Gafter-Gvili, A., Fraser, A., Paul, M., & Leibovici, L. (2005). Meta-analysis: Antibiotic prophylaxis reduces mortality in neutropenic patients. Annals of Internal Medicine, 142(12, Pt. 1), 979995.

To compare antibiotic prophylaxis with placebo, no intervention, or another antibiotic to prevent bacterial infections in patients with afebrile neutropenia

DATABASES USED: Electronic searches on the Cochrane Cancer Network Register of Trials (2005), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966–2005), EMBASE (1980–2005), and abstracts of conference proceedings; references of identified studies; the first author of each included trial was contacted.

FINAL NUMBER STUDIES INCLUDED = 101

TOTAL PATIENTS INCLUDED IN REVIEW: 12,599

KEY SAMPLE CHARACTERISTICS: RCTs or quasi-RCTs performed from 1973–2005; patients with cancer and neutropenia as a result of chemotherapy or bone marrow transplantation

Antibiotic prophylaxis significantly decreased the risk of death when compared with placebo or no intervention (RR 0.66 [95%CI 0.55 to 0.79]). The authors estimated the number needed to treat in order to prevent one death from all causes as 50 (95% CI 34 to 268). Prophylaxis with any antibiotic resulted in a significant decrease in the risk of infection-related death (RR 0.59 [95% CI 0.47 to 0.75]) and in the occurrence of fever (RR 0.77 [95% CI 0.74 to 0.81]). Quinolone prophylaxis reduced the risk for all-cause mortality (RR 0.52 [95% CI, 0.37 to 0.74] and the risk of infection-related mortality (RR 0.49 [95% CI 0.31 to 0.77]). 

Antibiotic prophylaxis resulted in a significant decrease in the occurrence of clinically documented infection (RR 0.66 [95% CI 0.61 to 0.73]), microbiologically documented infection (RR 0.53 [95% CI 0.48 to 0.58]), microbiologically documented gram-negative infection (RR 0.38 [95% CI 0.32 to 0.45]), microbiologically documented gram-positive infection (RR 0.44 [95% CI 0.38 to 0.51]), and bacteremia (RR 0.52 [95% CI 0.47 to 0.59]. Quinolone prophylaxis reduced the risk of bacteremia (RR 0.58 [95% CI 0.50 to 0.68]. When compared to placebo or no intervention, all prophylactic antibiotics caused more side effects (RR 1.59 [95% CI 1.37 to 1.85]. There was no statistically significant difference in the number of episodes of fungal infection when prophylactic antibiotics were compared to placebo (RR 1.07 [95% CI 0.83 to 1.37, 38 studies, 2,682 participants]).

When compared to placebo, patients given quinolones and sulfamethoxazole/trimethoprim (SMZ-TMP) were found to be at increased risk of harboring bacilli resistant to the specific drug than patients receiving placebo (RR 1.47 [95% CI 1.08 to 2.01]). For quinolones, the RR was 1.18 (95% CI 0.81 to 1.70) and for SMZ-TMP, 2.42 (95% CI 1.35 to 4.36). When quinolones were compared to SMZ-TMP, the following were significantly reduced: microbiologically documented infections (RR 0.72 [95%CI 0.6 to 0.86]) (comparison 5.2), gram-negative infections (RR 0.21 [95% CI 0.13 to 0.36]) (comparison 6.2), gram-negative bacteremia (RR 0.35 [95% CI 0.21 to 0.59]), and side effects (RR 0.74 [95%CI 0.63 to 0.87]). The addition of antibiotic against gram-positive infection to quinolones resulted in a significant decrease in the number of bacteremic episodes (RR 0.72 [95%CI 0.57 to 0.92], gram-positive infections (RR 0.49 [95% CI 0.37 to 0.64], and gram-positive bacteremia (RR 0.61 [95% CI 0.45 to 0.83]), and also in more side effects.

• Most studies were limited to patients with hematologic cancer (mostly leukemia).
• Most were conducted on hospitalized patients.
• Information on all-cause mortality could not be obtained for all of the studies.
• Many studies were dated.