Research Hospital
A patient who received prophylaxis pictured with study authors Sima Jeha, MD, and Joshua Wolf, MD Photo from Seth Dixon, St. Jude Children’s
Results of an observational study support targeted antibacterial prophylaxis in children undergoing induction therapy for acute lymphoblastic leukemia (ALL).
Prophylaxis effectively prevented febrile neutropenia and systemic infection in the children studied.
Prophylaxis with the drug levofloxacin reduced the use of treatment antibiotics and the incidence of Clostridium difficile infection.
“This research provides the first major evidence supporting targeted use of antibacterial prophylaxis for at-risk pediatric ALL patients, particularly use of the broad-spectrum antibiotic levofloxacin,” said study author Joshua Wolf, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“Prophylactic antibiotic therapy with levofloxacin is routine for at-risk adult ALL patients, but it has remained controversial in children. Until this study, evidence supporting the safety and efficacy of prophylactic antibiotic therapy in children with ALL has been sparse.”
Dr Wolf and his colleagues described their study in Clinical Infectious Diseases.
The study included 344 patients newly diagnosed with ALL who were enrolled in the St. Jude Total XVI clinical trial (NCT00549848). Patients were enrolled from 2007 to 2016.
Until July 2014, the patients received prophylactic antibiotic therapy at the discretion of their physicians. Patients typically received cefepime, ciprofloxacin, or vancomycin plus cefepime or ciprofloxacin. And prophylaxis was typically started at the onset of neutropenia after chemotherapy.
Beginning in August 2014, hospital treatment guidelines changed to recommend prophylactic levofloxacin during induction for ALL patients who develop neutropenia expected to last at least 7 days.
Dr Wolf and his colleagues used the change to compare infection rates and other questions in the following patient groups.
| Patient characteristics | No prophylaxis (n=173) | Levofloxacin prophylaxis (n=69) | Other prophylaxis (n=102) |
| Median age in years (range) | 5.8 (3-11.9) | 6.8 (3.9-11.1) | 7 (3.6-11.9) |
| B-ALL | 83% | 78% | 79% |
| Low-risk ALL | 51% | 54% | 50% |
| Standard-risk ALL | 47% | 41% | 42% |
| High-risk ALL | 2% | 6% | 8% |
| Median duration of neutropenia in days (range) | 17 (11-24) | 18 (12-23) | 20 (17-25) |
| Median duration of profound neutropenia in days (range) | 6 (2-13) | 7 (4-12) | 11 (5-16) |
Results
Researchers reported that patients with neutropenia who received any prophylactic therapy were far less likely than those who did not to develop fever, documented or likely infections, or bloodstream infections.
In a multivariate analysis, the adjusted odds ratios in patients who received prophylaxis, compared to those who did not, were as follows.
- Febrile neutropenia—0.23, P<0.001
- Febrile neutropenia with clinically documented infection—0.30, P=0.002
- Febrile neutropenia with microbiologically documented infection—0.25, P<0.001
- Clinically documented infection—0.54, P=0.02
- Microbiologically documented infection—0.40, P<0.001
- Bloodstream infection—0.30, P=0.008
- C difficile infection—0.38, P=0.04
- Likely bacterial infection—0.26, P<0.001
- Any enterocolitis—0.44, P=0.03.
Analysis also revealed that patients who received levofloxacin had a greater reduction in C difficile infection than patients who received other prophylaxis. The adjusted odds ratio was 0.04 (P<0.001).
However, there was no significant difference between the prophylaxis groups when it came to other infections.
Patients who received levofloxacin prophylaxis had significantly less exposure to other antibiotics than patients who received other prophylaxis or no prophylaxis.
This included exposure to cefepime/ceftazidime (P<0.001 for both comparisons), vancomycin (P<0.001 for both), meropenem (P<0.001 for both), and aminoglycosides (P=0.002 for no prophylaxis, P=0.04 for other prophylaxis).
The reduction in exposure to other antibiotics may partly explain why C difficile infections declined in levofloxacin-treated patients, Dr Wolf said.
He also noted that antibiotic resistance did not significantly increase in this study, despite the greater use of levofloxacin to prevent infections.
“We are cautiously optimistic that any impact of levofloxacin on antibacterial resistance will be balanced by the reduction in use of other antibiotics,” Dr Wolf said, “but long-term monitoring of antibiotic resistance patterns in young ALL patients will be needed to prove this.”
