enterobacter_sakazakii

8/7/2019 Enterobacter_sakazakii

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Enterobacter sakazakiiFact sheet

January 2008

What is Enterobacter sakazakii?Enterobacter sakazakiiis a motile, peritrichous, Gram-negative bacillus belonging to the

Family Enterobacteriaceae. E. sakazakiiis a rare cause of bloodstream and central nervous

system infections and it has been associated with necrotizing enterocolitis and sepsis,especially in neonates.

Who gets E. sakazakiiinfection?

Premature infants are at a greater risk than more mature infants, particularly pre-terminfants, low birth weight infants or immunocompromised infants. The lower acidity in thenew borns stomach especially that of the premature babies could be a contributing factor in

infant cases. E. sakazakiiinfections have also been reported in adults, but the outcomerelated to adult disease seems to be significantly milder.

What are the symptoms?

The common symptoms ofE. sakazakiiinfection in infants are sepsis, meningitis, or

necrotizing enterocolitis. The symptoms may be accompanied by seizures, brain abscess,hydrocephalus, developmental delay, and death (27). A publication from CDC (1) asserts

that 40-80% of infants infected with E. sakazakiidie.

Sources ofE. sakazakii

There is a paucity of information on the ecology ofE. sakazakii. The organism has beenisolated from diverse environments (hospitals, processing plants, homes), and different

foods (PIF, fermented bread, cheese, fresh and dried foods, soybean, herbs and spices). E.sakazakiican be found in the gut of some insects (19, 24).

CDC has suggested a correlation between E. sakazakiiinfection and powdered infantformula (PIF) (5, 28, 35). Food sources other than PIF have not been epidemiologically or

microbiologically confirmed as the source of infection.

The infective dose

It appears that low levels ofE. sakazakiiin powder infant formula (PIF) can lead to infectionin neonates (6). Pagatto et al. (31, 32) showed that high levels ofE. sakazakiiare

necessary to cause illness in animal models. The mishandling of PIF during preparation,

storage, and/or feeding can lead to growth ofE. sakazakiito potentially high levels (15).

Mode of transmission

Although E. sakazakiihas been detected in various food sources, a strong association has

been found only with PIF or the equipment used to prepare it (2, 3, 19, 29, 35). In 50-80%

of cases PIF was considered both the vehicle and the source (direct or indirect) ofE.sakazakii-induced illness. A risk profile conducted by FAO/WHO (2004) concluded that E.

sakazakiiwas emerging as a hazard in PIF causing infrequent but often severe infections ininfants (14).


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E. sakazakiiand PIF

Unlike liquid formulae, which are processed at a high enough temperature for sufficient timeto achieve commercial sterility, PIF are not sterile products and may occasionally contain

pathogens. E. sakazakiidoes not survive the pasteurization step during PIF manufacturingprocess; however, recontamination may occur at some stage during processing.

Contamination may also occur when caregivers use contaminated utensils in formula

preparation (29). Although E. sakazakiicannot grow in PIF, it can survive for a long time init, posing a greater potential risk if the product is temperature abused after hydration (3, 17,

24).

Growth and survival ofE. sakazakii

E. sakazakiigrows in a range of temperatures of 5.5 to 47C, with an optimum rangebetween 37 and 43C. The generation time (time needed to double a given bacterial

population) at 22C is of 37 - 44 minutes and around 20 min at 37C, depending on thestrains (9, 20, 28). A study by Iversen et al. showed that E. sakazakiigrew in reconstituted

PIF at refrigeration temperatures (5.5C) with a doubling time of 13.7 hours (20).

Although E. sakazakiiis not a heat resistant organism it was found to be more resistantthan other species of Family Enterobacteriaceae (4). Breeuwer et al. (3) suggested that the

osmotolerance of the organism may be more important in this latter regard; the organism

becoming more dominant in the environment. Jung and Park (23) emphasized on thephysiological diversity ofE. sakazakiistrains showing that strains isolated from PIF exhibited

D-values in the range of 3.52 to 3.58 minutes at 60C; strains isolated from brown rice hadD-values of 3.79 to 3.86 minutes in PIF, while some other strains isolated from agricultural

produce had D-values in the range of 4.40 to 4.79 minutes at 60C. It has been reportedthat E. sakazakiiare isolates are quite diverse and a sub-group of these isolates display a

higher thermotolerance (D58C of 9.9 min), while for the other group D58C was more than 10times lower (D58C = 0.80 min) (11). Based on decimal reduction time for E. sakazakiia

standard high temperature short time pasteurization process of 15 sec at 71.7C will result

in approximately 21-log reduction (20).

