta of Vietnam, farmers use large quantities of antimicrobials to raise small-scale chicken flocks, often including active ingredients regarded of “critical importance’” by the World Health Organization. Due to limitations in laboratory capacity, the choice of antimicrobials normally does not follow any empirical criteria of effectiveness. The aim of this study was to highlight non-critically important antimicrobials against which chicken pathogens are likely to be susceptible as a basis for treatment guidelines. Microtiter broth dilution method was performed to determine the minimal inhibitory concentration (MIC) of 12 commonly used antimicrobials for 58 isolates, including Ornithobacterium rhinotracheale (ORT) (n = 22), Gallibacterium anatis (n = 19), and Avibacterium endocarditidis (n = 17). Unfortunately, internationally accepted breakpoints for resistance in these organisms do not exist. We drew tentative epidemiological cut-offs (TECOFFs) for those antimicrobial-pathogen combinations where MIC distributions suggested the presence of a distinct non-wild-type population. Based on the observed results, doxycycline would be the drug of choice for A.endocarditidis (11.8% presumptive non-wild type) and G. anatis infections (5.3% presumptive non-wild type). A total of 13.6% ORT isolates were non-wild type with regards to oxytetracycline, making it the drug of choice against this pathogen. This study illustrates the challenges in interpreting susceptibility testing results and the need to establish internationally accepted breakpoints for veterinary pathogens. The full article can be accessed here: Download
34. The role of animals as a source of antimicrobial resistant nontyphoidal Salmonella causing invasive and non-invasive human disease in Vietnam
Nontyphoidal Salmonella (NTS) are associated with both diarrhea and bacteremia. Antimicrobial resistance (AMR) is common in NTS in low-middle income countries, but the major source(s) of AMR NTS in humans are not known. Here, we aimed to assess the role of animals as a source of AMR in human NTS infections in Vietnam. We retrospectively combined and analyzed 672 NTS human and animal isolates from four studies in southern Vietnam and compared serovars, sequence types (ST), and AMR profiles. We generated a population structure of circulating organisms and aimed to attribute sources of AMR in NTS causing invasive and noninvasive disease in humans using Bayesian multinomial mixture models.
Among 672 NTS isolates, 148 (22%) originated from human blood, 211 (31%) from human stool, and 313 (47%) from animal stool. The distribution of serovars, STs, and AMR profiles differed among sources; serovars Enteritidis, Typhimurium, and Weltevreden were the most common in human blood, human stool, and animals, respectively. We identified an association between the source of NTS and AMR profile; the majority of AMR isolates were isolated from human blood (p < 0.001). Modelling by ST-AMR profile found chickens and pigs were likely the major sources of AMR NTS in human blood and stool, respectively; but unsampled sources were found to be a major contributor.
Antimicrobial use in food animals is hypothesized to play role in the emergence of AMR in human pathogens. Our cross-sectional population-based approach suggests a significant overlap between AMR in NTS in animals and humans, but animal NTS does explain the full extent of AMR in human NTS infections in Vietnam.
35. Reducing Antimicrobial Usage in Small-Scale Chicken Farms in Vietnam: A 3-Year Intervention Study
Indiscriminate antimicrobial use (AMU) in animal production is a driver of antimicrobial resistance globally. There is a need to define sustainable interventions to reduce AMU in small-scale production systems, which currently represent the most widespread farming systems in South East Asia and many low- and middle-income countries. We conducted a before-and-after intervention study on a random sample of small-scale chicken farms in the Mekong Delta of Vietnam from 2016 to 2019. The study included a baseline followed by an intervention phase where farmers were provided with regular veterinary advice on flock health and husbandry, as well as antimicrobial replacement products. Of 102 recruited farms (raising >100 chickens per flock cycle), thirty-five (34.2%) entered the intervention phase, whilst the rest stopped raising chickens, mainly due to suboptimal flock performance. Through the implementation of our intervention, chicken flocks reduced levels of AMU by 66% [adjusted hazard ratio (HR) = 0.34; p = 0.002) from a baseline of 343.4 Animal Daily Doses per 1,000 chicken-days and decreased weekly mortality by 40% (adjusted HR = 0.60; p = 0.005) from a baseline mortality of 1.60 per 100 birds. Chicken bodyweight increased by 100 g (p = 0.002) in intervention flocks. Our findings demonstrate that the provision of veterinary advice can achieve substantial reductions in AMU in small-scale production systems without compromising flock health and productivity.
36. Antimicrobial use through consumption of medicated feeds in chicken flocks in the Mekong Delta of Vietnam: A three-year study before a ban on antimicrobial growth promoters
Antimicrobials are included in commercial animal feed rations in many low- and middle-income countries (LMICs). We measured antimicrobial use (AMU) in commercial feed products consumed by 338 small-scale chicken flocks in the Mekong Delta of Vietnam, before a gradual nationwide ban on prophylactic use of antimicrobials (including in commercial feeds) to be introduced in the country over the coming five years. We inspected the labels of commercial feeds and calculated amounts of antimicrobial active ingredients (AAIs) given to flocks. We framed these results in the context of overall AMU in chicken production, and highlighted those products that did not comply with Government regulations. Thirty-five of 99 (35.3%) different antimicrobial-containing feed products included at least one AAI. Eight different AAIs (avilamycin, bacitracin, chlortetracycline, colistin, enramycin, flavomycin, oxytetracycline, virginamycin) belonging to five classes were identified. Brooding feeds contained antimicrobials the most (60.0%), followed by grower (40.9%) and finisher feeds (20.0%). Quantitatively, chlortetracycline was consumed most (42.2 mg/kg SEM ±0.34; 50.0% of total use), followed by enramycin (18.4 mg/kg SEM ±0.03, 21.8%), bacitracin (16.4 mg/kg SEM ±0.20, 19.4%) and colistin (6.40 mg/kg SEM ± 4.21;7.6%). Other antimicrobials consumed were virgianamycin, avilamycin, flavomycin and oxytetracycline (each ≤0.50 mg/kg). Antimicrobials in commercial feeds were more commonly given to flocks in the earlier part of the production cycle. A total of 10 (9.3%) products were not compliant with existing Vietnamese regulation (06/2016/TT-BNNPTNT) either because they included a non-authorised AAI (4), had AAIs over the permitted limits (4), or both (2). A number of commercial feed formulations examined included colistin (polymyxin E), a critically important antimicrobial of highest priority for human medicine. These results illustrate the challenges for effective implementation and enforcement of restrictions of antimicrobials in commercial feeds in LMICs. Results from this study should help encourage discussion about policies on medicated feeds in LMICs.
