Effect of quinolone prophylaxis in afebrile neutropenic patients on microbial resistance: systematic review and meta-analysis

Abstract

Objectives: To assess the effect of quinolone prophylaxis following chemotherapy for malignancies on the emergence of resistant bacteria in neutropenic patients.

Methods: Systematic review and meta-analysis of randomized controlled trials comparing quinolone prophylaxis with placebo or no intervention, or another antibiotic, for the prevention of bacterial infections in afebrile neutropenic patients. The Cochrane Library, PubMed, Embase, conference proceedings and references were searched. Two reviewers independently applied selection criteria, carried out quality assessment and extracted the data. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Primary outcomes were rates of colonization and infection by quinolone-resistant bacteria.

Results: The search yielded 56 trials, 22 compared quinolones with placebo or no intervention. Data on colonization by resistant organisms could be extracted from 27 trials (48%). When compared with placebo or no intervention, there was a statistically non-significant increase in colonization with organisms resistant to quinolones (RR 1.68; 95% CI 0.71-4.00). There was no difference in the number of patients developing infections caused by resistant pathogens (RR 1.04; 95% CI 0.73-1.50). In trials comparing quinolones with trimethoprim/sulfamethoxazole, there were fewer incidents of colonization by bacteria resistant to the prophylactic agent in the quinolone arm than in the trimethoprim/sulfamethoxazole arm (RR 0.49; 95% CI 0.37-0.66). Data on baseline resistance of colonizing isolates, resistance development and cross-resistance to beta-lactam antibiotics were too scarce to analyse.

Conclusions: Patients treated with quinolones have a non-significant increase in colonization by quinolone-resistant bacteria. There is no difference in the number of infections caused by pathogens resistant to quinolones. As quinolone prophylaxis reduces the risk of death in neutropenic patients, the risk associated with colonization and infections caused by quinolone-resistant organisms does not outweigh the gain. Future trials should focus on better documentation of infections caused by resistant organisms.