1. EDUCATIONAL WORKSHOPS 2009 CASE PRESENTATION THREE “He’s got another one, doctor” A difficult case of recurrent MRSA bacteraemia Author: Nick Brown, Addenbrooke’s Hospital Acknowledgement: Sani Aliyu, Sandwell and West Birmingham Hospitals – now Addenbrooke’s Hospital Details of the original case report have been adapted to emphasise particular points

2. Sponsored through an unrestricted educational grant from Novartis Pharmaceutical Ltd to help support the cost of developing and hosting this educational workshop series

3. Background 65 y old male Past history of hypertension and cerebro-vascular disease July 2003 Aortic aneurysm and complications Endovascular aortic aneurysm repair (EVAR) post-operative bleed requiring laparotomy paraparesis secondary to spinal cord ischaemia long term suprapubic catheter longstanding sacral pressure sores Author: Nick Brown, Addenbrooke’s Hospital

4. July 2007 Admitted with fever four years after aneurysm repair Blood cultures MRSA (isolate 1) X-ray pelvis and transoesophageal echocardiogram (TOE) – normal 2 weeks iv vancomycin plus oral rifampicin, then stopped Question: What was the source of infection? How would you have treated it? Author: Nick Brown, Addenbrooke’s Hospital

5. July 2007 5 days later- pyrexia MRSA again in blood cultures (isolate 2) Re-started vancomycin plus rifampicin for 4 weeks Home on doxycycline plus rifampicin for a further 4 weeks Author: Nick Brown, Addenbrooke’s Hospital

6. November 2007 re-admitted with fever and back pain after 9 days at home Blood cultures MRSA (isolate 3) Transthoracic echocardiogram (TTE) – normal Magnetic resonance imaging (MRI) spine - normal WCC scan suggestive of increased uptake in lower vertebra 1 week vancomycin, then MIC for MRSA strain reported as 3 mg/L intravenous linezolid for 10 days, then home on further 4 weeks oral Author: Nick Brown, Addenbrooke’s Hospital

7. Imaging 1: Indium-111 labelled white cell scan showing localised area of increased uptake in the lower abdomen or perhaps in the vertebrae Here it is

8. Population analysis of GISA

9. January 2008 re-admitted in septic shock, day 38 linezolid MRSA in blood (isolate 4) intravenous daptomycin - five fold rise in CK, therefore stopped (was on a statin at the same time) blood cultures MRSA (isolate 5) Quinupristin/dalfopristin plus fusidic acid for 12 weeks Author: Nick Brown, Addenbrooke’s Hospital

10. Late February 2008 Blood cultures sterile by week 3 of quinupristin/dalfopristin plus fusidic acid inflammatory markers settling Computerised axial tomography (CT) scan at week 7 – ‘increased thickness of aneurysm wall compared to previous scans’ Author: Nick Brown, Addenbrooke’s Hospital

11. Imaging 2: Computerised tomography (CT) scan showing aortic graft in situ with thickening of the aortic wall

12. April 2008 Cardiothoracic review - no surgical intervention indicated 11 weeks into quinupristin/dalfopristin treatment septic again ESBL-producing E. coli in urine and femoral line tip meropenem for 10 days quinupristin/dalfopristin discontinued end of 12 weeks blood cultures just before quinupristin/dalfopristin stopped MRSA (isolate 6) Author: Nick Brown, Addenbrooke’s Hospital

13. April 2008 Quinupristin/dalfopristin re-started (1 week later) plus daptomycin 4mg/kg CK levels remain normal 2 weeks - Quinupristin/dalfopristin switched to gentamicin and daptomycin dose increased to 10mg/kg new femoral line Author: Nick Brown, Addenbrooke’s Hospital

14. Mid-July 2008 Gentamicin stopped after 4 weeks MRSA bacteraemia persists (isolate 7) 8 weeks into daptomycin treatment - progressive rise in MIC daptomycin MIC 0.125 mg/L initially, but peaked at 12.0 mg/L Isolates now also resistant to rifampicin and fusidic acid Positron emission tomography (PET) scan confirms aortic graft infection Author: Nick Brown, Addenbrooke’s Hospital

15. Imaging 3: Positron emission tomography (PET) scan showing increased tracer activity in relation to the aortic graft

16. End-July 2008 Aortic graft replaced Cultures of graft are negative, but S. aureus identified by 16s rDNA PCR Given iv linezolid, then oral fosfomycin, doxycycline plus chloamphenicol for 4 weeks End-August 2008 switched to oral doxycycline alone 12 sets of blood cultures negative as at 1 Oct 2008 Author: Nick Brown, Addenbrooke’s Hospital