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The Use of Fluoroquinolones as Prophylaxis in Neutropenia

Hamayun Imran, MD, MSca
Imad M. Tleyjeh, MD, MScb
aDivision of Pediatric Hematology/Oncology, University of
South Alabama, Mobile, Alabama, USA
bDepartment of Medicine, Division of Infectious Disease,
King Fahd Medical City, Riyadh, Saudi Arabia

Febrile neutropenia, one of the most serious adverse events encountered by physicians caring for cancer patients, results in lengthened hospital stays and an increased mortality rate. Thus, efficacious antibiotic prophylaxis should produce significant benefits. We performed a meta-analysis of randomized, blinded, placebo-controlled trials of fluoroquinolone prophylaxis in neutropenic patients using a random effects model for pooling dichotomous data. A total of 2,721 patients were randomized in 8 eligible trials. Results exhibited a consistent trend in reduction of all-cause mortality thus favoring the use of fluoroquinolone prophylaxis (relative risk [RR]: 0.76; 95% confidence interval [CI]: 0.54-1.08; p = 0.13). Analyses also favored fluoroquinolone prophylaxis for the prevention of febrile episodes (RR: 0.76; 95% CI: 0.55-1.03; p = 0.08); however, substantial inconsistencies in the results prevent a meaningful interpretation of the pooled data. Results of the subgroup analyses showed a significant reduction in febrile episodes with fluoroquinolone prophylaxis in outpatients with solid tumors including lymphoma compared with the inpatient hematology and stem cell transplant population included in these trials (RR: 0.34 [95% CI: 0.14-0.80] and 0.90 [95% CI: 0.70-1.16], respectively [p < 0.001]). The results also suggested a different effect with levofloxacin prophylaxis when trials that used levofloxacin were compared with trials of other fluoroquinolones (RR: 0.60 [95% CI: 0.33-1.10] and 0.89 [95% CI: 0.65-1.22], respectively [p = 0.01]). We also reviewed the recommendations by the National Comprehensive Cancer Network panel (1) which advises that fluoroquinolone prophylaxis be considered in patients with an expected duration of neutropenia of more than 7 days. The panel also believes that the benefit of prophylaxis in patients with hematologic malignancies on overall survival outweighs the events related to adverse effects and the development of resistance. This panel suggests levofloxacin as the preferred agent. With regard to surveillance for the emergence of resistant pathogens, fluoroquinolone prophylaxis should be considered in selected adult populations receiving cancer chemotherapy.

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