1. Dr Katherine Watson ST1 Microbiology Antibiotic Management of Neutropenic Sepsis at The James Cook University Hospital

2. Introduction  Review of trust antibiotic policy using:  Neutropenic Sepsis: Prevention and Management of Neutropenic Sepsis in Cancer Patients. NICE Guidelines, September 2012  Local antibiotic resistance rates in gram negative bacteraemias

3. NICE Guidelines  All patients should be offered:  Prophylaxis with fluoroquinolone antibiotics during expected periods of neutropenia  Piperacillin/tazobactam as initial empiric antibiotic therapy  Aminoglycosides not recommended  “ Unless patient specific or local microbiological contraindications”

4. Current Trust Antibiotic Policy  Neutrophil count < 1.0 x 10 9 /L plus any of the following:  Temp. > 38 o C at any time  Rigors  Hypothermia  Unexplained hypotension  Unexplained deterioration without pyrexia  Patients must receive intravenous antibiotics within 1 hour of presentation  First Line Antibiotic (pending culture results) Piperacillin/Tazobactam 4.5g tds  + Gentamicin 5mg/kg stat  First Line Antibiotic (pending culture results) Piperacillin/Tazobactam 4.5g tds  + Gentamicin 5mg/kg stat

5. Methods  APEX search  Positive blood cultures for patients under care of haematology consultants  Information recorded:  Organism identification  Antibiotic sensitivities of gram negative bacteria Piperacillin/tazobactam, meropenem, ciprofloxacin, gentamicin

6. Positive Blood Cultures  512 positive blood culture bottles taken between February 2009 and October 2012  151 patients  600 organisms cultured  267 gram positive bacteria (44.5%)  329 gram negative bacteria (54.8%)  4 fungi (0.7%)

7. Bacteria Identified  329 Gram negative bacteria:  108 E.coli 33.0%  103 KESC group 31.3%  60 Pseudomonas sp. 18.2%  23 Stenotrophomonas maltophilia6.9%  11 Acinetobacter sp. 3.3%  24 Other gram negative bacteria 7.3%

8. Antibiotic Resistance Pip/tazoMeropenemCiprofloxacinGentamicin SRSRSRSR E.coli999108010531071 Pseudomonas sp. 5915010591 1 KESC group 86171030949958 Acinetobacter sp. 110 0 074 All others 12873183172 Total 88%12%96%4%94%6%95%5% S=sensitive, R= resistant. Not all organisms have full sensitivities available on APEX, S. Maltophilia not included as poor correlation between antibiotic susceptibility and treatment outcome

9. 1. Fluoroquinolone Prophylaxis  However concerns regarding: Risk of antibiotic associated Clostridium difficile Development of antibiotic resistance  Action  Use of fluoroquinolone prophylaxis still under consideration  94% of gram negative bacteria sensitive to ciprofloxacin

10. 2. Piperacillin/tazobactam  35 piperacillin/tazobactam resistant gram negative bacteria 12 individuals, 2 with recurrent bacteraemias  Action  Continue to use as part of first line treatment of neutropenic sepsis  Not to use as a single agent  Local resistant rate of 12% in gram negative bacteria

11. 3. Aminoglycosides  Only 2 bacteraemias resistant to both piperacillin/tazobactam and gentamicin  Action  Gentamicin will continue to be given for at least the first 24 hours after admission To be reviewed with clinical response and culture results  99.2% of gram negative bacteria sensitive to either piperacillin/tazobactam or gentamicin

12. Conclusion  First line treatment of neutropenic sepsis to remain as piperacillin/tazobactam and gentamicin  High resistance rates to NICE recommended empiric agent  NICE guidelines comment on importance of local resistance patterns  “High rates of resistance to chosen empiric agent could lead to treatment failure”

13. Any Questions? Katherine.watson@stees.nhs.uk