Febrile neutropenia and infection in oncology: Viva

Branch 1: Recognition and the first-hour bundle

The candidate must open by naming the syndrome in one sentence: a single temperature of 38.5 degrees Celsius or higher, or 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, is febrile neutropenia, and this child meets both thresholds (Lehrnbecher et al., J Clin Oncol 2017, PMID 28459614). The first action is to treat him as presumed bacteraemic, because the signs of sepsis are blunted when the neutrophil count is near zero and fever is often the only reliable signal. The candidate should state the absolute-neutrophil-count formula aloud: the white cell count multiplied by the percentage of segmented neutrophils plus bands, divided by one hundred. [2]

The examiner will press on the urgency. The candidate should cite the systematic review of Koenig and colleagues, which found that a shorter time to antibiotics is associated with better clinical outcomes in patients with fever and neutropenia during chemotherapy for cancer, and should name the door-to-antibiotic target of under sixty minutes (Koenig et al., Support Care Cancer 2020, PMID 31264188). The UK audit of Morgan and Phillips documented that this first hour is still missed in a substantial fraction of children, so the candidate should stress that the blood cultures are drawn from every central-line lumen and peripherally before the dose, but they must never delay it. An avoidable delay here is an avoidable harm. [7]

The examiner will ask which empiric agent to give. The candidate should name an anti-pseudomonal beta-lactam as monotherapy, ceftazidime, piperacillin-tazobactam, cefepime, or meropenem, weight-dosed by the oncology protocol, because these cover Pseudomonas aeruginosa, which carries the highest mortality, alongside the common Gram-positive and Gram-negative organisms (Freifeld et al., Clin Infect Dis 2011, PMID 21258094). The candidate should then give the indications for adding vancomycin: suspected line infection, a serious soft-tissue or pulmonary focus, mucositis, haemodynamic instability, severe sepsis, or known colonisation with methicillin-resistant Staphylococcus aureus. Routine empiric vancomycin is not recommended because it adds nephrotoxicity without a mortality benefit. [1]

Branch 2: Risk stratification and disposition

The examiner will ask how the disposition is decided. The candidate should apply the International Pediatric Fever and Neutropenia Guideline high-risk and low-risk stratification: 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). The candidate should name the prospective SPOG 2003 FN study of Ammann and colleagues as the data backbone of the adverse-event prediction, and should state that this child, on induction with a profound count, is at the higher-risk end. [6][2]

The examiner will probe what the stratification changes. The candidate should state that the high-risk child is admitted for inpatient 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. The low-risk child, by contrast, who defervesces, has negative cultures, and has reliable follow-up, can step down to oral ciprofloxacin plus amoxicillin-clavulanate, or cefixime, and in carefully selected cases may complete the course as an outpatient, an approach supported by the systematic review and meta-analysis of Teuffel and colleagues. The candidate should add that a rural or remote child who would be managed as an outpatient low-risk is instead admitted, because the safety-net of rapid re-presentation is absent. [2][6]

Branch 3: Persistent fever and the line

The examiner will introduce a deterioration: the fever persists at 96 hours, with persistent severe neutropenia and negative repeat cultures. The candidate should recognise this as the signal for an invasive fungal infection or an occult focus, and should describe the persistent-fever pathway: re-examine the child, repeat the blood cultures, send a galactomannan and a beta-D-glucan, image with a high-resolution chest and, where indicated, sinus computed tomography, and add an empiric antifungal such as liposomal amphotericin B, caspofungin, or voriconazole (Lehrnbecher et al., J Clin Oncol 2017, PMID 28459614). The candidate should then offer the alternative of a pre-emptive strategy in which the galactomannan, beta-D-glucan, and imaging guide the start of a targeted antifungal, an approach supported by the randomised trial of Santolaya and colleagues in high-risk children. [11][2]

The examiner will then ask about the central line. The candidate should state that a simple exit-site infection may clear with antibiotics and local care, but that a tunnel infection, a port-pocket abscess, or a catheter-related bloodstream infection that persists beyond 72 hours of appropriate antibiotics requires line removal (Freifeld et al., Clin Infect Dis 2011, PMID 21258094). The candidate must name the line-removal organisms: Staphylococcus aureus, Pseudomonas aeruginosa, Candida, Bacillus, the atypical mycobacteria, and the vancomycin-resistant enterococci. The decision to remove a line is a combined surgical and infectious-diseases decision, made after the appropriate antibiotics are established and a plan for ongoing access is made. [1]

Branch 4: Supportive care and the closing

The examiner will ask what prevents the next episode. The candidate should describe the supportive-care strategy: meticulous oral hygiene to limit the mucositis that seeds viridans streptococci, strict aseptic line care, avoidance of rectal examinations and rectal suppositories, avoidance of non-steroidal anti-inflammatory drugs that mask the fever and impair platelet function, and antimicrobial prophylaxis with co-trimoxazole for Pneumocystis across the chemotherapy regimens and a fluoroquinolone such as levofloxacin in the deepest-neutropenia groups (Freifeld et al., Clin Infect Dis 2011, PMID 21258094). The candidate should clarify the role of granulocyte colony-stimulating factor: it is for primary prophylaxis in high-risk regimens and a considered adjunct in selected high-risk children, not a routine treatment of an established episode, because the evidence does not support a routine mortality benefit. [1][2]

The examiner will close by asking for the three things the team should remember. The candidate should state, first, door-to-antibiotic within the first hour, every time, with the cultures drawn before but never delaying the dose; second, the blunted inflammatory response means that well does not mean safe and afebrile does not mean well; and third, risk stratify to set the disposition and the duration, because the high-risk child stays on inpatient intravenous monotherapy for the duration of the neutropenia, while the carefully selected low-risk child can step down to oral therapy and, with a real safety-net, complete the course as an outpatient. [2][1][7]