australian enterococcal sepsis outcome program (aesop) 2016 · 5 results from the 1st january 2016...
TRANSCRIPT
AG AR
The Australian Group on Antimicrobial Resistance
Australian Enterococcal Sepsis Outcome Program (AESOP) 2016 Final Report
Prof. Geoffrey Coombs and Ms. Denise Daley on behalf of the Australian Group on Antimicrobial Resistance 6/23/2017
AGAR is funded by the Australian Commission of Safety and Quality in Health Care as part of the Antimicrobial Use and Resistance in Australia (AURA) Surveillance System.
1
Table of Contents Summary……………………………………………………………………………………………….……………..2
Background and Objectives…………………………………………………………………………………………4
Results………………………………………………………………………………………………………………...5
Enterococcal Episodes by Region……………..………………………….……………………………………….5
Place of Onset of Bacteraemia …………………………………………………………………………………….6
Thirty Day All-Cause Mortality………………………………………………………………………………………6
Patient Demographics ……………………………………………………………………………………………....8
Age and Gender…………………………………………………………………………………………….8
Principle Clinical Manifestation……………………………………………………………………………………11
Length of Stay……………………………………………………………………………………………………....13
Length of Stay Post Bacteraemic Episode …………………………………………………………….13
Length of Stay Post Bacteraemic Episode versus Place of Onset…………………………………..14
Antimicrobial Susceptibility Data………………………………………………………………………………….16
E. faecalis………………………………………………………………………………………………….16
E. faecium………………………………………………………………………………………………….18
Antimicrobial Resistance versus Place of Onset………………………………………………………………..20
E. faecalis………………………………………………………………………………………………….20
E. faecium………………………………………………………………………………………………….21
Trend Data (2013-2016)……………………………………………….…………………………………………..22
Enterococcus faecalis……………………………….……………………………………………………22
Enterococcus faecium……………………………………………………………………………………27
The Molecular Epidemiology of Enterococcus faecium………………………………………………………..32
van Genes…………………………………………………………………………………………………32
Multilocus Sequence Type (MLST).………………………….…......……….…………………………32
MLST and van genes……………………………………………………………………………………..33
Acknowledgements…………………………………………………………………………………………………38
References…………………………………………………………………………………………………………..40
2
Summary
In the 2016 survey, 1,058 episodes of enterococcal bacteraemia were reported.
The majority (95.2%) of enterococcal bacteraemic episodes were caused by E. faecalis or E.
faecium.
Onset
o E. faecalis 68.6% community-onset.
o E. faecium 27.6% community-onset.
Age and Gender
o The majority of episodes were in males (66.3%).
o Only 12.3% of episodes occurred in patients <40 years of age.
Mortality
o The overall 30-day mortality was 19.3%
o There was a significant difference in the 30 day all-cause mortality between E. faecium
and E. faecalis: 103/380 (27.1%) and 64/497 (12.9%) respectively (p<0.0001).
o There was a significant difference in the 30 day all-cause mortality between community
onset vs hospital onset enterococcal bacteraemia 61/461 (13.2%) and 116/456 (25.4%)
respectively (p<0.0001).
Clinical Manifestations
o For E. faecalis urinary tract infection was the most frequent principle clinical
manifestation.
o For E. faecium intra-abdominal infection other than biliary tract was the most frequent
principle clinical manifestation.
Length of Stay
o 21.7% of patients had a length of stay post enterococcal bacteraemia greater than 30
days
o There were no significant differences in mean LOS between E. faecium and E. faecalis episodes (p=0.6).
3
Vancomycin resistance and van genes
o 46.5% (192/413) of blood stream infections caused by E. faecium in Australia were
phenotypically vancomycin resistant.
o 49.3% of E. faecium (201/408) harboured vanA and/or vanB genes.
o A total of 203/413 (49.2%) of E. faecium harboured van genes or were phenotypically
vancomycin non-susceptible.
MLST
o There were 48 E. faecium multilocus sequence types of which M-type1, ST17, ST796, ST80, ST555, ST203, M-type3, ST78, and ST262 were the nine most frequently identified.
o vanA genes were detected in seven STs
o vanB genes were detected in ten STs.
4
Background and Objectives Globally enterococci are thought to account for approximately 10% of all bacteraemias, and in North America and Europe is the fourth and fifth leading cause of sepsis respectively.
1,2 Although in the 1970s
healthcare-associated enterococcal infections were primarily due to Enterococcus faecalis, there has been a steadily increasing prevalence of E. faecium nosocomial infections.
3-5 Worldwide the increase in
nosocomial E. faecium infections has primarily been due to the expansion of polyclonal hospital-adapted clonal complex (CC) 17 strains. While innately resistant to many classes of antibiotics, E. faecium CC17 has demonstrated a remarkable capacity to evolve new antimicrobial resistances. In 2009 the Infectious Diseases Society of America highlighted E. faecium as one of the key problem bacteria or ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens requiring new therapies.
6
The Australian Group on Antimicrobial Resistance (AGAR) is a network of laboratories located across Australia that commenced surveillance of antimicrobial resistance in Enterococcus species in 1995.
7 In
2011 AGAR commenced the Australian Enterococcal Sepsis Outcome Programme (AESOP).8 The
objective of AESOP 2016 was to determine the proportion of E. faecalis and E. faecium bacteraemia isolates demonstrating antimicrobial resistance with particular emphasis on: 1. Assessing susceptibility to ampicillin
2. Assessing susceptibility to glycopeptides
3. Molecular epidemiology of E. faecium
5
Results From the 1
st January 2016 to the 31
st December 2016, 1,058 episodes of enterococcal bacteraemia from
32 laboratories were included in AESOP 2016. Isolates were collected from all states and territories. A new Enterococcus sepsis episode in the same patient was recorded if it was confirmed by a further culture of blood taken more than 14 days after the initial positive culture. Each episode of bacteraemia was designated hospital onset (HO) if the first positive blood culture(s) in an episode was collected >48 hours after admission. Almost all enterococcal bacteraemic patients were admitted to hospital: 1,044/1,058 (98.7%).
