Rational selection of patients for antibacterial prophylaxis after chemotherapy.
OBJECTIVE
The SIGNIFICANT (Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/- Antibiotic in a Number of Tumours) trial reported a reduction in febrile episodes (FEs) among 1,565 patients with solid cancers and lymphomas receiving cyclical, myelosuppressive chemotherapy (causing grade 4 neutropenia) in a randomized, placebo-controlled, double-blind trial of levofloxacin (P = .01). In response to concerns that increased antibacterial prescribing selects for microbial resistance, we examined our data to explore the rationale for more limited prophylaxis.


METHODS
The risk of FE was calculated for control patients on first versus nonfirst cycles, with or without first-cycle FE, and within subgroups defined by cancer type, performance status (PS), age, and treatment context (adjuvant v nonadjuvant). Using the randomized trial data, the prophylactic efficacy of levofloxacin was examined for the same subgroups.


RESULTS
The per-cycle FE incidence was much lower on nonfirst (3.3%) versus first cycles (8.0%). Prophylaxis was less effective for nonfirst (odds ratio [OR] = 0.78; P = .16) compared with first cycles (OR = 0.42; P < .001). However, FE on cycle 1 predicted a much higher risk of FE and a trend to continued prophylactic efficacy on subsequent cycles. FE rate was greatest for testicular cancer (27.9%), then small-cell lung cancer (17.3%), and lowest for breast cancer (11.5%). Prophylactic efficacy was consistent across age, sex, PS, treatment context, and disease type (except possibly non-Hodgkin's lymphoma).


CONCLUSIONS
Under pressure to limit antibacterial use, these exploratory data support offering prophylactic levofloxacin on cycle 1 only of myelosuppressive cancer chemotherapy and on subsequent cycles after a cycle-1 fever. Prophylactic levofloxacin is effective regardless of age, PS, or tumor type.
Cullen
Michael H
MH
University Hospital Birmingham Cancer Centre, United Kingdom. michael.cullen@uhb.nhs.uk
Billingham
Lucinda J
LJ
Gaunt
Claire H
CH
Steven
Neil M
NM
D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006760:Hospitalization; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D015242:Ofloxacin / Q000627:therapeutic use*; D018579:Patient Selection; D010919:Placebos; D012307:Risk Factors
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D010919:Placebos; D064704:Levofloxacin; D015242:Ofloxacin