Gafter-Gvili, A., Paul, M., Fraser, A., & Leibovici, L. (2007). Effect of quinolone prophylaxis in afebrile neutropenic patients on microbial resistance: Systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy, 59, 522.

To compare antibiotic prophylaxis with placebo or no intervention or another antibiotic in patients with afebrile neutropenia

DATABASES USED: Cochrane Cancer Network Register of Trials (December 2004), Cochrane Library (Issue 4, 2004), EMBASE (January 1980–December 2004), and MEDLINE (January 1966–December 2004); the reference lists of all the articles also were searched.

FINAL NUMBER STUDIES INCLUDED = 95 RCTs

TOTAL PATIENTS INCLUDED IN REVIEW = 9,283 patients comparing prophylactic antibiotics with placebo, no intervention, or other prophylactic antibiotics

KEY SAMPLE CHARACTERISTICS: Sixty-four trials included only patients with hematologic malignancies, and nine trials consisted of more than 80% of patients with solid tumors. Twenty-seven studies included patients undergoing bone marrow transplantation (BMT).

Prophylactic antibiotics significantly decreased

• Overall mortality by 33% (although the effect was less robust in the well-designed trials)
• The risk of infection-related death by 42%
• Fever by 21%
• Clinically documented infections by 36%
• Microbiologically documented infections by 46%
• Gram-negative infections by 61%
• Gram-positive infections by 58%
• Bacteremia by 48%.

Fluoroquinolones, when compared with placebo or no intervention, decreased the risk of

• Overall mortality compared with placebo or no intervention by 48%
• Infection-related mortality by 62%
• Clinically documented infections by 47%
• Microbiologically documented infections by 50%
• Gram-negative infections by 74%
• Gram-positive infections by 71%
• Bacteremia by 36%.

The relative risk for adverse events was not statistically significant (relative risk 1.30 [confidence interval 0.61–2.76]). Comparatively, in trials comparing trimethoprim/sulfamethoxazole with placebo or no intervention, the corresponding estimates were statistically significant (relative risk 2.42 [confidence interval 1.35–4.36] and 3.63 [confidence interval 1.32–9.98], respectively). Moreover, in trials that compared fluoroquinolones with trimethoprim/sulfamethoxazole, less resistance developed to fluoroquinolones in the fluoroquinolone group than that developed to trimethoprim/sulfamethoxazole in the trimethoprim/sulfamethoxazole group (relative risk 0.45 [confidence interval 0.27–0.74]). When fluoroquinolones were compared with placebo, the number of fungal infection episodes did not statistically or significantly differ (relative risk 0.83 [confidence interval 0.56–1.22]).

Fluoroquinolone prophylaxis increased the risk of fluoroquinolone-resistant infections, but the increased risk was not statistically significant (relative risk 1.69 [confidence interval 0.73–3.92]).