Enterobacter sakazakii

Enterobacter sakazakii is an uncommon, but often fatal, invasive pathogen that causes bloodstream and central nervous system infections.  The gram-negative, non-spore-forming, rod-shaped bacterium is from the family Enterobacteriaceae – the same family that E. coli O157:H7 belongs to.

While E. sakazakii has caused disease in all age groups, it is likely that immunocompromised or medically debilitated infants are more susceptible to infections with E. sakazakii.  One contributing factor in infant cases could be that the stomach of newborns, especially of premature babies, is less acidic than that of adults.  Several outbreaks traced to contaminated infant formula have occurred in neonatal intensive care units worldwide. 

Symptoms of Enterobacter sakazakii Infection

Sepsis (bacteria in the blood), meningitis (inflammation of the lining of the brain), or necrotizing enterocolitis (severe intestinal infection) are common symptoms of Enterobacter sakazakii infection exhibited by infants.  These can be accompanied by seizures, brain abscess, hydrocephalus, developmental delay, and death.  Significant morbidity in the form of neurological deficits can result from infection, especially among those with bacterial meningitis and cerebritis.  The authors of an article that appeared in the August 2006 issue of Emerging Infectious Diseases, a publication from the Centers for Disease Control and Prevention, assert that 40%–80% of infants infected with Enterobacter sakazakii die.

Detection and Treatment of Enterobacter sakazakii

Enterobacter sakazakii can be detected when it is isolated from clinical samples using standard methods for the isolation of Enterobacteriaceae, which include spreading or streaking an overnight Enterobacteriacae enrichment broth and growing the bacterium in a controlled environment.  E. sakazakii has been isolated from human blood and tissue samples as well as from powdered milk formula. 

There is very little known about virulence factors and pathogenicity of E. sakazakii.  Some strains isolated in tissue cultures in the laboratory appear to indicate differences in virulence among E. sakazakii strains, and some strains may be non-pathogenic.

While the disease is usually responsive to antibiotic therapy, antibiotic resistance to drugs commonly used for initial treatment of suspected Enterobacter infection is increasing.  Most forms for Enterobacter have developed resistance to first-generation cephalosporins and are becoming increasingly resistant to second- and third-generation cephalosporins.  Long-term neurologic sequelae are well recognized.

Preventing Enterobacter sakazakii Infection

Although the reservoir of the organism is unknown in many cases, a growing number of outbreaks of infection among infants have provided compelling evidence that milk-based powdered infant formulas have served as the source of infection.  In several investigations of outbreaks of E. sakazakii infection that occurred among infants in neonatal intensive care units, investigators were able to show both statistical and microbiological association between infection and powdered infant formula consumption.

The FDA points out that powdered infant formulas are not commercially sterile products. Powdered milk-based infant formulas are heat-treated during processing, but unlike liquid formula products they are not subjected to high temperatures for sufficient time to make the final packaged product commercially sterile. Proper handling and use of infant formula products in the health-care setting is an important patient safety issue. Clinicians should be aware that powdered formulas are not sterile products and might contain opportunistic bacterial pathogens such as those in the family Enterobacteriacae, including E. sakazakii.

Risk for infection might depend on several factors, including the number of bacteria present in the product, handling after preparation, and underlying patient characteristics (e.g., immunosuppression, prematurity, or low birth weight). Because powdered formula is not sterile and can provide a good medium for growth, prolonged periods of storage or administration at room temperature might amplify the amount of bacteria already present. Health care providers might be able to reduce risks for hospitalized neonates by choosing alternatives to powdered formula when possible.

FDA recommends that powdered infant formulas not be used in neonatal intensive care settings unless there is no alternative available. If the only option available to address the nutritional needs of a particular infant is a powdered formula, risks of infection can be reduced by:

• Preparing only a small amount of reconstituted formula for each feeding to reduce the quantity and time that formula is held at room temperature for consumption; Minimizing the holding time, whether at room temperature or while under refrigeration, before a reconstituted formula is fed; and
• Minimizing the “hang-time” (i.e., the amount of time a formula is at room temperature in the feeding bag and accompanying lines during enteral tube feeding), with no “hang-time” exceeding 4 hours. Longer times should be avoided because of the potential for significant microbial growth in reconstituted infant formula.