Mikulska, M., Averbuch, D., Tissot, F., Cordonnier, C., Akova, M., Calandra, T., . . . European Conference on Infections in Leukemia. (2018). Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. Journal of Infection, 76, 20–37.

STUDY PURPOSE: To assess whether the recommendation by the European Conference on Infections in Leukemia to use fluoroquinolone prophylaxis for patients with high-risk neutropenia has resulted in a reduction in infection and mortality. A secondary objective was to assess the effect of fluoroquinolone prophylaxis on antibiotic resistance.

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: PubMed

YEARS INCLUDED: 2006-2014

INCLUSION CRITERIA: Article assessed fluoroquinolone prophylaxis among patients with high-risk neutropenia undergoing treatment for blood cancer or patients post-hematopoietic cell transplantation (HCT)

EXCLUSION CRITERIA: (a) No assessment of antibiotic prophylaxis; (b) unable to discern whether the research question was relevant; (c) antibiotic prophylaxis included a non-fluoroquinolone

TOTAL REFERENCES RETRIEVED: N = 68

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Multiple statistical methods were applied to evaluate the studies included in the review. In addition, community prevalence of fluoroquinolone resistance was evaluated based on study data included in the review and previous studies.

FINAL NUMBER STUDIES INCLUDED: 14 

TOTAL PATIENTS INCLUDED IN REVIEW: 5,930

SAMPLE RANGE ACROSS STUDIES: 45–1,981

KEY SAMPLE CHARACTERISTICS: Study populations included patients with acute leukemias, hematologic malignancies, or post-autologous or allogeneic HCT. Studies included years of observation from 1998–2012.

PHASE OF CARE: Active anti-tumor treatment

Of the 14 studies analyzed, 12 were observational and two were randomized controlled trials. Overall, the odds ratio with fluoroquinolone prophylaxis were:

• Overall mortality = 1.01; 95% confidence interval [0.73, 1.41]
• Bloodstream infections = 0.57; 95% CI [0.43, 0.74]
• Febrile neutropenia = 0.32; 95% CI [0.2, 0.5]

However, in the analysis of three meta-analyses, published since 2006, Gafter-Gvili et al. (2012) found a statistically significant decrease in overall mortality (2.8% versus 5.3%, p = 0.00012). The rate of infection caused by fluoroquinolone resistant bacteria was 4% for patients who received prophylaxis and for patients who did not receive prophylaxis. There is insufficient data to determine the role of fluoroquinolone prophylaxis on the appearance of new, resistant bacteria.

Fluoroquinolone prophylaxis did not reduce overall mortality for patients with high risk neutropenia. However, there is some evidence that it may reduce the rate of bloodstream infections and febrile neutropenia. Clinically, the impact of prophylaxis may be low since many patients still develop febrile neutropenia and other risks, including Clostridium difficile infection and fluoroquinolone toxicity, were not analyzed. However, since most international guidelines with the exception of Australia, recommend fluoroquinolone prophylaxis, and there is insufficient conclusive evidence to recommend otherwise, the overall recommendation is to follow institutional policies but seriously consider the risks and benefits of prophylaxis for each patient.

Most of the 14 studies included in the analysis (12) were observational.

In the absence of contraindication or risk of complication with prophylaxis, there is insufficient evidence to routinely omit fluoroquinolone prophylaxis. Consider the risks and benefits of fluoroquinolone prophylaxis for each patient individually. Recognize the clinical benefit for an individual may be minimal. Consider review and update to institutional policies accordingly.