Children with low risk febrile neutropenia without any identified focus will be started on IV antibiotics as per institutional protocol which usually includes combination therapy with antipseudomonal penicillin (piperacillin + tazobactam -if platelet counts is<20,000/mm3) or cephalosporin (cefoperazone + sulbactam – if platelet count is >20,000/mm3) and an aminoglycoside (amikacin). Whenever there is a respiratory focus, the child is started on Amoxycillin-clavulanic acid and amikacin. Whenever there is a gastrointestinal focus, the child will be started on cefoperazone + sulbactam and ofloxacin or metronidazole. The patients will receive these antibiotics at age and weight appropriate dosage on outpatient basis from day care.

The baseline investigations like complete blood counts (CBC), serum electrolytes, renal function tests (RFTs), liver function tests (LFTs), chest X-ray (CXR), blood culture and sensitivity and other microbiological samples if required will be sent routinely as per unit’s policy before initiation of empirical antibiotics. Along with the above-mentioned samples, 2 ml serum will also be taken for procalcitonin (PCT) estimation. The parents will be instructed to record temperature at least 3 times daily and also whenever the child is febrile and bring the temperature record for review. The child will be closely followed up clinically and a repeat sample for CBC and PCT estimation will be sent at 48 hours of starting empirical antibiotics. The child will be reviewed again at 72 hours of starting empirical antibiotics along with CBC, PCT and blood C/S report. Those children with negative/normalisation of PCT at 48 hours, afebrile period of atleast 24 hours and sterile blood culture will be randomised into two groups.

Intervention arm: Early discontinuation of empirical antibiotics (at 72 hours).

Control arm: Standard therapy with continuation of antibiotics for at least 7 days or until recovery of neutropenia i.e. ANC >500/mm³ which will be ascertained by repeat CBC every 2/3 days or as and when needed till 14 days of randomization.

We shall use computer generated block randomization with variable block size, to ensure an equal number of participants in each group. The randomisation blocks, thus generated, will be kept with an individual not involved in the enrolment of the subjects, administration of the intervention or the analysis of the data.

The randomisation data will be provided to an individual in the Department of Biostatistics, AIIMS, New Delhi, who will be involved in labelling of the envelopes as serial numbers that correspond to a given randomised patient number. The principal investigator shall open the next serially numbered envelopes upon enrolment of the patient. All the opened envelopes along with the patient allocation details and date of opening the envelopes will be kept safe by the principal investigator for future reference.

Allocation concealment will be ensured by using randomisation and identical opaque sealed envelopes.

The children belonging to both the groups will be followed by clinically for 14 days after randomization for primary and secondary end points and for 28 days for all-cause mortality.

Primary end points:

• Any recurrence of fever or any clinical signs/symptoms of infection relapse requiring restarting/upgradation of Antibiotics
• Need for hospitalization due to infectious etiology
• Death due to infectious etiology

Secondary end points:

• Number of days with antibiotic exposure
• Death due to any cause

During follow up, we will use the same criteria as mentioned earlier (single oral temperature of ≥ 38.3^◦C (101^◦F) or oral temperature of ≥ 38^◦C (100.4^◦F) for 1 hour for the definition of fever which is one of our primary end points. Restarting and upgradation of antibiotics will be done as per unit’s protocol for management of febrile neutropenia. However, we will keep low threshold for admission to wards in case the child developed infectious relapse during the study follow up in order to ensure safety.