Background Information on Enterobacter Sakazakii (E. sakazakii)

ISDI takes very seriously the reports identifying powdered infant formula as a source and vehicle for E. sakazakii(1)   infections. Reported cases of E. sakazakii infection in which powdered infant formula was identified as a source are uncommon and have occurred mainly in hospitalised, pre-term and very low-birth weight infants; nevertheless they were serious episodes.

• Over the past 20 years evidence has developed to implicate Enterobacter sakazakii as the cause of some cases of fatality and disease in premature babies, immuno-compromised newborn infants and more recently fragile newborn infants of up to a few weeks of age.
  
  
• The number of reported cases is very low but has been increasing recently, however at a very low level. This is largely due to improved awareness and detection. According to WHO’s “Questions and Answers on E. Sakazakii in powdered infant formula”, a review of English language science literature found a total of 48 cases of illnesses in infants induced by E. Sakazakii infection over the last 42 years. 
  
  
• E.sakazakii is considered harmful to very young infants with compromised health status. These might include: newborns up to 28 days old, pre-term infants, low-birth weight infants, immuno-compromised infants and infants of HIV-infected mothers. A review of cases between 1961-2003 found that 52 percent (approx 25 cases) were among low-birth weight infants most likely to get some kind of infant formulae. 
  
  
• Given the serious effects of E. Sakazakii, ISDI is working with the manufacturers of infant foods and global health agencies to minimize any possible risks associated with powdered infant formulas.
  
  
• Additionally ISDI is been working very closely with national and international health authorities to understand and take action to prevent infections via this pathogen. As such, one of ISDI's members was very pleased to participate in the February 2004 FAO/WHO workshop Enterobacter Sakazakii in Powdered Infant Formula. 

About E. sakazakii

• E. sakazakii is a vegetative microorganism belonging to the family of the Enterobacteriaceae. It is an opportunistic pathogen widely found in the environment.
  
  
• During many years the only published data on the isolation of E. sakazakii were cases of neonatal meningitis or necrotizing enterocolitis related to powdered infant formulae. This led to the establishment of a causal link. In some later cases the organism was isolated on utensils such as mixers used in bottle kitchens. Even though in some cases E. sakazakii could not be isolated from the infant formulae, a causal relationship was assumed.
  
  
• It is, however, only very recently that information on the widespread occurrence of E. sakazakii has become available. Recent publications have demonstrated that this microorganism can be found in a wide variety of foods, water and environments including homes and hospitals.
  
  
• The E. sakazakii has also been isolated in hospitals from clinical samples taken from adults. A recent article reported the presence of E. sakazakii in mother's milk stored in a milk bank.
  
  
• As a widespread bacteria, E. sakazakii can also be found in infant food manufacturing environments and this is usually the source of its possible presence in the infant formula powder. In general, the very low level of E. sakazakii in powdered infant formula, or contamination through preparation equipment does not result in adverse effects unless the growth of E. sakazakii bacteria is allowed through improper handling and storage.
  
  
• Contrary to common belief, E. sakazakii is a frequently-found, ubiquitous microorganism. Further research in this field is continuing and is expected to provide additional information on the widespread distribution of this organism and contribute to the better understanding on exposure.

How does E. sakazakii behave? Is it heat-resistant?

• E. sakazakii grows very rapidly in reconstituted infant formulae kept at room temperature. It is particularly well adapted to growth at temperatures around 37 – 44°C.
  
  
• Certain strains show an increased tolerance and resistance to temperatures around 50 – 60°C. In different publications, this characteristic has been referred to as “thermo-tolerance”, and has lead to the misunderstanding that this microorganism is heat-resistant.
  
  
• As shown in different publications, E. sakazakii is not heat-resistant and is readily killed at temperatures above 60°C, as applied in industrial processes, e.g. pasteurisation. This fact is acknowledged by governmental agencies such as the US-FDA and is not a point of debate among experts.

The vast majority of E. sakazakii infections occur in hospital neonatal intensive care units. Risk of infection arises when reconstituted formula is kept at room temperature (or warmer) for prolonged periods of time.  Improved training and hygiene in hospitals are critically important in avoiding E. sakazakii outbreaks.

• Health professionals should receive training and effective risk management guidelines on optimum hygiene practices for handling, storage and preparation of formula.  Following the comprehensive instructions on manufacturers’ labels best prevents the presence and growth of pathogenic bacteria in formula. 
  
  
• Hospitals must also ensure good hygiene in their preparation areas, including an anti-bacterial treatment before preparing the formula, and a concerted effort to minimize the time between preparation and consumption. 
  
