We report the case of a 37-week male infant born via spontaneous vaginal delivery who developed Salmonella berta sepsis and meningitis. The infant was born to a mother with active diarrhea and stool cultures growing S. berta. On day 3, the infant developed poor feeding, lethargy, apnea and bradycardia prompting a sepsis evaluation. Blood, stool and cerebrospinal fluid cultures were positive for S. berta. An electroencephalogram performed for posturing revealed neonatal status epilepticus. Extensive bilateral periventricular venous hemorrhagic infarctions with multiple herniations were seen on brain magnetic resonance imaging. The infant's condition continued to deteriorate despite maximal support and care was redirected towards comfort measures.
A 37-week male infant (birthweight 2320 grams) was born via spontaneous vaginal delivery to a 27-year-old G5P3 mother with a normal pregnancy and good prenatal care. Membranes were ruptured 6 h prior to delivery. Maternal history was significant for onset of diarrhea prior to delivery and presence of a high-risk contact in the father who worked at a local poultry factory. Of note, a stool culture sent with onset of symptoms grew a Salmonella species at 48 h.
The infant was reported to have done well initially with the exception of mild feeding intolerance. On day 3, he had an apnea-and-bradycardia event and was noted to be irritable and lethargic. Stool and blood cultures were obtained and ampicillin and gentamicin initiated. He required intubation and mechanical ventilation for recurrent, severe apneas and was transferred to our neonatal intensive care unit (NICU) for further management. A diffuse erythematous macular rash of the upper extremities and chest noted by the transport team (Figure 1) had almost completely resolved upon arrival to the NICU and after the first doses of antibiotics.
On admission, the infant was noted to be lethargic with poor perfusion and metabolic acidosis (arterial pH 7.23, pCO2 31 mm Hg, serum bicarbonate 9 mmol l−1, base deficit 13 mmol l−1, lactic acid 8.53 mmol l−1). Severe neutropenia (580 white blood cells μl−1, absolute neutrophil count 210 cells μl−1), as well as coagulopathy (internationalized normalized ratio 2.8, protime 35.6 s and partial thromboplastin time 77.2 s) and hyperbilirubinemia (total bilirubin 9.6 mg dl−1, conjugated 0.9 mg dl−1) were noted on admission labs. A lumbar puncture revealed cloudy, xanthochromic fluid containing 831 white blood cells (89% neutrophils, 3% bands), a protein count of 691 mg dl−1 and a glucose level of 5 mg dl−1, supporting a diagnosis of meningitis. Within 1 h of admission, the infant’s stool culture from the referring hospital was noted to grow a Salmonella species. Additionally, within 2.5 h of plating, the infant’s blood and cerebrospinal fluid cultures were also growing Salmonella species, Group D, later identified as Salmonella berta (minimum inhibitory concentration (mg ml−1): ampicillin <2, ceftriaxone <1, trimethoprim/sulfamethoxazole <20). Owing to severe Salmonella sepsis with meningitis and profound neutropenia, the infant received intravenous immunoglobulins, cefotaxime and filgrastim.
Shortly after admission, the infant had symmetric upper extremity extension lasting 30–45 s associated with leftward eye deviation and non-rhythmic, asymmetric kicking of either lower extremity. While posturing ceased after phenobarbital administration, a video electroencephalogram demonstrated the continued presence of frequent, prolonged electrographic seizures (>50% of the recording) that remained unresponsive to additional phenobarbital or levetiracetam. A brain magnetic resonance imaging showed large-territory bilateral supratentorial periventricular venous hemorrhagic infarctions with subfalcine, uncal and transtentorial herniations (Figure 2).
Results from the brain magnetic resonance imaging and video electroencephalogram were discussed with the family and the decision was made to redirect care to comfort measures. The patient expired shortly after extubation.
