Antibiotic use in human medicine, veterinary medicine, and agriculture has been linked to the rise of antibiotic resistance globally. We did a systematic review and meta-analysis to summarise the effect that interventions to reduce antibiotic use in food-producing animals have on the presence of antibiotic-resistant bacteria in animals and in humans. On July 14, 2016, we searched electronic databases (Agricola, AGRIS, BIOSIS Previews, CAB Abstracts, MEDLINE, Embase, Global Index Medicus, ProQuest Dissertations, Science Citation Index) and the grey literature. The search was updated on Jan 27, 2017. Inclusion criteria were original studies that reported on interventions to reduce antibiotic use in food-producing animals and compared presence of antibiotic-resistant bacteria between intervention and comparator groups in animals or in human beings. We extracted data from included studies and did meta-analyses using random effects models. The main outcome assessed was the risk difference in the proportion of antibiotic-resistant bacteria. A total of 181 studies met inclusion criteria. Of these, 179 (99%) described antibiotic resistance outcomes in animals, and 81 (45%) of these studies were included in the meta-analysis. 21 studies described antibiotic resistance outcomes in humans, and 13 (62%) of these studies were included in the meta-analysis. The pooled absolute risk reduction of the prevalence of antibiotic resistance in animals with interventions that restricted antibiotic use commonly ranged between 10 and 15% (total range 0–39), depending on the antibiotic class, sample type, and bacteria under assessment. Similarly, in the human studies, the pooled prevalence of antibiotic resistance reported was 24% lower in the intervention groups compared with control groups, with a stronger association seen for humans with direct contact with food-producing animals. Interventions that restrict antibiotic use in food-producing animals are associated with a reduction in the presence of antibiotic-resistant bacteria in these animals. A smaller body of evidence suggests a similar association in the studied human populations, particularly those with direct exposure to food-producing animals. The implications for the general human population are less clear, given the low number of studies. The overall findings have directly informed the development of WHO guidelines on the use of antibiotics in food-producing animals. World Health Organization.

The prevalence of antimicrobial resistance (AMR) is increasing in human and animal pathogens, becoming a concern worldwide. However, prevalence and characteristics of AMR of bovine mastitis pathogens in large Chinese dairy herds are still unclear. Therefore, our objective was to determine the AMR profile of bacteria isolated from clinical mastitis in large (>500 cows) Chinese dairy herds. A total of 541 isolates of the 5 most common species, Staphylococcus aureus (n = 103), non-aureus staphylococci (NAS; n = 107), Streptococcus species (n = 101), Klebsiella species (n = 130), and Escherichia coli (n = 100), isolated from bovine clinical mastitis on 45 dairy farms located in 10 provinces of China were included. Presence of AMR was determined by minimum inhibitory concentrations using the microdilution method. Prevalence of multidrug resistance (resistance to >2 antimicrobials) was 27% (148/541). A very wide distribution of minimum inhibitory concentrations was screened in all isolates, including Staph. aureus isolates, which were resistant to penicillin (66%). In addition, NAS (30%) were more resistant than Staph. aureus to oxacillin (84%), penicillin (62%), tetracycline (34%), and clindamycin (33%). Prevalence of resistance to tetracycline was high (59%) in Streptococcus spp. Additionally, prevalence of resistance of both E. coli and Klebsiella spp. was high to amoxicillin/clavulanate potassium (81 and 38%, respectively), followed by tetracycline (only Klebsiella spp. 32%). A high proportion (27%) of isolates were multidrug resistant; the most frequent combinations were clindamycin-cefalexin-tetracycline or enrofloxacin-cefalexin-penicillin patterns for Staph. aureus; enrofloxacin-oxacillin-penicillin-tetracycline patterns for NAS; clindamycin-enrofloxacin-tetracycline patterns for Streptococcus spp.; amoxicillin/clavulanate potassium-ceftiofur-polymyxin B patterns for Klebsiella spp.; and amoxicillin/clavulanate potassium-ceftiofur-polymyxin B patterns for E. coli. Resistance for 4 kinds of antimicrobials highly critical for human medicine, including daptomycin, vancomycin, imipenem, and polymyxin B, ranged from 0 to 24%. In conclusion, prevalence of AMR in mastitis pathogens was high on large Chinese dairy farms, potentially jeopardizing both antimicrobial efficacy and public health. Results of this study highlighted the need for improvements in antimicrobial stewardship and infection control programs in large Chinese dairy farms to reduce emergence of AMR.