  
• ISDI strongly supports the use of freshly reconstituted infant formula as a means to eliminate these problems.  
  
  
• ISDI questions the WHO-FAO report’s recommendation to use boiling water in the preparation of infant formula and strongly discourages this practice. Water at 100°C can scald an infant and lead to nutritional damage.
  
  
• Breastfeeding should be recommended as the ideal to mothers in all instances. Those who cannot, or choose not to, breastfeed should receive accurate information and education about good hygiene practices concerning the preparation and use of formula. Mothers should be taught to correctly prepare and use formula before leaving hospital, when necessary.
   
  

Infant food manufacturers take extensive measures at the factory level to ensure the highest level of product quality and safety.

• ISDI member companies strictly comply with national legislation and international recommendations based on scientific expertise to provide safe and nutritionally adapted infant food.
  
  
• Along with their normal strict hygiene standards, manufacturers take additional actions to minimise possible contamination of powder products, including with Enterobacteriacea.
  
  
• These include a series of rigorous processes that prevent contamination from production to the point of purchase by the consumer. For example, manufacturers:
  
  • Closely monitor ingredients, especially those added after the final step of heat-processing;
    
  • Take extensive measures to minimise Enterobacteriaceae or coliforms in the manufacturing environment to prevent post-process contamination;
    
  • Train personnel to ensure that hygiene control measures are understood and closely followed; and
    
  • Test finished products to confirm the effectiveness of these procedures.

Close cooperation between global and national health agencies, the infant foods industry, and health providers must continue. Collaboration on combined control measures will achieve the greatest degree of risk reduction.

• The FAO/WHO workshop noted that:
  
  • Reduction in the frequency of E. sakazakii contamination of infant formula powder might only reduce the risk of infection 4 to 5 fold, while minimising the time between preparation and consumption might reduce the risk 30 fold.
    
  • Infant formula manufacturers will continue to refine manufacturing processes to further reduce the presence of Enterobacteriacae in the manufacturing environment. Similarly, hospitals and consumers must act to minimize the risk of post-contamination.
    
  • Further research about the ecology, taxonomy, virulence or other characteristics of this pathogen is needed.
    
  • ISDI will continue to work with FAO and WHO; governments, and other concerned parties to revise existing Codex Alimentarius standards and recommendations to ensure they contribute to reducing the risk of Enterobacteriacae and other microorganisms.

Public Health Authorities: in summary, what is the current situation?

In recent years, public health authorities in different countries have become more alert, and have initiated surveillance activities, as well as more structured risk assessment activities.

• The CCFH requested the FAO/WHO to convene an expert consultation on pathogens of concern in powdered infant formulae. This scientific and technical consultation took place in Geneva (2-5 February, 2004) attended by participants from different fields and different countries (academia, public health authorities, epidemiologists, nutritionists, medical experts, international organisations and industry). The aim of this consultation was to provide the CCFH and in particular the drafting group as well as member states with input and recommendations (see comments above).
  
  
• In 2003, the German Federal Institute for Risk Assessment (BfR) organised an expert consultation, which concluded that there was a need for further investigations in different fields such as development of more suitable methods for E. sakazakii detection in order to gain more information on the incidence of this organism. It was also concluded that there was no urgent need to modify the regulations with respect to microbiological criteria.
  
  
• In the US, the FDA has performed limited surveys applying quite exhaustive sampling plans to investigate the occurrence of E. sakazakii in powdered infant formulae, which has led to several widely publicised recalls. An additional survey is ongoing. In March 2003, an FDA/CFSAN meeting was organised to review and discuss the issue.
  
  
• The US brought this issue to the attention of the Codex Committee on Food Hygiene (CCFH) during the 35th session and provided a risk profile of E. sakazakii in powdered infant formulae. As a consequence, the CCFH set up a drafting group led by Canada to initiate the revision of the recommended International Code of Hygienic Practices for Foods for Infants and Children (CAC/RCP21-1979).
  
  
• In the European Union, the Commission (DG SANCO ) intends to review the legislation related to pathogens and Enterobacteriaceae in infant formulae. The European Food Safety Authority (EFSA) has therefore been mandated to initiate the assessment(i). The first meeting took place in January 2004 and the second in  March 2004 where an industry representative was invited 
  
  
• Discussions have taken place between the Food Standards Agency (UK) and industry representatives recently.
  
  
• Surveys have also been performed in the Netherlands and are planned in other countries such as Denmark or Israel.
  
  
• Other agencies may initiate similar activities in the near future.

(1) Biering et. al., 1989, Simmons et al. 1989; Van Acker et al, 2001; CDC, 2002.

April 2004