Suggested initial antimicrobial therapy for high-risk* children with fever and chemotherapy-induced neutropenia^[1,2]

Fever and neutropenia in children with cancer or HCT is a medical emergency. Empiric-broad spectrum antibiotics should be given as soon as possible: within 60 minutes of triage and immediately after blood cultures have been obtained.
Suggested agents for broad-spectrum empiric IV therapy (1 of the following^¶):
Cefepime Meropenem Piperacillin-tazobactam
Selected limited indications for additional agents	Suggested additional agent(s)
Additional gram-positive (eg, vancomycin, clindamycin, linezolid) and/or gram-negative (eg, aminoglycosides) agents should be discontinued after 48 hours in children with no documented infection who remain clinically stable.
Signs of sepsis (eg, fever, hypotension, unexplained tachycardia and/or widened pulse pressure, mental status change, respiratory dysfunction)	Add agents with activity against gram-negative bacteria (eg, aminoglycoside, fluroquinolone) and MRSA (eg, vancomycin) after consultation with an expert in pediatric infectious diseases and an expert in critical care
Abdominal pain, rectal pain, perineal inflammation, or blood per rectum	Add metronidazole if not already receiving antibiotics active against anaerobes (eg, meropenem, piperacillin-tazobactam)
Suspected Clostridioides difficile infection	Nonsevere initial episode: Add metronidazole or oral vancomycin Severe initial episode: Add oral vancomycin Recurrent episode: Add oral vancomycin or oral fidaxomicin
Positive blood culture (before identification)
Gram-negative	Add an aminoglycoside and change the initial agent to a carbapenem (eg, meropenem) if a carbapenem was not chosen initially
Gram-positive	Add 1 of the following: Vancomycin Linezolid
Meningitis or suspected meningitis	Add vancomycin to antipseudomonal therapy with cefepime or meropenem^Δ
Radiographically documented pneumonia	Add vancomycin if MRSA suspected
Clinically suspected CVC infection	Add vancomycin^◊
Skin or soft tissue infection	Add 1 of the following: Vancomycin Clindamycin Linezolid
Known colonization with MRSA or penicillin- and cephalosporin-resistant Streptococcus pneumoniae	Add 1 of the following: Vancomycin Clindamycin Linezolid
Recent intensive chemotherapy associated with a high risk for infection with penicillin-resistant streptococci (eg, high-dose cytarabine)	Add 1 of the following: Vancomycin Clindamycin Linezolid
Prophylaxis with quinolones during afebrile neutropenia	Add 1 of the following: Vancomycin Clindamycin Linezolid

This table is intended for use with UpToDate content related to fever in children with fever and chemotherapy-induced neutropenia. Refer to UpToDate content for additional details (eg, risk stratification, doses, duration, modification of empiric therapy). The initial empiric regimen is individualized (eg, for drug allergies, organ dysfunction, use of prophylactic antimicrobial agents).

The combination of vancomycin and piperacillin-tazobactam is associated with increased risk of acute kidney injury and should be avoided.
Linezolid should be reserved for children known to be colonized with or previously infected with vancomycin-resistant gram-positive organisms.
Clindamycin should be chosen only if the rates of clindamycin resistance in the cancer center and community are acceptably low.

HCT: hematopoietic cell transplant; IV: intravenous; MRSA: methicillin-resistant Staphylococcus aureus; CVC: central venous catheter.
* Children are assessed to be at high risk of severe infection or complications at the onset of their episode of fever and neutropenia. They may be reassigned from low to high risk if the develop 1 or more of the high-risk criteria.
¶ For high-risk children following HCT, cefepime is preferred to meropenem and piperacillin-tazobactam.
Δ If meropenem is used as the broad-spectrum antipseudomonal agent, use the dose for central nervous system infections: 40 mg/kg IV every 8 hours (maximum of 2 g per dose).
◊ Alternatives to vancomycin include ceftaroline or daptomycin, although these agents are not used routinely.

References:

Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52:e56.
Lehrnbecher T, Robinson P, Fisher B, et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol 2017; 35:2082.

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Suggested initial antimicrobial therapy for high-risk* children with fever and chemotherapy-induced neutropenia[1,2]

Suggested initial antimicrobial therapy for high-risk* children with fever and chemotherapy-induced neutropenia^[1,2]