Meta-Analysis: Antibiotic Prophylaxis Reduces Mortality in Neutropenic Patients

21 June 2005 | Volume 142 Issue 12 Part 1 | Pages 979-995

Background: Bacterial infections are a major cause of illness and death in patients who are neutropenic after chemotherapy treatment for cancer. Trials have shown the efficacy of antibiotic prophylaxis in decreasing the incidence of bacterial infections but not in reducing mortality rates.

Purpose: To evaluate whether antibiotic prophylaxis in neutropenic patients reduces mortality and incidence of infection and to assess related adverse events.

Data Sources: The Cochrane Cancer Network register of trials (2004), The Cochrane Library (Issue 4, 2004), EMBASE (1980–2004), MEDLINE (1966–2004), and references of identified studies.

Study Selection: Randomized, controlled trials comparing antibiotic prophylaxis with placebo or no intervention or another antibiotic in afebrile neutropenic patients.

Data Extraction: Two reviewers independently appraised the quality of trials and extracted data.

Data Synthesis: Ninety-five trials performed between 1973 and 2004 met inclusion criteria. Fifty-two trials addressed quinolone prophylaxis. Antibiotic prophylaxis significantly decreased the risk for death when compared with placebo or no treatment (relative risk, 0.67 [95% CI, 0.55 to 0.81]). All prophylactic antibiotics were associated with an increased risk for adverse events (relative risk, 1.69 [CI, 1.14 to 2.50]). Fluoroquinolone prophylaxis reduced the risk for all-cause mortality (relative risk, 0.52 [CI, 0.35 to 0.77]), as well as infection-related mortality, fever, clinically documented infections, and microbiologically documented infections. Fluoroquinolone prophylaxis increased the risk for harboring bacilli resistant to the specific drug after treatment and adverse events, but these results were not statistically significant (relative risks, 1.69 [CI, 0.73 to 3.92]) and 1.30 [CI, 0.61 to 2.76], respectively).

Limitations: Most trials involved patients with hematologic cancer. Data on all-cause mortality were missing in 10 of 50 trials comparing prophylaxis with no prophylaxis. Effect estimates were larger in trials of unclear methodologic quality compared with trials of adequate methodologic quality.

Conclusions: Antibiotic prophylaxis for neutropenic patients undergoing cytotoxic therapy reduces mortality. Mortality was substantially reduced when analysis was limited to fluoroquinolones. Antibiotic prophylaxis, preferably with a fluoroquinolone, should be considered for neutropenic patients.

Editors' Notes Context Bacterial infections cause clinically significant illness and death in neutropenic patients. Contribution This meta-analysis summarizes 95 randomized trials of antibiotic prophylaxis in 9283 afebrile neutropenic patients with conditions such as hematologic cancer. Fluoroquinolone prophylaxis, evaluated in 55 trials, reduced the risk for fever, infections, and all-cause and infection-related mortality. Increased risks for adverse events and harboring drug-resistant bacteria were not statistically significant. Cautions Some trials did not report mortality outcomes. The benefit of antibiotics was lower in higher quality trials. Implications The benefits of antibiotic prophylaxis with a fluoroquinolone probably outweigh the harms in some patients with hematologic cancer and neutropenia. –The Editors

 

Author and Article Information

From Rabin Medical Center, Petah-Tiqva, Israel, and Tel-Aviv University, Tel Aviv, Israel.

Acknowledgments: The authors thank the Cochrane Gynaecological Cancer Collaborative Review Group for their support and review process and the authors who responded to their request for additional data.

Grant Support: By a research grant from Rabin Medical Center and an European Commission fifth framework International Society Technologies grant (TREAT project, grant no. 1999-11459).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Leonard Leibovici, MD, Department of Medicine E, Beilinson Campus, Petah-Tiqva 49100, Israel; e-mail, leibovic{at}post.tau.ac.il.

Current Author Addresses: Drs. Gafter-Gvili, Paul, and Leibovici and Ms. Fraser: Department of Medicine E, Beilinson Campus, Petah-Tiqva 49100, Israel.

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