Antipseudomonal beta-lactam within 1 h for febrile neutropenia, escalation rules, and prevention/treatment of TLS with fluids, rasburicase and early RRT.
At the bedside
Timed steps- 1
FN: antibiotics within 1 h
≤ 1 hCultures (peripheral + each lumen), then piperacillin-tazobactam 4.5 g q6h (or cefoperazone-sulbactam). Unstable: meropenem 1 g q8h + vancomycin ± polymyxin B (per NCDC 2025 and CRO risk).
- 2
When to add vancomycin
Haemodynamic instability, pneumonia, suspected line infection, skin/soft tissue infection, MRSA colonisation, Gram-positive bacteraemia pending ID; stop at 48 h if no Gram-positive infection.
- 3
Antifungal
If febrile after 72-96 h with negative cultures and unstable: CT chest, galactomannan/beta-D-glucan, and echinocandin or mould-active agent.
- 4
De-escalate/stop
Stop if afebrile for 3 days and cultures negative, with close observation, even before count recovery (ECIL-4 / NCDC).
- 5
TLS prevention
Risk-stratify (bulky lymphoma, ALL/AML with high WBC, high LDH, CKD). IV fluids 2-3 L/m²/day aiming urine output 80-100 mL/m²/h; allopurinol (intermediate risk); rasburicase (high risk). Avoid urinary alkalinisation.
- 6
Established TLS
Rasburicase 0.2 mg/kg; treat hyperkalaemia; do not treat asymptomatic hypocalcaemia (calcium-phosphate precipitation); early RRT for refractory hyperkalaemia, hyperphosphataemia, fluid overload or oliguria.
Stable FN
Piperacillin-tazobactam
- Dose
- 4.5 g q6h (extended infusion)
Unstable FN
Meropenem
- Dose
- 1 g q8h (+ vancomycin ± polymyxin B)
FN where local ESBL rates low
Cefepime
- Dose
- 2 g q8h
High-risk or established TLS
Rasburicase
- Dose
- 0.2 mg/kg over 30 min daily (up to 5 days)
- Worked example
- 70 kg: 14 mg; many units use a single 3-6 mg dose and repeat by uric acid
Check G6PD first (common in India).
TLS prevention
Allopurinol
- Dose
- 100 mg/m² q8h (max 800 mg/day)
- Worked example
- BSA 1.8 m²: 180 mg q8h (e.g. 200 mg q8h)
Cairo-Bishop laboratory TLS (≥ 2 within 3 days before to 7 days after therapy)
| Parameter | Threshold |
|---|---|
| Uric acid | ≥ 8 mg/dL or 25% rise |
| Potassium | ≥ 6 mmol/L or 25% rise |
| Phosphate | ≥ 4.5 mg/dL (adults) or 25% rise |
| Calcium | ≤ 7 mg/dL or 25% fall |
Clinical TLS = laboratory TLS + creatinine ≥ 1.5 × ULN, arrhythmia/sudden death, or seizure.
Calculators for this topic
References
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Febrile neutropenia
Step 1 of ~6
Cultures (peripheral + all lumens), lactate, CXR
Based on National Centre for Disease Control (DGHS, MoHFW) and Indian Council of Medical Research; Freifeld AG, Bow EJ, Sepkowitz KA, et al. Educational use; follow local protocol.
Pathophysiology
Neutropenia removes the main defence against bacteria and fungi; mucositis and lines permit translocation. TLS results from rapid tumour cell lysis releasing potassium, phosphate and nucleic acids (metabolised to uric acid), causing crystal nephropathy, arrhythmias and calcium-phosphate deposition.
Evidence
- IDSA 2010 FN guideline [Freifeld 2011]; NCDC/ICMR 2025 Indian FN regimens [NCDC 2025].
- TLS evidence-based review [Coiffier 2008]; Cairo-Bishop classification [Cairo 2004].
Controversies
- Early stopping of antibiotics before neutrophil recovery; prophylactic fluoroquinolones in high MDR settings.
🇮🇳 India notes
- High rates of ESBL and carbapenem resistance in Indian oncology units mean NCDC suggests meropenem + vancomycin ± polymyxin B for unstable FN.
- G6PD deficiency is common in several Indian communities; test before rasburicase.
References
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