Recurrent late-onset neonatal sepsis traced to breast milk: A case report

1 Introduction

Bloodstream infections are a significant cause of morbidity and mortality in the neonatal population [1, 2]. Many infection control guidelines and policies have been introduced into neonatal intensive care units (NICUs) to reduce the incidence of infection, including intravenous central catheter bundles, removal of indwelling devices (such as Foley catheters) as soon as they are no longer needed, and strict hand-washing protocols [3]. Despite these measures, the burden of sepsis and its consequences looms large in NICUs everywhere. The rate of late-onset neonatal sepsis (defined as bloodstream infection occurring after 72 hours of life) has been reported to be as high as 21%.n hospitalized infants, with the incidence and associated mortality proportional to the degree of prematurity [1, 4–6]. Furthermore, sepsis extends NICU length of stay and increases healthcare costs [7]. Sepsis-associated morbidities include the need for prolonged invasive ventilatory support, bronchopulmonary dysplasia, extended duration of total parenteral nutrition (and its attendant consequences), and adverse neurologic outcomes, especially with concomitant meningitis [1]. The consequences of bloodstream infection in the premature neonate are often more dire than in term infants because of the immaturity of the immune system as well as the presence of multiple co-morbidities.

Avoidance of bloodstream infections is of paramount importance in the provision of care in the NICU. Studies have shown that the use of breast milk reduces the rate of late-onset sepsis [8–10]. While donor human milk (milk donated by mothers with excess milk supply that is pooled and pasteurized) is available for babies whose mothers are not able to provide adequate volumes of their own breast milk, the milk provided by an infant’s own mother has the most appropriate nutrient composition for her infant and contains immunologic factors that reduce the likelihood of infection, including antibodies, cytokines, growth factors, lactoferrin, lysozyme and human milk oligosaccharides [8–11].

Despite its benefit in reducing infection, breast milk is not sterile. Studies have shown bacterial growth in culture or bacterial DNA isolation from breast milk with organisms such as Staphylococcus, Streptococcus, Corynebacterium, Propionibacterium, Lactobacillus, Bifidobacterium, Clostridium and Bacteroides demonstrated. This microbial landscape in breast milk is thought to help with both intestinal development and infant growth [11]. However, there are multiple reports of transmission of Klebsiella [12], E. coli, Listeria, Staphylococcus and Mycobacterium tuberculosis to infants from breast milk containing these organisms [13]. We present a case of maternal breast milk colonized with Klebsiella and Enterococcus that resulted in the death of one twin and persistent bacteremia in the other.

2 Case report

The mother was a 26-year-old previously healthy primigravida, whose pregnancy was conceived by in vitro fertilization, resulting in dichorionic, diamniotic white male twins. Because of preterm labor and a footling breech presentation of twin A, a Cesarean section was performed at 23 2/7 weeks’ gestation. Twin B had a birth weight of 680 g. He was intubated in the delivery room and placed on high frequency jet ventilation. Attempted placement of a nasogastric tube was met with resistance, and further evaluation for the presence of a tracheoesophageal fistula revealed an esophageal perforation, so the infant was transferred to our facility for further care.

At the time of transfer, the infant was receiving ampicillin and amikacin, with a plan for a seven-day course for presumed sepsis, given his clinical condition and the presence of foul-smelling fluid at the time of delivery of Twin A. Upon confirmation of the esophageal perforation, fluconazole was added, as was piperacillin-tazobactam on day seven; it was continued for an additional six days until an esophagram confirmed resolution of the perforation.

This infant’s early course was notable for a pneumothorax requiring placement of a thoracostomy tube, hyperglycemia requiring an insulin infusion, hypotension requiring vasoactive medications and hydrocortisone, and a hemodynamically significant patent ductus arteriosus necessitating treatment with two courses of ibuprofen, which resulted in nearly complete closure.

Trophic feeds with the mother’s breast milk were begun on day of life (DOL) 17, and within several hours, the infant declined clinically, requiring increased ventilatory and pressor support. Blood and urine cultures were negative, and the infant received a 48-hour course of antibiotics. On DOL 21, the infant’s twin expired from Klebsiella sepsis and fulminant necrotizing enterocolitis at the referring hospital. The mother’s milk grew Klebsiella pneumoniae, Enterococcus species, and coagulase-negative Staphylococcus. The mother had no known immunodeficiency or obvious skin wounds or infection/cellulitis on the breast that would predispose to infection; furthermore, she did not have mastitis.

Twin B improved clinically, and trophic feedings of the mother’s milk were restarted on DOL 22. Within 24 hours, he had another marked decompensation; blood and urine cultures were obtained. The blood grew Enterococcus faecalis, and given the history of prior culture-positive breast milk, multiple samples of the mother’s milk were sent for culture, including two frozen and thawed samples obtained at different time points, as well as one freshly pumped sample. The fresh milk grew Klebsiella aerogenes and Enterococcus faecalis, while the two frozen samples grew rare Staphylococcus epidermidis. Infant blood cultures were positive for Enterococcus on DOL 23, 25, 26, and 28; blood and CSF cultures obtained on DOL 27 were negative. The infant was treated with a ten-day course of piperacillin-tazobactam and gentamicin for eight days (for presumed necrotizing enterocolitis associated with the Enterococcus bacteremia), as well as ten days of ampicillin beyond the first negative blood culture. Advanced testing was not performed to confirm that the Enterococcus in the breast milk and infant’s blood culture were the same, but their susceptibility profiles were identical.

The remainder of infant’s NICU course was notable for the development of bronchopulmonary dysplasia as well as a urinary tract infection on DOL 96 from Enterococcus and Klebsiella and was treated with another ten-day course of piperacillin-tazobactam. Repeat testing of the mother’s milk two weeks after the initial samples were again positive for Enterococcus. The Infectious Disease service was consulted because of the reappearance of the same organisms, which they felt were the result of colonization of the GI tract rather than a new pathogenic process. Multiple Newborn Screens were without evidence of immunodeficiency.

3 Discussion

While breast milk feeding has been shown to reduce the risk of late-onset sepsis in neonates [8–10], there have been multiple reports of bacteria-contaminated breast milk transmitting infection to the recipient infants [12, 13]. This risk is modified by maternal factors, elements of the labor and delivery process, and an infant’s NICU course [11, 15]. In the case presented, not only was this infant fed breast milk colonized with pathogenic bacteria, but he also had factors that put him at risk for infection via the GI tract, including prematurity, delivery via cesarean section, maternal chorioamnionitis, an anatomical abnormality of the upper GI tract, and a prolonged course of broad-spectrum antibiotic therapy prior to commencement of feeding. While innate immunity provides an early defense to gastrointestinal invasion with pathologic bacteria, colonization with bacteria commences the development of specific immunity [16, 17]. Occupation of the GI tract by commensal bacteria further strengthens intestinal health and creates competition with potential pathogens to discourage their prosperity [15, 19]. However, multiple bacteria employ mechanisms to overcome these defenses so they can translocate from the GI tract into the bloodstream [20–24], causing sepsis and its consequences. While the freezing/thawing and pasteurization processes may eliminate the bacterial load in breast milk provided by mothers or donors, these processes also adversely affect the immune benefits of breast milk as well as its nutritional content [25–32].

Clinicians should consider culturing breast milk in infants who present with late-onset sepsis secondary to enteric bacteria.

Disclosures

The authors have no conflicts of interest to disclose. The work was not supported by any grant funding.