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Background Antimicrobial use in food-producing animals selects for antimicrobial resistance that can be transmitted to humans via food or other transmission routes. The World Health Organization (WHO) in 2005 ranked the medical importance of antimicrobials used in humans. In late 2017, to preserve the effectiveness of medically important antimicrobials for humans, WHO released guidelines on use of antimicrobials in food-producing animals that incorporated the latest WHO rankings. Methods WHO commissioned systematic reviews and literature reviews, and convened a Guideline Development Group (GDG) of external experts free of unacceptable conflicts-of-interest. The GDG assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and formulated recommendations using a structured evidence-to-decision approach that considered the balance of benefits and harms, feasibility, resource implications, and impact on equity. The resulting guidelines were peer-reviewed by an independent External Review Group and approved by the WHO Guidelines Review Committee. Results These guidelines recommend reductions in the overall use of medically important antimicrobials in food-producing animals, including complete restriction of use of antimicrobials for growth promotion and for disease prevention (i.e., in healthy animals considered at risk of infection). These guidelines also recommend that antimicrobials identified as critically important for humans not be used in food-producing animals for treatment or disease control unless susceptibility testing demonstrates the drug to be the only treatment option. Conclusions To preserve the effectiveness of medically important antimicrobials, veterinarians, farmers, regulatory agencies, and all other stakeholders are urged to adopt these recommendations and work towards implementation of these guidelines.

From 1 January to 31 December 2013, around Australia 26 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2013 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, (with particular emphasis on susceptibility to methicillin) and to characterise the molecular epidemiology of the isolates. Overall 19.1% of the 2,010 SAB episodes were methicillin resistant, which is significantly higher than that reported in most European countries. Although the SAB 30-day all cause mortality appears to be decreasing in Australia, methicillin-resistant SAB associated mortality remains high (20.1%) and was significantly higher than methicillin-sensitive SAB associated mortality (13%) (P0.0001). With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin sensitive S. aureus remains rare. However, in addition to the ß-lactams, approximately 50% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 20% were resistant to co-trimoxazole, tetracycline and gentamicin. Linezolid, daptomycin and teicoplanin resistance was detected in a small number of S. aureus isolates. Resistance to vancomycin was not detected. Resistance was largely attributable to 2 healthcare associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has now become the predominant healthcare associated clone in Australia. Approximately 60% of methicillin-resistant SAB were due to community associated clones. Although polyclonal, almost 50% of community associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C25] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. As CA-MRSA is well established in the Australian community, it is important antimicrobial resistance patterns in community and healthcare associated SAB is monitored as this information will guide therapeutic practices in treating S. aureus sepsis.

In 2012, the Australian Group on Antimicrobial Resistance (AGAR) conducted a community-onset period-prevalence survey of clinical Staphylococcus aureus isolated from hospital outpatients and general practice patients including nursing homes, long term care facilities and hospice patients. Day surgery and dialysis patients were excluded. Twenty-nine medical microbiology laboratories from all state and mainland territories participated. Isolates were tested by Vitek2® (AST-P612 card). Results were compared with previous AGAR community surveys. Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) increased significantly from 11.5% in 2000 to 17.9% in 2012 (P0.0001). Resistance to the non-ß-lactam antimicrobials varied between regions. No resistance was detected to vancomycin, teicoplanin or linezolid. Resistance in methicillin susceptible S. aureus was rare apart from erythromycin (12.8%) and was absent for vancomycin, teicoplanin, linezolid and daptomycin. The proportion of S. aureus characterised as health care-associated MRSA (HA-MRSA) was 5.1%. Three HA-MRSA clones were characterised, with 72.9% and 26.4% of HA-MRSA classified as ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA) respectively. Multi-clonal community-associated MRSA (CA-MRSA) accounted for 12.5% of all S. aureus. Regional variation in resistance in MRSA was primarily due to the differential distribution of the 2 major HA-MRSA clones; ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials, and ST22-IV [2B] (EMRSA-15), which is resistant to ciprofloxacin and typically erythromycin. Although the majority of CA-MRSA were non-multi-resistant, a significant expansion of Panton-Valentine leukocidin (PVL) positive CA-MRSA clones has occurred nationally. The mean age of patients (31.7 years, 95% CI 28.9-34.5) with a PVL positive CA-MRSA infection was significantly lower (P0.0001), than the mean age of patients with a PVL negative CA-MRSA infection (55.7 years, 95% CI 50.7-60.6). This shift in the molecular epidemiology of MRSA clones in the Australian community will potentially increase the number of young Australians with skin and soft tissue infections requiring hospitalisation.