Enterococcal Episodes by Region E. faecalis and E. faecium accounted for 95.2% of the isolates identified to species level (Table 1). Table 1: Enterococcal Episodes by region
Region E. faecalis E. faecium Enterococcus sp* Total
ACT 40 22 5 67
NSW 152 124 10 286
NT 7 4 2 13
Qld 100 43 8 151
SA 50 41 4 95
Tas 27 14 3 44
Vic 132 111 8 251
WA 87 54 10 151
Australia (%) 595 (56.2) 413 (39.0) 50 (4.7) 1,058
*E. casseliflavus (n=25), E. gallinarum (11), E. avium (8), E. raffinosus (3), E. hirae (3). ACT= Australian Capital Territory ; NSW = New South Wales ; NT = Northern Territory ; Qld = Queensland ; SA = South Australia, Tas = Tasmania ; Vic = Victoria ; WA = Western Australia.
6
Place of Onset of Bacteraemia Data on the place of onset was available for 1,058 (100%) episodes of enterococcal bacteraemia (Table 2). There was a significant difference between community and hospital-onset E. faecalis, E. faecium and Enterococcus sp. (Table 2). E. faecalis and Enterococcus sp were predominantly community-onset (blood taken on or before admission or <48hrs after hospital admission): 408/595 (68.6%; 95%CI: 64.7-72.3) and 38/49 (77.6%; 95%CI: 63.4-88.3) respectively. E. faecium was predominantly hospital-onset 299/414 (72.4%; 95%CI: 67.8-76.6). Table 2: Enterococcus faecalis and Enterococcus faecium by Place of Onset
Organism Community-onset (%)
Hospital-Onset (%) Total p
E. faecalis 408 (68.6) 187 (31.4) 595 <0.0001
E. faecium 114 (27.5) 299 (72.4) 413 <0.0001
Other Enterococcus sp
38 (77.6) 11 (22.4) 49 0.003
All 560 (52.9) 498 (47.1) 1,058
Thirty Day All-Cause Mortality The 30 day all-cause mortality data was available for 917 (86.7%) episodes of enterococcal bacteraemia (Table 3). The 30 day all-cause mortality for enterococcal bacteraemia was 19.3%. There was a significant difference in the 30 day all-cause mortality between community onset vs hospital onset enterococcal bacteraemia 61/461 (13.2%) and 116/456 (25.4%) respectively (p<0.0001). There was a significant difference in the 30 day all-cause mortality between E. faecium and E. faecalis: 103/379 (27.2%) and 64/497 (12.9%) respectively (p<0.0001). Table 3: Thirty Day All-cause Mortality: Enterococcus species versus Place of Onset.
Species Community-Onset Hospital-onset Total
N Mortality (%)
N Mortality (%)
N Mortality (%)
All E. faecalis 336 36 (10.7) 161 28 (17.4) 497 64 (12.9)
All E. faecium 95 20 (21.1) 284 83 (29.1) 379 103 (27.2)
Other Enterococcus sp
30 5 (16.7) 11 5 (45.5) 41 10 (24.4)
All 461 61 (13.2) 456 116 (25.4) 917 177 (19.3)
7
Thirty day all-cause mortality data, place of onset and vancomycin susceptibility was known for 379 (91.7%) E.faecium episodes (Table 4). There was no significant difference between vancomycin non-susceptible (VRE) and vancomycin susceptible E. faecium (VSE): 52/181 (28.7%) and 51/199 (25.6%) respectively (p=0.57) There were no significant differences between place of onset for all E. faecium (p=0.16), VRE (p=0.49) or VSE (p=0.29) Table 4: E. faecium: By Place of Onset, Thirty Day All-cause Mortality and Vancomycin Susceptibility
Species Community-Onset Hospital-Onset Total
N Mortality (%) N Mortality (%)
N Mortality (%)
Vancomycin non-susceptible E. faecium
39 9 (23.1) 142 43 (30.3) 181 52 (28.7)
Vancomycin susceptible E. faecium
56 11 (19.6) 142 40 (28.2) 199 51 (25.6)
All E. faecium 95 20 (21.1) 284 83 (29.1) 379 103 (27.2)
8
Patient Demographics Age and Gender Age and gender were available for 1,058 (100%) enterococcal bacteraemic patients (Table 5 and Figures 1 - 3). Increasing age is a risk factor for enterococcal bacteraemia with only 130/1,058 (12.3% 95%CI=10.4-14.4) of episodes in patients aged 40 years and younger. The majority of episodes were in male patients: 701/1,058 (66.3% 95%CI=63.4-19.2). Table 5: Enterococcus Bacteraemia by Decade of Life and Gender
Decade Female Male Total M/100F
1 18 23 41 128
2 4 3 7 75
3 12 19 31 158
4 23 28 51 122
5 34 44 78 129
6 48 84 132 175
7 67 162 229 242
8 80 159 239 199
9 47 143 190 304
10 23 34 57 148
11 1 2 3 200
Total 357 701 1,058 196
M/100F = males per 100 females
9
Figure 1: Enterococcal Bacteraemia by Decade of Life and Gender
Figure 2: E. faecalis Bacteraemia by Decade of Life and Gender
10
Figure 3: E. faecium Bacteraemia by Decade of Life and Gender
11