Non-aureus staphylococci (NAS), the microorganisms most frequently isolated from bovine milk worldwide, are a heterogeneous group of numerous species. To establish their importance as a group, the distribution of individual species needs to be determined. In the present study, NAS intramammary infection (IMI) was defined as a milk sample containing ≥1,000 cfu/mL in pure or mixed culture that was obtained from a cohort of cows assembled by the Canadian Bovine Mastitis Research Network. Overall, 6,213 (6.3%) of 98,233 quarter-milk samples from 5,149 cows and 20,305 udder quarters were associated with an NAS IMI. Of the 6,213 phenotypically identified NAS isolates, 5,509 (89%) were stored by the Canadian Bovine Mastitis Research Network Mastitis Pathogen Collection and characterized using partial sequencing of the rpoB housekeeping gene, confirming 5,434 isolates as NAS. Prevalence of each NAS species IMI was estimated using Bayesian models, with presence of a specific NAS species as the outcome. Overall quarter-level NAS IMI prevalence was 26%. The most prevalent species causing IMI were Staphylococcus chromogenes (13%), Staphylococcus simulans (4%), Staphylococcus haemolyticus (3%), Staphylococcus xylosus (2%), and Staphylococcus epidermidis (1%). The prevalence of NAS IMI as a group was highest in first-parity heifers and was evenly distributed throughout cows in parities ≥2. The IMI prevalence of some species such as S. chromogenes, S. simulans, and S. epidermidis differed among parities. Overall prevalence of NAS IMI was 35% at calving, decreased over the next 10 d, and then gradually increased until the end of lactation. The prevalence of S. chromogenes, Staphylococcus gallinarum, Staphylococcus cohnii, and Staphylococcus capitis was highest at calving, whereas the prevalence of S. chromogenes, S. haemolyticus, S. xylosus, and S. cohnii increased during lactation. Although the overall prevalence of NAS IMI was similar across barn types, the prevalence of S. simulans, S. xylosus, S. cohnii, Staphylococcus saprophyticus, S. capitis, and Staphylococcus arlettae IMI was higher in tiestall barns; the prevalence of S. epidermidis IMI was lowest; and the prevalence of S. chromogenes and Staphylococcus sciuri IMI was highest in bedded-pack barns. Staphylococcus simulans, S. epidermidis, S. xylosus, and S. cohnii IMI were more prevalent in herds with intermediate to high bulk milk somatic cell count (BMSCC) and S. haemolyticus IMI was more prevalent in herds with high BMSCC, whereas other common NAS species IMI were equally prevalent in all 3 BMSCC categories. Distribution of NAS species IMI differed among the 4 regions of Canada. In conclusion, distribution differed considerably among NAS species IMI; therefore, accurate identification (species level) is essential for studying NAS epidemiology.

The effect of non-aureus staphylococci (NAS) in bovine mammary health is controversial. Overall, NAS intramammary infections (IMI) increase somatic cell count (SCC), with an effect categorized as mild, mostly causing subclinical or mild to moderate clinical mastitis. However, based on recent studies, specific NAS may affect the udder more severely. Some of these apparent discrepancies could be attributed to the large number of species that compose the NAS group. The objectives of this study were to determine (1) the SCC of quarters infected by individual NAS species compared with NAS as a group, culture-negative, and major pathogen-infected quarters; (2) the distribution of NAS species isolated from quarters with low SCC (<200,000 cells/mL) and high SCC (≥200,000 cells/mL), and clinical mastitis; and (3) the prevalence of NAS species across quarters with low and high SCC. A total of 5,507 NAS isolates, 3,561 from low SCC quarters, 1,873 from high SCC quarters, and 73 from clinical mastitis cases, were obtained from the National Cohort of Dairy Farms of the Canadian Bovine Mastitis Research Network. Of quarters with low SCC, high SCC, or clinical mastitis, 7.6, 18.5, and 4.3% were NAS positive, respectively. The effect of NAS IMI on SCC was estimated using mixed-effect linear regression; prevalence of NAS IMI was estimated using Bayesian analyses. Mean SCC of NAS-positive quarters was 70,000 cells/mL, which was higher than culture-negative quarters (32,000 cells/mL) and lower than major pathogen-positive quarters (129,000 to 183,000 cells/mL). Compared with other NAS species, SCC was highest in quarters positive for Staphylococcus capitis, Staphylococcus gallinarum, Staphylococcus hyicus, Staphylococcus agnetis, or Staphylococcus simulans. In NAS-positive quarters, Staphylococcus xylosus (12.6%), Staphylococcus cohnii (3.1%), and Staphylococcus equorum (0.6%) were more frequently isolated from quarters with low SCC than other NAS species, whereas Staphylococcus sciuri (14%) was most frequently isolated from clinical mastitis cases. Finally, in NAS-positive quarters, Staphylococcus chromogenes, S. simulans, Staphylococcus epidermidis, and Staphylococcus haemolyticus were isolated with similar frequency from among low SCC and high SCC quarters and clinical mastitis cases. Staphylococcus chromogenes, S. simulans, S. xylosus, S. haemolyticus, S. epidermidis, S. agnetis, Staphylococcus arlettae, S. capitis, S. gallinarum, S. sciuri, and Staphylococcus warneri were more prevalent in high than in low SCC quarters. Because the NAS are a large, heterogeneous group, considering them as a single group rather than at the species, or even subspecies level, has undoubtedly contributed to apparent discrepancies among studies as to their distribution and importance in IMI and mastitis.