In 2011, the Australian Group on Antimicrobial Resistance (AGAR) conducted a period-prevalence survey of clinical Staphylococcus aureus isolated from hospital inpatients. Twenty-nine microbiology laboratories from all states and mainland territories participated. Specimens were collected more than 48 hours post-admission. Isolates were tested by Vitek2® antimicrobial susceptibility card (AST-P612 card). Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) was 30.3%; ranging from 19.9% in Western Australia to 36.8% in New South Wales/Australian Capital Territory. Resistance to the non-ß-lactam antimicrobials was common except for rifampicin, fusidic acid, high-level mupirocin and daptomycin. No resistance was detected for vancomycin, teicoplanin or linezolid. Antibiotic resistance in methicillin susceptible S. aureus (MSSA) was rare apart from erythromycin (13.2%) and there was no resistance to vancomycin, teicoplanin or linezolid. Inducible clindamycin resistance was the norm for erythromycin resistant, clindamycin intermediate/susceptible S. aureus in Australia with 90.6% of MRSA and 83.1% of MSSA with this phenotype having a positive double disc diffusion test (D-test). The proportion of S. aureus characterised as being healthcare-associated MRSA (HA-MRSA) was 18.2%, ranging from 4.5% in Western Australia to 28.0% in New South Wales/Australian Capital Territory. Four HA-MRSA clones were characterised and 98.8% of HA-MRSA isolates were classified as either ST22-IV [2B] (EMRSA-15) or ST239-III [3A] (Aus-2/3 EMRSA). Multiclonal community-associated MRSA (CA-MRSA) accounted for 11.7% of all S. aureus. In Australia, regional variation in resistance is due to the differential distribution of MRSA clones between regions, particularly for the major HA-MRSA clone, ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials.

In 2009, the Australian Group on Antimicrobial Resistance (AGAR) conducted a period-prevalence survey of clinical Staphylococcus aureus isolated from hospital inpatients. Thirty medical microbiology laboratories from each state and mainland territory participated. Specimens were collected more than 48 hours post-admission. Isolates were tested by Vitek2 (AST-P579 card) and by Etest for daptomycin. Nationally, the proportion of S. aureus that were MRSA was 33.6%, ranging from 27.3% in South Australia to 41.4% in New South Wales/Australian Capital Territory. Resistance to the non-beta-lactam antimicrobials was common except for rifampicin, fusidic acid, daptomycin and high-level mupirocin. No resistance was detected for vancomycin, teicoplanin, quinupristin-dalfopristin or linezolid. Resistance in the methicillin susceptible S. aureus (MSSA) was rare apart from erythromycin (12%) and absent for vancomycin, teicoplanin, daptomycin, quinupristin-dalfopristin and linezolid. The proportion of methicillin resistant S. aureus (MRSA) has remained stable since the first AGAR inpatient survey in 2005 yet during the same time frame resistance to many antimicrobials, in particular tetracycline, trimethoprim-sulphamethoxazole and gentamicin, has significantly decreased. This suggests that non-multi-resistant community-associated MRSA (CA-MRSA) clones are becoming more common in the hospital setting and replacing the long-established multi-resistant clones such as ST239-III (Aus 2/3 EMRSA). Given hospital outbreaks of CA-MRSA are thought to be extremely rare it is most likely that patients colonised at admission with CA-MRSA have become infected with the colonising strain during their hospital stay.

Biennial community-based Staphylococcus aureus antimicrobial surveillance programs have been performed by the Australian Group for Antimicrobial Resistance (AGAR) since 2000. Over this time the percentage of S. aureus identified as methicillin resistant has increased significantly from 10.3% in 2000 to 16% in 2006. This increase has occurred throughout Australia and has been due to the emergence of community-associated MRSA (CA-MRSA) clones. However, healthcare associated MRSA were still predominant in New South Wales/Australian Capital Territory and Victoria/Tasmania. In the 2006 survey CA-MRSA accounted for 8.8% of community-onset S. aureus infections. Although multiple CA-MRSA clones were characterised, the predominate clone identified was Queensland (Qld) MRSA (ST93-MRSA-IV) a Panton-Valentine leukocidin (PVL) positive MRSA that was first reported in Queensland and northern New South Wales in 2003 but has now spread throughout Australia. Several international PVL-positive CA-MRSA clones were also identified including USA300 MRSA (ST8-MRSA-IV). In addition, PVL was detected in an EMRSA-15 (ST22-MRSA-IV) isolate; a hospital associated MRSA clone that is known to be highly transmissible in the healthcare setting. With the introduction of the international clones and the transmission of Qld MRSA throughout the country, over 50% of CA-MRSA in Australia are now PVL positive. This change in the epidemiology of CA-MRSA in the Australian community will potentially result in an increase in skin and soft tissue infections in young Australians. As infections caused by these strains frequently results in hospitalisation their emergence is a major health concern.