Principle Clinical Manifestation Principle clinical manifestation was known for 1,004 (94.9%) episodes of enterococcal bacteraemia (Table 6). Overall the most common principle clinical manifestation was urinary tract infection n=178 (17.7%), followed by intra-abdominal infection n=153 (15.2%). Of the hospital-onset episodes where data was known, the most common principle clinical manifestation was intra-abdominal infection (20.0%). Of the community-onset episodes where data was known, the most common principle clinical manifestation was urinary tract disease (24.1%). There were no significant differences for principle clinical manifestation between genders. Table 6: Principle Clinical Manifestation and Gender
Principle Clinical Manifestation Male (%) Female (%) Total
Urinary tract infection 128 (19.3) 50 (14.6) 178
Intra-abdominal infection other than biliary tract 97 (14.7) 56 (16.4) 153
Biliary tract infection (including cholangitis) 93 (14.0) 56 (16.4) 149
No focus 93 (14.0) 54 (15.8) 147
Device-related infection without metastatic focus 59 (8.9) 32 (9.4) 91
Febrile neutropenia 60 (9.1) 26 (7.6) 86
Endocarditis L-sided 55 (8.3) 17 (5.0) 72
Other clinical syndrome 33 (5.0) 19 (5.6) 52
Skin and Skin Structure 22 (3.3) 15 (4.4) 37
Osteomyelitis/Septic Arthritis 12 (1.8) 4 (1.2) 16
Device-related infection with metastatic focus 6 (0.9) 6 (1.8) 12
Endocarditis R-sided 4 (0.6) 7 (2.0) 11
Total 662 342 1,004
12
Principle manifestation was known for 959 (95.1%) of the E. faecalis and E. faecium episodes (Table 7). The most common clinical manifestation for E. faecalis was urinary tract infection while for E. faecium it was intra-abdominal infection other than biliary tract. Significant differences were seen between E. faecalis and E. faecium for five clinical manifestations.
Table 7: Principle Clinical Manifestation: Enterococcus faecalis versus Enterococcus faecium
Principle Clinical Manifestation E. faecalis E. faecium pa
Urinary tract infection 147 (26.4) 28 (7.0) <0.001
Intra-abdominal infection other than biliary tract 63 (11.3) 86 (21.4) <0.001
No focus 79 (14.2) 61 (15.2) ns
Biliary tract infection (including cholangitis) 41 (7.4) 84 (20.9) <0.001
Device-related infection without metastatic focus 53 (9.5) 36 (9.0) ns
Febrile neutropenia 18 (3.2) 67 (16.7) <0.001
Endocarditis L-sided 67 (12.1) 5 (1.2) <0.001
Other clinical syndrome 32 (5.8) 17 (4.2) ns
Skin and Skin Structure 26 (4.7) 11 (2.7) ns
Osteomyelitis/Septic Arthritis 12 (2.2) 3 (0.7) ns
Device-related infection with metastatic focus 9 (1.6) 3 (0.7) ns
Endocarditis R-sided 9 (1.6) 1 (0.2) ns
Total 556 402
a Test of significance between E. faecalis and E. faecium: ns=not significant
13
Length of Stay Post Bacteraemic Episode Length of stay (LOS) data was known for 1,012 (95.7%) episodes of enterococcal bacteraemia. 21.7% of patients had a LOS post enterococcal bacteraemia > 30 days (Table 8). There were no significant differences in mean LOS between E. faecium and E. faecalis episodes (p=0.6). Table 8: Enterococcal Bacteraemia Episodes by Length of Stay
Length of Stay (days)
Mean E. faecalis E. faecium Enterococcus sp.
Total (%)
<7 4 126 (22.5) 93 (23.0) 14 (29.8) 233 (23.0)
7-14 10 155 (27.6) 92 (22.7) 18 (38.3) 265 (26.2)
15-30 21 147 (26.2) 125 (30.9) 8 (17.0) 280 (27.7)
>30 54 122 (21.7) 91 (22.5) 7 (14.9) 220 (21.7)
Not admitted
11 (2.0) 3 (0.7) 14 (1.4)
Total 561 404 47 1,012
Mean LOS 19.2 20.1 13.7
There were no significant differences in mean LOS between vancomycin susceptible and non-susceptible E. faecium (p=0.3) (Table 9). Table 9: E. faecium Bacteraemia Episodes by Length of Stay and Vancomycin susceptibility
Length of Stay (days)
E. faecium
Vanc non-susceptible
E. faecium
Vanc susceptible
Total (%)
<7 38 (20.0) 55 (25.7) 93 (23.0)
7-14 39 (20.5) 53 (24.8) 92 (22.8)
15-30 64 (33.7) 61 (28.5) 125 (30.9)
>30 47 (24.7) 44 (20.6) 91 (22.5)
Not admitted
2 (1.1) 1 (0.5) 3 (0.7)
Total 190 214 404
Mean LOS 21.2 19.0
14
Length of Stay Post Bacteraemic Episode versus Place of Onset There was a significant difference in mean LOS between patients with community onset vs hospital onset E. faecalis bacteraemia (p=0.03) (Table 10). Table 10: E. faecalis Episodes: Length of Stay and Place of Onset
Length of Stay (Days)
Community –Onset (%) Hospital–Onset (%) Total (%)
<7 97 (25.3) 29 (16.3) 126 (22.5)
7-14 113 (29.5) 42 (23.6) 155 (27.6)
15-30 91 (23.8) 56 (31.5) 147 (26.2)
>30 71 (18.5) 51 (28.7) 122 (21.7)
Not admitted 11 (2.9) 11 (2.0)
Total 383 178 210
Mean LOS 15.2 18.1
There was a significant difference in mean LOS between patients with community onset vs hospital onset E. faecium bacteraemia (p=0.005) (Table 11).
