1. case 5
Facilitator version

2. Admission 66 year-old man Admitted for 2nd cycle chemotherapy
Chronic myelomonocytic leukaemia
Diagnosed 6/12 previously
Skin and lymph node involvement
1st cycle complicated by right lower lobe pneumonia
Empiric treated with meropenem and gentamicin x 8/7
No pathogen identified. Empiric treatment with meropenem, gentamicin. Settled.

3. Admission - history PMHx COPD Osteoarthritis MI - 20 years ago
Allergic to penicillin – throat swelling
Medications
Valaciclovir
Pantoprazole
Nicotine patch
Aqueous cream
Throat swelling with penicillin

4. Admission - examination
Dry flaky skin rash
PICC – right arm (in situ x 2/12)
Otherwise no abnormal findings
Creatinine 112 (normal range )
WCC 6.5 (normal range )

5. Days 2-6 Bone marrow aspirate Chemotherapy Fludarabine Cytarabine gCSF
Well throughout
Weekend leave
Bone marrow aspirate – hypercellular, appearance consistent with remission from CMML

6. Day 9 Returned from weekend leave Neutropenic WCC 0.6 Neuts 0.6 Hb 8.3
Plts 177
Afebrile, no complaints
Platelets 117

7. Days 10-11
Day 10
Afebrile
Diarrhoea x 1 – sample sent for C. difficile PCR
Day 11
Diarrhoea x 2
C. difficile PCR positive
Contact precautions
Oral metronidazole
In single room accomodation

8. Days 12-13 3-4 episodes diarrhoea per day Afebrile
Continued on metronidazole

9. Day 14 (Saturday) WCC 0.1 10.25 Patient complained of rigors
Temp 39.4°C
BP 143/83
HR 95
RR 19
O2 sats 95% (on room air) EWS 4
Neut count not routinely reported on call, was 0.0 on day 13

10. Irish national early warning score

11. Irish national EWS – escalation protocol

12. What’s wrong with the patient?

13. What’s wrong with the patient?
Neutropenic fever
Single oral temperature > 38.3°C or
Temperature > 38.0°C sustained for > 1 hour

14. Day 14 10.30 Blood cultures drawn (PICC and peripheral)
Medical review requested
10.50
Seen by haematology registrar on call

15. What are the potential sources of fever?

16. What are the potential sources of fever?
C. difficile colitis
Neutropenic enterocolitis
PICC line
Pneumonia
Skin and mucous membranes
Oral infection
Perianal infection
Bone marrow aspirate site

17. Day 14 10.50 Seen by haematology registrar on call No abdominal pain
Diarrhoea settling
No sore throat
No cough, no SOB
No urinary symptoms
No change in rash
PICC working

18. Day 14 Examination Throat – no erythema, no exudate
PICC site – no erythema, clean
Chest – clear to auscultation
Abdomen – soft, non-tender
Plan
Blood cultures, MSU
CXR
Antibiotics

19. What do you need to consider when choosing antibiotic therapy?

20. What do you need to consider when choosing antibiotic therapy?
Patient history
Antibiotic allergies
Symptoms
Signs
Recent antibiotic therapy
Culture results
Institutional resistance patterns/pathogens

21. Our patient Current C. difficile infection
Penicillin allergy – throat swelling
No localising symptoms or signs
Antibiotic x 1/12 ago for pneumonia
No antibiotic prophylaxis
No recent isolates
Not known to be colonised with MDRO (admission and weekly screens for MRSA, VRE, ESBL and CRE negative)
Admission and weekly screens for MRSA, VRE, ESBL and CRE negative

22. Antibiotics prescribed
Meropenem 1g iv 8-hourly – first dose given at 11.30
Gentamicin 300mg iv – first dose given at 11.28
(weight 62kg, creatinine 101)

23. What do you think of the antibiotic choice?

24. What do you think of the antibiotic choice?
Monotherapy versus combination therapy
Penicillin allergy and use of carbapenem

