Tuesday, 8 July 2014

Bacillus cereus infections (update)



Publication of the main findings from the PHE and MHRA investigation into the Bacillus cereus outbreak in the U.K. (issued by Public Health England).

Public Health England (PHE) and the Medicines and Healthcare products Regulatory Agency (MHRA) are in the final stages of their investigations into the outbreak of Bacillus cereus in the implicated intravenous liquid (Total Parenteral Nutrition, TPN).

Since the last update on 12 June 2014, a further case has been identified and the total number of cases linked to this investigation is 23 (19 confirmed and 4 possible cases). This baby has sadly died and our thoughts are with the family. This is the third confirmed case to have died and all 3 cases have been reported to the coroner.

The baby most recently identified received the implicated batch of TPN from 27 May 2014 but did not immediately develop sepsis so did not fit the case definition of the outbreak at that time. However, recent microbiological tests have shown the presence of the outbreak strain.

The strain of Bacillus cereus identified in the 19 cases confirmed as infected, has also since been identified in environmental samples collected from the day of manufacture (27 May 2014), located within the particular sterile area at ITH Pharma where the specific TPN supplies were manufactured. These specific TPN supplies were recalled by the MHRA on 4 June 2014.

Bacillus cereus is a common bacteria found widely in the environment in dust, soil and vegetation. Bacillus cereus produces very hardy spores, which make it persistent in the environment. Under certain conditions, the bacteria produces a number of toxins which can cause illness.

There is sufficient scientific evidence to indicate that the contamination was introduced into these specific TPN supplies during manufacture in a particular sterile manufacturing area at ITH Pharma on 27 May 2014 and MHRA’s investigations of the production process of TPN have found no evidence to suggest that individual ingredients, components or materials used were the cause of the contamination.

The MHRA has inspected ITH Pharma’s manufacturing facility and undertaken a rigorous and thorough review of the manufacturing processes and conditions within which the specific TPN supplies were manufactured. Based on the information obtained, there is sufficient evidence to indicate an isolated incident. Appropriate immediate action has since been taken at ITH Pharma’s facility to avoid a recurrence. The MHRA continues to allow TPN, a critical product, to be manufactured at ITH Pharma and therefore be supplied to patients.

Unopened supplies of the contaminated TPN (manufactured on 27 May 2014 at ITH Pharma) were collected from a few hospitals and these have been confirmed to contain the same strain of bacteria. Other tests on unopened TPN products manufactured by ITH Pharma after 27 May 2014 have all been clear of the bacteria.

A public health investigation that compared 18 confirmed cases with a comparison group of babies who did not have the outbreak strain of Bacillus cereus demonstrated a highly significant association between receiving TPN manufactured on 27 May 2014 and being infected by the outbreak strain.
Professor Mike Catchpole, PHE Incident Director, said:
"There are still some elements of our investigation that need finalising but the main findings have all pointed towards there being a single incident that occurred on one day and was associated with the illness seen in the babies. We are reassured that this was a very rare occurrence as we have not seen this particular strain of bacteria in any product made since that day and there has been no further illness."
Gerald Heddell, the MHRA’s Director of Inspection, Enforcement and Standards, said:
"At this stage, our investigation has provided sufficient evidence to indicate that the contamination was introduced into the specific Total Parenteral Nutrition (TPN) supplies during manufacture in a particular sterile manufacturing area at ITH Pharma on the 27 May 2014.
There is no evidence to suggest that individual ingredients, components or materials used for the manufacture of TPN on 27 May 2014 were the cause of the contamination. However, what we do know from our investigation is that the strain of Bacillus cereus which infected the babies has also been identified at ITH Pharma’s manufacturing facility and within some of the unopened TPN supplies manufactured on the 27 May 2014. 
From our investigation to date, we continue to believe this was an isolated incident and that appropriate immediate action has been taken at ITH Pharma’s facility to avoid a recurrence. Therefore we are allowing this critical product to be supplied to patients while our investigation continues."
Posted by Tim Sandle