Evid Based Nurs 9:50 doi:10.1136/ebn.9.2.50
  • Treatment

Review: antibiotic prophylaxis reduces mortality in patients with neutropenia

 Q Does antibiotic prophylaxis, particularly fluoroquinolone prophylaxis, reduce mortality in patients with neutropenia?


GraphicData sources:

Medline (1966–2004), EMBASE/Excerpta Medica (1980–2004), Cochrane Cancer Network register of trials (December 2004), Cochrane Library (Issue 4, 2004), and references of included studies and reviews.

GraphicStudy selection and assessment:

published and unpublished randomised controlled trials (RCTs) in any language that compared antibiotic therapy with placebo, no intervention, or other antibiotics for prophylaxis of bacterial infection in patients with neutropenia. Individual study quality was assessed based on allocation concealment, generation of allocation sequence, blinding, and intention to treat analysis.


primary outcome was all cause mortality; secondary outcomes included infection related mortality, fungal infection, adverse events, and risk of harbouring drug resistant bacilli.


95 RCTs (n = 9283, mostly adults) met the selection criteria. 64 trials included only patients with haematological malignant conditions. Meta-analyses (using a fixed effects model) showed that antibiotic prophylaxis reduced all cause mortality (table) and infection related mortality (table), did not increase fungal infections (relative risk increase [RRI] 7%, 95% CI −17 to 37), and increased adverse events (RRI 57%, 95% CI 33 to 86) more than placebo or no intervention. Fluoroquinolone prophylaxis reduced all cause mortality (table) and infection related mortality (table) more than placebo or no intervention; the groups did not differ for adverse events (RRI 30%, CI –39 to 176), fungal infections (RRI 17%, CI –22 to 44), or harbouring drug resistant bacilli (RRI 69%, CI –27 to 292).


Antibiotic prophylaxis reduces all cause and infection related mortality in patients with neutropenia and does not increase fungal infections. Fluoroquinolone prophylaxis reduces mortality but does not increase adverse events.


  1. Sarah Hart, RGN, MSc
  1. Royal Marsden Hospital, London, UK

      The debate on the use of prophylactic antibiotics during the neutropenic phases of immunosuppressive treatment is long standing. The review by Gafter-Gvili et al provides an important reappraisal of the value of prophylactic antibiotics. The authors conclude that prophylactic antibiotics reduce both all cause mortality and infection related mortality in patients with neutropenia.

      Meta-regression showed no association between trial outcomes and many covariates, including year in which the trial began. This covariate is a proxy for the possible effect of treatment advances over time, given that the included studies covered a wide range of dates (1973–2004). However, 64 of the 95 included studies were limited to patients with haematological cancers, and further exploration of the role of antibiotics in neutropenic patients with other types of cancers is warranted.

      An issue that remains unresolved is whether antibiotic prophylaxis should commence at the start of chemotherapy or at the onset of neutropenia. Only 17 trials delayed prophylaxis until the onset of neutropenia. Such a regimen minimises exposure to antibiotics, and prudent use of antibiotics is important to decrease the risk of developing resistant infections. Patients in studies using fluoroquinolones had an increased risk of harbouring resistant bacilli after treatment (relative risk increase 69%, 95% CI –27 to 292). Although the result is not significant, the confidence interval is sufficiently wide to raise concerns. Meta-regression again found no association between the year a trial commenced and outcome, suggesting no reduction in antibiotic efficacy over time. However, such evidence is not as powerful as a trial comparing different timing of initiation of prophylaxis.

      Routine prophylaxis is not endorsed,1 but the meticulous review by Gafter-Gvili et al suggests that reconsideration of the prevailing view is justified. In the interim, current decisions about treatment should be based on local needs and consider types of patients and causative micro-organisms.


      Antibiotic prophylaxis v placebo or no intervention (control) in patients with neutropenia*

 Q Does antibiotic prophylaxis, particularly fluoroquinolone prophylaxis, reduce mortality in patients with neutropenia?


      • For correspondence: Dr A Gafter-Gvili, Department of Medicine, Rabin Medical Center, Petah-Tiqva, Israel. anatga{at}

      • Source of funding: European Commission fifth framework International Society Technologies grant.

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