Dr Abby Douglas

ID registrar

Victorian Infectious Diseases Service

Royal Melbourne Hospital

7th July 2015

Mrs I - admission 8th Feb 2015

63yo lady diagnosed with AML

Hickman inserted: 9/2

Induction chemotherapy 7 + 3: 11/2

Febrile neutropenia: 18/2-26/2

Piperacillin-tazobactam or Meropenem 18/2-2/3

Vancomycin 19/2- 28/2

No source found

Routine VRE screening 8/2, 15/2, 22/2 negative

VRE screening swab 1/3 - Van A VRE

Discharged home 3/3, well, PMN 0.7

Second admission

5th March Readmitted

Failed induction – identified on BMAT

Contact isolation (due to van A VRE)

Re-induction chemotherapy

Febrile neutropenia

Commenced empiric antibiotics

piperacillin tazobactam plus daptomycin

Why daptomycin?….

Context: VRE in haem unit at RMH

2013-2014:

Several cases of VRE bacteraemias in haematology patients

Clinically severe sepsis – often requiring ICU, at least one death

Meeting ICU/ haem/ VIDS

Approved empiric teicoplanin or daptomycin (rather than vancomycin) for haem patients with severe sepsis who were known to be VRE colonised

Screening of all haem patients (5 north) weekly for VRE

What happened next Outbreak of Van A VRE in 5 north from Nov 2014

24 patients positive on screening or clinical isolates 1 imported

17 screening swabs

2 bacteraemias

4 non-blood isolates (2 urine, pelvic drain, infected haemorrhoid)

6 deaths in these patients (1 from sepsis, others unrelated)

Plus 6 non-5 north patients. Only 1 with possible epidemologic link to 5 north

0

2

4

6

8

Nov Dec Jan Feb Mar Apr May

No

of

cases

Month

VanA on Haem/Onc ward

Cases

Deaths

E.faecium at RMH 1/11/14 – 29/6/15

Non-VRE VanB VanA Total

E.faecium

Blood cultures 3 7 3 13

Non-BC

specimens

- Urine

- Pelvic collection

- Infected

haemorrhoid

29 74 8

(6)

(1)

(1)

111

Screening swabs - 87 24 111

The outbreak: 5 north

16/11/14 17/11/14 18/11/14 19/11/14 20/11/14 21/11/14 22/11/14 23/11/14 24/11/14 25/11/14 26/11/14 27/11/14 28/11/14 29/11/14 30/11/14 1/12/14 2/12/14 3/12/14 4/12/14 5/12/14 6/12/14 7/12/14 8/12/14 9/12/14 10/12/14 11/12/14 12/12/14 13/12/14 14/12/14 15/12/14 16/12/14 17/12/14 18/12/14 19/12/14 20/12/14 21/12/14 22/12/14 23/12/14 24/12/14 25/12/14 26/12/14 27/12/14 28/12/14 29/12/14 30/12/14 31/12/14 1/1/15 2/1/15 3/1/15 4/1/15 5/1/15 6/1/15 7/1/15 8/1/15 9/1/15 10/1/15 11/1/15 12/1/15 13/1/15 14/1/15 15/1/15 16/1/15 17/1/15 18/1/15 19/1/15 20/1/15

5N 16

5 WDC > 5N 15 5N 15 5N 15 5N 15 5N 15 Home 5WDC 5WDC 5WDC 5WDC > 5N 7 5N 7 5N 7 5N 7 5N 7> 2 5N 2 5N 2 5N 2> Home 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC

9E 4 9E 4 9E 4> D/c 5WDC 5WDC 5WDC 5N 1 5N 1>7> 8 5N 8 5N 8> D/c

5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 12 5N 12 5N 12 5N 12 HITH HITH HITH HITH HITH HITH HITH HITH HITH HITH HITH HITH HITH 5N 16 Home

