Among children with acute leukemia receiving intensive chemotherapy, receipt of levofloxacin prophylaxis compared with no prophylaxis resulted in a significant reduction in bacteremia, according to a study recently published in JAMA.
Bacteremia is a leading cause of morbidity and mortality in children receiving intensive chemotherapy for acute myeloid leukemia (AML) and relapsed acute lymphoblastic leukemia (ALL), as well as for those undergoing hematopoietic stem cell transplantation. Previous trials demonstrate the use of prophylactic antibiotics decrease risk for infections and death in adult patients with neutropenia secondary to cancer therapy. Further, data describing prophylactic antibiotics in children with cancer are limited. However, the adoption of antibacterial prophylaxis is tempered by potential negative consequences including Clostridium difficile-associated diarrhea, bacterial resistance, and musculoskeletal toxicities. Therefore, this open-label, randomized trial determined the efficacy and risks for levofloxacin prophylaxis in children receiving intensive chemotherapy for acute leukemia who were undergoing hematopoietic stem cell transplantation.
Between 2011 and 2016, 76 centers in the United States and Canada, 613 patients (age, 6 months-21 years) receiving intensive chemotherapy were enrolled and evaluated in 2 separate groups: acute leukemia, consisting of AML or relapsed ALL (n=195), and those undergoing hematopoietic stem cell transplantation (n=418). Patients with acute leukemia were randomly assigned to receive either levofloxacin prophylaxis for 2 consecutive cycles of chemotherapy (n=100) or no prophylaxis (n=100). Patients undergoing hematopoietic stem cell transplantation were randomly assigned to receive either levofloxacin prophylaxis during 1 hematopoietic stem cell transplantation procedure (n=210) or no prophylaxis. Patient follow-up was completed in 2017. The primary outcome was the occurrence of bacteremia during 2 chemotherapy cycles (acute leukemia) or 1 transplant procedure. Secondary outcomes included fever and neutropenia, severe infection, invasive fungal disease, C difficile-associated diarrhea, and musculoskeletal toxic effects. The mean duration of levofloxacin for the prophylaxis and no prophylaxis groups were 14.6 and 0.3 days per 30 days at risk for the acute leukemia group, and 13.8 and 0.4 days per 30 days at risk for the hematopoietic stem cell transplantation group.
Among 195 patients with acute leukemia, the likelihood of bacteremia was significantly lower in the levofloxacin prophylaxis group than in the control group (21.9% vs 43.4%; P =.001), whereas among 418 patients undergoing hematopoietic stem cell transplantation, the risk for bacteremia was not significantly lower in the levofloxacin prophylaxis group (11.0% vs 17.3%; P =.06). Further, when all patients were combined, levofloxacin significantly reduced the likelihood of bacteremia (P <.001). Among the 123 bacteremia episodes, Viridans group streptococci represented the most common cultured organisms in both the acute leukemia and hematopoietic stem cell transplantation groups. Fever and neutropenia were less common in the levofloxacin group (71.2% vs 82.1%; P =.002). There were no significant differences in severe infection (3.6% vs 5.9%; P =.20), invasive fungal disease (2.9% vs 2.0%; P =.41), C difficile-associated diarrhea (2.3% vs 5.2%; P =.07), or musculoskeletal toxic effects at 2 months (11.4% vs 16.3%; P =.15) or at 12 months (10.1% vs 14.4%; P =.28) between the levofloxacin and control groups.
Overall, the study authors concluded that, “[l]evofloxacin prophylaxis significantly reduced the risk of bacteremia in children with acute leukemia receiving intensive chemotherapy but not in those undergoing stem cell transplantation.”
Alexander S, Fisher BT, Gaur AH, et al. Effect of levofloxacin prophylaxis on bacteremia in children with acute leukemia or undergoing hematopoietic stem cell transplantation, a randomized clinical trial. JAMA. 2018; 320(10):995-1004. doi:10.1001/jama.2018.12512