Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2018.

From 1 January to 31 December 2018, thirty-six institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2018 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 methicillin-resistant isolates. A total of 2,673 S. aureus bacteraemia episodes were reported, of which 78.9% were community-onset. A total of 17.4% of S. aureus isolates were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 17.1% which was not significantly higher than the 13.6% mortality associated with methicillin-susceptible SAB (p = 0.1). With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However in addition to the ß-lactams approximately 42% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin, 36% to ciprofloxacin and approximately 13% resistant to co-trimoxazole, tetracycline and gentamicin. When applying the EUCAST breakpoints teicoplanin resistance was detected in two S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). The ST22-IV [2B] (EMRSA-15) clone is the predominant healthcare-associated clone in Australia. Seventy-eight percent of methicillin-resistant SAB episodes in 2018 were due to community-associated clones. Although polyclonal, approximately 76.3% of community-associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA), ST5-IV [2B], ST45-VT [5C2&5], ST1-IV [2B], ST30-IV [2B], ST78-IV [2B] and ST97-IV [2B]. Community-associated MRSA, in particular the ST45-VT [5C2&5] clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The ST45-VT [5C2&5] clone accounted for 11.7% of CA-MRSA. As CA-MRSA is well established in the Australian community, it is important that antimicrobial resistance patterns in community- and healthcare-associated SAB are monitored, as this information will guide therapeutic practices in treating S. aureus sepsis.

Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Sepsis Outcome Programme (AESOP) Annual Report 2018.

From 1 January to 31 December 2018, thirty-six institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2018 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the E. faecium isolates. Of the 1,248 unique episodes of bacteraemia investigated, 93.5% were caused by either E. faecalis (54.2%) or E. faecium (39.3%). Ampicillin resistance was not detected in E. faecalis but was detected in 89.4% of E. faecium. Vancomycin non-susceptibility was not detected in E. faecalis but was reported in 45.0% of E. faecium. Overall 49.3% of E. faecium isolates harboured vanA or vanB genes. Of the vanA/vanB positive E. faecium isolates, 52.9% harboured vanA genes and 46.2% vanB genes; 0.8% harboured both vanA and vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is substantially higher than that seen in most European countries. E. faecium consisted of 59 multilocus sequence types (STs) of which 74.4% of isolates were classified into six major STs containing ten or more isolates. All major STs belong to clonal cluster (CC) 17, a major hospital-adapted polyclonal E. faecium cluster. The predominant STs (ST17, ST1424, ST796, ST80, ST1421, and ST262) were found across most regions of Australia. The most predominant clone was ST17 which was identified in all regions except the Australian Capital Territory and the Northern Territory. Overall, 55.8% of isolates belonging to the six predominant STs harboured vanA or vanB genes. The AESOP 2018 study has shown that enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin-resistant vanA- or vanB-harbouring E. faecium which have limited treatment options.

Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Sepsis Outcome Programme (AESOP) Annual Report 2017.

From 1 January to 31 December 2017, 36 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2017 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the E. faecium isolates. Of the 1,137 unique episodes of bacteraemia investigated, 95.2% were caused by either E. faecalis (52.9%) or E. faecium (42.3%). Ampicillin resistance was not detected in E. faecalis but in 89.6% of E. faecium. Vancomycin non-susceptibility was reported in 0.3% and 47.0% of E. faecalis and E. faecium respectively. Overall 50.9% of E. faecium harboured vanA or vanB genes. For the vanA/B positive E. faecium isolates, 49.6% harboured vanB genes and 49.2% vanA genes; 1.2% harboured vanA and vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium consisted of 76 multilocus sequence types (STs) of which 77% of isolates were classified into nine major STs containing ten or more isolates. All major STs belong to clonal cluster (CC) 17, a major hospital-adapted polyclonal E. faecium cluster. Seven of the nine predominant STs (ST80, ST1421, ST17, ST296, ST555, ST203 and ST18) were found across most regions of Australia. The most predominant clone was ST17 which was identified in all regions except the Australian Capital Territory, the Northern Territory and Tasmania. Overall 60.7% of isolates belonging to the nine predominant STs harboured vanA or vanB genes. The AESOP 2017 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA or vanB E. faecium which have limited treatment options.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2017.