Gurtler and Beuchat reported that E. sakazakiisurvival in PIF was generally favored by low

water activity (aw) and low storage temperature. E. sakazakiiis resistant to desiccationover a wide range of aw (0.25-0.86) and temperatures (4-30C), but it has not been

markedly affected by PIF composition (18).

Microbiological criteria

Based on new epidemiologically evidence, and the emergence ofE. sakazakiias anopportunistic pathogen for a specific group of infants, FAO-WHO identified the need for

modifications of the original specifications for PIF (14). The switch from coliforms toEnterobacteriaceae was considered a necessary step.


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Table1. Current situation (2007) with respect to microbiological criteria for infant formulae at CodexAlimentarius and EC levelsc (Commission Regulation (EC) No 1441/2007 of 5 December 2007; Cordier,2008)

Standard and criteria (sample size) n c m M

CAC/RCP 21-1979 (CAC, 1979)

Mesophilic aerobic counts

Colifrorms

SalmonellaCAC/RCP 21- 1979, proposed revision (CCFH,2007)

Mesophilic aerobic counts

Enterobacteriaceae

Enterobacter sakazakii

Salmonella

EC 2073/2005 (EC, 2005)

Enterobacteriaceae

Enterobacter sakazakii

Salmonella

5

5

60

5

10

30

60

10

30

30

2

1

0

2

2

0

0

0

0

0

103


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Data available from the PIF industry indicate a reduction in both E. sakazakiiand Salmonella in

PIF through strict separation of the wet and dry phases of product manufacture, and through theuse of dry-cleaning procedures (8).

What caregivers can do to prevent the infection

To reduce the risk of infection, the reconstitution of PIF should be undertaken by caregivers usinggood hygienic measures and in accordance with the product manufacturers food safety guidelines.

Because PIF is not sterile, FDA (36) recommends, it not be used in neonatal intensive care unless

there is no alternative available. If there is no other option risks of infections can be reduced by:

Use of hot water (>70C (158F)) during the reconstitution of powder. (36, 9). Cooling after reconstitution is needed to limit the growth ofE. sakazakii(9).

Minimizing the holding time of reconstituted formula, whether at room temperature orwhile under refrigeration, before the reconstituted formula is fed (36).

Minimizing the hang-time in tube feeding situations (5, 35).

In addition to the use of hot water (> 70C) to reconstituting powdered formulae, the WHOsuggests to reduce the enteral (tube) feeding hang times to 2 h (30). Reduction in the

frequency ofE. sakazakiicontamination of PIF might only reduce the risk of infection 4 to 5 fold,while minimizing the time between preparation and consumption might reduce the risk 30 fold.

FAO/WHO meeting (15,16) acknowledged that not all PIF products were formulated to be mixed

at 70C and recognized that, if the use of hot water is recommended, specific labeling may berequired (8, 12, 25). Kim et al. (25) showed the importance of preventing contamination of

surfaces in areas where PIF is reconstituted and fed to infants because E. sakazakiican attachand form biofilms on those surfaces.

More information on preparing formula in infant care settings is available at:

http://www.who.int/foodsafety/publications/micro/PIF_Poster_en.pdf

References:

1. Bowen A.B., C.R.Braden. 2006. Invasive Enterobacter sakazakiidisease in infants.

Emerg. Infect. Dis. August Publication.http://www.cdc.gov/ncidod/EID/vol12no08/05-1509.htm

2. Bowen A.B., C.R.Braden. 2008. Enterobacter sakazakiidisease and epidemiology. In:Enterobacter sakazakii(emerging issues in food safety). Ed. By J.M. Farber and S.J.

Forsythe. ASM Press. Washington, D.C.p: 101-126.3. Breeuwer, P., A. Lardeau, M. Peterz and H.M. Joosten. 2003. Desiccation and heat

tolerance ofEnterobacter sakazakii.J. Appl. Microbiol. 95:967-973.4. Buchanan, R. 2003. Resistance Thermal and Other. Presentation to the United States

Food and Drug Administration Food Advisory Committee, 18-19 March 2003. Available at:

http://www.fda.gov/ohrms/dockets/ac/03/slides/3939s1_Buchanan.ppt#259,6,Comparison of D58C-Values for Different Enterobacteriaceae.

