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Is Cronobacter Sakazakii Infection Possible in an Exclusively Breastfed Premature Neonate in the Neonatal Intensive Care Unit?

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Is Cronobacter Sakazakii Infection Possible in an Exclusively Breastfed Premature Neonate in the Neonatal Intensive Care Unit? Journal of Perinatology (2014) 34, 408–409 & 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp PERINATAL/NEONATAL CASE PRESENTATION Is Cronobacter sakazakii infection possible in an exclusively breastfed premature neonate in the neonatal intensive care unit? S Ravisankar1, SS Syed2, P Garg1 and J Higginson1 Cronobacter species are Gram-negative rods that may cause life-threatening infections in neonates and infants. They belong to the family of Enterobacteriaceae. The first case was published in 1961 in England and about 150 cases have been reported thus far in the literature. The worst form of infection results in meningitis, leaving survivors with devastating neurological sequelae. We present the case of a premature neonate who was exclusively gavage fed with non-fortified breast milk and developed culture positive sepsis for Cronobacter sakazakii with clinical signs of meningitis at 18 days of life. She had a very traumatic course and survived the illness, but questions remain as to how she obtained this infection and her future neurodevelopmental outcomes. Journal of Perinatology (2014) 34, 408–409; doi:10.1038/jp.2014.14 Keywords: Cronobacter sakazakii; Enterobacter sakazakii; premature neonate; breast milk INTRODUCTION added for suspected meningitis. The workup was consistent with Urmenyi, et al.1 described the first two neonatal cases in 1958 in sepsis and cerebrospinal fluid (CSF) showed leukocytosis, increased England. They were born at 38 and 32 weeks gestation, developed protein and low glucose. Her blood culture grew Enterobacter meningitis and died shortly later. Autopsies from both patients species at 18 h, which was later classified as Cronobacter sakazakii revealed similar findings—swollen cerebral hemispheres with the pan sensitive to all antibiotics on the testing panel. Head US showed white matter transformed into a soft hemorrhagic mass. The abnormal brain with a hemorrhagic infarct in the right periven- organism was identified as pigmented Cloaca or Aerobacter cloacae, tricular white matter. Two weeks later magnetic resonance imaging a Gram-negative non-encapsulated rod of the coli aerogenous group. (MRI) of the brain revealed extensive signal abnormalities in the By 1980, a new name, Enterobacter sakazakii, was proposed based on cerebral hemispheres consistent with severe meningoencephalitis, the differences between E. sakazakii and E. cloacae in DNA–DNA with an area in the right cerebral hemisphere showing fluid hybridization, biochemical reaction and production of yellow worrisome for a brain abscess versus cystic encephalomalacia pigment.2 In 2007, Iversen et al.3 reclassified these bacteria into a (Figure 1). Antibiotic therapy was switched to meropenem for new genus called Cronobacter. Currently seven species4 have been 28 days and gentamicin for 21 days per Infectious Diseases. identified, including C. sakazakii, C. malonaticus, C. turicensis, Head computerized tomography (Figure 2) 2 weeks later showed C. muytjensii, C. dublinensis, C. condiment and C. universalis. extensive edematous changes in the right cerebral hemisphere with a cystic-appearing lesion occupying most of the area. During the acute phase of illness, she required extensive hemodynamic and CASE ventilatory support. The family was fully aware of the patient’s condition and possible outcomes. The baby survived and was We present a 27-week premature neonate born by spontaneous discharged with outpatient palliative care. However, she was vaginal delivery to a 28-year-old G2 P2 mother. Pregnancy was readmitted 3 weeks later due to massive increase in head complicated by history of gonococcal and chlamydial infections and circumference and a ventriculoperitoneal shunt was placed. onset of premature labor. The mother received two doses of betamethasone and three doses of ampicillin before delivery. The neonate was assigned Apgar scores of 5, 6 and 7 at 1, 5 and 10 min, respectively and placed on continuous positive airway pressure DISCUSSION (CPAP) on admission. Birth weight was 1.140 kg, which was Cronobacter sakazakii is a motile peritrichous Gram-negative rod.5 appropriate for gestational age and admission clinical exam was It is an emerging opportunistic human pathogen and the normal. She remained stable with negative initial head ultrasound etiological agent of life-threatening bacterial infections in infants (US), negative blood cultures at 48 h and was weaned off CPAP to and premature neonates, with those weighing less than 2.5 kg room air on day of life 11. She was supported with total parenteral being most susceptible.6 Meningitis, necrotizing