Bucaneve, G., Micozzi, A., Menichetti, F., Martino, P., Dionisi, M.S., Martinelli, G., . . . Del Favero, A. (2005). Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. New England Journal of Medicine, 353, 977–987.

Adult patients with cancer whose chemotherapy-induced neutropenia (absolute neutrophil count [ANC] greater than 1,000) was expected to occur for more than seven days were treated with oral levofloxacin 500 mg or placebo from the start of chemotherapy until the resolution of neutropenia.

Primary endpoint:

• Incidence of fever

Secondary endpoints:

• Type and number of microbiologically-documented infections
• Use of parenteral antimicrobials
• Compliance
• Tolerability
• Survival 
   

• 760 hospitalized adult patients with cancer who were expected to develop chemotherapy-induced neutropenia lasting longer than seven days.
• The sample included patients with the following types of cancer: leukemia, 49%; non-Hodgkin lymphoma or Hodgkin disease, 31%; other hematologic cancers,13%; and solid tumors, 7%.

• Inpatient
• 35 medical centers in Italy

the study was a prospective, multicenter, randomized, double-blind, placebo-controlled trial,

• Patients were examined daily for signs of infection.
• In the event of fever or suspected infection, microbiologic cultures were obtained, including at least two separate blood cultures.
• Infections were classified according to definitions of the European Organisation for Research and Treatment of Cancer ( EORTC).
• Compliance was determined by counting pills.

The incidence of fever (axillary temperature 38.5°C or higher, or 38°C at least twice during a 12-hour period) was 65% in the levofloxacin prophylaxis group versus 85% in the placebo group (p = 0.001). Microbiologically documented infection occurred in 22% of patients in the levofloxacin group and 39% of patients in the control group (absolute risk reduction 17%, 95% confidence interval [CI] [24, 10], p < 0.001).

In the levofloxacin group, the incidence of bacteremias (risk reduction 16%, 95% CI [22, 9], p < 0.001) and single-agent gram-negative bacteremias (risk reduction of 7%, 95% CI [10, 2], p < 0.01) was lower.

Death from infection occurred in 2.4% of patients in the levofloxacin group and 3.8% of patients in control group (p = 0.36).

The median duration of prophylaxis was 14 days for patients with solid tumors or lymphoma and 25 days for patients with leukemia.

Overall mortality was 3% in the levofloxacin group and 5% in the placebo group (p = 0.15). Infection-related mortality was 2% in the levofloxacin group and 4% in the placebo group (p = 0.36).

Compliance and reported adverse events were similar in both groups.

The prevalence of fluoroquinolone-resistant bacteremias was 41 of 339 (12%) in the levofloxacin group and 32 of 336 (9.5%) in the control group, but this result was not statistically significant.

The total cost of antibiotics per patient was less in the levofloxacin-treated group. The mean cost of antibiotics was €1,953 in the levofloxacin group and €2,841 in the control group.
 

Most of the patients had hematologic malignancies, so the study supports the use of antibacterial prophylaxis in this population. However, survival advantage with antibiotic prophylaxis was not demonstrated in the study.

There is concern that routine use of antibiotics is associated with an increase in resistant organisms.

The discussion section states that the study provides evidence that prophylaxis is economical because risk of fever is reduced.