Enterobacter sakazakii

In

Powdere

d Infant

Formula

DR. ABDULRAHMAN LOTFYPreventive Medicine – Jahra Hospital

October 2011

FDA warning to health professionals

powdered infant formula not to be used in neonatal intensive care settings.

Enterobacter sakazakii Opportunistic pathogen that can cause infections

such as necrotizing enterocolitis, bacteraemia, meningitis and brain abscess/lesions.

The species was defined in 1980, by Farmer et al.

Gram-negative straight rod

Enterobacteriaciae family (Coliform bacterium).

the cells are motile (flagellated) and do not form spores.

The Organism

Electron Microscope Photo

web site (http://www.magma.ca/~scimat/E_sakaza.htm).

What is the magnitude of the problem?

The frequency in infants appears to be very low, yet the disease is devastating.

Despite the low frequency of reported infections, mortality rate is relatively high (33%).

SEVERITY

FREQUENCY

Risk FactorsAGE

(3 days to 4 years )

Birth weight

Immunocompromised

• 50% ≤ 1week of age

• 75% < 1 month of age

• 75% Low birth weights ≤ 2.5 kg

• Malignancy

CLINICAL MANIFESTATIONS & Clinical Manifestations Complications:

Reported infection

cases

Meningitis

Brain sepsis

Seizers

Bacteraemia

Ventriculitis (inflammation in the

ventricles of the brain).

Brain cysts and abscesses,

Cerebral infarction,

Hydrocephalus (abnormal increase in

the amount of cerebrospinal fluid within the cranial cavity

Necrotizing enterocolitis (localized

death of small and large intestine tissues).

Death may occur within a few hours to several days.

Mortality Rate:

50%• premature

• Low BW

30%• Full term

• Normal BW

Fatality From Meningitis*

62%

14%

Before use of cephalosporines

After use of cephalosporines

*Only one death has been reported in the absence of meningitis, a neonate exhibiting bacteremia.

Antibiotic Susceptibility of E. sakazakii

Susceptibility Resistence Ampicillin,

Tetracycline,

Chloramphenicol,

Gentamicin, and

third-generation cephalosporins.

aminoglycosides :Although E. sakazakii isolates are typically

susceptible to it , such antibiotics are not recommended for primary treatment because of poor penetration into the central nervous system.

Cefazolin, and

extended-spectrum penicillins.

Treatment

After 1985

3rd generation cephalosporines

Ampicillin Gentamycin

Before 1985

Ampicillin GentamycinAnd/or

Chloramphenicol

Sporadic cases and outbreaks of Enterobacter sakazakii infection for which powdered infant

formula (PIF) was implicated as the source agent.

Drudy D et al. Clin Infect Dis. 2006;42:996-1002

© 2006 by the Infectious Diseases Society of America

Is the risk similar in all regions and countries?

Under

reporting

Lack of Awareness

Limitation of current

surveillance

Reporting only in a few developed

countries

A significant public health problem

IF is widely used

the presence of E.s. in infant formula

The potential effect in infants

Source of E. sakazakii Infections In early cases of E. sakazakii infections, an environmental

source of the organism could not be identified

Vertical transmission is not documented.

Dried infant formula, has been identified epidemiologically as the source of E. sakazakii in three outbreaks of neonatal meningitis and linked to one outbreak of necrotizing enterocolitis.

Ecology of E. sakazakiiFlies( Fruit Flies, Stable)

Dust

Rodents & bird dung

Surface water & Soil

domestic animals, cattle and raw cow’s milk

Mud & rotting wood

Food

E. Sakazakii and flies household flies, were found to carry E. sakazakii.

Similarly, E. sakazakii has been isolated from the gut flora of fruit flies, with no differences in distribution between males and females. Surprisingly, the organism was only isolated from a culture of fruit flies propagated in 1998 and not from a colony of flies over 30 years old.

Foods from which the organism has been isolated

Meat & minced beef,

Sausages

Vegetables,(Lettuce, alfalfa sprouts)

Tofu;

Bread,

Cheese;

Rice seed

•Herbs & spices

•Sous (licorice drink)

•Dried products (infant cereal,, spices, whey, egg yolk , flour/meal)

Occurrence in food production environments and households

PIF and E. sakazakii

Powdered milk substitute infant formulas are the principal sources from which E. sakazakii has been isolated.

WHO – NO E.s. in BF. In the current state of

knowledge, no exclusively BF infants have been reported to have Enterobacter sakazakii infections.

Based on the available information, in 50-80 % of cases, PIF is both the vehicle and the source (direct or indirect) of E. sakazakii induced illness.

BF IF

Survey - 1988 E . sakazakii was isolated from 20 of 141 dried infant

formulas from 35 countries in a 1988 survey

latest study ( 2008 published 2010) In 2008 a study was done

in Japan showed that E.sakazakii isolated in 6% of PIF samples suggesting that commercially available PIF products can be contaminated with this type of bacteria

How does infant formula get contaminated with Enterobacter sakazakii?

Basically there are three routes by which Enterobacter sakazakii can enter infant formula:

1. Raw material used for producing the formula;

2. Contamination of the formula or other dry ingredients after pasteurization

3. Contamination of the formula as it is being reconstituted by the caregiver just prior to feeding.

colony-forming unit (CFU )is a measure of viable bacterial or fungal numbers. Unlike direct microscopic counts where all cells, dead and living, are counted, CFU measures viable cells. For convenience the results are given as CFU/mL (colony-forming units per milliliter) for liquids, and CFU/g (colony-forming units per gram) for solids.

Current Regulations Affecting Occurrence of E. sakazakii in Powdered Infant Formulas

Regulations governing the prevalence of E. sakazakii in powdered infant formulas falls under the hygienic requirements for allowable levels of coliforms.

For the Codex Alimentarius, these requirements include: minimum of four of five control samples with < 3 coliforms/g and

a maximum of one of five control samples with >3 but ≤ 20 coliforms/g.

Based upon these test parameters, dry milk-based infant formula that contains E.sakazakii at levels of < 1 organism per 100 g of formula would not be reliably detected.

What do we

do now??

Recommendations & Preventative Strategies The promotion of

breast milk feeding,

The World Health Organization recommends that infants should be exclusively breast-fed for the first 6 months of life.

Infants who are not breast-fed should be provided with a suitable breast milk substitute, formulated in accordance with Codex Alimentarius Commission standards.

To reduce the risk of infection in infants fed PIF, recommendations have been made for the preparation and storage of PIF

Inclusion of warnings on powdered infant formula packages that they may be contaminated with ES.

Education:

The ideal practice of re-warming of reconstituted formula.

Better understanding of the progression and pathogenesis ES related diseases

Why education?

Many individuals unaware that PIF is not a sterile product

Lack information on how handling, storage and preparation practices can influence the risk

Effective risk communication practices needed for the public and health professionals

Summary & Conclusion E. sakazakii is a pathogenic microorganism

The precise pathogenesis of ES remains a mystery.

Natural habitat is not known yet

Found in infant formula

Thermo-tolerant

FDA recommend method need some improvement

There are much more work to be done…….

Appropriate measures by parents, infant formula manufacturers, and health care providers, as well as understanding of the pathogenesis, are important in the prevention.