NCCN Makes Changes to Its Guidelines for Treating Fever and by luckboy


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NCCN Makes Changes to Its Guidelines for Treating Fever and Neutropenia


National Comprehensive Cancer Network (NCCN) panel reports significant changes to guidelines for managing fever and neutropenia in cancer patients, including the recommendation that fever be defined as a single temperature reading of higher than 38.3°C orally or a temperature of 38.0°C or above that persists for more than 1 hour. The updated guidelines advise against routine addition of vancomycin to regimens for patients with febrile neutropenia, Alison Freifeld, MD, reported at the 9th Annual Conference of the NCCN. Dr. Freifeld pointed out that standards of fever and neutropenia management developed in the 1970s have dramatically improved outcomes of cancer therapy, but that developing management paradigms is a dynamic process. Dr. Freifeld is Associate Professor of Internal Medicine, University of Nebraska Medical Center, Omaha. The NCCN guidelines developed in 2002 defined fever as a single temperature of 38.0°C. “We thought this was a bit too liberal because cancer patients may have a low-grade fever for a variety of reasons, including chemotherapy itself,” Dr. Freifeld said. The more restrictive

2004 guidelines bring NCCN recommendations into line with those from the Infectious Diseases Society of America and the American Society of Clinical Oncology. In addition to history and physical examination, the new guidelines recommend that a work-up for neutropenia includes historical information such as the time since previous chemotherapy. Evaluation should include two sets of blood cultures, but Dr. Freifeld emphasized that this does not necessarily mean cultures from two different sites. “In the past it has been suggested that you should obtain one set of blood cultures from the line and another peripherally. There are now data suggesting that obtaining both sets of cultures from the line, if there is an indwelling catheter, is acceptable. The volume of blood cultured (20–40 mL per sample) is far more predictive of obtaining an identifiable isolate than getting two separate sites of culture,” Dr. Freifeld said. The NCCN review of antibiotic regimens in fever and neutropenia highlighted the fact that all the successful regimens are bactericidal against gram-negative rods (such as Pseudomonas aeruginosa) and are bactericidal in the absence of white blood cells. Dr. Freifeld said that the panel found that adding vancomycin provided no ad-

vantage as empiric therapy except in patients at high risk for serious gram-positive infections. The recommendation was for initial monotherapy with cefepime (Maxipime), ceftazidime, imipenem/cilastatin (Primaxin), or meropenem (Merrem). The panel also found no advantage to adding vancomycin for patients who have persistent fever despite treatment with broad-spectrum antibiotics for a few days. Caution was also urged regarding empiric use of the newer drugs linezolid (Zyvox), quinupristin/dalfopristin (Synercid), or daptomycin (Cubicin). The ability to select out “high-risk” patients for closer monitoring and prophylactic treatment would be clinically valuable. NCCN analysis found that a potential shortfall of two commonly used, validated prediction methods (the Talcott rule and the Multinational Association for Supportive Care in Cancer rule) is that neither includes duration of neutropenia as a risk factor. Dr. Freifeld suggested that the “high-risk” designation be applied to patients with an absolute neutrophil count of less than 100/mm³ for 7 days or longer or who are inpatients at the time of developing fever and neutropenia. “Review of the low-risk patient should include an assessment for whether or not the patient would be eligible for outpatient therapy. This involved a careful examination, a review of the lab results, and a review of the social criteria for home therapy,” Dr. Freifeld said.





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