Volume 120 Number 4, Part 1
promote and participate in the conduct of clinical trials in infants and children, when possible. It is only through such efforts that the need for off-label prescribing can be reduced.
Ralph E. Kauffman, MD Professor, Pediatrics and Pharmacology Director, Division of Clinical Pharmacology/Toxicology Wayne State University School of Medicine Children's Hospital of Michigan Detroit, MI 48201 REFERENCES
1. Bergman I, Steeves M, Burckart G, Thompson A. Reversible neurologic abnormalities associated with prolonged intravenous midazolam and fentanyl administration. J PEDIATR 1991;119:644-9. 2. Lane JC, Tennison MB, Lawless ST, Greenwood RS, Zaritsky AL. Movement disorder after withdrawal of fentanyl infusion. J PEDIATR 1991;119:649-51. 3. Arnold JH, Truog RD, Scavone JM, Fenton T. Changes in the pharmacodynamic response to fentanyl in neonates during continuous infusion. J PEDIATR 1991;119:639-43.
M a n a g e m e n t of the febrile patient with cancer and neutropenia To The Editor: The otherwise excellent review on the diagnosis and treatment of infection in the child with cancer by Pizzo et al. 1 omitted a key management issue for a sizable number of these patients. In most pediatric oncology centers, a large percentage (approximately 60% in our experience) of children admitted for diagnosis and management of fever and neutropenia have negative blood culture results, defervesce within several days, appear well, but continue to exhibit neutropenia. How long are such patients to remain in the hospital, receiving broad-spectrum parenterat antibiotics? Pizzo et al. failed to explain how they would manage such patients. They implied that these patients should continue to receive antibiotics for 7 to 14 days. Only when "recovery of the leukocyte count" (which was not defined but presumably means a rise in the number of neutrophils to 500/mm 3) occurs was it deemed safe to discontinue antibiotic therapy. The authors quoted a study performed in the late 1970s2 supporting this approach; in this study, patients whose antibiotics were discontinued, but who continued to have neutropenia, had an unacceptably high incidence of recurrent fever. In the majority of these children, however, antibiotic therapy was discontinued 1 week or more before recovery from neutropenia. A year ago a colleague and I published data showing that relatively "low risk" children hospitalized for fever and neutropenia who have negative blood culture results, resolution of fever, and appear well can usually have parenteral antibiotic therapy discontinued and be safely dischai'ged from the hospital) This initial study and a follow-up trial, including an additional 107 episodes of fever and neutropenia, indicated that evidence of bone marrow re-
Editorial correspondence
669
covery (rising monocyte, neutrophil, and/or other blood count values despite persistence of absolute neutropenia) predicted an uneventful postdischarge course.4 In our center we recently completed a third (and prospective) study of this subject (unpublished observations). When the data from all three series were pooled, 218 consecutive "low risk" children with fever and neutropenia who had evidence of marrow recovery (i.e., a rising neutrophil count) had antibiotic therapy discontinued and were discharged from the hospital despite an absolute neutrophil count
promote and participate in the conduct of clinical trials in infants and children, when possible. It is only through such efforts that the need for off-label prescribing can be reduced.
Ralph E. Kauffman, MD Professor, Pediatrics and Pharmacology Director, Division of Clinical Pharmacology/Toxicology Wayne State University School of Medicine Children's Hospital of Michigan Detroit, MI 48201 REFERENCES
1. Bergman I, Steeves M, Burckart G, Thompson A. Reversible neurologic abnormalities associated with prolonged intravenous midazolam and fentanyl administration. J PEDIATR 1991;119:644-9. 2. Lane JC, Tennison MB, Lawless ST, Greenwood RS, Zaritsky AL. Movement disorder after withdrawal of fentanyl infusion. J PEDIATR 1991;119:649-51. 3. Arnold JH, Truog RD, Scavone JM, Fenton T. Changes in the pharmacodynamic response to fentanyl in neonates during continuous infusion. J PEDIATR 1991;119:639-43.
M a n a g e m e n t of the febrile patient with cancer and neutropenia To The Editor: The otherwise excellent review on the diagnosis and treatment of infection in the child with cancer by Pizzo et al. 1 omitted a key management issue for a sizable number of these patients. In most pediatric oncology centers, a large percentage (approximately 60% in our experience) of children admitted for diagnosis and management of fever and neutropenia have negative blood culture results, defervesce within several days, appear well, but continue to exhibit neutropenia. How long are such patients to remain in the hospital, receiving broad-spectrum parenterat antibiotics? Pizzo et al. failed to explain how they would manage such patients. They implied that these patients should continue to receive antibiotics for 7 to 14 days. Only when "recovery of the leukocyte count" (which was not defined but presumably means a rise in the number of neutrophils to 500/mm 3) occurs was it deemed safe to discontinue antibiotic therapy. The authors quoted a study performed in the late 1970s2 supporting this approach; in this study, patients whose antibiotics were discontinued, but who continued to have neutropenia, had an unacceptably high incidence of recurrent fever. In the majority of these children, however, antibiotic therapy was discontinued 1 week or more before recovery from neutropenia. A year ago a colleague and I published data showing that relatively "low risk" children hospitalized for fever and neutropenia who have negative blood culture results, resolution of fever, and appear well can usually have parenteral antibiotic therapy discontinued and be safely dischai'ged from the hospital) This initial study and a follow-up trial, including an additional 107 episodes of fever and neutropenia, indicated that evidence of bone marrow re-
Editorial correspondence
669
covery (rising monocyte, neutrophil, and/or other blood count values despite persistence of absolute neutropenia) predicted an uneventful postdischarge course.4 In our center we recently completed a third (and prospective) study of this subject (unpublished observations). When the data from all three series were pooled, 218 consecutive "low risk" children with fever and neutropenia who had evidence of marrow recovery (i.e., a rising neutrophil count) had antibiotic therapy discontinued and were discharged from the hospital despite an absolute neutrophil count