5WDC 5WDC 5WDC 5WDC 5WDC 6SW 57 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 2S 11 2S 11 2S 16 2S 14 2S 16 2S 16 2S 16 2S 16 2S 16 5N 11>2 5N 2 5N 1 5N 1 5N 1 5N 1 5N 16 5N 16 5N 16 6SE 4 6SE 4 6SE 4 6SE 4 6SE 4 6SE 4

5WDC 5WDC 3E>HITH 5WDC>HITH 5WDC>HITH HITH HITH HITH HITH>5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 9E 11 9E 11 9E 11 9E 11

APU 11 APU 11 RAPU 27>9W20>8>CCU5 CCU 5 CCU 5 5N 5 > 15 5N 15 5N 15 5N 15 5N 15 5N 15 5N 15 5N 15 5N 15 5N 15 5N 15 5N 15 2S 16 2S 16 2S 16 2S 16 2S 16 5N 6 5N 6 5N 6 5N 6 5N 6 2S 11 2S 11 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3

5WDC 5RC 5WDC 13C 5N 2 5N 2 5N 2 5N 4 5N 4 5N 4 5N 14 Home 5N 5 > leave 5N 17 5N 17 5N 17 5N 17 5N 12 5N 12 Home 5N 16 5N 14 5N 14 5N 14 5N 14 5N 12 5N 9 Home 5WDC 2AC 5WDC 14C 5WDC 10C

5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 11 > 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 Home 5WDC 5WDC > 5N 12 > 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 2S 16 2S 16 2S 16 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 2S 16 2S 16 2S 16 2S 16 2S 16 5N 1 5N 1 5N 1 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16

5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 17 5N 17 5N 17 5N 15 5N 14 5N 14 5N 14 5N 14 5N 14 5N 14 5N 14 5N 17 5N 17 5N 17 Home 5WDC

5WDC > 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 Home 5N 13 > 2 5N 2 5N 2 7WPC 9 7WPC 9 7WPC 9 7WPC 9 7WPC 9

5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 5E 2 Home 5WDC 5WDC 5WDC 5WDC > HITH 5>3 5N 8 > 5E 9 HITH 20 HITH 20 HITH 20 5WDC > HITH 4

5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 2 5N 2 5N 2 5N 2 5N 2

5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC

5E 3>5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5 5E 5> HIH 18 HIH 18 HIH 18 HIH 18 HIH 18 HIH 18 HIH 18>D/c 5WDC 5WDC 5N 6> 4 5N 4 5N 4 5N 4> D/c 5WDC 5WDC HIH 26 HIH 26> 10 HIH 10> 9 HIH 9 HIH 9 HIH 9 HIH 9 HIH 9 HIH 9>10>9 HIH 9 HIH 9 HIH 9 HIH 9

5N 10 5N 10 5N 10 > 9>17 5N 17 5N 17 5N 17 5N 17 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7

SSU 21 5N 5 5WDC 5WDC 5WDC 5WDC

RAPU 31>APU 13 Home 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 13 5N 1 5N 2 5N7 > Home 5WDC 15C 5N 1 5N 1 5N 1 5N 1 5N 1 Home

5WDC 14C 5WDC 1AC

16/11/14 20/01/15

21/1/15 22/1/15 23/1/15 24/1/15 25/1/15 26/1/15 27/1/15 28/1/15 29/1/15 30/1/15 31/1/15 1/2/15 2/2/15 3/2/15 4/2/15 5/2/15 6/2/15 7/2/15 8/2/15 9/2/15 10/2/15 11/2/15 12/2/15 13/2/15 14/2/15 15/2/15 16/2/15 17/2/15 18/2/15 19/2/15 20/2/15 21/2/15 22/2/15 23/2/15 24/2/15 25/2/15 26/2/15 27/2/15 28/2/15 1/3/15 2/3/15 3/3/15 4/3/15 5/3/15 6/3/15 7/3/15 8/3/15 9/3/15 10/3/15 11/3/15 12/3/15 13/3/15 14/3/15 15/3/15 16/3/15 17/3/15 18/3/15 19/3/15 20/3/15 21/3/15 22/3/15 23/3/15 24/3/15

