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[size=20px]An otherwise healthy two-year old girl is undergoing induction chemotherapy for high grade neuroblastoma. She develops fever, tachycardia and irritability. Absolute neutrophil count (ANC) is 0 and is not expected to increase for the next 10 days. Her blood pressure is normal. CXR shows a new right lower lobe infiltrate. Cultures are sent. Initial antibiotic therapy for this patient with febrile neutropenia should be

 

A piperacillin-tazobactam and caspofungin

 

B ampicillin, gentamicin, and metronidazole

 

C piperacillin-tazobactam and vancomycin

 

D piperacillin-tazobactam

 

E vancomycin, gentamicin, metronidazole, and caspofungin​[/size]

  • Author

correct answer

D piperacillin-tazobactam

 

This patient is considered a high risk febrile neutropenic patient given the prolonged duration of neutropenia relative to new onset pneumonia. Monotherapy with piperacillin-tazobactam, an antipseudomonal beta-lactam, is appropriate initial therapy.

 

Febrile neutropenia (FN) is defined as an ANC of < 500 cells/microliter or < 1,000 cells/microliter with a projected nadir of < 500 cells/microliter in the next 24 hours AND a single temperature of >38.5 C (101 F) or two measurements of >38.0 C 100.4 F) within one hour. FN is the most common complication of patients undergoing chemotherapy, estimated at over 60,000 episodes annually, with mortality ranging from 0.7% and 3.9%.

 

The National Comprehensive Cancer Network (NCCN) has developed guidelines for the care of patients with FN based on being stratified as low or high risk. Low risk patients have good performance status, few medical comorbid conditions, adequate hepatic and renal function, expected neutropenic duration of less than 7 days, and Multinational Association of Supportive Care in Cancer (MASCC) Index of 21 or higher. High risk patients have clinical signs of hypotension, pneumonia, new onset abdominal pain, renal or hepatic changes, and neurologic changes. They have an expected duration of neutropenia for greater than 7 days and MASCC less than 21.

 

Low risk FN can be initially managed either as an outpatient or inpatient (weak recommendation, moderate quality) with oral antibiotics (weak recommendation, moderate quality evidence) if the child can reliably tolerate medications through this route of administration. High risk FN patients require admission to the hospital with empiric intravenous antibiotic monotherapy using antipseudomonal beta-lactam, a fourth generation cephalosporin, or a carbapenem(strong recommendation, high quality evidence). A second gram negative agent or glycopeptide for patients are recommended if the patient is clinically unstable, when a resistant infection is suspected, or for centers with a high rate of resistant pathogens (strong recommendation, moderate quality evidence). If patients respond to initial empiric antibiotic therapy, double coverage for gram-negative infection or empirical glycopeptide should be discontinued after 24 to 72 hours if there is no specific microbiologic indication to continue combination therapy (strong recommendation, moderate-quality evidence). In patients with persistent fevers who become clinically unstable, the initial antibacterial therapy should be escalated to include coverage for resistant gram negative, gram positive and anaerobic bacteria (strong recommendation, very low quality evidence).

 

In all patients, antibiotics should be discontinued if there are negative cultures at 48 hours and the patient remains afebrile for at least 24 hours with evidence of recovery.

 

Empiric antifungal therapy (caspofungin or liposomal amphotericin B) is recommended for patients with FN who are considered high risk for invasive fungal infections. These patients include those with acute myeloid leukemia, high risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia or children undergoing allogeneic hematopoietic stem cell transplantation with prolonged neutropenia and on high-dose corticosteroids.

 

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