Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas.
BACKGROUND
The role of prophylactic antibacterial agents after chemotherapy remains controversial.


METHODS
We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients were randomly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period. The primary outcome was the incidence of clinically documented febrile episodes (temperature of more than 38 degrees C) attributed to infection. Secondary outcomes included the incidence of all probable infections, severe infections, and hospitalization but did not include a systematic evaluation of antibacterial resistance.


RESULTS
A total of 1565 patients underwent randomization (784 to placebo and 781 to levofloxacin). The tumors included breast cancer (35.4 percent), lung cancer (22.5 percent), testicular cancer (14.4 percent), and lymphoma (12.8 percent). During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P<0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P=0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P=0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P=0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P=0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections.


CONCLUSIONS
Among patients receiving chemotherapy for solid tumors or lymphoma, the prophylactic use of levofloxacin reduces the incidence of fever, probable infection, and hospitalization.
Cullen
Michael
M
University Hospital Birmingham Cancer Centre, Birmingham, United Kingdom. michael.cullen@uhb.nhs.uk
Steven
Neil
N
Billingham
Lucinda
L
Gaunt
Claire
C
Hastings
Mark
M
Simmonds
Peter
P
Stuart
Nicholas
N
Rea
Daniel
D
Bower
Mark
M
Fernando
Indrajit
I
Huddart
Robert
R
Gollins
Simon
S
Stanley
Andrew
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001424:Bacterial Infections / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005334:Fever / Q000209:etiology / Q000517:prevention & control; D006760:Hospitalization; D006801:Humans; D007958:Leukocyte Count; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications; D015242:Ofloxacin / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D064704:Levofloxacin; D015242:Ofloxacin