T2Bacteria® Negative De-escalation

67-year-old female admitted for reduced intensity conditioning followed by Stem Cell transplant for acute myelogenous leukemia.

Discussion

Patients undergoing cytotoxic chemotherapy and hematopoietic stem-cell transplantation (HSCT) are at high risk for infection, particularly during the period of neutropenia and are often prescribed antibiotic prophylaxis with fluroquinolones. The majority of patients who develop fever during neutropenia have no identifiable site of infection and no positive culture results. IDSA guidelines recommend that every patient with fever and neutropenia receive empiric antibiotic therapy with an antipseudomonal beta lactam urgently after presentation, because infection may progress rapidly.1

De-escalation of antimicrobials is challenging in these scenarios, where cultures remain negative, and patients are often exposed to extended durations of broad-spectrum antimicrobials as information is not available to target therapy. This puts the patient at risk for collateral damage associated with antimicrobial therapy such as antimicrobial resistance and toxicity. T2Bacteria negative results in 3-5 hours can help clinicians to improve their empiric therapy for bloodstream infections by providing key information to help narrow a patient’s empiric therapy.

At the time of febrile episode in this case, the patient was on levofloxacin 500 mg daily for bacterial prophylaxis. She had blood cultures obtained and T2Bacteria ordered and was then initiated on broad spectrumtherapy with cefepime 2g IV q8h. Due to the patient’s history of recent HSCT, profound immunosuppression and neutropenia, she was at risk for organisms such as P. aeruginosa in addition to other common causes of febrile neutropenia such as Enterobacteriaceae and Gram-positive commensal bacteria.

The patient received 3 doses of cefepime (~24 hours of therapy) then therapy was de-escalated to ceftriaxone based on negative T2Bacteria Panel results to avoid unnecessary continuation of the broad spectrum, antipseudomonal beta-lactam. Ceftriaxone was continued for 4 more days until the patient defervesced, was hemodynamically stable, afebrile and displayed no other sign or symptom of infection. Once treatment of the febrile neutropenic episode was complete, the levofloxacin prophylaxis was reinitiated.

Presentation

67-year-old female admitted for reduced intensity conditioning followed by Stem Cell transplant for acute myelogenous leukemia. She also received methotrexate and tacrolimus for graft-versus-host disease prophylaxis. Patient's clinical course was complicated by grade 3 nausea, vomiting and mucositis, hyperglycemia and new onset left bundle branch block. Six days after transplant the patient developed febrile neutropenia with profound neutropenia, in which stat blood cultures (x2), T2Bacteria, procalcitonin and lactic acid were drawn, a chest X-ray was taken and cefepime was immediately initiated.

Patient Selection Criteria

Febrile neutropenia in patient with recent HSCT and profound neutropenia.

Evaluation and Treatment Decision

Diagnosis: Neutropenic fever.

Empiric Therapy: The patient was on levofloxacin 500 mg daily for bacterial prophylaxis at time of febrile episode. The patient was initiated on cefepime 2g IV q8h at time of fever spike.

Cefepime was chosen for coverage of common causative pathogens identified in febrile neutropenia.

Procalcitonin, lactic acid, and chest X-ray were benign with no positive findings.

T2Bacteria Panel Result: Negative for all panel pathogens (P. aeruginosa, E. faecium, S. aureus, E. coli and K. pneumoniae.)  

Blood Culture Result: no growth

Decision making based on T2Bacteria Result

A rapid T2Bacteria negative result allowed for ruling out of the most common ESKAPE pathogens. The high negative predictive value (99.7%) of the T2Bacteria Panel provided important diagnostic information that allowed for more informed treatment decisions, including early de-escalation of empiric antibiotic regimen, sparing the patient from unnecessary broad spectrum antibiotics and the potential risks associated with their prolonged therapy.

1. Freifeld AG, 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; 52:427-31.

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  • According to the CDC, of the 154 million prescriptions for antibiotics written in doctors' offices and emergency departments each year, 30% are unnecessary.12