1. CASE 3
Dr Albert J Mifsud Consultant Public Health Microbiologist for South East London
Public Health England

2. Mr Travers*
56 year old civil engineer working in various locations in central Europe for previous 5 years
Generally fit and well
* fictitious name

3. Initial presentation: April 12
Presented to his general practitioner with symptoms of bladder outflow obstruction
Prostate Specific Antigen (PSA) performed: 4.9ng/ml
Referred to urology clinic in local DGH
Returned to Romania

4. Urology Clinic, July 2012 Symptoms On examination
urinary frequency (increasing over several months)
reduced flow (increasing over years)
some perineal discomfort (new)
On examination
apyrexial
Sl. tender mildly uniformly enlarged prostate

5. Investigations MSU (microscopy) PSA
35WBCs
No growth (routine culture)
PSA
4.8ng/ml
In view of persistently elevated PSA, listed for prostate biopsy
Returned to contract work abroad

6. Prostate biopsy: November 12
Pre-assessment
‘Penicillin allergy’ documented in notes
5th November (09:30hrs) : biopsy performed under LA
Ciprofloxacin 500mg commenced 2hrs prior to biopsy
Prescription for Ciprofloxacin 500mg bd 3days issued

7. Do you agree with this course of action?

8. Do you agree with this course of action?
Co-ordinator prompts
Should investigation and treatment for prostatitis have been undertaken (avoid as outside scope of this topic)?
Is ciprofloxacin an appropriate agent to be used for prophylaxis for TRUS (avoid as outside scope of this topic)?

9. Post-biopsy course Circa 18hrs post biopsy (03:00hrs, 6th Nov)
developed rigors
felt unwell
temp: 39.8oC
pulse rate: 110bpm
bp: 135/70mmHg
Admitted under Urology team (04:00hrs)
diagnosis of sepsis post TRUS biopsy + SIRS

10. What would you do now?

11. What would you do now? Co-ordinator prompts (1) Further history
Elucidation of nature of allergy as not done prev.
Nature of symptoms (with respect to prostatitis)
Investigations
Routine
Blood culture / rpt. MSU

12. Co-ordinator prompts (2)
Severity assessment
Assessment of need for supportive care
Antibiotics: Discussion around nature of allergy and antibiotics advised / contra-indicated

13. Initial management Blood cultures collected Treatment decision:
‘IV antibiotics: Tigecycline as allergic to Amoxil’
100mg loading dose (within 30mins), 50mg bd
FBC, U&E, CRP: largely normal

14. Do you agree with this approach?

15. Do you agree with this approach?
Co-ordinator prompts
September 2010: US FDA safety communication
April 2011: UK MHRA safety warning

16. Progress, 6th November 15:20hrs, while on Tigecycline:
further rigors
microbiology contacted. Notes state:
repeat blood / urine cultures
single dose of gentamicin
later (untimed):
temp 40.8oC
haematuria

17. 7th November 01:00hrs temp 38.2oC; pulse rate 112bpm; BP 79/47mmHg
Lactate: Not Done
urinary retention (catheterised)
resuscitation with fluids
reviewed by ITU team

18. What do you do now?

19. What do you do now? Co-ordinator prompts
Recent guidance: haemodynamically unstable patients should be transferred to ITU
Given that gentamicin had been given <10hrs earlier, would you change antibiotics? Risk of resistance given residence in C Europe?

20. 7th November Overnight Frequent reviews by ITU team
Assessed not to require ITU care
Urine output: >30mls/hr
Blood pressure: 120/65  86/58mmHg

21. 7th November
13:00hrs
Blood cultures: Gram negative rods

22. What do you do now?

23. What do you do now? Co-ordinator prompt
Any change in antibiotic administration at this time?

24. 8th November Progress: Pyrexia, tachycardia settled
Hypotension persisted (80-100mgHg systolic)

25. 8th November Blood culture result: Urine result - similar
E.coli
S gentamicin, imipenem, tigecycline, R ciprofloxacin, ESBL pattern
Urine result - similar
Microbiologist advice (telephone) :
continue tigecycline 48hrs, switch to imipenem if no improvement

26. Do you agree with this approach?

27. Do you agree with this approach?
Co-ordinator prompt
Is tigecycline appropriate in bacteremia?
Why not carbapenem?
If allergy status is cause for concern, options limited, maybe fosfomycin IV; combination therapy?
How long would you treat prostatis?

28. 9th– 18th November
Initial improvement, but interspersed with hypotensive periods
Microbiology advice (telephone) 9th Nov:
Continue gent (but incorrect info provided)
Switch to imipenem, ‘with caution’ due to allergy
However, tigecycline continued
Eventual improvement: discharged (18/11) after 12d course of tigecycline

29. Selected blood results
Date time
WCC
(x109/L)
Neuts
Plats
Creat
μmol/L
CRP
(mg/L)
6/11 04:24
6.9
6.4
101 93 5
7/11 00:55
10.9
10.5 58
178
106
8/11 03:33
8.6
7.6 28
144
231
9/11 09:02
16.8
14.6 43 92
215
10/11 09:28
14.1
11.2 62 90
114
11/11 16:00
12.2 88 87 61
14/11 11:39
19.1
14.5
352 98
16/11 09:07
435

30. Relapse, December 2012
1st December (i.e. 8 days later) presented with 2 day history of dysuria, frequency and shivering.
On examination: temp 37.8oC, tachycardic (120bpm) but normotensive (115/70mmHg)
Drug chart: ‘penicillin  headache’
Re-started on tigecycline

31. What would you do now?

32. What would you do now? Co-ordinator prompts
Meets SIRS / Sepsis criteria?
Further investigations / considerations?
Antibiotic choices?

33. Progress (2nd day)
Next day developed pyrexia (38.4oC), but remained haemodynamically stable
Discussed with microbiology (telephone): gentamicin advised
Remained pyrexial: MRI scan showed multiple abscesses within prostate
Blood cultures, urine from 2/12: coliform with sens pattern as previously
Microbiologist advised gent + mz

34. Subsequent progress Rapid recovery ensued over next 24hrs
Microbiologist advice (telephone): ‘only option is full 14day course of gentamicin plus metronidazole’
Meticulous monitoring of gentamicin levels with Hartford nomogram undertaken eGFR: 64mls/min/1.73m2 creatinine:106µmol/l

35. Do you agree with this advice?

36. Do you agree with this advice?
Co-ordinator prompts
Should audiometry be done routinely in pts receiving gentamicin beyond few days? BNF advises monitoring of renal, auditory and vestibular function in patients with renal impairment;
BNF advises caution if dose continued for >7days.

37. Outcome Presented to GP 1 wk later with unsteadiness: elaborate
Diagnosis of vestibular failure due to gentamicin made.

38. Lessons learnt

39. Lessons learnt Co-ordinator prompts:
Importance of investigating allergies at earliest opportunity and document in notes
What are true risks of use of penicillins and beta-lactams in such patients
Alternatives in apparently-true Type I hypersensitivity
Benefit of audiometry if long-term aminoglycosides contemplated