Shinohara, A., Yoshiki, Y., Masamoto, Y., Hangaishi, A., Nannya, Y., & Kurokawa, M. (2013). Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced febrile neutropenia in patients with hematological malignancies. Leukemia and Lymphoma, 54, 794–798.

To evaluate the efficacy of antibiotic prophylaxis with tosufloxacin or moxifloxacin in adult patients (aged 16 years or older) with hematologic malignancies who were treated with chemotherapy that induced neutropenia and had an absolute neutrophil count less than 500/mcL for five days or longer

From 2004–2006, patients were treated with prophylactic tosufloxacin 150 mg three times daily, and from 2007–2008, patients were treated with prophylactic moxifloxacin 400 mg daily. All patients in both groups were treated with prophylactic antifungal therapy with either fluconazole or itraconazole.

• N = 349 episodes (270 in the tosufloxacin group and 79 in the moxifloxacin group) in 161 patients (116 in the tosufloxacin  group and 45 in the moxifloxacin group)  
• MEAN AGE = 50.7 years in the tosufloxacin group and 53.5 years in moxifloxacin group
• MALES: 57.8% in the tosufloxacin group and 57.8% in the moxifloxacin group, FEMALES: 42.2% in the tosufloxacin group and 42.2% in the moxifloxacin group
• KEY DISEASE CHARACTERISTICS: All patients in the tosufloxacin group and the moxifloxacin group had hematologic malignancies including acute myeloid leukemia (AML) (64.4% and 62%, respectively), lymphoma (9.6% and 10.1%, respectively), acute lymphocytic leukemia (ALL) (15.2% and 5.1%, respectively), and other (10.7% and 22.8%, respectively). More patients had ALL in the tosufloxacin group compared with the moxifloxacin group (p = 0.021). About 7% of patients in both groups were autologous hematopoietic cell transplant recipients.
• OTHER KEY SAMPLE CHARACTERISTICS: Excluded patients included allogeneic stem cell transplant recipients, patients treated with palliative chemotherapy, patients who had a fever or documented infection at the start of chemotherapy, and patients who received antibiotics five days prior to admission.

• SITE: Single site   
• SETTING TYPE: Inpatient   
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

• Retrospective

• Fluoroquinolone resistance was determined according to criteria set forth in “Performance Standards for Antimicrobial Susceptibility Testing”, approved by the U.S. National Committee for Clinical and Laboratory Standards.
• Clostridium difficile-associated diarrhea (CDAD) was defined as a positive Clostridium difficile toxin A assay in the setting of loose stools or watery diarrhea.
• The diagnostic criteria for proven, probable, and possible fungal infection were based on the revised European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria.

Comparison of moxifloxacin to tosufloxacin demonstrated a significantly decreased cumulative incidence of febrile neutropenia (74.7% [59 of 79] and 81.1% [219 of 270], respectively, p = 0.044]; increased incidence of fungal infection in the moxifloxacin group (10.1% compared to 4.1% in the tosufloxacin group, p = 0.048); and no cases of CDAD in either group. No significant difference was seen between groups for the mean duration of neutropenia (17.6 days and 17.9 days, respectively, p = 0.853); documented infection (20.3% and 25.9%, respectively, p = 0.373); mortality (0% and 1.9%, respectively, p = 0.592); or fluoroquinolone-resistant infections (7.6% and 9.3%, respectively, p = 0.823). A subgroup analysis of patients with AML showed a higher incidence of febrile neutropenia in the tosufloxacin group (94.1% versus 71.1%, p = 0.013), perhaps related to the observation that the patients with AML had a longer duration of neutropenia (mean = 20.6 days) than the other patients (mean = 13 days) (p < 0.01). A second subgroup analysis showed that moxifloxacin was more effective in preventing febrile neutropenia in patients with neutropenia lasting 15 days or longer (incidence: 73.8% and 89.7%, respectively, p = 0.008) and had no effect on the incidence in patients with neutropenia lasting 14 days or less (p = 0.930).

Moxifloxacin was more effective than tosufloxacin in preventing febrile neutropenia in patients with AML who were most likely to have a longer duration of neutropenia (15 days or longer). No differences in the incidence of documented infections, fluoroquinolone-resistant infections, or overall mortality were observed.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: The major study limitation is that it's a nonrandomized, retrospective study with data collected from two different time periods (tosufloxacin data from 2004–2006 and moxifloxacin data from 2007–2008). Another potential limitation, although presumed to be minor, is the risk of variation in the degree of patient compliance with oral prophylaxis.

Antibiotic prophylaxis with moxifloxacin is more effective than tosufloxacin in reducing the incidence of febrile neutropenia in high-risk patients who are expected to have a long duration of neutropenia. However, moxifloxacin was associated with more fungal infections. Nurses need to educate and counsel patients regarding antibiotic prophylaxis to enhance adherence, appropriate side effect reporting, and self-monitoring for signs of infection.