Table 11: E. faecium Episodes: Length of Stay and Place of Onset
Length of Stay (Days)
Community –Onset (%) Hospital–Onset (%) Total (%)
<7 32 (29.4) 61 (20.6) 93 (23.0)
7-14 34 (31.2) 58 (19.6) 92 (22.8)
15-30 29 (26.6) 96 (32.8) 125 (30.9)
>30 11 (10.1) 80 (27.0) 91 (22.5)
Not admitted 3 (2.8) 3 (0.7)
Total 109 295 404
Mean LOS 15.1 21.9
15
There was no significant difference in mean LOS between patients with community onset vs hospital onset E. faecium vancomycin non-susceptible bacteraemia (p=0.08) (Table 12). Table 12: Vancomycin Non-susceptible E. faecium Episodes: By Length of Stay and Place of Onset
Length of Stay (Days)
Community –Onset (%) Hospital –Onset (%) Total (%)
<7 7 (15.9) 31 (21.2) 38 (20.0)
7-14 17 (38.6) 22 (15.1) 39 (20.5)
15-30 14 (31.8) 50 (34.2) 64 (33.7)
>30 4 (9.1) 43 (29.5) 47 (24.7)
Not admitted 2 (4.5) 2 (1.1)
Total 44 146 190
Mean LOS 16.4 22.6
There was a significant difference in mean LOS between patients with community onset vs hospital onset E. faecium vancomycin susceptible bacteraemia (p=0.05) (Table 13). Table 13: Vancomycin Susceptible E. faecium Episodes: By Length of Stay and Place of Onset
Length of Stay (Days)
Community –Onset (%) Hospital –Onset (%) Total (%)
<7 25 (38.5) 30 (20.1) 55 (25.7)
7-14 17 (26.2) 36 (24.2) 53 (24.8)
15-30 15 (23.1) 46 (30.9) 62 (28.5)
>30 7 (10.8) 37 (24.8) 44 (20.6)
Not admitted 1 (1.5) 1 (0.5)
Total 65 149 214
Mean LOS 14.3 21.0
Antimicrobial Susceptibility Data The number and proportion of E. faecalis non-susceptible to ampicillin and the non-β-lactam antimicrobials by region is shown in Table 14. Table 14: The number tested and proportion of E. faecalis isolates non-susceptible to ampicillin and the non-β-lactam antimicrobials by region. Results using CLSI (C) and EUCAST (E) breakpoints are shown where the breakpoints differ.
Antimicrobial ACT NSW NT QLD SA Tas Vic WA Australia
Ampicillin No. tested No. non-susceptible (%)
40 0
152
0
7 0
98 0
49
1 (2.0)
27 0
132
1 (0.8)
87 0
592
2 (0.3)
Vancomycin No. tested %non-susceptible
40 0
152
0
7 0
97 0
50
1 (2.0)
27 0
132
0
87 0
592
1 (0.2)
Erythromycin No. tested %non-susceptible
40
33 (82.5)
152
134 (88.2)
7
6 (85.7)
98
91 (92.9)
49
46 (93.9)
14
13 (92.9)
132
123 (93.2)
87
76 (87.4)
579
522 (90.2)
Tetracycline No. tested %non-susceptible
40
31 (77.5)
119
80 (67.2)
7
5 (71.4)
98
73 (74.5)
17
12 (70.6)
132
96 (72.7)
87
64 (73.6)
514
374 (72.8)
Doxycycline No. tested %non-susceptible
33
17 (51.5)
32
20 (62.5)
65
37 (59.6)
Ciprofloxacin No. tested %non-susceptible
33
7 (21.2)
152
26 (17.1)
7
1 (14.3)
85
8 (9.4)
49
12 (24.5)
14
3 (21.4)
132
18 (13.6)
87
11 (12.6)
559
86 (15.4)
Teicoplanin (C) (>8) No. tested %non-susceptible
40
0
152
0
7 0
97 0
50 0
27 0
132
0
87 0
592
0
17
Antimicrobial ACT NSW NT QLD SA Tas Vic WA Australia
Teicoplanin (E) (>2) No. tested %non-susceptible
40
0
152
0
7 0
97 0
50 0
27 0
132
0
87 0
592
0
Linezolid (C) (>2) No. tested %non-susceptible
40
2 (5.0)
151
5 (3.3)
7 0
98
2 (2.0)
49 0
27
1 (3.7)
132
4 (3.0)
87
3 (3.4)
591
17 (2.9)
Linezolid (E) (>4) No. tested %non-susceptible
40 0
151
0
7 0
98
2 (2.0)
49 0
27 0
132
0
97 0
591
2 (0.3)
Nitrofurantoin (C) (>32) No. tested %non-susceptible
40
1 (2.5)
152
0
7 0
97 0
49
1 (2.0)
27 0
132
0
87
1 (1.1)
591
3 (0.5)
Nitrofurantoin (E) (>64) No. tested %non-susceptible
40 0
152
0
7 0
97 0
49 0
27 0
132
0
87 0
591
0
High Level Gentamicin No. tested %non-susceptible
40
9 (22.5)
149
42 (28.2)
7
2 (28.6)
98
28 (28.6)
49
15 (30.6)
27
4 (14.8)
132
29 (22.0)
87
14 (16.1)
589
143 (24.3)
Daptomycin No. tested %non-susceptible
39 0
150
0
7 0
98
1 (1.0)
45 0
14 0
127
1 (0.8)
87 0
567
2 (0.4)
ACT= Australian Capital Territory, NSW = New South Wales, NT = Northern Territory, Qld = Queensland, SA = South Australia, Tas = Tasmania, Vic = Victoria, WA = Western Australia.
