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Meta-Analysis: Antibiotic Prophylaxis Reduces Mortality in Neutropenic Patients

Anat Gafter-Gvili, MD; Abigail Fraser, MPH; Mical Paul, MD; and Leonard Leibovici, MD
[+] Article and Author 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@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.


Ann Intern Med. 2005;142(12_Part_1):979-995. doi:10.7326/0003-4819-142-12_Part_1-200506210-00008
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We included 95 studies performed between 1973 and 2004 in our review (12106) (Figure 1). (Excluded trials can be found in the Appendix.) The trials randomly assigned 9283 patients, mostly adults. Fifty trials compared a prophylactic antibiotic with placebo or no intervention, of which 17 trials evaluated fluoroquinolones (Table 1; Appendix Table 1 and Appendix Table 2). Forty-five studies compared different prophylactic regimens, of which 30 trials compared fluoroquinolones with other antibiotics and 5 trials compared different types of fluoroquinolones (ciprofloxacin, ofloxacin, norfloxacin, or pefloxacin) in the 2 study groups. Sixty-four trials included only patients with hematologic malignant conditions: mostly acute leukemia but also lymphoma, chronic myelocytic leukemia in blast crisis, and multiple myeloma. Nine trials included more than 80% patients with solid tumors (breast, lung, ovary, and germ cell tumors). Twenty-seven studies included patients who underwent bone marrow transplantation. Patients were hospitalized for the duration of prophylaxis in 77 trials, 2 trials included both outpatients and inpatients, and 10 trials included only outpatients. The remaining 6 trials did not report the trial setting.

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Figures

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Figure 1. RCT = randomized, controlled trial.
Publications identified for study and exclusions.
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Figure 2. RR = relative risk; TMP-SMZ = trimethoprim–sulfamethoxazole.
All-cause mortality: antibiotic prophylaxis versus placebo or no intervention.
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Figure 3. RR = relative risk.
Infection-related mortality: fluoroquinolones versus placebo or no intervention.
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Figure 4. RR = relative risk.
Febrile patients: fluoroquinolones versus placebo or no intervention.
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Appendix Figure 1.
Funnel plot of all studies reporting all-cause mortality comparing antibiotic prophylaxis with placebo or no intervention.
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Appendix Figure 2. RR = relative risk; TMP-SMZ = trimethoprim–sulfamethoxazole.
Infection-related mortality: antibiotic prophylaxis versus placebo or no intervention.
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Appendix Figure 3. EORTC = European Organization for Research and Treatment of Cancer; RR = relative risk; TMP-SMZ = trimethoprim–sulfamethoxazole.
Febrile patients and episodes: antibiotic prophylaxis versus placebo or no intervention.
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Appendix Figure 4. RR = relative risk; TMP-SMZ = trimethoprim–sulfamethoxazole.
Clinically documented infections: antibiotic prophylaxis versus placebo or no intervention.
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Appendix Figure 5. EORTC = European Organization for Research and Treatment of Cancer; RR = relative risk; TMP-SMZ = trimethoprim–sulfamethoxazole.
Microbiologically documented infections: antibiotic prophylaxis versus placebo or no intervention.
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Appendix Figure 6. RR = relative risk.
Clinically documented infections: fluoroquinolones versus placebo or no intervention.
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Appendix Figure 7. RR = relative risk.
Microbiologically documented infections: fluoroquinolones versus placebo or no intervention.
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Appendix Figure 8.
Funnel plot of studies comparing all-cause mortality in fluoroquinolones with placebo or no intervention.
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