Ciprofloxacin plus piperacillin compared with tobramycin plus piperacillin as empirical therapy in febrile neutropenic patients. A randomized, double-blind trial.
BACKGROUND
Therapy with an aminoglycoside and a beta-lactam remains common empirical therapy for febrile neutropenic patients. Concerns of aminoglycoside-induced ototoxicity and nephrotoxicity have led to studies of alternate regimens.


OBJECTIVE
To determine whether ciprofloxacin-piperacillin is equivalent to tobramycin-piperacillin as empirical therapy for neutropenic fever.


METHODS
Randomized, double-blind multicenter trial.


METHODS
Seven U.S. university-affiliated hospitals and one private research center.


METHODS
Febrile (temperature >/= 38 degrees C), neutropenic (neutrophil level < 1 x 10(9) cells/L) hospitalized patients who had leukemia, lymphoma, or solid tumors, or were undergoing bone marrow transplantation.


METHODS
Patients received piperacillin, 50 mg/kg of body weight intravenously every 4 hours, and ciprofloxacin, 400 mg intravenously every 8 hours, or tobramycin, 2 mg/kg intravenously every 8 hours.


METHODS
Success was defined as resolution of infection and previously positive cultures without the need to give additional antimicrobial agents.


RESULTS
543 febrile episodes were evaluated, of which 471 were clinically evaluable (234 in the ciprofloxacin-piperacillin group and 237 in the tobramycin-piperacillin group). Success rates in the ciprofloxacin-piperacillin group (63 of 234 febrile episodes) and tobramycin-piperacillin group (52 of 237 episodes) were similar (27% vs. 22%, respectively; difference, 5.0 percentage points [95% CI, -2.3 to 12.8 percentage points]), as was survival (96.2% of patients receiving ciprofloxacin-piperacillin versus 94.1% of patients receiving tobramycin-piperacillin; difference, 2.1 percentage points [CI, -2.2 to 6.4 percentage points]). Additions to the initial antimicrobial regimen were the most common reason for treatment failure in both groups (accounting for 67% of failures in the ciprofloxacin-piperacillin group and 72% in the tobramycin-piperacillin group; difference, 5.0 percentage points [CI, -13.8 to 3.7 percentage points]). Fevers resolved faster in patients receiving ciprofloxacin-piperacillin than in patients receiving tobramycin-piperacillin (mean, 5 vs. 6 days) (P = 0.005). No significant differences in adverse events or toxicity were noted (P = 0.083).


CONCLUSIONS
Ciprofloxacin-piperacillin is as safe and effective as tobramycin-piperacillin for empirical therapy of neutropenic fever.
Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1042, USA.
James E
JE
Peacock
Deirdre A
DA
Herrington
James C
JC
Wade
Hillard M
HM
Lazarus
Michael D
MD
Reed
Jane W
JW
Sinclair
Daniel C
DC
Haverstock
Steven F
SF
Kowalsky
David D
DD
Hurd
Deborah A
DA
Cushing
Colleen P
CP
Harman
Gerald R
GR
Donowitz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002939:Ciprofloxacin / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007938:Leukemia / Q000150:complications; D008223:Lymphoma / Q000150:complications; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D009894:Opportunistic Infections / Q000188:drug therapy / Q000209:etiology; D010406:Penicillins / Q000009:adverse effects / Q000627:therapeutic use; D010878:Piperacillin / Q000009:adverse effects / Q000627:therapeutic use*; D014031:Tobramycin / Q000009:adverse effects / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010406:Penicillins; D002939:Ciprofloxacin; D014031:Tobramycin; D010878:Piperacillin