Levofloxacin Prophylaxis During Induction Therapy for Pediatric Acute Lymphoblastic Leukemia

Abstract

Background: Infection is the most important cause of treatment-related morbidity and mortality in pediatric patients treated for acute lymphoblastic leukemia (ALL). Although routine in adults with leukemia, antibacterial prophylaxis is controversial in pediatrics because of insufficient evidence for its efficacy or antibiotic choice and concerns about promoting antibiotic resistance and Clostridium difficile infection.

Methods: This was a single-center, observational cohort study of patients with newly diagnosed ALL, comparing prospectively collected infection-related outcomes in patients who received no prophylaxis, levofloxacin prophylaxis, or other prophylaxis during induction therapy on the total XVI study. A propensity score-weighted logistic regression model was used to adjust for confounders.

Results: Of 344 included patients, 173 received no prophylaxis, 69 received levofloxacin prophylaxis, and 102 received other prophylaxis regimens. Patients receiving prophylaxis had longer duration of neutropenia. Prophylaxis reduced the odds of febrile neutropenia, likely bacterial infection, and bloodstream infection by ≥70%. Levofloxacin prophylaxis alone reduced these infections, but it also reduced cephalosporin, aminoglycoside, and vancomycin exposure and reduced the odds of C. difficile infection by >95%. No increase in breakthrough infections with antibiotic-resistant organisms was seen, but this cannot be excluded.

Conclusions: This is the largest study to date of antibacterial prophylaxis during induction therapy for pediatric ALL and the first to include a broad-spectrum fluoroquinolone. Prophylaxis prevented febrile neutropenia and systemic infection. Levofloxacin prophylaxis also minimized the use of treatment antibiotics and drastically reduced C. difficile infection. Although long-term antibiotic-resistance monitoring is needed, these data support using targeted prophylaxis with levofloxacin in children undergoing induction chemotherapy for ALL.

Clinical trials registration: NCT00549848.

Keywords: Clostridium difficile; child; leukemia; levofloxacin; prophylaxis.

Figure 1.

Antibiotic exposure during induction for each antibiotic prophylaxis group. Data are shown in a box plot; each box plot illustrates the upper and lower quartile (box), median (line inside box), adjacent values (whiskers), and outliers (open circles). Antibiotic exposure and cumulative antibiotic exposure were significantly greater in patients receiving levofloxacin or other prophylaxis than in those receiving no prophylaxis (P < .001 for all comparisons). However, patients receiving levofloxacin prophylaxis had less exposure to cefepime/ceftazidime, vancomycin, meropenem, or aminoglycosides (data not shown) when compared with those receiving no prophylaxis (P < .001, P < .001, P < .001, and P = .002, respectively) or other prophylaxis (P < . 001, P < .001, P < .001, and P = .04, respectively).

Figure 2.

Kaplan-Meier analysis of time to infectious complications during induction for each antibiotic prophylaxis group. Patients receiving levofloxacin prophylaxis during induction therapy for pediatric acute lymphoblastic leukemia had a lower cumulative incidence of C. difficile infection (A) than those receiving no prophylaxis (P = .008) or other prophylaxis regimens (P = .01) and a lower cumulative incidence of enterocolitis (B) than those receiving no prophylaxis (P = .03). Patients receiving any prophylaxis had a lower cumulative incidence of febrile neutropenia (C) (P < .001) and likely bacterial infection (D) (P < .001), but there was no significant difference in the cumulative incidence of febrile neutropenia or likely bacterial infection between patients receiving levofloxacin and those receiving other prophylaxis regimens (P = .52 and P = .36, respectively).