37. A novel method for measuring phenotypic colistin resistance in Escherichia coli populations from chicken flocks
Colistin is extensively used in animal production in many low- and middle-income countries. There is a need to develop methodologies to benchmark and monitor changes in resistance among mixed commensal bacterial populations in farms. We aimed to evaluate the performance of a broth microdilution method based on culturing a pooled Escherichia coli suspension (30-50 organisms) obtained from each sample. To confirm the biological basis and sensitivity of the method, we cultured 16 combinations of one colistin-susceptible and one mcr-1 encoded colistin-resistant E. coli in the presence of 2mg/L colistin. Optical density (OD600nm) readings over time were used to generate a growth curve, and these values were adjusted to the values obtained in the absence of colistin (adjusted Area Under the Curve, AUCadj). The median limit of detection was 1 resistant in 104 susceptible colonies [1st – 3rd quartile, 102:1 -105:1]. We applied this method to 108 pooled faecal samples from 36 chicken flocks from the Mekong Delta (Vietnam), and determined the correlation between this method and the prevalence of colistin resistance in individual colonies harvested from field samples, determined by the Minimum Inhibitory Concentration. The overall prevalence of colistin resistance at sample and isolate level (estimated from the AUCadj) was 38.9% [95%CI, 29.8-48.8%] and 19.4% (SD± 26.3%), respectively. Increased colistin resistance was associated with recent (2 weeks) use of colistin (OR=3.67) and other, non-colistin antimicrobials (OR=1.84). Our method is a sensitive and affordable approach to monitor changes in colistin resistance in E. coli populations from faecal samples over time.IMPORTANCE Colistin (polymyxin E) is an antimicrobial with poor solubility in agar-based media, and therefore broth microdilution is the only available method for phenotypic resistance. However, estimating colistin resistance in mixed Escherichia coli populations is laborious since it requires individual colony isolation, identification and susceptibility testing. We developed a growth-based microdilution method suitable for pooled faecal samples. We validated the method by comparing it with individual MIC of 909 E. coli isolates; we then tested 108 pooled faecal samples from 36 healthy chicken flocks collected over their production cycle. A higher level of resistance was seen in flocks recently treated with colistin in water, although the observed generated resistance was short-lived. Our method is affordable, and may potentially be integrated into surveillance systems aiming at estimating the prevalence of resistance at colony level in flocks/herds. Furthermore, it may also be adapted to other complex biological systems, such as farms and abattoirs.
38. Differential antimicrobial susceptibility profiles between symptomatic and asymptomatic non-typhoidal Salmonella infections in Vietnamese children
Non-typhoidal Salmonella (NTS) serovars, sequences types and antimicrobial susceptibility profiles have specific associations with animal and human infections in Vietnam. Antimicrobial resistance may have an effect on the manifestation of human NTS infections, with isolates from asymptomatic individuals being more susceptible to antimicrobials than those associated with animals and human diarrhoea.
39. Effects of prophylactic and therapeutic antimicrobial uses in small‐scale chicken flocks
Antimicrobials are extensively used both prophylactically and therapeutically in poultry production. Despite this, there are little data on the effect of antimicrobial use (AMU) on disease incidence rate and per cent mortality. We investigated the relationships between AMU and disease and between AMU and mortality using data from a large (n = 322 flocks) cohort of small‐scale chicken flocks in the Mekong Delta, Vietnam, that were followed longitudinally from day old to slaughter (5,566 observation weeks). We developed a parameterized algorithm to emulate a randomized control trial from observational data by categorizing the observation weeks into ‘non‐AMU’, ‘prophylactic AMU’ and ‘therapeutic AMU’. To evaluate the prophylactic AMU effect, we compared the frequencies of clinical signs in ‘non‐AMU’ and ‘prophylactic AMU’ periods. To analyse therapeutic AMU, we compared weekly per cent mortality between the weeks of disease episodes before and after AMU. Analyses were stratified by clinical signs (4) and antimicrobial classes (13). Prophylactic AMU never reduced the probability of disease, and some antimicrobial classes such as lincosamides, amphenicols and penicillins increased the risk. The risk of diarrhoea consistently increased with prophylactic AMU. Therapeutic AMU often had an effect on mortality, but the pattern was inconsistent across the combinations of antimicrobial classes and clinical signs with 14/29 decreasing and 11/29 increasing the per cent weekly mortality. Lincosamides, methenamines and cephalosporins were the only three antimicrobial classes that always decreased the mortality when used therapeutically. Results were robust respective to the parameters values of the weeks categorization algorithm. This information should help support policy efforts and interventions aiming at reducing AMU in animal production.