Levofloxacin Prophylaxis Beneficial Despite Antimicrobial Resistance

NEW YORK APR 28, 2005 (Reuters Health) - Levofloxacin prophylaxis for chemotherapy-related neutropenia may reduce morbidity and infection-related mortality, even though its use is associated with antimicrobial resistance, according to a report in the April 15th issue of Clinical Infectious Diseases.

"Despite increasing fluoroquinolone resistance, fluoroquinolone prophylaxis may still be effective for infection prevention during neutropenia," Dr. Stefan Reuter from University Hospital of Ulm, Germany told Reuters Health. "Incidence rates of significant infection rather than relative rates of bacterial resistance should guide antibiotic policy changes in this setting."

Dr. Reuter and colleagues assessed the impact of discontinuing levofloxacin prophylaxis and then reintroducing it on the incidence of fever, bacteremia and mortality among 310 patients with neutropenia following chemotherapy for hematologic malignancies.

Before levofloxacin prophylaxis was discontinued, 4.8% of patients had gram-negative bacteremia, 18.7% had gram-positive bacteremia, and infection-related mortality was 1%, the authors report.

During 3 weeks when levofloxacin prophylaxis was interrupted, 4 of 9 patients (44.4%) had gram-negative bacteremia and 3 patients (33.3%) died, the report indicates.

After levofloxacin prophylaxis was reinstituted, 5.7% of patients had gram-negative bacteremia, 17.1% had gram-positive bacteremia, and infection-related mortality returned to 1% (1 of 70 patients), the researchers note.

During levofloxacin prophylaxis, 12 of 19 gram-negative isolates and 59 of 70 gram-positive isolates were resistant to fluoroquinolones, the investigators report, compared with 0 of 4 gram-negative and 1 of 3 gram-negative isolates during the 3-week hiatus from prophylaxis.

"If the observed rate of resistance continues at the same pace, fluoroquinolone prophylaxis may become ineffective in the future," the authors caution. "Thus, continued monitoring of the incidence rate of gram-negative bacteremia is warranted for the timely detection of a loss in the efficacy of fluoroquinolone prophylaxis."

"This study is probably the first to suggest that fluoroquinolone prophylaxis has a significant impact on infection-related mortality," writes Dr. Stephen H. Zinner from Harvard Medical School, Boston, in a related editorial.

"The current study...supports the continuing interest in defining optimal methods for minimizing or preventing serious bacterial infections in patients with neutropenia and cancer."

"Further studies will include the continued surveillance under prolonged levofloxacin prophylaxis and the testing of moxifloxacin as a prophylactic agent," Dr. Reuter said.

SOURCE:

• Clinical Infectious Diseases 2005;40:1087-1093,1094-1095.