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Levofloxacin lowers risk for bacteremia in pediatric acute leukemia
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Prophylactic levofloxacin significantly decreased the risk for bacteremia among children receiving intensive chemotherapy for acute myeloid leukemia or relapsed acute lymphoblastic leukemia, according to results from a multicenter, open-label, randomized trial.
However, levofloxacin did not lower bacteremia risk among children undergoing hematopoietic stem cell transplantation.
Bacteremia is a leading cause of morbidity and mortality among children undergoing intensive chemotherapy for AML and relapsed ALL, and for those undergoing HSCT. Although data exist on the benefits of prophylactic antibiotics among adults, data are lacking for children.
Sarah Alexander, MD, FRCPC, staff oncologist and clinical director in the division of hematology and oncology at The Hospital for Sick Children in Toronto, and colleagues assessed the safety and efficacy of levofloxacin prophylaxis in 626 children receiving intensive chemotherapy for AML or ALL, or undergoing HSCT across 76 centers in the U.S. and Canada between September 2011 and April 2016.
In October 2016 — at which time the planned target enrollment had been reached — the Children’s Oncology Group data and safety monitoring committee recommended early termination of the trial due to the demonstrated efficacy of levofloxacin in the acute leukemia arm.
Follow-up completed in September 2017.
Researchers randomly assigned 200 patients with AML or ALL (median age, 11 years; 46% female) to levofloxacin prophylaxis (primary analysis, n = 96) for two consecutive cycles of chemotherapy or no prophylaxis (primary analysis, n = 99). Researchers randomly assigned 424 patients undergoing HSCT (median age, 7 years; 38% female) to levofloxacin prophylaxis during HSCT (primary analysis, n = 210) or no prophylaxis (primary analysis, n = 208).
Patients aged 6 months to 5 years received levofloxacin via infusion or orally in a 10-mg/kg twice-daily dose, and those aged older than 5 years received a 10-mg/kg once-daily dose.
The occurrence of bacteremia during two chemotherapy cycles or during one HSCT procedure served as primary outcome. Incidence of fever, neutropenia, severe infection, invasive fungal disease, Clostridium difficile-associated diarrhea and musculoskeletal adverse events served as secondary outcomes.
Among those with AML or ALL, the risk for bacteremia significantly decreased with levofloxacin (21.9% vs. 43.4%; risk difference, 21.6%; 95% CI, 8.8-34.4; P = .001).
However, levofloxacin did not significantly decrease risk for bacteremia among those undergoing HSCT (11% vs 17.3%; risk difference, 6.3%; 95% CI, 0.3-13; P = .06).
More patients in the control arms experienced fever and neutropenia (82.1% vs. 71.2%; risk difference, 10.8%; 95% CI, 4.2-17.5; P = .002). No significant differences were observed for any other adverse events.
The researchers noted several study limitations, including the open-label nature of the trial; its evaluation of short-term prophylaxis while the effect of long-term prophylaxis requires further study; and the effect of levofloxacin may have been overestimated due to early trial termination in patients with AML and ALL. Also, episodes of possible fungal disease based on clinical or radiographic findings were not included; therefore, the frequency of invasive fungal disease may have been underestimated.
“Further study is required to assess the utility of levofloxacin prophylaxis on the largest group of pediatric patients with leukemia, those undergoing primary therapy for ALL,” the researchers wrote. – by Jennifer Southall
Disclosures: The trail was sponsored by the NCI. Alexander reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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