Yemm, K.E., Barreto, J.N., Mara, K.C., Dierkhising, R.A., Gangat, N., & Tosh, P.K. (2018). A comparison of levofloxacin and oral third-generation cephalosporins as antibacterial prophylaxis in acute leukaemia patients during chemotherapy-induced neutropenia. Journal of Antimicrobial Chemotherapy, 73, 204–211.

To compare the efficacy (measured via incidence of febrile neutropenia [FN]) of levofloxacin versus oral third-generation cephalosporins (OTGCs) given as antibacterial prophylaxis during chemotherapy-induced neutropenia in high-risk patients with hematological malignancies. The goal was to demonstrate non-inferiority of OTGCs as an alternate therapy if fluoroquinolones were contraindicated. Secondary outcomes measured the incidence of bacterial infection between prophylactic drugs and compared the specific microorganisms identified in positive cultures.

Following induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), high-risk patients were prescribed levofloxacin 500 mg daily as antibiotic prophylaxis if appropriate. Similar patients who could not take levofloxacin because of intolerance, allergy, drug interaction, or previous adverse drug reactions were prescribed OTGCs (either cefdinir 300 mg twice daily or cefpodoxime 200 mg twice daily). The duration of antibiotic therapy was not specified. Chart reviews began with the start of antibiotic prophylaxis and continued until the earliest of 30 days following the last dose of antibiotic prophylaxis, the beginning of consolidation chemotherapy administration, or death. The two groups were compared for incidence of FN and for the secondary outcomes.

• N: 120   
• AGE: Median = 58.6 years (range = 19-80)
• MALES: 65%  
• FEMALES: 35%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: AML and MDS
• OTHER KEY SAMPLE CHARACTERISTICS: N/A

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Mayo Clinic, Rochester, MN

PHASE OF CARE: Active anti-tumor treatment

Retrospective chart review, matching patients by OTGCs versus levofloxacin in a 1:2 ratio. Matching factors were age (plus or minus 5 years) and the Charlson comorbidity index (plus or minus 3).

Using retrospective chart review, researchers compared the incidence of FN, time to onset of FN, duration of neutropenia, site of infection, morphology of recovered organisms, and resistance to prophylactic agent.

The incidence of FN within 30 days of initiation of antibiotic prophylaxis was 83.4% (95% CI [65.8, 91.9]) in the OTGC group and 92.5% (95% CI [83.8, 96.5]) in the levofloxacin group, and was similar between the two groups (HR = 0.9, 95% CI [0.54, 1.52], p = 0.7). The median duration of neutropenia was also similar between the two groups, with 46 days (IQR = 26-67 days) for OTGCs and 39 days (IQR = 27-49 days) for levofloxacin. Similarly, the duration of prophylaxis prior to the onset of FN was comparable between the two groups (8 days for OTGCs, IQR = 6-12 days; and 8.5 days for levofloxacin, IQR = 5-13.5 days). Patients receiving OTGCs were significantly more likely to require ICU admission than those receiving levofloxacin (p = 0.04). The two groups had no significant differences in site of infection (p = 0.91) and morphology of recovered microorganism (p = 0.74). The OTGC group experienced significantly more cultures positive for Enterobacter (p = 0.043) than the levofloxacin group.

Although antibiotic prophylaxis with levofloxacin demonstrated advantages over OTGCs in the areas of avoidance of ICU admission and avoidance of cultures positive for the Enterobacter microorganism, OTGCs offer an acceptable alternative for those patients in whom fluoroquinolones are contraindicated.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: Data collected were from only the first episode of FN following antibiotic prophylaxis.

The positive culture site was an implanted central venous catheter in the majority of patients (61.5%). This reinforces the need for nurses to maintain meticulous hand hygiene and infection control practices when working with central venous catheters.