5WDC 5WDC 5

5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 4BB 5WDC 5RC 5WDC 7BB 5WDC 15C 5N 1 Home 5N 16 5N 16 Home

T/L 3>ED ED> 5N 2 5N 2 5N 2 5N 2 5N 2 5N 2 5N 2 > RIP

6SE 4 6SE 4 6SE 4 6SE 4 6SE 4 6SE 4 6SE 4 6SE 4 6SE 4 6SE 4> 5N 3 5N 3 5N 3 5N 3 > 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 9E 18 9E 18 9E 18 9E 18 9E 18 9E 18 OR> 4S 53 4S 3 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12

9E 11 9E 11> Home 5WDC

5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5> 16 5N 16 5N 16 5N 16 5N 16 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 1 5N 1 5N 1 5N 1

5WDC 18C 5WDC Hold 5N 6 Tran 8> Home 5N 4 > 17 Home 5WDC 12C 5WDC 10C 5WDC 1AC 1W 1 Oro/Maxfacial 1C 1W

5N 16 5N 16 RIP

3E > 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 5N 6 5N 6 5N 6 5N 6 5N 6>ICU 18 ICU 18> 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6> D/c 5WDC 5N 6 5N 6 5N 6 5N 6 5N 6> D/c 5N 16 5N 16> 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 Home 5WDC 2AC 5WDC 12C

7WPC 9 7WPC 9 7WPC 9 7WPC 9 7WPC 9 RIP

HITH 4 HITH 4 HITH 4 HITH 4 HITH 3 HITH 4 5WDC>5N 17,5,3,4,6 5N 6 5N 6 5N 6 5N 6 5N 6 > 16 5N 16> HIH 3 HIH 3 HIH 3 HIH 3 >5WDC >HIH4 HIH 4> 1 HIH 1 HIH 1 HIH 1 HIH 1 HIH 1 HIH 1> 5WDC>HIH HIH 1 HIH 1 HIH 1> 2 HIH 2 HIH2> 5WDC>HIH 5WDC 5WDC 2AC 5WDC 1AC 5WDC 6BB

5N 2 5N 2 5N 2 5N 2 5N 2 5N 2 5N 6 > 4 5N 4 5N 4 5N 4 5N 4 5N 4 5N 4> D/c 5WDC 17C 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6> D/c 5WDC> 5N 2 5N 2 5N 2> 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 17 5N 17 5N 17 5N 17

5WDC >CCU 4 CCU 4> 5N 6 5N 6 5N 6 5N 6 5N 6 > 2 5N 2 5N 2 5N 2 5N 2 5N 2 5N2 5N 2 5N 2 5N 2 5N 2 5N 2 5N 2 5N 2> D/c RIP

HIH 9 HIH 9 HIH9>5WDC>HIH9 HIH 9 HIH 9>11 HIH 11 HIH 11 HIH 11>10 HIH 10 HIH 10 HIH 10>9 HIH 9 HIH 9 HIH9> 5WDC>5N16 5N 16> 5E 9 5E 9 5E 9 5E 9 5E 9 5E 9 5E 9 5E 9 5E 9> ICU18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 ICU 18 > 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 >2S 18 2S 18 2S 18 2S 18 2S 18 > 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8

5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10> 12 5N 12 5N 12> 2 5N 2 5N 2 5N 2 5N 2> 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5WDC 1AC 5WDC 10C > 5N 4 5N 4 5N 4 > 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 > 5N 5 5N 5 5N 5 5N 5 5N 5 5N 5 5N 3 5N 3 5N 3 5N 3

5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 Home 5WDC 3 5N 8 5N 8 5N 8 5N 8 5N 8 5N 8 Home 5WDC 1 5N 14 5N 14 5N 14 5N 14 5N 14 5N 14 Home 5WDC 5 5WDC 4 >5N 1 5N 1 5N 1 5N 1 Home 5WDC 4RC>5N 16 Home