enterocolitis and nutrition and trophic feeds with breast milk were started on day of sepsis are the most commonly reported consequences of the life 9. She suddenly deteriorated on day of life 18 with increasing infection.6 Since the index case in 1958, about 150 cases have lethargy, new onset of apneas, bulging anterior fontanel and been reported in the literature in neonates and infants.7 The abdominal distension. Full septic workup was initiated and she was natural environment of Cronobacter is not known, but it has been started on intravenous nafcillin and gentamicin. She was intubated isolated from many sources6—infant formula, cheese, cereal, due to worsening acidosis and apneas. The following morning, she meats and so on. Consumption of contaminated powdered infant started seizing and a lumbar puncture was done. Cefotaxime was formula has been epidemiologically linked to several clinical cases 1Department of Pediatrics, East Carolina University, Greenville, NC, USA and 2Department of Pediatrics, East Carolina University, Vidant Medical Center, Greenville, NC, USA. Correspondence: Dr SS Syed, Department of Pediatrics, East Carolina University, Vidant Medical Center, Medical Annex – Suite 229, Greenville, NC 27834, USA. E-mail: [email protected] Received 17 July 2013; revised 18 October 2013; accepted 6 January 2014 C. sakazakii infection in a breastfed neonate S Ravisankar et al 409 this population concluded that C. sakazakii infection is very rare and is outside of epidemic proportions.9 Review of the literature reveals that no exclusively breastfed infants have been reported to have C. sakazakii infections. We present the case of a 27-week premature infant who was gavage fed breast milk without fortification and suddenly deterio- rated to develop sepsis and meningitis evidenced by the positive blood culture and extensive caseation of the brain parenchyma as seen on MRI. Although most neonates will have positive CSF cultures, our patient had two negative CSF cultures (including an anterior fontanel aspirate) despite significant pleocytosis. Despite initiating early appropriate antibiotic therapy, our neonate suffered extensive residual damages from the infection. Though rare, it is well understood that C. sakazakii meningitis results in severe encepha- lomalacia resulting in ventriculitis, hydrocephalus, seizure disorders, sensorineural hearing loss, cerebral palsy and global development delays amongst survivors and has a high mortality rate of 40 to 80%.10 Recent literature reveals evidence of stored breast milk being contaminated11 and the possibility of colonization of feeding tubes12 by forming biofilms with C. sakazakii. In our patient, we tested the mother’s breast milk and it was negative for any con- tamination or infection. Therefore C. sakazakii should also be considered in premature neonates who are exclusively breastfed. Figure 1. Brain magnetic resonance imaging showing extensive CONCLUSION signal abnormalities at the cerebral hemispheres, right greater than The source of contamination for the onset of infection in this left. Right cerebral hemispheres having a large area measuring 3 premature neonate who was exclusively breastfed remains unknown, 3.3 Â 7.5 Â 4.8 cm with central signal characteristics suggestive of thus warranting more research to understand its environment and fluid is worrisome for brain abscess versus cystic encephalomalacia. mode of transmission of this infection which is devastating in premature infants. CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1 Urmenyi AM, Franklin AW. Neonatal death from pigmented coliform infection. Lancet 1961; 1: 313–315. 2 Yan QQ, Condell O, Power K, Butler F, Tall BD, Fanning S. Cronobacter species (formerly known as Enterobacter sakazakii) in powdered infant formula: a review of our current understanding of the biology of this bacterium. J Appl Microbiol 2012; 113:1–15. 3 Iversen C, Lehner A, Mullane N, Bidlas E, Cleenwerck I, Marugg J. The taxonomy of Enterobacter sakazakii: proposal of a new genus Cronobacter gen. nov. and descriptions of Cronobacter sakazakii comb. nov. Cronobacter sakazakii subsp. sakazakii, comb. nov., Cronobacter sakazakii subsp. malonaticus subsp. nov., Cronobacter turicensis sp. nov., Cronobacter muytjensii sp. nov., Cronobacter dublinensis sp. nov. and Cronobacter genomospecies 1. BMC Evol Biol 2007; 7: 64. 4 Cetinkaya E, Joseph S, Ayhan K, Forsythe S. Comparison of methods for the microbilogical identification and profiling of Cronobacter species from ingredients used in the preparation of infant formula. Mol Cell Probes 2013; 27: 60–64. 5 Nazarowec-White M, Farber JM. Enterobacter sakazakii: a review. Int J Food Microbiol 1997; 34: 103–113. 6 Hunter CJ, Bean JF. Cronobacter: an emerging opportunistic pathogen associated with neonatal meningitis, sepsis and necrotizing enterocolitis. J Perinatol 2013; 33: 581–585. 7 Friedemann M. Epidemiology of invasive
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