18
The number and proportion of E. faecium non-susceptible to ampicillin and the non-β-lactam antimicrobials by region is shown in Table 15. Table 15: The number tested and proportion of E. faecium isolates non-susceptible to ampicillin and the non-β-lactam antimicrobials by region. Results using CLSI (C) and EUCAST (E) breakpoints are shown where the breakpoints differ.
Antimicrobial ACT NSW NT QLD SA Tas Vic WA Australia
Ampicillin No. tested No. non-susceptible (%)
22
20 (90.9)
123
113 (91.9)
4
4 (100)
43
39 (90.7)
41
41 (100)
14
12 (85.7)
111
98 (88.3)
54
50 (92.6)
412
377 (91.5)
Vancomycin No. tested %non-susceptible
22
15 (68.2)
124
59 (47.6)
4
3 (75.0)
43
13 (30.2)
41
20 (48.8)
14
6 (42.9)
111
68 (61.3)
54
8 (14.8)
413
192 (46.5)
Erythromycin No. tested %non-susceptible
22
21 (95.5)
124
121 (97.6)
4
4 (100)
42
38 (90.5)
41
40 (97.6)
12
11 (91.7)
111
104 (93.7)
54
50 (92.6)
410
389 (94.9)
Tetracycline No. tested %non-susceptible
22
9 (40.9)
98
45 (45.9)
4
4 (100)
43
36 (83.7)
9
5 (55.6)
12
8 (66.7)
111
87 (78.4)
54
41 (75.9)
353
235 (66.6)
Doxycycline No. tested %non-susceptible
26
5 (19.2)
32
16 (50.0)
58
21 (36.2)
Ciprofloxacin No. tested %non-susceptible
19
17 (89.5)
124
114 (92.7)
4
4 (100)
39
35 (89.7)
41
41 (100)
12
11 (91.7)
111
99 (89.2)
54
50 (92.6)
404
372 (92.1)
Teicoplanin (C) (>8) No. tested %non-susceptible
22
8 (36.4)
124
46 (37.1)
4 0
43
1 (2.3)
41 0
14 0
111
15 (13.5)
54
5 (9.3)
413
75 (18.2)
Teicoplanin (E) (>2) No. tested %non-susceptible
22
9 (40.9)
124
48 (38.7)
4 0
43
1 (2.3)
41 0
14 0
111
15 (13.5)
54
5 (9.3)
413
78 (18.9)
19
Antimicrobial ACT NSW NT QLD SA Tas Vic WA Australia
Linezolid (C) (>2) No. tested %non-susceptible
22 0
120
0
4 0
43 0
41
1 (2.4)
14 0
110
0
54
1 (1.9)
408
2 (0.5)
Linezolid (E) (>4) No. tested %non-susceptible
22 0
120
0
4 0
43 0
41 0
14 0
110
0
54 0
408
0
Nitrofurantoin (C) (>32) No. tested %non-susceptible
22
22 (100)
123
105 (85.4)
4
2 (50.0)
42
38 (90.5)
41
38 (92.7)
14
5 (35.7)
111
65 (58.6)
54
44 (81.5)
411
319 (77.6)
Nitrofurantoin (E) (>64) No. tested %non-susceptible
22
17 (77.3)
122
70 (57.4)
4 0
42
22 (52.4)
41
31 (75.6)
14
3 (21.4)
111
30 (27.0)
54
23 (42.6)
410
196 (47.8)
High Level Gentamicin No. tested %non-susceptible
22
16 (72.7)
117
82 (70.3)
4
4 (100)
42
16 (38.1)
40
30 (75.0)
14
8 (57.1)
110
43 (39.1)
54
13 (24.1)
403
212 (52.6)
ACT= Australian Capital Territory, NSW = New South Wales, NT = Northern Territory, Qld = Queensland, SA = South Australia, Tas = Tasmania, Vic = Victoria, WA = Western Australia
20
Antimicrobial Resistance Versus Place of Onset – E. faecalis The antimicrobial resistance results for community-onset and hospital-onset E. faecalis episodes are shown in Table 16. There were no significant differences in antibiotic resistance for community and hospital-onset E. faecalis bacteraemia. Table 16: The number tested and proportion of E. faecalis isolates non-susceptible to ampicillin and the non-β-lactam antimicrobials by place of onset. Results using CLSI (C) and EUCAST (E) breakpoints are shown where the breakpoints differ.
Antimicrobial Number Tested
Community-onset (CO) %R
Hospital-onset (HO) %R
Ampicillin (C) 592 0 0.5
Ampicillin (E) 592 0 0.5
Vancomycin 592 0 1.1
Erythromycin 579 89.0 93.0
Tetracycline 514 71.2 76.1
Doxycycline 65 52.3 66.7
Ciprofloxacin 559 13.9 18.4
Teicoplanin (C) 592 0 0
Teicoplanin (E) 592 0 0
Linezolid (C) 591 3.2 2.2
Linezolid (E) 591 0.5 0
Nitrofurantoin (C) 591 0 1.6
Nitrofurantoin (E) 591 0 0
High-level Gentamicin 589 24.1 24.6
Daptomycin 567 0.5 0.6
21
Antimicrobial Resistance Versus Place of Onset – E. faecium The antimicrobial resistance results for community-onset and hospital-onset E. faecium episodes are shown in Table 17. There were significant differences in antibiotic resistance to ampicillin, ciprofloxacin and high-level gentamicin for community and hospital-onset E. faecium bacteraemia. Table 17: The number tested and proportion of E. faecium isolates non-susceptible to ampicillin and the non-β-lactam antimicrobials by place of onset. Results using CLSI (C) and EUCAST (E) breakpoints are shown where the breakpoints differ.
