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Switching Fluoroquinolones in Patients With Neutropenia May Increase Infection Risks: Presented at ICAAC

By Paula Moyer

WASHINGTON, DC -- December 19, 2005 -- Researchers have found that moxifloxacin (Avelox) could contribute to an increased rate of Clostridium difficile colitis when compared with levofloxacin (Levaquin) in patients with hematologic cancers who have prolonged neutropenia.

The investigators recommend that physicians exercise caution when considering a switch from 1 fluoroquinolone agent to another in patients with neutropenia who are on antibiotic prophylaxis.

Principal investigator Stefan Reuter, MD, assistant professor of internal medicine, University Hospital, Ulm, Germany, presented the findings here on December 17^th at the 45^th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

Dr. Reuter and coinvestigators had noticed a problem in patients who were switched from levofloxacin to moxifloxacin (Avelox). "Both the number of Gram-negative bacteremias and the number of infections of Clostridium difficile with associated diarrhea were higher under moxifloxacin-prophylaxis as compared to levofloxacin," he said.

"These findings may indicate that fluoroquinolones are not interchangeable in the neutropenia setting," he added.

However, he stressed that the findings were based on patients from 1 center, and that further research would be necessary before concluding definitively that such a switch is detrimental.

The investigators conducted the study because they had assumed moxifloxacin -- the broadest of the antibacterial agents -- might make an ideal prophylactic agent to use in treating patients with neutropenia.

They conducted a prospective observational study in which moxifloxacin was used as a prophylactic agent for 1 year for the treatment of 156 patients with hematologic cancers who had prolonged neutropenia.

The investigators assessed the rates of Gram-negative or -positive bacteremia, rates of C. difficile-positive tests, and deaths from infection during the study period. They compared these rates with those of a historical control group of 235 patients who had been treated with levofloxacin prior to the study period. They then compared these findings to those of 30 patients in whom levofloxacin was reintroduced in a postobservational study period of 19 weeks.

The study included all patients undergoing chemotherapy for hematological malignancies with an expected duration of neutropenia of at least 5 days. The investigators followed patients prospectively from the first day of neutropenia until 2 days after their neutrophil levels returned to normal.

The investigators compared 283 neutropenic episodes with moxifloxacin prophylaxis to 451 episodes with levofloxacin prophylaxis. Gram-negative bacteremia was detected in 10.6% of patients on moxifloxacin and 5.5% of the historical control group on levofloxacin.

In the postobservational period the investigators documented 1 episode of Gram-negative bacteremia during 25 neutropenic episodes (4%). The investigators are still following these patients, Dr. Reuter said.

The rates of C. difficile infection were 31.1% in the patients treated with moxifloxacin, 6.3% in the historical controls, and 13.6% in the patients treated with levofloxacin in the postobservational study.

Rates of Gram-positive bacteremia were 16% for the moxifloxacin group, 19% for the historical controls, and 31.4% for those treated with levofloxacin after the observational study.

Death rates related to infection were 6.4% in the moxifloxacin group, 4.3% in the historical controls, and 6.7% in the postobservation period group.

"We don't know if the switch back to levofloxacin caused the drops in Gram-negative bacteremia and C. difficile," Dr. Reuter said. "Because the hospital instituted more diligent infection control measures at the same time, it is difficult to discern which caused the decrease in infection."


[Presentation title: Moxifloxacin-Prophylaxis During Neutropenia in Patients With Hemato-Oncological Malignancies. Abstract K-1540]

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