5. CDC. 2002. Enterobacter sakazakiiinfections associated with the use of powdered infantformula Tennessee, 2001. MMWR, 51: 298-300.

http://www.cdc.gov/mmwr/PDF/wk/mm5114.pdf6. Clark, N.C., B.C. Hill, C.M. OHara, O. Steingrimsson, and R. C. Cooksey. 1990.

Epidemiologic typingofEnterobacter sakazakiiin two neonatal nosocomial outbreaks.Diagn.Microbial. Infect. Dis.13:467-472.

7. Commission Regulation (EC) No 1441/2007 of 5 December 2007 amending regulation (EC)

No 2073/2005 on microbiological criteria for foodstuffs. 2007. Official Journal of theEuropean Union. L 322/12-29.

8. Cordier, J-L. 2008. Production of Powdered Infant Formulae and Microbiological ControlMeasures. In: Enterobacter sakazakii(emerging issues in food safety). Ed. By J.M. Farber

and S.J. Forsythe. ASM Press. Washington, D.C.p: 145-185.


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9. Dauga, C. and P. Breeuwer. 2008. Taxonomy and physiology ofEnterobacter sakazakii.

In: Enterobacter sakazakii(emerging issues in food safety). Ed. By J.M. Farber and S.J.Forsythe. ASM Press. Washington, D.C.p: 1-26.

10.Drudy, D., N.R. Quinn, P.G. Wall, and S. Fanning. 2006. Enterobactersakazakii: anemergent pathogen in powdered infant formula. Clin. Infect. Dis. 42:996-1002.

11.Edelson-Mammel, S.G. and R.L. Buchanan. 2004. Thermal inactivation ofEnterobactersakazakiiin rehydrated infant formula.J. Food Prot.67: 60-63.

12.Estuningsih, S. and N. Abdullah Sani. 2008. Powdered infant formula in developing andother countries- Issues and prospects. In: Enterobacter sakazakii(emerging issues in

food safety). Ed. By J.M. Farber and S.J. Forsythe. ASM Press. Washington, D.C.p: 221-234.

13.Farber, J.M., F. Pagotto, and J.-L. Cordier. 2008. Regulatory aspects. In: Enterobacter

sakazakii(emerging issues in food safety). Ed. By J.M. Farber and S.J. Forsythe. ASMPress. Washington, D.C.p: 235-253.

14.Food and Agricultural Organization of the United Nations (FAO) and the World HealthOrganization (WHO).2004. Enterobacter sakazakiiand other organisms in powdered

infant formula. Microbiological Risk Assessment Series 6.

http://www.fao.org/ag/AGN/jemra/enterobacter_en.stm15.Food and Agricultural Organization of the United Nations (FAO) / World Health

Organization (WHO).2006. Enterobacter sakazakiiand Salmonella in powdered infantformula: Meeting report. Microbiological Risk Assessment Series 10.

http://www.fao.org/ag/AGN/jemra/enterobacter_en.stm16.World Health Organization.2007. Guidelines for the safe preparation and handling of

powdered infant formula.

http://www.who.int/foodsafety/publications/micro/pif2007/en/index.html

17.Food Safety Authority of Ireland. 2007. Enterobacter sakazakii.

http://www.fsai.ie/publications/factsheet/factsheet_enterobacter_sakazakii.pdf18.Gurtler, J.B.and L.R. Beuchat. 2007. Survival ofEnterobacter sakazakiiin powdered infant

formula as affected by composition, water activity, and temperature.J. Food. Prot.70:1579-1586.

19.Ivarsen, C and S. J. Forsythe. 2004 a. Isolation ofEnterobacter sakazakiiand otherEnterobacteriaceaefrom powdered infant formula milk and related products. Food Microbiol.

21: 771-777.

20.Iversen, C., M. Lane, S.J. Forsythe. 2004 b. The growth profile, thermotolerance and

biofilm formation ofEnterobacter sakazakiigrown in infant formula milk. Lett. Appl.Microbiol.38:378-382.