In 2005 the Australian Group for Antimicrobial Resistance (AGAR) conducted a survey of the prevalence of antimicrobial resistance in unique clinical isolates of Streptococcus pneumoniae. Twenty laboratories from the 5 mainland states and the Australian Capital Territory collected 1,776 isolates prospectively and tested them by disk diffusion, Etest and/or agar dilution against a range of antimicrobials. Data from this survey were compared with AGAR surveys conducted in 1989, 1994, 1999 and 2002. Non-susceptibility to penicillin was detected in 28.0% of isolates, 22.7% were erythromycin resistant, 15.6% clindamycin resistant, 18.4% tetracycline resistant and 31.0% trimethoprim-sulphamethoxazole resistant. Levofloxacin resistance was detected in only 4 of 1,775 (0.2%) isolates tested. Intermediate resistance to levofloxacin was detected in another 4 isolates. Moxifloxacin resistance was present in 2 isolates with minimum inhibitory concentrations of 3 mg/L and 4 mg/L. Seventeen point three per cent of isolates were multi-resistant (acquired resistance to more than 2 drug classes). Trend data show an increase in penicillin non-susceptible strains in each survey from 1989 to 2005. Between 1999 and 2005 the proportion of invasive strains with high-level resistance increased from 2.6% to 5.4%. After a rapid emergence and rise in resistance between 1989 and 1999, recent studies have documented a continuing rise in resistance to all non-beta-lactams except trimethoprim-sulphamethoxazole.

The Australian Group on Antimicrobial Resistance studied the epidemiology and outcomes of Staphylococcus aureus bacteraemia in selected Australian hospitals in 2005-06. Seventeen hospital-based laboratories collected basic demographic, susceptibility and patient outcome data on all cases of S. aureus bacteraemia for 5 to 24 months during the study period. There were 1,511 cases of bacteraemia documented, of which 66% occurred in males and 32% originated from vascular access devices. Bacteraemia had a community onset in 60% of cases, although 31% of these were health-care associated. Overall, 57% of episodes were health-care related. Methicillin-resistant Staphylococcus aureus (MRSA) was the responsible pathogen in 24% of instances; of these 53% were of the typical multi-resistant hospital type, and 29% were of the community-associated type. Seven per cent of all staphylococcal bacteraemias were caused by community-associated MRSA strain types, attesting to the growing size of this problem in Australia. Outcomes were available for 51% of cases and in those the all-cause mortality at 7 days or discharge (whichever came earlier) was 11.2%. Age was strongly associated with mortality; the rate for patients aged more than 60 years was 18%. Sepsis originating from intravascular access devices had a lower mortality rate of 5%. S. aureus bacteraemia is a common community and hospital infection with a significant mortality. A nationally co-ordinated program documenting the incidence and outcomes of this disease would likely lead to measures designed to reduce the incidence and improve outcomes of this disease.

The Australian Group for Antimicrobial Resistance conducted a survey of the prevalence of antimicrobial resistance in unique clinical isolates of Staphylococcus aureus from patients admitted to hospital for more than 48 hours. Thirty-two laboratories from all states and territories collected 2,908 isolates from 1 May 2005, of which 31.9% were methicillin-resistant Staphylococcus aureus (MRSA). The regional prevalence of MRSA varied significantly (P0.0001) from 22.5% in Western Australia to 43.4% in New South Wales/Australian Capital Territory. Prevalence of MRSA from individual laboratories varied even more from 4% to 58%. This variation was explained in part by distribution of age with the risk of MRSA significantly (P0.0001) increasing with age. Other unmeasured factors including hospital activity and infection control practices in the individual institution may have also contributed. Further investigation is warranted as reductions in prevalence would reduce morbidity, mortality and healthcare costs.

The Australian Group for Antimicrobial Resistance (AGAR) has played a unique role in surveillance of antimicrobial resistance in Australia. It has a broad laboratory membership representing the major teaching hospitals in all Australian capitals and more recently major private pathology laboratories in most states. The use of an active surveillance strategy with standard methodology for collection and examination of clinically significant isolates has produced data accurately reflecting the changing prevalence of antimicrobial resistance in major hospitals as well as the community. AGAR has documented the spread of methicillin-resistant Staphylococcus aureus in Australian hospitals in the late 1980s and throughout the 1990s. Surveys of antimicrobial resistance in enterococci have monitored the emergence of vancomycin-resistant enterococci as an important nosocomial pathogen in Australia. AGAR has also conducted major national surveys of resistance in Streptococcus pneumoniae, community isolates of Staphylococcus aureus, Haemophilus influenzae and in the Enterobacteriaceae. These and other activities have given AGAR a unique perspective on emerging patterns of resistance in key pathogens in Australia. The recent extension of membership to include more private pathology laboratories may provide the opportunity to conduct more representative community based surveys.