Write a short note on febrile neutropenia.

Definition

Febrile neutropenia is an oncological emergency, defined as:

• Fever — a single oral temperature ≥ 38.3 °C, or ≥ 38.0 °C sustained for one hour
• with neutropenia — absolute neutrophil count < 0.5 × 10⁹/L, or < 1.0 × 10⁹/L with a predicted fall below 0.5

Severity of risk relates to the depth and duration of neutropenia — profound (< 0.1 × 10⁹/L) and prolonged (> 7 days) neutropenia carries the highest risk.

It is an emergency because the neutropenic patient cannot mount an inflammatory response: the usual localising signs of infection — pus, consolidation, erythema — are muted or absent, and fever may be the only manifestation of overwhelming sepsis, which can kill within hours.

Causes

• Cytotoxic chemotherapy — by far the commonest, with the nadir typically 7–14 days after a cycle.
• Haematological malignancy with marrow infiltration — leukaemia, lymphoma, myeloma, myelodysplasia.
• Aplastic anaemia; marrow infiltration by solid tumour.
• Radiotherapy to large marrow-bearing areas.
• Drugs — carbimazole, clozapine, sulphonamides, antiepileptics, chloramphenicol.
• Severe sepsis itself; HIV; nutritional deficiency (B12, folate, copper).

Organisms

• Gram-positive organisms now predominate in many centres, reflecting the use of indwelling central venous catheters: coagulase-negative staphylococci, *Staphylococcus aureus*, streptococci, enterococci.
• Gram-negative organisms cause the most rapidly fatal infections: *Escherichia coli*, *Klebsiella*, *Pseudomonas aeruginosa* — and in India, multidrug-resistant and carbapenem-resistant Gram-negative organisms are an increasing and serious problem.
• Fungal infection — *Candida*, and *Aspergillus* with prolonged neutropenia; suspect after 4–7 days of persistent fever despite antibacterials.
• Viral — herpes simplex, varicella zoster, CMV; reactivation of tuberculosis is an important consideration in India.
• No source is identified in up to half of episodes — which does not lessen the urgency.

Clinical Assessment

Look actively for a source, remembering that signs will be subtle:

• Mouth and pharynx — mucositis, ulceration, candidiasis (a very common portal of entry)
• Skin and central venous catheter site — erythema, tenderness, discharge
• Perianal region — examine it, but do NOT perform a digital rectal examination or use rectal thermometers, which risk bacteraemia and abscess formation in a neutropenic patient
• Chest — infiltrates may be absent on X-ray until neutrophils recover
• Abdomen — neutropenic enterocolitis (typhlitis): right iliac fossa pain, fever and diarrhoea, with bowel wall thickening on CT; a life-threatening complication
• Urinary tract — pyuria may be absent
• Skin lesions — ecthyma gangrenosum (a necrotic ulcer with black eschar) is highly suggestive of *Pseudomonas* bacteraemia

Risk Stratification — Mascc Score

The Multinational Association for Supportive Care in Cancer (MASCC) risk index identifies patients who may be safely managed as outpatients with oral antibiotics. It scores:

• Burden of illness (no or mild symptoms scores highest; moderate symptoms score lower)
• No hypotension
• No chronic obstructive pulmonary disease
• Solid tumour, or haematological malignancy with no previous fungal infection
• No dehydration requiring parenteral fluids
• Outpatient status at onset of fever
• Age under 60

A score of 21 or more (of a maximum 26) identifies LOW RISK; a lower score indicates high risk requiring admission and intravenous therapy.

Investigations

Do not delay antibiotics to complete these:

• Blood cultures — from a peripheral vein AND from each lumen of any central venous catheter, before antibiotics.
• CBC with differential, renal and liver function, electrolytes, CRP, lactate, coagulation profile.
• Urinalysis and culture; chest X-ray; cultures from any suspicious site — sputum, stool (including *C. difficile* toxin), wound and catheter exit site swabs.
• CT chest and abdomen for persistent fever, to detect fungal infection and typhlitis; serum galactomannan and beta-D-glucan for invasive fungal disease.
• Echocardiography if endocarditis is suspected.

Management

1. EMPIRICAL BROAD-SPECTRUM INTRAVENOUS ANTIBIOTICS WITHIN ONE HOUR — the single most important determinant of survival. Do not wait for cultures, imaging, or the neutrophil count to be confirmed.

• Anti-pseudomonal beta-lactam monotherapy (piperacillin-tazobactam, cefepime, meropenem) is standard.
• Add a glycopeptide (vancomycin/teicoplanin) for suspected line infection, skin or soft tissue infection, haemodynamic instability, known MRSA colonisation, or severe mucositis — but not routinely.
• Add an aminoglycoside for severe sepsis or known resistant Gram-negative colonisation.
• Escalate or modify according to local antibiograms — this matters greatly in India, where resistance patterns vary widely between institutions.

2. Resuscitation and supportive care

Fluids and vasopressors for septic shock, oxygen, and organ support; analgesia and mouth care for mucositis; nutrition; and strict hand hygiene and protective isolation.

3. Ongoing management

• Reassess daily. If fever persists beyond 4–7 days despite broad-spectrum antibacterials, add empirical antifungal therapy (an echinocandin or liposomal amphotericin B) and investigate for fungal disease.
• De-escalate antibiotics once the organism is identified; continue until the patient is afebrile and the neutrophil count is recovering.
• Remove the central line if there is tunnel infection, persistent bacteraemia despite appropriate therapy, or infection with *S. aureus*, *Candida* or resistant organisms.

4. Prevention

• G-CSF prophylaxis for regimens with a high risk of febrile neutropenia, and for secondary prophylaxis after a previous episode.
• Antibacterial, antifungal and antiviral prophylaxis in selected high-risk patients (prolonged expected neutropenia, allogeneic transplant).
• Patient education — the most valuable low-cost intervention: every patient receiving chemotherapy must be told to check their temperature and attend hospital immediately if it exceeds 38 °C, and must be given a card and a contact number. Delay in presentation is a major cause of death.