Systematic review and meta-analysis of the risk of microbial contamination of parenteral doses prepared under aseptic techniques in clinical and pharmaceutical environments: an update

Background: Administration of parenteral doses with microbial contamination can lead to infective morbidity or death.

Aim: To test whether aseptic preparation of parenteral doses or additives to sterile doses undertaken in dedicated pharmaceutical rather than clinical environments reduces the risk of microbial dose contamination.

Methods: Data identified from a systematic review were examined using random effects meta-analyses, and t-tests were used to compare dose contamination frequencies.

Findings: In all, 16,552 doses from 34 studies (33 records) were identified. For all the data combined there was a significantly higher frequency of contamination of doses prepared in clinical than in pharmaceutical environments {3.7% [95% confidence interval (CI): 2.2, 6.2; N = 10,272 doses] vs 0.5% (95% CI: 0.1, 1.6; N = 6280 doses); P = 0.007}. Contamination of doses was significantly higher when prepared as individual lots than as part of a batch in pharmaceutical environments [2.1% (95% CI: 0.7, 5.8; N = 168 doses) vs 0.2% (95% CI: 0.1, 0.9; N = 6112 doses); P = 0.002]. There was a significantly higher frequency of dose contamination if additions were made to sterile parenteral doses in clinical environments [risk ratio: 2.121 (95% CI: 1.093, 4.114); P = 0.026]. The overall quality of the studies was judged to be low.

Conclusion: Reported rates of parenteral dose contamination were orders of magnitude higher than accepted reference standards, which may increase infection risk. The limited evidence on contamination rates supports dose preparation in pharmaceutical rather than clinical environments, and does not support batch preparation in clinical environments.