Antimicrobial Number Tested
Community-onset (CO) %R
Hospital-onset (HO) %R
P*
Ampicillin (C) 413 77.2 96.0 <0.0001
Ampicillin (E) 413 78.1 96.7 <0.0001
Vancomycin 413 39.5 49.2 ns
Erythromycin 410 92.0 96.0 ns
Tetracycline 353 58.8 69.5 ns
Doxycycline 58 46.7 32.6 ns
Ciprofloxacin 404 80.2 96.6 <0.0001
Teicoplanin (C) 413 14.9 19.3 ns
Teicoplanin (E) 413 14.9 20.4 ns
Linezolid (C) 408 1.8 0 ns
Linezolid (E) 408 0 0
Nitrofurantoin (C) 410 79.6 77.1 ns
Nitrofurantoin (E) 410 40.7 50.5 ns
High-level Gentamicin
403 42.5 56.6 0.015
*test of significance between %R CO and HO; ns=not significant
22
Trend Data (2013-2016)
Enterococcus faecalis The following figures show the trends in antimicrobial non-susceptibility for E. faecalis by region from 2013 to 2016 (Figures. 4 – 12)
Figure 4: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from the Australian Capital Territory (2013-2016)
Figure 5: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from New South Wales (2013-2016)
Note: Decreasing trend in ciprofloxacin (Chi-sq. for trend = 9.47, p=0.002) and tetracycline resistance (Chi-sq. for trend = 4.781, p=0.03).
23
Figure 6: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from the Northern Territory (2013-2016)
Figure 7: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from Queensland (2013-2016)
Note: Decreasing trend in ciprofloxacin resistance (Chi-sq. for trend = 4.125, p=0.04) and high-level gentamicin resistance (Chi-sq. for trend = 4.921, p=0.03) and an increasing trend in erythromycin resistance (Chi-sq. for trend = 5.415, p=0.02)
24
Figure 8: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from South Australia (2013-2016)
Note: Decreasing trend in ciprofloxacin resistance (Chi-sq. for trend = 3.854, p=0.05), an increasing trend in erythromycin resistance (Chi-sq. for trend =
Figure 9: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from Tasmania (2013-2016)
Resistance levels in erythromycin, tetracycline and ciprofloxacin reflect the addition of another hospital added to the AGAR in 2016.
25
Figure 10: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from Victoria (2013-2016)
Figure 11: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from Western Australia (2013-2016)
Note: Increasing trend in erythromycin resistance (Chi-sq. for trend = 3.782, p=0.05)
26
Figure 12: The Antimicrobial Non-susceptibility Results of E. faecalis Isolates from Australia (2013-2016)
Note: A decreasing trend in ciprofloxacin (Chi-sq. for trend = 11.224, p=0.0008) and high-level gentamicin resistance (Chi-sq. for trend = 14.738, p=0.0001).
27
Enterococcus faecium The following figures show the trends in antimicrobial non-susceptibility for E. faecium by region from 2013 to 2016 (Figures. 13 - 21)
Figure 13: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from the Australian Capital Territory (2013-2016).
Note: Increasing trend in tetracycline (Chi-sq. for trend = 5.352, p=0.02) and teicoplanin resistance (Chi-sq. for trend = 7.447, p=0.006).
Figure 14: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from New South Wales (2013-2016).
Note: Overall a decreasing trend in ampicillin and high-level gentamicin resistance (Chi-sq. for trend = 4.595, p=0.03) and (Chi-sq. for trend = 8.133, p=0.004) respectively. However an increase from 83.2% to 91.9% for ampicillin and 65% to 70.9% for high-level gentamicin in 2015 and 2016 was observed.
28
Figure 15: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from the Northern Territory (2013-2016).
Figure 16: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from Queensland (2013-2016).
Note: Decreasing trend in high-level gentamicin resistance (Chi-sq. for trend = 13.541, p=0.0002). Increasing trend in resistance in tetracycline (Chi-sq. for trend = 7.161 p=0.008).
29
Figure 17: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from South Australia (2013-2016).
Note: Increasing trend in ampicillin (Chi-sq. for trend = 4.025, p=0.05), erythromycin (Chi-sq. for trend = 8.578, p=0.003), high-level gentamicin (Chi-sq. for trend = 40.321, p<0.0001) and vancomycin resistance (Chi-sq. for trend = 7.816, p=0.005).
Figure 18: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from Tasmania (2013-2016).
Decreasing trend in resistance for nitrofurantoin (Chi-sq. for trend =3.94, p=0.05).Increasing trend in vancomycin resistance (Chi-sq. for trend = 8.082, p=0.002).
Increased resistance levels reflect a new hospital added in 2016
30
Figure 19: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from Victoria (2013-2016).
Note: Decreasing trend in resistance in high-level gentamicin (Chi-sq. for trend = 6.779, p=0.009). Increasing trend in teicoplanin (Chi –sq. for trend = 13.192, 0.0003) and vancomycin resistance (Chi-sq. for trend = 9.746, p=0.002)
Figure 20: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from Western Australia (2013-2016).
Note: Decreasing trend in high-level gentamicin (Ch-sq. for trend = 4.254, p=0.04). Increasing trend in resistance for tetracycline (Chi-sq. for trend = 19.805, p=<0.0001), teicoplanin (Chi-sq. for trend = 5.604, p=0.02) and vancomycin (Chi-sq. for trend = 4.15, p=0.04)
31
Figure 21: The Antimicrobial Non-susceptibility Results of E. faecium Isolates from Australia (2013-2016).