Salmonella infections, although uncommon in the United States, represent the second most common bacterial cause of diarrhea behind Campylobacter.1 Salmonella bacteria are gram-negative bacilli with approximately 2500 serotypes. Half of the confirmed isolates in the United States are caused by serotypes Enteritidis, Typhimurium and Newport.2 Infection typically occurs following poor hand hygiene after handling or ingestion of undercooked meats. Incidence is highest in those less than 4 years of age and the immunosuppressed.2
The incubation period for most Salmonella infections is 6–72 h, with an illness lasting from 4 to 7 days. Most symptoms (diarrhea, abdominal cramps, fever) are related to infection of the distal small intestine and colon.3 In 5–10% of cases, bacteremia and severe localized disease can occur.2 Meningitis, the least common site of extra-gastrointestinal infection, is associated with significant morbidity and a case fatality rate of 70–90%.4
The treatment of Salmonella infections is primarily supportive. The use of antibiotics is generally avoided in adults and older children due to the risk of inducing a carrier state. However, antibiotics are appropriate in infants younger than 3 months as well as immune-compromised patients. In infants, treatment with amoxicillin and ceftriaxone for a minimum of 4–6 weeks is recommended.2
Our case vignette illustrates a rare fatal case of neonatal Salmonella infection and meningitis and emphasizes the need to develop guidelines for the management of both mothers and infants when infectious diarrheal illness is suspected.
Our patient was born via vaginal delivery to a mother with watery diarrhea due to S. berta infection. Loose stools are relatively common in women during the peripartum period, especially during treatment of preterm labor with magnesium sulfate and following vaginal delivery.5 There are currently no treatment or management recommendations to guide clinicians caring for mothers with suspected infectious diarrhea in the peripartum period. Universal screening of all pregnant women reveals an overall low Salmonella carrier rate (0.2–0.3%), a low incidence of symptoms (28–30%) in carriers and higher incidence in late summer and fall.6,7 Conversely, pregnant women with diarrhea have a low rate of Salmonella infection, indicating that screening of mothers in the peripartum period based solely on the presence of diarrhea is not an effective strategy.7 A more selective approach targeting women with diarrheal illnesses in the peripartum period and other risk factors including onset prior to labor, presence of blood in stool, fever, high-risk contacts, occurrence in late summer or fall and signs of fetal distress may be more effective in preventing neonatal transmission.6 In this case, the patient’s mother had several risk factors including diarrhea preceding onset of labor, systemic symptoms as well as presence of a high-risk contact. This type of targeted screening would increase the yield of testing and allow for early treatment of mother and infant, a critical step for optimal outcomes.
Currently, there are no data to guide pediatricians in the care of infants born to mothers with infectious diarrhea. Conventional risk factors for sepsis including preterm labor, prolonged rupture of membranes, chorioamnionitis, maternal Group B Streptococcus positive status and poor prenatal care were absent in our patient.8 Ampicillin and gentamicin were appropriately started with first symptoms; however, this occurred approximately 41 h after birth and did not initially include a cephalosporin to account for the growing incidence of ampicillin-resistant Salmonella species.
This is the first published case of neonatal S. berta infection. It illustrates that Salmonella infection in the newborn period can have devastating consequences and that maternal infectious diarrhea during the peripartum period may be important to consider when evaluating sepsis risk in newborns. A common-sense approach may be to evaluate maternal diarrhea when risk factors for an infectious etiology are present. In addition, a reasonable approach may be to consider all infants born to mothers with confirmed or suspected infectious diarrhea at risk for sepsis and to initiate observation with antibiotics for 48 h pending culture results.1,6 More research is needed to develop a systematic, evidence-based approach to the management of infectious diarrhea in the peripartum period in order to optimize the care of these mothers and their infants.
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The authors declare no conflict of interest.
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Bowe, A., Fischer, M., Waggoner-Fountain, L. et al. Salmonella berta meningitis in a term neonate. J Perinatol 34, 798–799 (2014). https://doi.org/10.1038/jp.2014.98
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