Prevention of Infection in Patients With Hematologic Cancer and Persistent Fever Caused by a Low White Blood Cell Count
Prevention of Infection in Patients With Hematologic Cancer and Persistent Fever Caused by a Low White Blood Cell Count
RATIONALE: Antibiotic therapy may prevent the development of infection in patients with
 hematologic cancer and the persistent fever caused by a low white blood cell count. It is not
 yet known which regimen of antibiotics is most effective in preventing infection in these
 patients.

 PURPOSE: Randomized phase III trial to study the effectiveness of piperacillin-tazobactam
 with or without vancomycin in reducing fever in patients who have leukemia, lymphoma, or
 Hodgkin's disease.
OBJECTIVES: I. Compare the efficacy of piperacillin and tazobactam with or without vancomycin
 in reducing fever in patients with hematological malignancies and persistent febrile
 granulocytopenia.

 OUTLINE: This is a randomized, double blind, multicenter study. Patients receive
 piperacillin/tazobactam IV over 20-30 minutes every 6 hours. Patients who become afebrile
 within 48-60 hours after beginning treatment continue to receive piperacillin/tazobactam
 alone. These afebrile patients continue treatment for a minimum of 7 days, of which 4 must be
 consecutive without fever. Patients who are still febrile after the initial 48-60 hours are
 randomized to continue on piperacillin/tazobactam alone or with vancomycin. Vancomycin IV is
 administered over at least 1 hour twice daily. Treatment continues for a maximum of 28 days
 in the absence of persistent fever. Patients are followed at 7-10 days after completion of
 therapy.

 PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Leukemia, lymphoma, or Hodgkin's disease OR Stem cell
 transplantation or bone marrow transplantation (allogenic or autologous) for a neoplastic
 disease Absolute granulocyte count no greater than 1,000/mm3 anticipated to fall below
 500/mm3 within 24-48 hours, and expected to last for longer than 7 days from onset of fever
 Fever (i.e., oral or axillary temperature at least 38.5 degrees C or 101.3 degrees F once,
 or at least 38 degrees C or 100.4 degrees F on two or more occasions separated at least by
 1 hour during a 12 hour period) Presumed infection

 PATIENT CHARACTERISTICS: Age: 2 and over Performance status: Not moribund or comatose for
 any reason with little hope of recovery Life expectancy: At least 48 hours Hematopoietic:
 See Disease Characteristics Hepatic: No hepatic stupor or coma Renal: Adults: No renal
 failure requiring hemodialysis or peritoneal dialysis OR Creatinine no greater than 2.25
 mg/dL OR Creatinine clearance at least 40 mL/min Children: No renal impairment (i.e.,
 creatinine greater than upper limit of normal) Pulmonary: No lung infiltrate Other: No
 known allergy to piperacillin, tazobactam, or vancomycin No history of immediate or
 accelerated reaction to beta-lactam antibiotics No prior inclusion in this study No
 catheter related infection No known HIV infection Not pregnant or nursing

 PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: Not
 specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not
 specified Other: At least 4 days since prior intravenous antibacterial agents Oral
 antibiotics for prophylaxis of bacterial infection allowed At least 30 days since prior
 treatment with any other investigational antibiotic No other concurrent antibiotics except
 trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia