title: 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.
abstract: BACKGROUND
  Administration of parenteral doses with microbial contamination can lead to infective morbidity or death.
  
  
  OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK; Southampton Pharmacy Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. Electronic address: Peter.Austin@uhs.nhs.uk.
authors.forename: P D
authors.initials: PD
authors.lastname: Austin
authors.affiliation: Southampton Pharmacy Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Health Sciences, University of Southampton, Southampton, UK.
authors.forename: K S
authors.initials: KS
authors.lastname: Hand
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK; Institute of Human Nutrition, University of Southampton, Southampton, UK; National Institute for Health Research, Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: M
authors.initials: M
authors.lastname: Elia
mesh_terms: D004339:Drug Compounding / Q000379:methods*; D004340:Drug Contamination; D006272:Health Facility Environment; D006801:Humans; D010604:Pharmacy; D018570:Risk Assessment
keywords: Aseptic; Batch; Contamination; Environment; Individual lots