Levofloxacin Prevents Infection in Neutropenic Cancer Patients

NEW YORK SEP 07, 2005  (Reuters Health) - Fears of bacterial resistance have generally prevented the prophylactic use of fluoroquinolones in patients with cancer and neutropenia.  However, two placebo-controlled clinical trials reported in The New England Journal of Medicine on September 8th show that prophylactic levofloxacin during periods of neutropenia reduces the incidence of febrile episodes and other infection-related outcomes.

Italian researchers led by Dr. Albano Del Favero at the Universita di Perugia included in their prospective study 760 consecutive hospitalized patients with leukemia, lymphoma or solid tumors in whom neutropenia was expected to persist for more than 7 days.  Patients were randomly assigned to oral levofloxacin 500 mg daily (n = 384) or placebo (n = 376). 

Prophylaxis was continued in all patients until neutropenia resolved.  Empirical antibacterial therapy was initiated when an infection was suspected.

The incidence of fever was significantly lower in the levofloxacin group (65% versus 85%, p = 0.001).  Levofloxacin treatment was associated with significantly lower rates of infection, gram-negative bacteremia, and polymicrobial bacteremia, although there was no significant difference between groups in mortality through the end of the neutropenic period.

The authors estimate that the total cost of antibiotics was lower in the levofloxacin group (mean 1953 euro versus 2841 euro; p < 0.001).

In the second study, lead investigator Dr. Michael Cullen at the University Hospital Birmingham Cancer Centre and colleagues in the UK randomly assigned 781 patients with solid tumors or lymphoma to daily levofloxacin 500 mg and 784 to placebo.  Patients received treatment while undergoing six cycles of chemotherapy during the 7 days of anticipated neutropenia during each cycle.

During the entire course of chemotherapy, levofloxacin was associated with significantly fewer febrile episodes (10.8% versus 15.2%; p = 0.01).

The authors also observed a 27% reduction in hospitalizations for infections during all six cycles of chemotherapy (p = 0.004) in the treatment group, which amounts to a savings of 38 hospital days per 100 patients given prophylactic treatment.

In an accompanying editorial, NEJM deputy editor Dr. Lindsey R. Baden comments that, while the two studies suggest a significant benefit of levofloxacin prophylaxis, they leave unanswered questions regarding "the patients at greatest risk, the period of increased risk, and the likelihood of the emergence of resistant organisms."

She maintains that if a cancer center adopts a strategy of prophylactic antimicrobial therapy, "it should be accompanied by vigorous infection-control practices and careful monitoring for the emergence of resistant organisms."

SOURCE:

• N Engl J Med 2005;353:977-998,1052-1054.