Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.
BACKGROUND
The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention.


METHODS
We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma).


RESULTS
An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma.


CONCLUSIONS
Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known.
Bucaneve
Giampaolo
G
Policlinico Monteluce, Perugia, Italy.
Micozzi
Alessandra
A
Menichetti
Francesco
F
Martino
Pietro
P
Dionisi
M Stella
MS
Martinelli
Giovanni
G
Allione
Bernardino
B
D'Antonio
Domenico
D
Buelli
Maurizio
M
Nosari
A Maria
AM
Cilloni
Daniela
D
Zuffa
Eliana
E
Cantaffa
Renato
R
Specchia
Giorgina
G
Amadori
Sergio
S
Fabbiano
Francesco
F
Deliliers
Giorgio Lambertenghi
GL
Lauria
Francesco
F
Foà
Robin
R
Del Favero
Albano
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016470:Bacteremia / Q000382:microbiology / Q000401:mortality; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005335:Fever of Unknown Origin / Q000517:prevention & control; D006801:Humans; D064704:Levofloxacin; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D015242:Ofloxacin / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D064704:Levofloxacin; D015242:Ofloxacin