Date of Graduation

8-15-2009

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

Mark Pedemonte, MD

Second Advisor

Rob Rosenow PharmD, OD

Third Advisor

Annjanette Sommers MS, PA-C

Abstract

Background: Neutropenia is the most common adverse effect of chemotherapy treatment but is often necessary to destroy malignant disorders and neoplasms. As a patient undergoes most chemotherapeutic regimens, myelosuppression occurs and reduces the patient’s ability to fight infection from harmful pathogens. As neutropenia worsens, enteric flora are able to invade and proliferate, and opportunistic bacteria can cause new infections. Antibiotics are available as focused and empiric treatment for these infections but are not recommended for use in prevention. The use of antibiotics as prophylaxis in cancer patients with neutropenia is controversial with published data supporting many conclusions.

Hypothesis: Current data available over the last decade is bringing consensus to prevention of fever and mortality with the prophylactic use of fluoroquinolones in neutropenic cancer patients. It is hypothesized that a review of this newer set of data will confirm the efficacy of fluoroquinolones as prevention of fever and mortality in this patient population.

Study Design: A systematic review was performed to examine the pertinent published literature.

Methods: Inclusion keywords were determined for searching articles among multiple databases. Studies eligible for inclusion into this review must be using a fluoroquinolone for prophylaxis in neutropenic cancer patients receiving chemotherapy, be randomized controlled trials in the English language, and have a publication date no earlier than the year 2000. Standard evidence based medicine critical review appraisals were applied as well as scoring according to Jadad analysis to assess quality and validity of each study. Relative risk, relative risk reduction, absolute risk reduction, number needed to treat, and a precision index were calculated or included, as available. Qualitative weighting of these assessments was made during discussion and conclusion.

Results: The review of literature and use of inclusion and exclusion criteria yielded six pertinent articles with patient populations ranging from 70 to 1,565 individuals (Table I). The relative risk for fever or infection ranged from 0.19 (p < 0.001) to 0.81(p = 0.02) and for mortality ranged from 0.0 (p =0.022) to 0.60 (95% CI -0.05 to 0.005). Number needed to treat ranged from 3.1 to 22.7 for fever, and from 4.5 to 100 for mortality. Jadad scoring ranged between 1 and 5 (out of 5) with two trials scoring ≤2 and 4 trials scoring ≥4.

Conclusion: After weighing the results of EBM reviews, Jadad scoring, and conclusive findings of these studies, there is more evidence that prophylactic use of fluoroquinolones prevents fever and mortality in treatment groups compared to control groups, with benefit increasing as severity of myelosuppression increases. According to this systematic review, prophylactic fluoroquinolone use for prevention of fever is recommended for all neutropenic cancer patients receiving chemotherapy.

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