Treatment of clinical mastitis (CM) and use of antimicrobials for dry cow therapy are responsible for the majority of animal-defined daily doses of antimicrobial use (AMU) on dairy farms. However, advancements made in the last decade have enabled excluding nonsevere CM cases from antimicrobial treatment that have a high probability of cure without antimicrobials (no bacterial causes or gram-negative, excluding Klebsiella spp.) and cases with a low bacteriological cure rate (chronic cases). These advancements include availability of rapid diagnostic tests and improved udder health management practices, which reduced the incidence and infection pressure of contagious CM pathogens. This review informed an evidence-based protocol for selective CM treatment decisions based on a combination of rapid diagnostic test results, review of somatic cell count and CM records, and elucidated consequences in terms of udder health, AMU, and farm economics. Relatively fast identification of the causative agent is the most important factor in selective CM treatment protocols. Many reported studies did not indicate detrimental udder health consequences (e.g., reduced clinical or bacteriological cures, increased somatic cell count, increased culling rate, or increased recurrence of CM later in lactation) after initiating selective CM treatment protocols using on-farm testing. The magnitude of AMU reduction following a selective CM treatment protocol implementation depended on the causal pathogen distribution and protocol characteristics. Uptake of selective treatment of nonsevere CM cases differs across regions and is dependent on management systems and adoption of udder health programs. No economic losses or animal welfare issues are expected when adopting a selective versus blanket CM treatment protocol. Therefore, selective CM treatment of nonsevere cases can be a practical tool to aid AMU reduction on dairy farms.

The objective of this study was to isolate and identify the main staphylococcal species causing bovine mastitis in 10 Brazilian dairy herds and study their capability to produce enterotoxins. Herds were selected based on size and use of milking technology, and farms were visited once during the study. All mammary glands of all lactating cows were screened using the California Mastitis Test (CMT) and a strip cup. A single aseptic milk sample (20 mL) was collected from all CMT-positive quarters. Identification of Staphylococcus spp. was performed using conventional microbiology, and PCR was used to determine the presence of enterotoxin-encoding genes (sea, seb, sec, and sed). Of the 1,318 CMT-positive milk samples, Staphylococcus spp. were isolated from 263 (19.9%). Of these isolates, 135 (51%) were coagulase-positive staphylococci (CPS) and 128 (49%) were coagulase-negative staphylococci (CNS). Eighteen different species of CNS were isolated, among which S. warneri, S. epidermidis and S. hyicus were the most frequent. The distribution of Staphylococcus species was different among herds: S. epidermidis was found in 8 herds, S. warneri was found in 7 herds, and S. hyicus in 6 herds. Some of the CNS species (S. saprophyticus ssp. saprophyticus, S. auricularis, S. capitis, and S. chromogenes) were isolated in only one of the farms. Genes related to production of enterotoxins were found in 66% (n=85) of all CNS and in 35% of the CPS isolates. For both CNS and CPS isolates, the most frequently identified enterotoxin genes were sea, seb, and sec; the prevalence of sea differed between CPS (9.5%) and CNS (35.1%) isolates. Staphylococcus warneri isolates showed a greater percentage of sea than seb, sec, or sed, whereas S. hyicus isolates showed a greater percentage of sea than sec. Over 60% of CNS belonged to 3 major species, which carried 62.2 to 81.3% of the enterotoxin genes. The high prevalence highlights the potential for food poisoning caused by these species. For possible high-risk situations for food poisoning, such as milk produced with total bacterial counts greater than regulatory levels and stored under inappropriate temperatures, monitoring contamination with CNS could be important to protect human health. Because the prevalence of CNS intramammary infections in dairy herds is usually high, and these species can be found in great numbers in bulk milk, identification of risk factors for production of staphylococcal enterotoxins should be considered in future studies.