Neutropenic sepsis case Dr Suzy FitzGerald

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 No pathogen identified. Empiric treatment with meropenem, gentamicin. Settled.

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

Admission - examination Dry flaky skin rash PICC – right arm (in situ x 2/12) Otherwise no abnormal findings Creatinine 112 (normal range 62-106) WCC 6.5 (normal range 3.5-11)

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

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

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

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

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

What’s wrong with the patient?

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

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

What are the potential sources of fever?

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

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

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

What do you need to consider when choosing antibiotic therapy?

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

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

Antibiotics prescribed Meropenem 1g iv 8-hourly – first dose given at 11.30 Gentamicin 300mg iv – first dose given at 11.28

Recommendations for empiric antibiotics in neutropenic sepsis IDSA, 2010 Monotherapy with piptazobactam or carbapenem or ceftazidime or cefipime Penicillin hypersensitivity – clindamycin and ciprofloxacin or vancomycin and aztreonam NICE clinical guideline, 2012 Monotherapy with piptazobactam No specific recommendation for penicillin allergy

What about the timing of the antibiotics?

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 11.28 and 11.30 1NI Cancer Network neutropenic sepsis guidelines, 2010 2NICE Clinical Guidelines 151, 2012

Day 14 Day 15 10.25 12.55 13.10 13.45 14.50 15.50 16.50 17.50 06.00 09.30 11.30

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 17.50 on day 14 Advised continue meropenem and gentamicin Gentamicin 300mg given Repeat blood cultures No gentamicin level done, creatinine 101 – in normal range

CXR – day 15

Day 16 Blood cultures (day 14) Line – Klebsiella pneumoniae Peripheral - sterile to date Blood cultures (day 15) Line – sterile to date 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

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

What do you advise now?

What do you advise now? Antibiotic options Continue meropenem Change to ciprofloxacin – C. difficile infection Change to aztreonam Remove PICC? Line cultures positive No other source found Care bundle for PICC – completed daily – no signs infection recorded during admission

IV catheter removal IDSA, 2010 – if CRBSI, 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

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)

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