Haematology & Oncology

Neutropenic Sepsis

Anticancer treatment removes the neutrophils that both contain infection and generate its localising signs, so bacteraemia can progress to shock in a patient who still looks well.

In a nutshell

Neutropenic sepsis is sepsis after anticancer treatment with a neutrophil count of 0.5 × 10^9/L or lower, plus fever above 38°C or any other sign of significant sepsis. Give piperacillin with tazobactam 4.5 g intravenously every 6 hours within one hour of arrival, without waiting for the count or the cultures.

Classic presentation

A patient ten days after chemotherapy with rigors and a temperature of 38.5°C, no cough, no dysuria and an entirely normal examination.

Key points

Neutropenia here is 0.5 × 10^9/L or lower, or 1.0 × 10^9/L or lower after recent chemotherapy.
The UK Oncology Nursing Society (UKONS) also triggers the pathway on a pending count within six weeks of anticancer treatment.
MASCC (Multinational Association for Supportive Care in Cancer) index: seven items scored out of 26, and 21 or more means low risk of septic complications.
High risk means a NEWS2 (National Early Warning Score 2) of 7 or more, septic shock, haematological malignancy or cellular therapy.
Lactate above 2 mmol/L or acute kidney injury counts as hypoperfusion and moves a moderate-risk patient onto the high-risk pathway.
Piperacillin with tazobactam 4.5 g is piperacillin 4 g plus tazobactam 500 mg; reduce to 8-hourly if creatinine clearance is 20 to 40 mL/minute.
Vancomycin can be loaded at 25 to 30 mg/kg (usual maximum 2 g) in seriously ill patients before the 15 to 20 mg/kg maintenance dose.
Avoid gentamicin and amikacin in myeloma and myasthenia gravis, and after platinum-based chemotherapy in the past week.
Low-risk oral therapy excludes haematological malignancy, cellular therapy and previous invasive fungal infection, and needs a patient who tolerates oral medicine.
Discharge requires a carer, a telephone, an emergency department within an hour, next-day review and written warning-sign advice.

First-line investigation

FBC with differential plus blood cultures, kidney and liver function with albumin, CRP and lactate, all sent alongside the first antibiotic dose rather than before it.

Management

Give the antibiotic before you have the count

Anyone unwell within 30 days of systemic anticancer treatment has neutropenic sepsis until proved otherwise. Refer immediately and treat as an emergency.^1,3
Piperacillin with tazobactam 4.5 g intravenously every 6 hours, infused over 30 minutes. Door to needle under one hour for every patient, whatever the NEWS2 score.^5,2,4,6
Take blood cultures, FBC, kidney and liver function with albumin, CRP and lactate at the same time as the dose, never before it.^1,2

Resuscitate and adapt the regimen

If high risk, give 250 mL of balanced crystalloid such as Hartmann's over 10 to 15 minutes within one hour, repeating to 1000 mL and reassessing after each bolus.^3,6
Penicillin allergy: ceftazidime 2 g intravenously every 8 hours, or aztreonam 2 g every 6 hours if the reaction was anaphylaxis, each with teicoplanin or vancomycin.⁴
Suspected ESBL (extended-spectrum beta-lactamase) or other resistant Gram-negative organism: meropenem 1 g intravenously every 8 hours.^4,8
Add gram-positive cover only for MRSA or a suspected line source. Teicoplanin 6 mg/kg 12-hourly for 3 doses then daily, or vancomycin 15 to 20 mg/kg 8 to 12 hourly.^1,4,9,10
Gentamicin is not routine. If indicated, 5 to 7 mg/kg once daily by infusion, adjusted on levels, with renal monitoring and a 3 to 4 day limit.^1,11,4

Escalate rather than reshuffle the antibiotics

Call oncology or haematology, microbiology and critical care for hypotension, hypoxia, confusion, lactate above 2 mmol/L, NEWS2 of 7 or more, or no response within one hour.^3,4,2
Do not change the antibiotic for persistent fever alone. Change it for clinical deterioration, a new focus or a microbiology result.¹
Do not remove the central venous access device as part of initial management, and do not request a routine chest X-ray.¹

Stratify, step down, discharge

Score risk within 24 hours using the MASCC index. A score of 21 or more, with a NEWS2 of 4 or less, is low risk.^1,7,4
Switch intravenous to oral after 48 hours only once reassessed low risk: levofloxacin 500 mg twice daily, or co-amoxiclav 500/125 mg three times daily with ciprofloxacin 500 mg twice daily.^1,4,7,12
Stop empirical antibiotics once the episode has responded, irrespective of the neutrophil count. Only discharge with a carer, telephone access and next-day review arranged.^1,4

Prevent the next episode

Give written and verbal information on neutropenic sepsis, the 24-hour specialist oncology contact route and when to return, before and throughout anticancer treatment.¹
Ciprofloxacin prophylaxis in an anticipated neutropenic period and G-CSF (granulocyte colony-stimulating factor) are specialist decisions, restricted by Medicines and Healthcare products Regulatory Agency advice.^1,13

Exam traps

Giving the antibiotic before the neutrophil count is back is correct, not sloppy. Waiting for the FBC or for cultures is the classic FY2 error.
No fever does not exclude it. A temperature below 36°C, or simply feeling unwell after chemotherapy, is enough to trigger the pathway.
A normal examination is expected, not reassuring: without neutrophils there is no pus, no consolidation and no line erythema.
Do not add gentamicin or a glycopeptide routinely; NICE withholds both unless there is a patient-specific or microbiological indication.
Do not pull the central line on admission. Initial empirical management leaves vascular access devices in place.
Persistent fever alone is not a reason to change the antibiotic, and neutrophil recovery is not needed before stopping it.
The neutropenic frequency of piperacillin with tazobactam is 4.5 g every 6 hours, not the every-8-hours dose used for other infections.
MASCC is scored after the first dose, to choose the pathway. It never decides whether to treat.

Illustrations

Mechanism of neutropenic sepsisFlow diagram from anticancer treatment through marrow suppression and mucosal injury to bacteraemia with few localising signs.PassFinals · original

Door-to-needle pathway, target under one hourPathway diagram showing assessment, cultures and the first empirical antibiotic dose running in parallel, with no wait for the neutrophil count.PassFinals · original

Blood film showing severe neutropeniaPeripheral blood film at low power demonstrating markedly reduced neutrophils after marrow suppression; correlate with the FBC differential.Roberto J. Galindo, Wikimedia Commons · CC-BY-SA-3.0

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.