Inaba, H., Gaur, A.H., Cao, X., Flynn, P.M., Pounds, S.B., Avutu, V., . . . Rubnitz, J.E. (2014). Feasibility, efficacy, and adverse effects of outpatient antibacterial prophylaxis in children with acute myeloid leukemia. Cancer, 120, 1985–1992. 

To examine the effects of antibiotic prophylaxis on bacterial infections, antibiotic sensitivity, and nasal and rectal culture findings

Prophylaxis was outpatient administration of antibacterials after myelosuppressive therapy and the onset of an absolute neutrophil count ≤ 0.5 x 10⁹/L in the absence of fever or other indicators of infection. Prophylaxis was discontinued when the neutrophil count exceeded 0.1 x 10⁹/L. All patients were on a study protocol in which the prophylactic regimens used were amended on an ongoing basis based on short-term findings. In general, patients received IV cefepime every 12 hours, or vancomycin every 12 hours with oral cephalosporin, oral ciprofloxacin, or IV cefepime. All patients received antifungal prophylaxis with voriconazole or echinocandin, pneumocystis prophylaxis, and did not receive colony-stimulating factors. Patients were trained to administer the IV antibiotics. Patients who presented with neutropenia and fever were admitted and treated empirically. Patients had surveillance cultures of the nares and rectum at each admission for detection of resistant organisms. Patients were grouped according to the type of prophylaxis received: A: oral cephalosporin only, B: protocol as described.

• N = 103 
• AGE RANGE = 1–21 years, 46% were 10–21 years
• MEDIAN AGE: 8.7 years
• MALES: 52.4%, FEMALES: 47.5%
• KEY DISEASE CHARACTERISTICS: All had acute myeloid leukemia (AML)
• OTHER KEY SAMPLE CHARACTERISTICS: 73% were Caucasian, 23% African American

• SITE: Single site  
• SETTING TYPE: Multiple settings  
• LOCATION: St. Judes Hospital

• PHASE OF CARE: Active antitumor treatment

• Retrospective analysis of a previous prospective trial

• Infection and febrile neutropenia defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) 3.0
• Fever–oral temperature of 38º C persisting for one hour, or single oral temperature of 38.3º C
• Blood stream infection as defined by Centers for Disease Control and Prevention criteria

Most common infectious events were neutropenia with fever of unknown origin; bloodstream infections; and infections of the skin/mucosa, GI tract, and upper respiratory tract. There was no difference between groups in episodes of fever of unknown origin. Patients who received the full prophylaxis protocol had significantly fewer infectious episodes of any type during induction 1 (p = 0.002), induction 2 (p = 0.0002), and consolidation (p = 0.001). Patients receiving the full vancomycin-based regimen had higher incidence of vancomycin-resistant enterococci (VRE) isolates from surveillance, and three cases also had VRE bacteremia.

Outpatient IV antibiotic prophylaxis was feasible and reduced the incidence of documented infection and bacteremia. Patients receiving vancomycin-based prophylaxis had lower rates of infectious events and had higher incidence of VRE isolates from surveillance.

• Risk of bias (no random assignment)

This study showed that provision of outpatient IV antibiotic prophylaxis to children, administered by their parents, was feasible and effective in reducing infectious events. Findings point to the ongoing need for managing the intensity and duration of prophylaxis to minimize development of resistant bacterial strains.