A Systematic Review and Meta-Analysis of the Risk of Microbial Contamination of Aseptically Prepared Doses in Different Environments

Abstract

ABSTRACT Purpose To review microbial contamination rates and examine guidelines about preparation of individual and batch doses using aseptic techniques within pharmaceutical (controlled) and clinical (ward and theatre) environments. Methods Systematic review and meta-analysis. Results A total of 18 studies (7293 doses) were identified for analysis. A lower rate of contamination was found in a pharmaceutical compared to clinical environments when preparing either individual (6.8% v 3.3%; p=0.051; 10 studies (8 clinical 2 pharmaceutical)) or batch doses (8% v 0.05%; p<0.001; 6 studies (5 clinical 1 pharmaceutical)). Batch doses were found to be less frequently contaminated than individual doses in a pharmaceutical environment (1% v 0.05%; p<0.001; 4 studies (3 individual 1 batch)) but no significant difference in a clinical environment (6.8% v 8%; not significant; 13 studies (8 individual 5 batch). Additions to doses for parenteral administration in a clinical environment were found to have a significantly greater risk of contamination compared no additions using a fixed effect model (relative risk 2.736 (95% CI 1.292, 5.796); p=0.009; 3 studies; test of heterogeneity, I2=66.45%, p=0.055) although no difference was found using a random effect model (relative risk 1.459 (95% CI 0.240, 8.882); p=0.682). Overall, the studies used variable methodology and were not judged to be of high quality. Conclusion Despite study limitations, the data support the view that there is lower risk of contamination when aseptic dose preparation is carried out in a pharmaceutical rather than a clinical environment. The data also suggest aseptic batch preparation, rather than individual dose preparation, is associated with a lower risk of dose contamination in a pharmaceutical environment. The risk of dose contamination is intuitively likely to be reduced by minimising the number of aseptic manipulations, particularly in a clinical environment, but the evidence base needs to be strengthened.