Febrile neutropenia and infection in oncology: SAQ

This child has febrile neutropenia complicating induction chemotherapy, and he has mucositis which makes him high-risk, so he must be treated as presumed bacteraemic and managed as a same-hour emergency. The single temperature of 38.9 degrees Celsius meets the fever threshold of 38.5 degrees Celsius or higher on one reading, and his absolute neutrophil count of 0.2 times ten to the ninth per litre is well under the 0.5 threshold. The plan is recognition, blood cultures, and empiric anti-pseudomonal monotherapy within the first hour. [2]

Question 1 (10 marks)

Define febrile neutropenia, outline your immediate management of this child in the first hour, and explain how you would risk-stratify him and what that stratification means for his disposition and duration of therapy. [2]

Febrile neutropenia is defined as a single oral or axillary temperature of 38.5 degrees Celsius or higher, or a temperature of 38.0 degrees Celsius or higher sustained over one hour, in a child with an absolute neutrophil count under 0.5 times ten to the ninth per litre, or under 1.0 with an expected fall (Lehrnbecher et al., J Clin Oncol 2017, PMID 28459614). The absolute neutrophil count is calculated as the white cell count multiplied by the percentage of segmented neutrophils plus bands, divided by one hundred. This child meets the definition on both the temperature and the count. [2]

The immediate management is the first-hour bundle. Recognise the syndrome and start the clock; assess the airway, breathing and circulation and look briefly for a focus and for the high-risk features; draw blood cultures from every lumen of the central line and peripherally before the first antibiotic dose but never delaying it; send a urinalysis and take a chest radiograph where indicated; then start the empiric intravenous anti-pseudomonal beta-lactam within the first hour (Freifeld et al., Clin Infect Dis 2011, PMID 21258094). The standard monotherapy options are ceftazidime, piperacillin-tazobactam, cefepime, or meropenem, weight-dosed by the oncology protocol. In shock, resuscitate with isotonic crystalloid boluses of 10 mL per kilogram titrated to perfusion and escalate to vasoactive support. [1]

Vancomycin is added, not substituted, when there is a defined indication: a suspected line infection, a serious soft-tissue or pulmonary focus, mucositis, haemodynamic instability, severe sepsis or septic shock, or known colonisation with methicillin-resistant Staphylococcus aureus. This child has mucositis, which is a defined indication for adding vancomycin, and so a glycopeptide is added to his beta-lactam. Routine empiric vancomycin is not recommended because it adds nephrotoxicity without a mortality benefit. [1][2]

Risk stratification uses the International Pediatric Fever and Neutropenia Guideline criteria. A child is high-risk if any of inpatient onset, clinical instability, a comorbidity such as mucositis or renal or hepatic impairment, anticipated prolonged neutropenia over seven days, relapsed or refractory leukaemia, significant immunosuppression, or a suspected serious focal infection is present; all other children are low-risk (Lehrnbecher et al., J Clin Oncol 2017, PMID 28459614). This child is high-risk by virtue of the mucositis and the induction window, and so he is managed as an inpatient on intravenous monotherapy for the duration of the neutropenia, continuing at least until afebrile and until the absolute neutrophil count is recovering above 0.5 and rising. A low-risk child, by contrast, would be the candidate for oral step-down and selected outpatient care. The SPOG 2003 FN study of Ammann and colleagues underpins the prediction of adverse events that drives this stratification. [6]

Question 2 (10 marks)

Three days later the child is still febrile, with persistent severe neutropenia and repeat blood cultures that remain negative. His central line exit site is now erythematous and tender along the tunnel, and he has grown Staphylococcus aureus in one of two line lumens. Outline the persistent-fever pathway, the empiric versus pre-emptive antifungal strategy, and your management of the central line. [2]

Persistent fever beyond 96 hours in a high-risk child signals an invasive fungal infection or an occult focus, and the recommended step is to re-examine the child, repeat the blood cultures, image for a hidden focus with a high-resolution chest and, where indicated, sinus computed tomography, and add an empiric antifungal agent (Lehrnbecher et al., J Clin Oncol 2017, PMID 28459614). The empiric options are liposomal amphotericin B, an echinocandin such as caspofungin, or voriconazole. An alternative is a pre-emptive strategy in which the galactomannan assay, the beta-D-glucan, and the computed-tomography findings guide the start of a targeted antifungal, an approach supported by the randomised trial of Santolaya and colleagues in high-risk children. The pre-emptive strategy aims to reduce unnecessary antifungal exposure without compromising outcomes. [2]

The central line now shows a tunnel infection, and Staphylococcus aureus has been grown from one lumen. A tunnel infection and a port-pocket abscess require line removal, as do bacteraemias with the organisms that are poorly cleared through a line: Staphylococcus aureus, Pseudomonas aeruginosa, Candida, Bacillus, atypical mycobacteria, and vancomycin-resistant enterococci (Freifeld et al., Clin Infect Dis 2011, PMID 21258094). A simple exit-site infection may clear with antibiotics and local care, but a tunnel infection does not, and Staphylococcus aureus bacteraemia is a line-removal organism. The decision is a combined surgical and infectious-diseases decision, and the line is removed after the appropriate antibiotics are established and a plan for ongoing access is made. [1]

In parallel, the supportive-care strategy is maintained: meticulous oral hygiene for the mucositis, strict aseptic line technique, avoidance of rectal instrumentation and of non-steroidal anti-inflammatory drugs, and continuation of the co-trimoxazole prophylaxis for Pneumocystis. The antimicrobial-duration principle is to narrow or stop when the cultures and the recovery allow, continuing only as long as the indication persists. [1][2]