Role of prophylactic antibiotics in the prevention of infections after chemotherapy: a literature review.
Febrile neutropenia is a serious sequel of chemotherapy and can result in significant morbidity and mortality. The use of prophylactic antibiotics during neutropenia to reduce this complication has been widely investigated. Historical trials that tested a variety of approaches were generally small and reported mixed results. Because of the lack of compelling evidence and concerns over emergence of resistance, international guidance has continued to recommend against the routine use of antibiotic prophylaxis in this setting. The 2 recently published, large, randomized, double-blind, placebo-controlled trials of levofloxacin versus placebo have challenged the reluctance to adopt the policy of prophylaxis. The GIMEMA trial focused on patients receiving high-dose inpatient chemotherapy for hematologic and solid tumors. Levofloxacin prophylaxis significantly reduced febrile episodes and microbiologically documented infection and bacteremia. In contrast, the SIGNIFICANT trial randomized patients receiving cyclic, outpatient, standard-dose chemotherapy for a variety of solid tumors and lymphoma. Significant reductions in febrile neutropenia episodes and hospitalization for the treatment of infection were demonstrated with prophylaxis. A recent metaanalysis has conclusively demonstrated a reduction in mortality resulting from the use of prophylactic fluoroquinolones for the duration of neutropenia in patients with acute leukemia and after high-dose chemotherapy, and for the first cycle of standard-dose chemotherapy in patients with solid tumors and lymphomas. An inevitable consequence of antibiotic use is the development of resistance. Although there is no doubt this can occur in individual patients and in treatment centers using fluoroquinolone prophylaxis, there is little evidence that patients are harmed as a result. Nevertheless, the induction of bacterial resistance should be avoided in principle, and more work is needed to limit prescribing of antibacterial agents to situations supported by a secure evidence base. When a secure evidence base exists, as is the case now for prophylaxis after chemotherapy, further work is needed to identify subgroups of patients who benefit most from prophylaxis so that it can be applied rationally and efficiently.
Moon
Sarah
S
The Cancer Centre, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Cancer Centre, UK.
Williams
Sarah
S
Cullen
Michael
M