5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 5WDC 3E 1 > 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4 5E 4

ED 5WDC > 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11

5N 13 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 Home 5WDC 11C>5N 8 5N 8 5N 8 5N 8 Transit>home 5WDC 10C 5WDC 1A>5N 7 5N7 5N 16 5N 16 Home 5WDC 6BB 5N 1 5N 1 5N 1 5N 1 5N 1 Transit>Home 3S 27 5N 3 5N 3 5N 3 5N 3 Home 5N 12

5N 1 5N 15 5N 15 5N 15 5N 9 5N 9

5N 17 5N 6 5N 6 5N 6 5N 6

5WDC Hold 5WDC 6BB 9E 8 9E 8 9E 8 9E 8 7WPC 7WPC 7WPC 7WPC

RAPU 26 9E 17>15 5SE 16 9E 10 9E 10 9E 10 9E 10 5SE 13 5SE 10 5SE 10 5SE 10 5SE 10 5SE 10 Home

21/01/15 24/03/15

25/3/15 26/3/15 27/3/15 28/3/15 29/3/15 30/3/15 31/3/15 1/4/15 2/4/15 3/4/15 4/4/15 5/4/15 6/4/15 7/4/15 8/4/15 9/4/15 10/4/15 11/4/15 12/4/15 13/4/15 14/4/15 15/4/15 16/4/15 17/4/15 18/4/15 19/4/15 20/4/15 21/4/15 22/4/15 23/4/15 24/4/15 25/4/15 26/4/15 27/4/15 28/4/15 29/4/15 30/4/15 1/5/15 2/5/15 3/5/15 4/5/15 5/5/15 6/5/15 7/5/15 8/5/15 9/5/15 10/5/15 11/5/15 12/5/15 13/5/15 14/5/15 15/5/15 16/5/15 17/5/15

5WDC 4RC 2SW

5WDC 7BB 5WDC 2AC 5WDC 17C 5WDC 14C 5WDC 4RC 5WDC 13C 5WDC 4RC 5WDC 8BB 5WDC 2AC 5WDC C5 5WDC 4RC 5WDC 4RC 5WDC 6BB 5WDC 11C 5WDC 3RC 5WDC 3RC 5WDC 8BB 5WDC 9C 5WDC 2AC

3E 1>4S 52 4S 3 Home ED > 4S 17 4S 17 4S 17

9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 9E 12 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1 6SE 1

5WDC 12C 5WDC 3RC

5N 12>10 5N 10 5N 10 5N 10 5N 10 5N 10 2S 8 2S 8 5E 6 5E 6 5E 6 5N 1 > 5 > 17 Home 5WDC 5RC 5WDC 2AC

HITH HITH HITH HITH 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 6 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 5E 3 Home 9E 18 9E 18 5N 1 > Home

5N 3 5N 12 5N 12 5N 12 5N 12 Home 5N 5 > 16 5N 16 5N 16 5N 16 5N 16 5N 12 5N 12 5N 17 5N 17 5N 17 5N 17 Home APU 17 Home 5WDC 9C 5WDC 16C

5N 17 5N 17 RIP

5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 5E 8 2S 9 2S 9 2S 9 5E 3 2S 9 2S 9 2S 9 2S 9 5E 9>8 5E 8 5E 8 2S 8 2S 8

5N 10>12 5N 12 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 Home 5WDC 3RC 5WDC 8BB 2E 3 > Home 5WDC 6BB 5WDC 5RC 5WDC 1AC>3E>5E 5 5E 5 5E 5 5E 5 5E 5

ED 5SW 44 5SW 44 Home 5WDC 1AC 5WDC 3RC

5E 4 5E 4 5E 4 5E 4 5E 4 Home 5WDC 6BB 5WDC 2AC

5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 17 5N 17 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 5N 11 Home 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 Home 5WDC Hold>5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 5N 3 Home 5WDC 12C

