2 3 4 Use of the BacT / ALERT ® System for Rapid Detection of Microbial 5 Contamination in a Pilot Study using Pancreatic Islet

1 Short Form Paper 2 3 4 Use of the BacT/ALERT® System for Rapid Detection of Microbial 5 Contamination in a Pilot Study using Pancreatic Islet Cell Products 6 7 Running Title: BacT/ALERT® System for Islet Cell Sterility Testing 8 9 Laura Murray1, Neil McGowan2, John Fleming1 and Laura Bailey2,3* 10 11 1 Donation Testing Department, Scottish National Blood Transfusion Service, 25 Shelley Road, 12 Glasgow 13 2 SNBTS Cell Therapy Development Centre, Scottish National Blood Transfusion Service, SCRM 14 Building, The University of Edinburgh, Edinburgh bioQuarter, 5 Little France Drive, Edinburgh 15 3Islet Isolation Laboratory, Tissues & Cells Directorate, Scottish National Blood Transfusion 16 Service, 21 Ellen’s Glen Road, Edinburgh 17 18 *Corresponding Author: 19 Laura Bailey, SNBTS Cell Therapy Development Centre, SCRM Building, The University of 20 Edinburgh, Edinburgh bioQuarter, 5 Little France Drive, Edinburgh. [email protected] 21 22 23 Abstract 24 25 At the SNBTS Islet Isolation Laboratory manual sterility testing data shows that 26 contamination rates are 57.7% for pancreas transport fluid, 4.3% for post27 purification islet samples and 0% for pre-transplant islet samples. This pilot 28 study presents the BacT/Alert® System as an alternative to manual testing, to 29 give more rapid and sensitive sterility results for islet cell products. 30 31 Main Text 32 33 Islet transplantation is a minimally invasive procedure for the treatment of Type 34 1 Diabetes characterised by recurrent severe hypoglycaemia, and glycaemic 35 unawareness. In this treatment, Islets of Langerhans are isolated from donor 36 pancreata and infused into the portal vein of a diabetic recipient. The Edmonton 37 Protocol for islet isolation and transplantation, published in 2000, demonstrated 38 excellent patient outcomes following islet transplantation (1,2). As a result islet 39 transplantation is now used worldwide as an alternative to whole pancreas 40 transplant for the treatment of severe, uncontrolled Type 1 Diabetes. Despite the 41 widespread use of this treatment, little has been published on the microbial 42 contamination rates of islet cell products, and suitable methods for microbial 43 detection prior to transplantation. Here we present microorganism 44 contamination rates from the SNBTS Islet Isolation Laboratory and compare 45 standard manual sterility testing methods with results from the rapid detection 46 BacT/ALERT® System. A rapid detection of microbial contamination is of benefit 47 for islet transplantation because products are generally transplanted 24-48 48 hours post isolation, prior to microbial detection using standard European 49 Pharmacopoeia (EP) inoculation methods. 50 51 JCM Accepts, published online ahead of print on 16 July 2014 J. Clin. Microbiol. doi:10.1128/JCM.00447-14 Copyright © 2014, American Society for Microbiology. All Rights Reserved.