21.Iversen C, P. Druggan, S.J. Forsythe. 2004. A selective differential medium for

Enterobacter sakazakii, a preliminary study. Int. J. Food Microbiol. 96: 1339.22.Ivarsen, C and S. J. Forsythe. 2006. Comparison on media for the isolation of

Enterobacter sakazakii.Appl. Environ. Microbiol. 73: 48-52.

23.Jung, M-K., & Park, J-H. 2006. Prevalence and thermal stability ofEnterobacter sakazakiifrom unprocessed ready-to-eat agricultural products and powdered infant formulas. Food

Sci. Biotechnol. 15: 152-157.24.Kandhai, C., M. Reij, L. Gorris, O. Guillaume-Gentil, M. Van Schothorst. 2004. Occurrence

ofEnterobacter sakazakiiin food production environments and households. The Lancet,363: 39-40.

25.Kim, H., J-H. Ryu, and L. R. Beuchat. 2006. Attachment of and Biofilm Formation by

Enterobacter sakazakiion Stainless Steel and Enteral Feeding Tubes.Appl. Environ.Microbiol.72: 58465856.

26.Mullane, N.R., J. Murray, D. Drudy, N. Prentice, P. White, P.G. Wall, A. Parton, and S.Fanning. 2006. Detection ofEnterobacter sakazakiiin dried infant formula by cationic-

magnetic-bead capture.Appl. Environ. Microbiol. 72 : 6325-6330.27.Muytjens, H.L., H.C. Zanen, H.J. Sonderkamp, L.A. Kolee, I.K. Wachsmuth, and J.J.

Farmer. 1983. Analysis of eight cases of neonatal meningitis and sepsis due to

Enterobacter sakazakii. J. Clin. Microbiol. 18:115-120.28.Nazarowec-White, M and J.M. Farber. 1997. Incidence, survival, and growth of

Enterobacter sakazakiiin infant formula.J. Food Prot.60: 226-230.


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29.Noriega, F.R., K.L. Kotloff, M.A. Martin, and R.S. Schwalbe. 1990. Nosocomial bacteremia

caused by Enterobacter sakazakiiand Leuconostoc mesenteroidesresulting from extrinsiccontamination of infant formula. Pediatr. Infect. Dis.9:447-449.

30.OConnor, D.L., J.Brennan, S. Dello, and L. Streitenberger. 2008. Use of nonsterilenutritionals for neonates in the hospitals and after hospital discharge: control measures

currently instituted at one tertiary care institution. In: Enterobacter sakazakii(emergingissues in food safety). Ed. By J.M. Farber and S.J. Forsythe. ASM Press. Washington, D.C.

p: 187-220.31.Pagotto, F., Nazarowec-White, M, S. Bidawid and J.M. Farber. 2003. Enterobacter

sakazakii: infectivity and enterotoxin production in vitro and in vivo.J. Food Prot.66: 370-375.

32.Pagotto, F., Farber, J.M., and Lenati, R. 2008. Pathogenicity ofEnterobacter sakazakii. In:

Enterobacter sakazakii(emerging issues in food safety). Ed. By J.M. Farber and S.J.Forsythe. ASM Press. Washington, D.C.p: 127-144.

33.Seo, K. H. and R. E. Brackett. 2005. Rapid, specific detection ofEnterobacter sakazakiiininfant formula using a real-time PCR assay. J. Food Prot. 68: 5963.

34.United States Department of Agriculture/Food Safety and Inspection Service/Regulations &

Policy. Codex Alimentarius. Delegates report, 39th of the Codex Committee on FoodHygiene, Oct 30-Nov 4, 2007, New Delhi, India.

http://www.fsis.usda.gov/regulations_&_policies/Delegate_Report_39CCFH/index.asp35.Van Acker J., De Smet F., Muyldermans G., Bougatef A., Naessens A., Lauwers A. 2001.

Outbreak of necrotizing enterocolitis associated with Enterobacter sakazakiiin powderedmilk formula.J. Clin. Microbiol.. 39 : 293-297.

36.United States Food and Drug Administration/ Center for Food Safety and Applied Nutrition.

Office of Nutritional Products, Labeling and Dietary Supplements. 2002. Healthprofessionals letter on Enterobacter sakazakiiinfections associated with use of powdered

(dry) infant formulas in neonatal intensive care units.http://www.cfsan.fda.gov/~dms/inf-ltr3.html

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