Synopsis
Treat neutropenic sepsis immediately, identify when persistent fever or focal signs indicate invasive fungal disease, combine CT, biomarkers and tissue sampling, and choose prophylactic, empirical or targeted mould therapy safely.
- Neutropenic sepsis is the immediate emergency: take peripheral and line blood cultures if this does not delay treatment and give empirical antibacterial therapy at once.
- NICE first-line intravenous antibacterial treatment is piperacillin with tazobactam unless patient-specific allergy, prior resistant colonisation or local microbiology indicates another regimen.
- Invasive fungal risk rises with profound neutropenia below 0.5 × 10⁹/L lasting more than seven days, acute leukaemia, allogeneic transplantation, graft-versus-host disease, corticosteroids and prior mould colonisation.
- Persistent or recurrent fever after four to seven days of broad antibacterial treatment in a high-risk patient should trigger fungal assessment; fever alone is not a species diagnosis.
- First-line fungal assessment combines urgent CT chest, serum galactomannan, 1,3-beta-D-glucan and mould PCR according to local policy, plus targeted sinus, brain or abdominal imaging.
- Obtain BAL, sterile-site fluid or tissue for microscopy, culture, histology and molecular identification before antifungal therapy when safe; treatment must not wait in a deteriorating patient.
- Empirical options include liposomal amphotericin B 3 mg/kg intravenously daily or caspofungin 70 mg intravenously once then 50 mg daily, chosen from prophylaxis, syndrome and local pathway.
- Posaconazole modified-release prophylaxis for selected high-risk AML or MDS induction is 300 mg twice on day one then 300 mg once daily, with interactions and exposure monitored.
Key red flags
Hypotension, rising lactate, confusion, oliguria, respiratory distress or rapidly progressive organ dysfunction requires immediate sepsis resuscitation and critical-care review.
Neutropenia at or below 0.5 × 10⁹/L with fever above 38°C or other clinically significant sepsis meets the NICE definition of neutropenic sepsis.
New pleuritic pain, haemoptysis, focal hypoxaemia or pulmonary nodules during prolonged neutropenia suggests angioinvasive mould disease.
Facial pain, nasal eschar, orbital swelling, ophthalmoplegia or visual change raises invasive fungal sinusitis and mandates urgent ENT, ophthalmic and surgical assessment.
A necrotic skin lesion, focal neurological sign, persistent abdominal pain or liver or spleen lesions may be the accessible clue to disseminated fungal disease.
Breakthrough infection while taking posaconazole or another mould-active prophylactic demands level and adherence review, susceptibility testing and usually treatment from another antifungal class.
Fever continues or recurs after four to seven days of broad antibacterial therapy while profound neutropenia is expected to last beyond seven days.
Dry cough, pleuritic pain, haemoptysis, hypoxaemia or CT nodules may reflect vascular invasion despite minimal auscultatory findings.
Investigation priorities
Identify bacterial or fungal bloodstream infection while preserving the no-delay emergency antibiotic standard.
Detect early nodules, halo haemorrhage, infarcts, consolidation or cavitation missed by plain radiography.
Management branches
A patient receiving anticancer treatment becomes unwell with suspected neutropenic sepsis.
- Perform ABCDE, lactate, FBC, renal and liver profiles, CRP and blood cultures, including central-line cultures where feasible, while summoning haematology and critical-care support.
- Give piperacillin-tazobactam immediately as NICE first-line beta-lactam monotherapy unless allergy, prior resistant carriage, infection site or local surveillance dictates an alternative.
- A common adult regimen is piperacillin-tazobactam 4.5 g intravenously every six to eight hours, adjusted for renal function and the locally approved neutropenic-sepsis protocol.
- Do not add an aminoglycoside or glycopeptide routinely; use additional coverage only for a defined clinical or microbiological indication.