Hafez, H.A., Yousif, D., Abbassi, M., Elborai, Y., & Elhaddad, A. (2015). Prophylactic levofloxacin in pediatric neutropenic patients during autologous hematopoietic stem cell transplantation. Clinical Transplantation, 29, 1112–1118. 

To assess the effectiveness of prophylactic fluoroquinolone prophylaxis in pediatric patients with neutropenia

Levofloxacin was begun as part of standard prophylactic antimicrobial regimens at doses of 10 mg/kg/d for patients aged 5 years or younger from the beginning of conditioning until a documented fever. Additional prophylactic measures were oral acyclovir, oral fluconazole, and oral TMP-SMX. Prophylaxis was continued until neutropenia resolved with an absolute neutrophil count greater than 500, fever, or other signs of infection. Outcomes of those on levofloxacin were compared to historical controls. All other prophylaxis was the same in both controls and those in the study group.

• N = 96   
• MEDIAN AGE = 4 years
• AGE RANGE = 1.1–17 years
• MALES: 68.8%, FEMALES: 31.2%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All were undergoing hematopoietic cell transplantation.

• SITE: Multi-site   
• SETTING TYPE: Inpatient    
• LOCATION: Egypt

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Cohort comparison with historical controls

• Fever-free days
• Confirmed bacterial infection by microbiologic samples

Those receiving levofloxacin had a longer duration of fever-free days (p < 0.001), and the relative risk for febrile episodes in control patients was 2.1 (95% confidence interval [1.4, 3.2]). Frequency of documented infection was similar in both groups, but the frequency of gram-negative infections were less in the experimental group (6% versus 15%). This difference was not statistically significant. No difference in prevalence of resistant organisms was observed. The duration of empiric antibiotic use was lower in those receiving levofloxacin prophylaxis (p < 0.001), as was the use of empiric antifungal agents (p < 0.001). No signs of levofloxacin toxicity were observed in any patients.

Levofloxacin prophylaxis in pediatric patients undergoing cell transplantation was associated with the delayed onset of fever and less use of antibiotic and antifungal administration. Insufficient data existed to evaluate the potential effect of prophylaxis on the emergence of resistant organisms.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Decisions to use antibiotics and antifungals empirically was not based on any standard guideline.  
• Comparison to historical controls introduces the potential of history threats to validity.

There have been concerns about the use of quinolones in pediatric patients in general, and concerns that routine antibiotic prophylaxis can result in the emergence of resistant organisms within institutions. The findings from this study revealed that levofloxacin use in children was not associated with toxicities and did delay onset of fever and slightly lower rates of confirmed infections in neutropenic children undergoing hematopoietic cell transplantation. Additional research in pediatric patients is needed to fully evaluate the benefits and potential effects in terms of the emergence of resistant organisms.