From 1 January to 31 December 2017, 36 institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2017 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 methicillin-resistant isolates. A total of 2,515 S. aureus bacteraemia episodes were reported, of which 77% were community-onset. Approximately one in five S. aureus (19.0%) were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 18.7% which was significantly higher than the 14.0% mortality associated with methicillin-susceptible SAB. With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However in addition to the ß-lactams approximately 42% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 14% resistant to co-trimoxazole, tetracycline and gentamicin. When applying the EUCAST breakpoints teicoplanin resistance was detected in five S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) is the predominant healthcare-associated clone in Australia. Seventy-five percent of methicillin-resistant SAB were due to community-associated clones. Although polyclonal approximately 74% of community-associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA), ST5-IV [2B], ST45-VT [5C2&5] and ST1-IV [2B]. CA-MRSA, in particular the ST45-VT [5C2&5] clone has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. ST45-VT [5C2&5] accounted for 12.8% of CA-MRSA. 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.

Evolution of a 72-Kilobase Cointegrant, Conjugative Multiresistance Plasmid in Community-Associated Methicillin-Resistant Staphylococcus aureus Isolates from the Early 1990s.

Horizontal transfer of plasmids encoding antimicrobial resistance and virulence determinants has been instrumental in Staphylococcus aureus evolution, including the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA). In the early 1990s, the first CA-MRSA strain isolated in Western Australia (WA), WA-5, encoded cadmium, tetracycline, and penicillin resistance genes on plasmid pWBG753 (∼30 kb). WA-5 and pWBG753 appeared only briefly in WA; however, fusidic acid resistance plasmids related to pWBG753 were also present in the first European CA-MRSA isolates at the time. Here, we characterize a 72-kb conjugative plasmid, pWBG731, present in multiresistant WA-5-like clones from the same period. pWBG731 was a cointegrant formed from pWBG753 and a pWBG749 family conjugative plasmid. pWBG731 carried mupirocin, trimethoprim, cadmium, and penicillin resistance genes. The stepwise evolution of pWBG731 likely occurred through the combined actions of IS257, IS257-dependent miniature inverted-repeat transposable elements (MITEs), and the BinL resolution system of the ß-lactamase transposon Tn552 An evolutionarily intermediate ∼42-kb nonconjugative plasmid, pWBG715, possessed the same resistance genes as pWBG731 but retained an integrated copy of the small tetracycline resistance plasmid pT181. IS257 likely facilitated the replacement of pT181 with conjugation genes on pWBG731, thus enabling autonomous transfer. Like conjugative plasmid pWBG749, pWBG731 also mobilized nonconjugative plasmids carrying oriT mimics. It seems likely that pWBG731 represents the product of multiple recombination events between the WA-5 pWBG753 plasmid and other mobile genetic elements present in indigenous community-associated methicillin-sensitive S. aureus (CA-MSSA) isolates. The molecular evolution of pWBG731 saliently illustrates how diverse mobile genetic elements can together facilitate rapid accrual and horizontal dissemination of multiresistance in S. aureus CA-MRSA.

Severe Disease Caused by Community-Associated MRSA ST398 Type V, Australia, 2017.

Using whole-genome sequencing, we identified a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) sequence type (ST) 398 type V (5C2&5) isolate (typically found in China) in Australia in 2017. This CA-MRSA ST398 variant was highly virulent, similar to other related CA-MRSAs of ST398. This strain should be monitored to prevent more widespread dissemination.

Complete Genome Sequence of a Staphylococcus aureus Sequence Type 612 Isolate from an Australian Horse.

Staphylococcus aureus is a serious pathogen of humans and animals. Multilocus sequence type 612 is dominant and highly virulent in South African hospitals but relatively uncommon elsewhere. We present the complete genome sequence of methicillin-resistant Staphylococcus aureus strain SVH7513, isolated from a horse at a veterinary clinic in New South Wales, Australia.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2016.

From 1st January to 31st December 2016, 32 institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2016 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 methicillin-resistant isolates. A total of 2,540 S.aureus bacteraemia episodes were reported, of which 19.7% were methicillin-resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 23.1%, which was significantly higher than the 15.3% mortality associated with methicillin-susceptible SAB. With the exception of the ß-lactams and erythromycin, antimicrobial-resistance in methicillin-susceptible S.aureus (MSSA) was rare. However, in addition to the ß-lactams approximately 45% of methicillin-resistant S.aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 14% resistant to co-trimoxazole, tetracycline and gentamicin. When applying the EUCAST breakpoints, teicoplanin resistance was detected in two S.aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials 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) is the predominant healthcare associated clone in Australia. Seventy two percent of methicillin-resistant SAB were due to community associated clones. Although polyclonal almost 60% of community associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA), ST5-IV [2B] and ST1-IV [2B]. CA-MRSA in particular the ST45-VT [5C2&5] clone has acquired multiple antimicrobial-resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. Twelve percent of CA-MRSA were ST45-VT [5C2&5]. 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.

Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Sepsis Outcome Programme(AESOP) Annual Report 2015.

From 1st January to 31st December 2015, 31 Australian institutions participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2015 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 1,009 unique episodes of bacteraemia investigated, 95.4% were caused by either E. faecalis (55.7%) or E. faecium (39.6%). Ampicillin resistance was detected in 0.2% of E. faecalis and in 86.0% of E. faecium. Vancomycin non-susceptibility was reported in 0.4% and 50.1% of E. faecalis and E. faecium respectively. Overall 56.2% of E. faecium harboured vanA or vanB genes. For the vanA/B positive E. faecium isolates, 61.0% harboured vanB genes and 36.8% vanA genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium consisted of 49 multilocus sequence types (STs) of which 85.6% of isolates were classified into 11 major STs containing five or more isolates. All major STs belong to clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. Four of the five predominant STs (ST796, ST555, ST203, and ST80) were found across most regions of Australia. The second most predominant clone was non-typable by multilocus sequence typing and found only in NSW and the ACT. Overall 73.9% of isolates belonging to the five predominant STs harboured vanA or vanB genes. In conclusion, the AESOP 2015 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA or vanB E. faecium which have limited treatment options.

Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Sepsis Outcome Programme (AESOP) Annual Report 2016.

From 1st January to 31st December 2016, 32 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2016 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the E. faecium isolates. Of the 1,058 unique episodes of bacteraemia investigated, 95.2% were caused by either E. faecalis (56.2%) or E. faecium (39.0%) Ampicillin resistance was detected in 0.2% of E. faecalis and in 91.5% of E. faecium. Vancomycin non-susceptibility was reported in 0.3% and 47.7% of E. faecalis and E. faecium respectively. Overall, 49.3% of E. faecium harboured vanA or vanB genes. For the vanA/B positive E. faecium isolates, 55.2% harboured vanB genes and 42.8% vanA genes, 2% harboured vanA and vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium consisted of 48 multilocus sequence types (STs) of which 90.2% of isolates were classified into 13 major STs containing 5 or more isolates. All major STs belong to clonal cluster (C) 17, a major hospital-adapted polyclonal E. faecium cluster. Four of the 6 predominant STs (ST17, ST796, ST80 and ST203) were found across most regions of Australia. The most predominant clone ST1421 (previously known as M-type 1) does not have a pstS housekeeping gene and was found in NSW, the ACT and Victoria. This clone was first described in ASSOP 2015. Overall 74% of isolates belonging to the 6 predominant STs harboured vanA or vanB genes. The AESOP 2016 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA or vanB E. faecium which have limited treatment options.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2015.

The Australian Group on Antimicrobial Resistance (AGAR) performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2015 survey was the third year to focus on blood stream infections, and included Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter species. Seven thousand three hundred and thirty species, comprising Enterobacteriaceae (6,567, 89.6%), P. aeruginosa (660, 9.0%) and Acinetobacter species (103, 1.4%), were tested using commercial automated methods (Vitek® 2, BioMérieux; Phoenix™, BD) and results were analysed using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2016). Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 10.6%/10.6% of E. coli (CLSI/EUCAST criteria) and 5.9%/5.9% of Klebsiella pneumoniae, and 8.4%/8.4% K. oxytoca. Non-susceptibility rates to ciprofloxacin were 12.6%/13.6% for E. coli, 3.9%/7.2% for K. pneumoniae, 0.4%/0.4% for K. oxytoca, 3.4%/4.0% for Enterobacter cloacae, and 6.3%/6.5% for Pseudomonas aeruginosa. Resistance rates to piperacillin-tazobactam were 2.8%/6.3%, 3.5%/6.4%, 8.9%/10.2%, 15.9%/20.6%, and 7.1%/13.9% for the same four species respectively. Twenty-two isolates were shown to harbour a carbapenemase gene, 14 blaIMP, four blaOXA-48, one blaKPC, one blaGES, one blaNDM+OXA-48, and one blaIMP+VIM.

Clonal Expansion of New Penicillin-Resistant Clade of Neisseria meningitidis Serogroup W Clonal Complex 11, Australia.

In Western Australia, Neisseria meningitidis serogroup W clonal complex 11 became the predominant cause of invasive meningococcal disease in 2016. We used core-genome analysis to show emergence of a penicillin-resistant clade that had the penA_253 allele. This new penicillin-resistant clade might affect treatment regimens for this disease.