Yeh, T., Liu, H., Hou, J., Chen, K., Huang, T., Chang, C., & Liang, D. (2014). Severe infections in children with acute leukemia undergoing intensive chemotherapy can successfully be prevented by ciprofloxacin, voriconazole, or micafungin prophylaxis. Cancer, 120, 1255–1262. 

To investigate the effectiveness of antibiotic and antifungal prophylaxis during intensive chemotherapy for acute leukemia in children and to assess the impact on days of intensive care, changes in antibiotic resistance, and medical cost

Oral ciprofloxacin 300 mg/m²every 12 hours was given when patients became neutropenic and when seven days of neutropenia were expected. Oral voriconazole 4 mg/kg every 12 hours was initiated at the onset of neutropenia in patients with acute myeloid leukemia (AML) and after seven days of neutropenia in patients with acute lymphoblastic leukemia (ALL). IV micafungin was substituted for oriconazole during induction and reinduction chemotherapy. Prophylaxis was discontinued when patients' absolute neutrophil counts recovered to > 100/mcL. Probable invasive fungal infection (IFI) was not included in analysis. Data were analyzed from patients prior to the use of prophylaxis and from patients during the prophylaxis period.

• N = 113  
• MEAN AGE: 4.4 years (range = 0.2–18 years)
• MALES: 40%, FEMALES: 60%
• KEY DISEASE CHARACTERISTICS: AML or ALL

• SITE: Single-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Taiwan

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

Retrospective cohort comparison study

• Bloodstream infection was defined by the isolation of bacteria from blood cultures and clinical signs of systemic infection.
• IFI was diagnosed according to the culture or histology of infected tissue.

In the preprophylaxis period, there were 25 episodes of bloodstream infection among 62 patients, and in the prophylaxis period there were five episodes among 51 patients (p < .01). Preprophylaxis, there were 12 episodes of IFI compared to zero episodes during prophylaxis (p < .01). There were fewer episodes of febrile neutropenia with prophylaxis (p = .01). Ciprofloxacin resistance of E-coli Klebsiella pneumoniae, pseudomonas aeruginosa, and serratia marcescens was significantly reduced during the prophylaxis period. Other gram-negative bacilli did not change with regard to ciprofloxacin resistance between the two periods of time. 39% of patients had hepatotoxicity during prophylaxis with micafungin leading to dose modification in three patients and discontinuation in seven patients. Intensive-care stays due to infection and total cost were significantly lower during the prophylaxis period.

Prophylaxis decreased the occurrence of febrile neutropenia, bloodstream infections, IFI, intensive care length of stay due to infection, and cost for patients with ALL and AML. There was no increase in ciprofloxacin resistance associated with prophylaxis with this agent.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)

This study demonstrates the efficacy of antibiotic and antifungal prophylaxis in children receiving intensive chemotherapy for ALL and AML. There has been limited evidence of prophylaxis use and outcomes in children. Children safely received ciprofloxacin for antibiotic prophylaxis. In this particular study, there was no increase in ciprofloxacin resistant organisms during the time prophylaxis was used; however, analysis was done over a limited period of time and is not seen as conclusive. Continued monitoring for the development of drug resistance is important in organizations providing this type of prophylaxis as a routine. Findings here support the cost effectiveness of prophylaxis, showing lower intensive care stay lengths and overall cost during the time prophylaxis was used.