Levofloxacin Prophylaxis Shown to Be Cost-effective in Pediatric ALL, AML

Levofloxacin prophylaxis is a cost-effective therapy for children with leukemia who receive intensive chemotherapy, according to a new study.

Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) have high overall survival (OS) rates, of 90% and 60%-65%, respectively. Among the minority of patients who do not survive, serious bacterial infection is a common culprit. The risk of such infections is particularly high in patients who undergo intensive chemotherapy.

Corresponding author Marie-Claude Pelland-Marcotte, MD, of The Hospital for Sick Children, in Toronto, and colleagues wanted to evaluate whether giving children with ALL and AML levofloxacin (Levaquin) as a prophylactic might be a cost-effective method by which to avoid infection and infection-related morbidity and mortality. They reported their findings in the journal Pediatric Blood & Cancer.

Pelland-Marcotte and colleagues performed a literature review and identified a single randomized controlled trial that looked at levofloxacin prophylaxis in childhood AML and relapsed ALL. The study showed rates of fever and neutropenia were lower among children given the drug compared to those who did not receive prophylaxis, 71.2% versus 82.1%. Rates of bacteremia were also lower, at 21.9% among the levofloxacin arm compared to 43.4% among those receiving no prophylaxis.

Using those data as a backdrop, Pelland-Marcotte and colleagues performed a cost-utility analysis to see whether the impact of levofloxacin justified its cost.

They found that use of levofloxacin resulted in a cost savings of $542.44. Patients receiving the drug also had an increased survival of 0.13 quality-adjusted life years (QALYs).

“The direct cost of antibiotic prophylaxis and its side effects were relatively minor compared to its benefits,” the authors wrote.

The investigators added that on their probabilistic sensitivity analysis, the probability of the prophylaxis not being cost effective was less than 1%, using a willingness to pay threshold of $50,000.

One question that remains unanswered is whether the cost-effectiveness of the prophylaxis might change if patients receive multiple cycles of chemotherapy. The authors said there’s a chance the cost effectiveness would increase over multiple cycles, though they said other factors must also be considered.

“It is also possible that prolonged exposure to levofloxacin over more than two cycles of chemotherapy increases the risk of antibacterial resistance and adverse effects,” they wrote.

Though they said the decision of whether or not to administer levofloxacin as a prophylactic should ultimately be based on clinical factors, the authors believe the economic case is strong.

Another issue that may impact decisions, however, is the effort by many hospitals to implement policies that restrict antibiotic use in order to protect against drug resistance.

Pelland-Marcotte and colleagues calculated that the risk of resistant infections would not change their bottom line conclusion that levofloxacin prophylaxis has a favorable cost/benefit ratio.

“Nonetheless, further research about short- and long-term antimicrobial resistance following antibiotic prophylaxis is greatly needed,” they said.

Another question raised by the study is whether parents would be amenable to the use of the drug. The authors said previous research on parents’ willingness to pay thresholds for a prophylactic suggests the drug would still be cost-effective, particularly if most patients received the drug orally, as opposed to intravenously.

Lastly, the authors noted that while the data in the study was based on Canadian patients, they expect the findings would be generalizable to other countries. However, they said it is not yet known if the findings would be generalizable to other types of cancer or therapy.

Reference

Maser B, Pelland-Marcotte MC, Alexander S, Sung L, Gupta S. Levofloxacin prophylaxis in hospitalized children with leukemia: A cost-utility analysis. Pediatr Blood Cancer. Published online August 12, 2020. doi:10.1002/pbc.28643