5N 1 5N 1 5N 1 Home 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 Home 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16 5N 16

5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 9 5N 1 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 10 5N 1 5N 1 5N 1 5N 1 5N 1 5N 1 Home 5WD 15C 5WDC 17C 3E 1 > 5N 2 5N 2 5N 2 5N 2 Home 5N 17 5N 17 5N 17 5N 17 5N 17 5N 17 Home

5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 5N 6 2S 20 2S 20 2S 20 5N 6 5N 6 5N 6 2S 4 > 8 2S 8 2S 8 2S 8 2S 8 2S 8 2S 8 2S 8 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 5N 7 Home

7WPC 7WPC 7WPC 7WPC 7WPC Home 5WDC 14C > 5N 7 5N 7 5N 7 5N 7 Transit . Home APU 2 5N 14 5N 14 5SE 5

6SW 51 6SW 43>5N10 5N 10 5N 10 5N 10 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12 5N 12

25/03/15 17/05/15

Not admitted

Not Van A colonised

New Van A VRE

Van A colonised inpatient

Death

Imported VanA

VanB

VanA

VanA and

Van B

Back to Mrs I’s case

Day 1 Day 24 post

induction

Re-admitted

as failed

induction on

BMAT

Day 2 Commenced

on FLAG-

AMSA

reinduction

Day 3-4 Fevers

with 1st

two

doses

ARA-C

Piperacillin-tazobactam

daptomycin

Day 17 Febrile

neutropenia

Rigors

No obvious

source

vancomycin

Day 17/18 Blood cultures

flagged for

GPC 6/6

bottles

Day 18 E.faecium

identified 6/6

bottles

Dapto 6mg/kg

3 days (4mg/kg)

PMN <0.5

E.faecium - initial sensitivities

Amoxicillin R

Penicillin R

Teicoplanin R

Vancomycin R

Linezolid S

(Daptomycin not tested routinely)

Current admission Day 20 Changed

dapto to

10mg/kg

Hickman

removed

Day 21

Fevers

ongoing

HD stable

+ve BCs

ongoing

daptomycin

Day 18 E.Faecium

identified 6/6

bottles

Dapto 6mg/kg

Day 22 Daptomycin

E-test

requested

Day 23 DAPTOMYCIN

RESISTANT

Switched to

linezolid

linezolid

Day 24 Afebrile

Clinically

improved

(24h linez)

Day 26 Last positive

blood culture

Day 31 TOE

negative for

IE

Day 40 Linezolid

ceased

Remained well

thereafter

PMN <0.5

Incidence of daptomycin resistance in VRE?

Initially unclear how many VanA VRE cases were non-

susceptible Not routinely tested

Retrospective testing of screening + clinical isolates of

VanA

25 isolates tested

19 5N isolates

6 dapto

non-susceptible

13 dapto susceptible

6 non-5N isolates

3 dapto

non-susceptible

3 dapto

susceptible

Daptomycin use prior to resistance

Our patient

Screening swab VRE 1/3/15- MIC 4

Daptomycin 4mg/kg for 3 days in between

Blood culture VRE 22/3/15- MIC 12

9

dapto-nonsusc

isolates

2

Prior daptomycin

7

No prior

daptomycin

Induction of

resistance

possible

? Spread from

other patients

On 5 north, isolates with dapto MIC=12

? ? ?

Our patient

Dapto non-

susceptible

?7/3-22/3

Patient B

No dapto

Colonised 22/3

Patient C

No dapto

Colonised 30/3

Patient D

No dapto

Colonised 19/4

?

?

Clinically significant VRE in

Australia 1994

VanB outbreak Austin 2007

Pre -2006:

all VSE & VRE - ST17

By 2009

82% of blood isolates ST203

All dominant STs first appeared in VSEfm, then

appeared in different patients as VREfm

The impact of VRE Previous opinion….