Note: Decreasing trend in high-level gentamicin (Chi-sq. for trend = 8.666, p=0.003). Increasing trend in tetracycline (Chi-sq. for trend = 12.982, p=0.0003), teicoplanin (Chi-sq. for trend = 41.78, p=<0.0001) and vancomycin resistance (Chi-sq. for trend = 17.319, p<0.0001).
32
The Molecular Epidemiology of Enterococcus faecium
van Genes vanA/B PCR results were available for 408 (98.8%) of the 413 E. faecium isolates. vanA and vanB genes were detected in 90 and 115 isolates respectively, of which four isolates contained both vanA and vanB genes. For the vancomycin intermediate/resistant E. faecium isolates, vanA was detected in 83 isolates and vanB was detected in 110 isolates of which four isolates contained both vanA and vanB genes. vanA and/or vanB genes were detected in all isolates with vancomycin MIC’s >4mg/L. For the vancomycin susceptible E. faecium isolates (MIC<=4mg/L), vanA was detected in seven isolates (vancomycin MIC ≤ 1 mg/L) and vanB was detected in four isolates (vancomycin MIC ≤ 1 mg/L).
Multilocus Sequence Type (MLST) Of the 413 E. faecium isolates reported, 400 (96.9%) were available for typing by WGS (Table 20). Based on the MLST, 48 sequence types (STs) were identified (One isolate still to be determined). Overall 84% of E. faecium could be characterised into nine STs: M-type1 (64 isolates); ST17 (59 isolates); ST796 (56 isolates); ST80 (51 isolates); ST555 (39 isolates); ST203 (26 isolates); M-type3 (15 isolates); ST78 (13 isolates) and ST262 (12 isolates).
The M-type isolates are missing the pstS housekeeping gene. In 2015 M-type 1 was identified in New South Wales and the ACT. In the 2016 study there were four M-types each differing by one of the six housekeeping genes. M-type1 first identified in 2015 was the most common E. faecium clone in 2016.
M-type 1 was identified in New South Wales, the Australian Capital Territory and Victoria.
ST17 was isolated in all regions except the Northern Territory and Tasmania.
ST796 was the most predominant strain in Victoria with six isolates from Tasmania, two from New South Wales and South Australia and single isolates from the Northern Territory and Queensland.
ST80 was identified in all regions except the Northern Territory and Tasmania
ST555 was identified in all regions with the exception of the Australian Capital Territory and New South Wales, and was the predominant ST in South Australia.
ST203 was identified in all regions except the Northern Territory.
M-type 3 was identified exclusively in New South Wales
ST78 was isolated in New South Wales and Queensland.
ST262 was identified exclusively in South Australia.
There were 30 STs with only a single isolate.
33
MLST and van genes vanA was detected in seven STs; M- type1 (51 isolates); ST80 (17 isolates), M-type3 (11 isolates); ST203 (3 isolates), ST17 (1 isolate), ST555 (1 isolate) and ST78 (1 isolate) (Table 21). vanB was detected in ten STs: ST796 (54 isolates), ST555 (17 isolates), ST203 (14 isolates), ST78 (11 isolates), ST80 (5 isolates), ST17 (4 isolates), ST262 (2 isolates) M- type1 and ST414 (1 isolate each) (Table 21). The MLST of one vanB isolate is still to be determined. A combination of vanA and vanB genes were identified was found in three isolates: ST80 (2 isolates) and ST252 (I isolate).
34
Table 20: The number and proportion of Enterococcus faecium MLST by region
ACT n %
NSW n %
NT n %
QLD n %
SA n %
Tas n %
Vic n %
WA n %
Australia n %
M-type 1 15 68.2% 40 34.8% 9 8.1% 64 16.0%
17 1 4.5% 5 4.3% 22 52.4% 2 5.1% 8 7.2% 21 39.6% 59 14.8%
796 2 1.7% 1 25.0% 1 2.4% 2 5.1% 6 42.9% 44 39.6% 56 14.0%
80 3 13.6% 19 16.5% 3 7.1% 1 2.6% 15 13.5% 10 51 12.8%
555 2 50.0% 1 2.4% 19 48.7% 3 21.4% 1 0.9% 13 39 9.8%
203 1 4.5% 6 5.2% 4 9.5% 3 7.7% 1 7.1% 10 9.0% 1 26 6.5%
M-type 3 15 13.0% 15 3.8%
78 7 6.1% 6 14.3% 13 3.3%
262 12 30.8% 12 3.0%
117 4 3.5% 1 2.4% 1 7.1% 1 7 1.8%
192 2 14.3% 4 3.6% 6 1.5%
18 1 0.9% 1 2.4% 1 0.9% 2 5 1.3%
M-type 2 5 4.3% 5 1.3%
94 1 2.4% 1 0.9% 1 3 0.8%
22 2 1.8% 2 0.5%
252 2 1.8% 2 0.5%
855 2 1.7% 2 0.5%
92slv 2 1.8% 2 0.5%
6 1 0.9% 1 0.3%
12 1 0.9% 1 0.3%
19 1 0.9% 1 0.3%
27 1 2.4% 1 0.3%
32 1 0.9% 1 0.3%
54 1 0.9% 1 0.3%
92 1 0.9% 1 0.3%
210 1 25.0% 1 0.3%
212 1 4.5% 1 0.3%
266 1 0.9% 1 0.3%
327 1 0.9% 1 0.3%
35
ACT n %
NSW n %
NT n %
QLD n %
SA n %
Tas n %
Vic n %
WA n %
Australia n %
361 1 1 0.3%
414 1 0.9% 1 0.3%
604 1 7.1% 1 0.3%
612 1 0.9% 1 0.3%
717 1 0.9% 1 0.3%
755 1 0.9% 1 0.3%
779 1 0.9% 1 0.3%
800 1 1 0.3%
994 1 0.9% 1 0.3%
1036 1 4.5% 1 0.3%
1051 1 0.9% 1 0.3%
1192 1 0.9% 1 0.3%
109slv 1 0.9% 1 0.3%
713dlv 1 2.4% 1 0.3%
80slv 1 0.9% 1 0.3%
M-type 4 1 0.9% 1 0.3%
New -2 1 0.9% 1 0.3%
New-1 1 1 0.3%
New-3 1 1 0.3%
to be advised
1 0.9% 1 0.3%
Total 22 100.0 115 100.0 4 100.0 42 100.0 39 100.0 14 100.0 111 100.0 53 400 100.0 ACT= Australian Capital Territory, NSW = New South Wales, NT = Northern Territory, Qld = Queensland, SA = South Australia, Tas = Tasmania, Vic = Victoria, WA = Western Australia.
