Lee, S.S.F., Fulford, A.E., Quinn, M.A., Seabrook, J., & Rajakumar, I. (2018). Levofloxacin for febrile neutropenia prophylaxis in acute myeloid leukemia patients associated with reduction in hospital admissions. Supportive Care in Cancer, 26, 1499–1504.

To evaluate the safety and efficacy of oral levofloxacin in preventing febrile neutropenia (FN) in patients who have received consolidation chemotherapy for acute myeloid leukemia (AML)

Following consolidation chemotherapy with: (1) cytarabine 3 g/m² IV q 12 hours on days 1, 3, and 5; (2) fludarabine 30 mg/m² IV on days 1-5, and cytarabine 2 g/m² IV on days 1-5, with or without filgrastim 300-480 mcg SQ daily beginning on day 6 until neutrophil recovery; or (3) mitoxantrone 6 mg/m² IV on days 1-3 and cytarabine 2 g/m² IV q 12 hours on days 1-3 for cycle 1 and 1 g/m² for cycle 2; hematologists chose whether to prescribe levofloxacin or not. This retrospective chart review compared the levofloxacin group to the no levofloxacin group. The primary efficacy outcome compared rehospitalization rates between those who received levofloxacin and those who did not. Secondary outcomes assessed duration of antibiotic treatment needed for FN and compared rates of Clostridium difficile-associated diarrhea (CDAD) between the two groups.

• N = 100   
• AGE: 18 years or older, 31% were aged 60 years or older; mean = 51.2 years
• MALES: 50%  
• FEMALES: 50%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: AML

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: London, Ontario, Canada

PHASE OF CARE: Transition phase after active treatment

Retrospective chart review of AML patients, 50 of whom had received levofloxacin following consolidation chemotherapy and 50 of whom had not.

To evaluate the primary outcome, researchers tracked the rate of hospital readmission because of FN. Secondary outcomes considered the total number of days of antibiotic therapy required to recover from FN and counted the number of days between hospital discharge after consolidation chemotherapy and readmission for FN. Safety outcomes compared the rate of CDAD between the levofloxacin and no levofloxacin groups within 30 days following hospital discharge following consolidation chemotherapy, the relative rates of positive blood cultures in FN patients, the relative rates of resistance to levofloxacin from positive bacterial cultures, and the impact of levofloxacin on the spectrum of bacteria identified from positive cultures.

Following the first cycle of consolidation chemotherapy, 42% of patients who received levofloxacin were readmitted for FN. The no levofloxacin group had a readmission rate of 72% (p = 0.002). Results following all cycles of consolidation chemotherapy were less dramatic but still demonstrated the benefit of levofloxacin therapy (51.4% readmission for FN in the levofloxacin group, compared to 67% in the no levofloxacin” group (p = 0.023). There were no significant differences between the two groups in terms of total number of antibiotic treatment days (median 11 versus 10, p = 0.639), mean day of readmission after discharge from receiving consolidation chemotherapy (11.58 versus 10.37, p = 0.205), and rate of positive bacterial culture in readmitted FN patients (28.9 versus 42.9, p = 0.148).

This study supports the previously-established Infectious Diseases Society of America and National Comprehensive Cancer Network guidelines for antibiotic prophylaxis for cancer patients at high risk of developing FN. Levofloxacin use had no significant impact on any of the secondary outcome measures.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• Other limitations/explanation: The patients in this study received one of three different regimens of consolidation chemotherapy, but the study did not divide these patients into different arms. Furthermore, the dose and duration of levofloxacin therapy were not standardized.

This retrospective chart review did not separate the various consolidation chemotherapy regimens into separate arms. The authors searched until they found the intended sample size of patients who had received levofloxacin and those who had not. Of note, the levofloxacin dose and duration of fluoroquinolone therapy was not standardized.