“patients died with VRE, not from VRE”

However…

Globally, enterococci approx 10% of all bacteremias

Up to 35% of E.faecium bacteraemia are VRE in Europe

Up to 60% E.faecium bacteraemia are VRE in US

Enterococci now most common cause of CLABSIs in

Australia (60% are VRE)

Significant mortality, particularly for haem/oncology patients

Pinholt M et al. Clin Microbiol Infect 2014; 20:145-51

Worth LJ et al. Am J Infect Control 2015- Published online

Australian Enterococcal Sepsis Outcome Program (AESOP),

developed by AGAR

Calendar year 2011

1079 enterococcal isolates from BCs

61% E.faecalis, 35% E.faecium

E.faecium: 36% vanc resistant

VSE - 9% harboured vanB gene

VRE - 107 total, only 2 had vanA gene, 104 had vanB

2 major STs: ST203 and ST17 isolated across Australia

Mx of Van A VRE bacteraemia

3 meta-analyses: shown linezolid to be superior daptomycin

All retrospective data, non-randomised, heterogeneous

populations

Balli et al

(n=967)

Chuang et al

(n=1188)

Whang et al

(n=1074)

30-day

mortality

(dapto vs linez)

OR 1.61 (1.08-

2.40)

OR 1.43 (1.09-

1.86)

OR 1.3 (1.1-

1.8)

Relapse rate

(dapto vs linez)

OR 2.51 (0.94-

6.72)

OR 2.65 (1.03-

6.78)

N/A

Clinical cure OR 1.04 (0.63-

1.72)

OR 0.85 (0.48-

1.49)

OR 1.2 (0.7-

2.0)

Microbiol cure OR 0.75 (0.41-

1.39)

OR 0.67 (0.42-

1.06)

OR 1.0 (0.4-

1.7)

Adverse events No difference No difference N/A

Balli EP et al. Antimicrob Agents Chemother 2014;58:734-739

Chuang YC et al. BMC Infect Dis 2014;13:687

Whang DW et al. Antimicrob Agents Chemother 2013;57:5013-5018

Retrospective study US Veterans Affairs patients 2004-

2013 (N=644)

Daptomycin susceptibility not routinely reported

10% of patients tested- all susceptible

Median daptomycin dose was 5.9mg/kg

Treatment failure - composite of:

30 day all cause mortality

Microbiological failure

Recurrence of VRE-BSI within 60 days

Significant benefit daptomycin vs linezolid

Overall treatment failure 61%, 30-day all-cause mortality 38%

Adverse events: no stat sign difference in thrombocytopenia or CK

elevation

Britt N et al. Clin Infect Dis, Advanced Access June 10 2015

Survival Lack of micro clearance

Britt N et al. Clin Infect Dis, Advanced Access June 10 2015

Daptomycin-resistant VREfm First case reported US (Lesho et al 2006)

Single hospital in NYC (Kamboj et al 2011)

Dramatic increase in DNSE bacteraemia from 3% in 2007 to 15% in 2009

Rest of the world: Recent publications from Asia, Europe, Australia/NZ,

Latin America - all 100% daptomycin sensitive

Lesho EP et al. J Clin Microbiol 2006; 44 (2):673

Kamboj M et al. Infect Control Hosp Epidemiol 2011; 32 (4): 391-394

Chitnis S et al. Indian J Med Res 2013;137:191-196

Wang JT et al. Diagn Microbiol Infect Dis 2013;75:406-411

Sader HS et al. J Chemother 2011;23:200-206

Berenger R et al. Med Mal Infect 2011;41:405-409

Bell JM et al. Pathology 2010;42:470-473

Sader HS et al. Diagn Microbiol Infect Dis 2013;75:417-422

Reliability of susceptibility testing

Single laboratory noted increase in DNSE: 8% 24%

? true vs lab-based error (using microscan)

Tested this against broth microdilution (BMD), etest

BMD was gold standard

Risk factors for daptomycin resistance (DNSE)