25. Recommendations for empiric antibiotics in neutropenic sepsis
IDSA, 2010 (Freifeld et al, CID, 2011:52)
Monotherapy with piptazobactam or carbapenem or ceftazidime or cefipime
Penicillin hypersensitivity – clindamycin and ciprofloxacin or vancomycin and aztreonam
NICE clinical guideline, 2012 (CG 151)
Monotherapy with piptazobactam
No specific recommendation for penicillin allergy

26. Carbapenem use in penicillin allergy
Systematic review (Kula et al, CID, 2014)
Cross-reactivity between penicillins and carbapenems for IgE-mediated reactions is very low – caution advised
Cross-reactivity between cephalosporins and carbapenems may be higher – minimal data available

27. What about the timing of the antibiotics?

28. What about the timing of the antibiotics?
Febrile neutropenia = medical emergency
Empiric antibiotics should be given within one hour of presentation1, 2
Fever recorded at 10.25
Seen by registrar at 10.50
Antibiotics given at and 11.30
1NI Cancer Network neutropenic sepsis guidelines, 2010
2NICE Clinical Guidelines 151, 2012

29. Day Day

30. Day 15 Blood cultures (day 14)
Line – both bottles – Gram negative bacilli
Peripheral – sterile to date
11.45
Haematology registrar phoned by microbiology registrar
Patient afebrile since on day 14
Advised continue meropenem and gentamicin, repeat blood cultures
Gentamicin 300mg given (no gentamicin level done, creatinine 103)
No gentamicin level done, creatinine 101 – in normal range

31. CXR – day 15

32. Day 16 Blood cultures (day 14)
Line – Klebsiella pneumoniae (MALDI-TOF)
Direct susceptibilty test –susceptible to coamoxiclav, ciprofloxacin, gentamicin, cefuroxime
Peripheral - sterile to date
Blood cultures (day 15)
Line and peripheral – sterile to date
Trough gentamicin level 2.4 – dose held
Patient remains afebrile, diarrhoea resolved
ID by MALDI-TOF. Direct sens – looks susceptible to cefpodoxime, cipro, gent, cefoxitin, cefuroxime, coamox. Target gentamicin level <1.0; gentamicin held

33. Day 17 Blood cultures (day 14)
Line – Klebsiella pneumoniae – resistant to amoxicillin only
Peripheral - sterile to date
Blood cultures (day 15)
Line – sterile to date
MSU (day 14) – WCC < 1, no growth
Patient remains afebrile

34. What do you advise now?

35. What do you advise now? Antibiotic options with penicillin allergy
Continue meropenem
Change to ciprofloxacin – C. difficile infection
Change to aztreonam
Remove PICC?
Line cultures positive
No other source found
VIP (visual infusion phlebitis) scores recorded daily = 0
Care bundle for PICC – completed daily – no signs infection recorded during admission

36. IV catheter removal IDSA, 2010 (Freifeld et al, CID, 2011:52)
If CRBSI in neutropenic patient, remove catheter if: -
S. aureus, P. aeruginosa, fungi or mycobacteria
tunnel infection or port pocket site infection
septic thrombosis
infective endocarditis
sepsis with haemodynamic instability
BSI persisting for > 72 hours despite appropriate antibiotics

37. Day 17 Seen by consultant microbiologist Afebrile No diarrhoea WCC 0.1
EWS 0
Advice
Consider removal of PICC
Change meropenem to aztreonam
Give one more dose of gentamicin (level = 0.5)

38. Progress PICC not removed Changed to aztreonam on day 17
Gentamicin stopped on day 18 (4 days in total)
Metronidazole stopped on day 24 (14 days in total)
Aztreonam stopped on day 28 (15 days mero/azt)
Remained afebrile
Discharged home on day 29 - WCC 1.8, neut 1.3
Line remains in situ, blood cultures sterile