36
Table 21: The number and proportion of Enterococcus faecium MLST harbouring vanA/B genes.
MLST vanA n %
vanB n %
vanAB n %
Not detected n %
M-type 1 51 79.7% 1 1.6% 12 18.8%
17 1 1.7% 4 6.8% 54 91.5%
796 54 96.4% 2 3.6%
80 17 33.3% 5 9.8% 2 3.9% 27 52.9%
555 1 2.6% 17 43.6% 21 53.8%
203 3 11.5% 14 53.8% 9 34.6%
M-type 3 11 73.3% 4 26.7%
78 1 7.7% 11 84.6% 1 7.7%
262 2 16.7% 10 83.3%
117 7 100%
192 6 100%
18 5 100%
M-type 2 5 100%
94 3 100%
22 2 100%
252 1 50% 1 50%
855 2 100%
92slv 2 100%
6 1 100%
12 1 100%
19 1 100%
27 1 100%
32 1 100%
54 1 100%
92 1 100%
210 1 100%
212 1 100%
266 1 100%
327 1 100%
37
MLST vanA n %
vanB n %
vanAB n %
Not detected n %
361 1 100%
414 1 100%
604 1 100%
612 1 100%
717 1 100%
779 1 100%
800 1 100%
994 1 100%
1036 1 100%
1051 1 100%
1192 1 100%
109slv 1 100%
M-type 4 1 100%
New-3 1 100%
713dlv 1 100%
80slv 1 100%
New-1 1 100%
New -2 1 100%
755 1 100%
To be advised 1 100%
Total 85 21.3% 110 27.5% 3 0.8% 202 50.5%
38
Acknowledgements We gratefully acknowledge Ms Yung Thin Lee and Dr Stanley Pang, Antimicrobial Resistance and
Infectious Disease Laboratory, School of Veterinary and Life Sciences, Murdoch University, WA and the
participating members of the AGAR:
Australian Capital Territory
Peter Collignon and Susan Bradbury, The Canberra Hospital
New South Wales
Thomas Gottlieb and Graham Robertson, Concord Hospital
James Branley and Linda Douglass, Nepean Hospital
Peter Huntington, Royal North Shore Hospital
Sebastian van Hal and Bradley Watson, Royal Prince Alfred Hospital
Jon Iredell and Andrew Ginn, Westmead Hospital
Rod Givney and Ian Winney, John Hunter Hospital
Peter Newton and Melissa Hoddle, Wollongong Hospital
Northern Territory
Rob Baird and Jann Hennessy, Royal Darwin Hospital
James McLeod, Alice Springs Hospital
Queensland
Enzo Binotto and Bronwyn Thomsett, Pathology Queensland Cairns Base Hospital
Graeme Nimmo and Narelle George, Pathology Queensland Central Laboratory
Petra Derrington and Sharon Dal-Cin, Pathology Queensland Gold Coast Hospital
Robert Horvath and Laura Martin, Pathology Queensland Prince Charles Hospital
Naomi Runnegar and Joel Douglas, Pathology Queensland Princess Alexandra Hospital
Jenny Robson and Georgia Peachey, Sullivan Nicolaides Pathology
South Australia
Kelly Papanaoum and Nicholas Wells, SA Pathology (Flinders Medical Centre)
Morgyn Warner and Kija Smith, SA Pathology (Royal Adelaide Hospital and Women’s and Children’s
Hospital)
39
Tasmania
Louise Cooley and David Jones, Royal Hobart Hospital
Pankaja Kalukottege and Kathy Wilcox, Launceston General Hospital
Victoria
Denis Spelman and Rose Bernhard, The Alfred Hospital
Paul Johnson and Elizabeth Grabsch, Austin Hospital
Tony Korman and Despina Kotsanas, Monash Medical Centre
Andrew Daley and Gena Gonis, Royal Women’s Hospital
Mary Jo Waters and Lisa Brenton, St Vincent’s Hospital
Western Australia
David McGechie and Denise Daley, PathWest Laboratory Medicine – WA Fiona Stanley Hospital
Ronan Murray and Jacinta Bowman, PathWest Laboratory Medicine – WA Queen Elizabeth II Hospital
Michael Leung, PathWest Laboratory Medicine – Remote WA
Owen Robinson and Geoffrey Coombs, PathWest Laboratory Medicine – WA Royal Perth Hospital
Sudha Pottumarthy-Boddu and Fay Kappler, St John of God Pathology, Murdoch
Shalinie Perera and Ian Meyer, Western Diagnostic Pathology, Joondalup Hospital
40
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