60% of patients with DNSE colonisation and/or infection had prior daptomycin exposure

78% of those with VRE bacteraemia

Other risk factors

concomitant GI process (76%)

Immunocompromise (84%)

8 hospitals in Detroit, US - Retrospective case-control study

Exposure to daptomycin in 3 months prior was uncommon

Multivariate analysis: factors assoc with DNSE

Higher comorbidity

Presence of indwelling devices

Exposure to cephalosporins and/or metronidazole in 3

months prior

Immunosuppression

These findings similar to another study (Kamboj et al 2011)

Of 18 cases of DNSE, only 2 had prior daptomycin exposure

Kamboj M et al. Infect Control Hosp Epidemiol 2011; 32 (4): 391-394

Outcomes in DNSE infections

Judge et al 2012 (60 cases, 70 controls)

Similar in-hospital & 3-month mortality to dapto-suscep

5% of DNSE isolates were also linezolid resistant

Kelesidis et al 2011

Only 8 cases reported clinical & microbiological outcomes

All 8 cases had failure of Rx (100%)

Wudhikarn et al 2013, US

8 haematology patients with DNSE: 4 blood, 4 urine

○ 2 died due to DNSE sepsis (25%)

Judge T et al. Infect Control Hosp Epi 2012;33:1250-1254

Kelesidis et al. Clin Infect Dis 2011; 52(2):228-234

Wudhikarn K et al. Ann Hematol 2013;92:129-131

Daptomycin dosing

Benvenuto et al 2006 - healthy volunteers

Dapto well tolerated up to 12mg/kg daily for 14 days

Moise et al 2009

Retrospective observational of patients who received does

>8mg/kg (94 pts), median duration of therapy: 15 days

37/94 had enterococcus infection

Approx 50% patients had bacteraemia or IE

6.4% adverse events likely related to daptomycin

○ 3.2% with CK elevation, all “non-serious”

Benvenuto et al. Antimicrob Agents Chemother 2006; 50: 3245-9

Moise et al. Ann Pharmacother 2009; 43: 1211-1219

Combination therapy?

Sakoulas et al 2012

Observation: amp- and dapto-resistant case responded

clinically to ampicillin plus daptomycin

In vitro analysis of this isolate

In media containing ampicillin, dapto MIC decreased

from 1.0 to 0.38mg/L

VRE had a reduced net positive surface charge

The VRE was more susceptible to killing by peptides

Werth et al 2015

Similar finding in 6 isolates of DNSE with ampicillin as

well as ceftobiprole

Sakoulas et al. Antimicrob Agents Chemother 2012; 56: 838-44

Werth BJ et al. J Antimicrob Chemother 2015;70:489-493

Moise PA et al. IN PRESS. Clin Therapeutics 2015

Retrospective study of large multicentre registry

Patients with VRE bacteraemia who received at least 3

days of daptomycin +/- concomitant beta lactams (n=262) Ampicillin, third-gen ceph, pip-taz, cefepime (unknown indication)

All were susceptible to dapto, some with high MIC (3-4)

Median dapto dose 6mg/kg (range 2.9-9.5mg/kg)

Tre

atm

ent success

In summary Van A VRE is an emerging problem in Australian

hospitals

Van A VRE can spread very rapidly in a hospital

environment, esp ST203 strain

There are cases of daptomycin resistance, which

would not be known without specific testing

Best treatment of Van A VRE - jury is still out

There is an urgent need for access to real-time data

on Van A VRE epidemiology in hospitals (and other

resistant bacteria)

Other hospitals’ experiences

Have you been seeing VanA VRE

infections?

Do you test for daptomycin resistance?

Do you have patients who are unwell

with VRE infection?

Thankyou!

Dr Caroline Marshall

Dr Kirsty Buising

Dr Monica Slavin

Dr Ben Howden

Dr Paul Johnson

Dr Vanessa Clifford and Royal

Melbourne microbiology lab