A systematic review and meta-analysis of the risk of microbial contamination of aseptically prepared doses in different environments

Abstract

Purpose. To review microbial contamination rates about preparation of individual and batch doses using aseptic techniques within pharmaceutical (controlled) and clinical (ward and theatre) environments. Methods. Systematic review, involving amalgamation of data using a random effect model and metaanalysis. Results. A total of 19 studies from 17 reports (7277 doses), mostly single arm studies, were identified for analysis. The overall contamination rates for doses prepared in clinical environments were found to be 5.0% (95% CI; 1.8%, 13.1%, n = 8 studies) for individual doses and 2.0% (95% CI; 0.3%, 13.1%; n = 5) for doses prepared as part of a batch. Rates for doses prepared in pharmaceutical environments were found to be 1.9% (95% CI; 0.8%, 4.2%; n = 5) for individual doses and 0.0% (95% CI; 0.0%, 0.8%; n= 1) for doses prepared as part of a batch. The results indicate greater overall contamination rates of doses prepared in clinical than pharmaceutical environments, in those prepared individually than in batch preparation, and in those in which additions rather than no additions were made. Significant differences were only found between pharmaceutical and clinical environments for batch doses, and between batch and individual doses prepared in a pharmaceutical environment. The studies differed substantially in sample size, interventions and comparison conditions, especially in the clinical setting. The quality of the data was judged to be low. Conclusion. Contamination rates in clinical and pharmaceutical environments were commonly found to be unacceptably high. Intuitive recommendations for reducing contamination rates by carrying out the procedures in a pharmaceutical environment using batch doses are supported by an evidence base that needs to be strengthened further.