Sever Sepsis After Probiotic Treatment With Escherichia coli NISSLE 1917

To the Editors: We report a case of an eutrophic preterm infant with a gestational age of 28 weeks and a birth weight of 935 g. The early postnatal phase was uncomplicated. On postnatal day 13, the infant developed gastroenteritis due to a rotavirus and adenovirus coinfection. A blood culture had no growth. To facilitate the physiologic intestinal bacterial flora on day 15 of life, we initiated a probiotic treatment with Escherichia coli NISSLE 1917 in the recommended dosage for this age group (1 mL once a day), with an immediate positive effect on the oral feeding. On postnatal day 25, a dramatic deterioration occurred with the infant showing a sepsis syndrome with fever, apnea attacks and hypotension. Blood cultures yielded E. coli, which was showing pulsed field gelelectrophoresis to be E. coli Nissle 1917 with clonal identity to the strain used therapeutically (Fig. 1). After intensified therapy with vasopressors, antibiotic treatment active against the isolated strain (meropenem in combination with vancomycine because of the central venous catheter), and intravenous immunoglobulins the patient stabilized and at 10 weeks of age was discharged in good clinical condition.FIGURE 1.: Result of the pulsed field gel electrophoresis. Lane 1: E. coli strain NISSLE 1917. Lane 2: E. coli strain isolated of the blood culture.Colonization with potentially pathogenic Gram negative bacteria is a risk factor for the development of necrotizing enterocolitis. Therefore, probiotics as live microbial supplements in preterms are used with the objective to support the intestinal colonization as well as to prevent infections or side effects of antibiotic drugs.1 It is unknown whether probiotic treatment increases or decreases the risk of invasive infection in preterm infants weighing less than 1500 g. The safety of this therapy is uncertain. Because of the immaturity of the gastrointestinal tract and of the local and systemic immune system in preterm infants the risk of systemic infections is increased. In a small study with 27 healthy newborns, E. coli strain NISSLE 1917 colonized the intestines within a few days and was well tolerated.2 Despite the fact that many studies have shown that E. coli NISSLE can replace pathogenic bacteria in the intestinal flora by means of intensive adherence to epithelial cells, analysis of the genomic structure has revealed a potential pathogenicity.3 Sepsis associated with probiotic supplementation in preterm infants with a very low birth weight (<1500 g) has not been previously reported. The immaturity of the immune system as well as the gastrointestinal tract combined with an increased permeability of the intestinal wall related to infection with rotavirus and adenovirus resulting in translocation of bacteria from the mucous membranes to the blood stream. After the neonatal period the probiotic prophylaxis is associated with an increased risk of sepsis in patients with severe acute pancreatitis and AIDS.4,5 In infancy, only a few case reports exist describing sepsis or meningitis complicated by Lactobacillus GG and Saccharomyces cerevisiae independent of probiotic supplementation.6,7 All cases of sepsis related to probiotics have occurred in patients with underlying immune compromise or chronic disease. Many case reports of probiotic sepsis describe patients with preexisting intestinal pathology, a common indication for probiotic use, but also associated with an increased risk of probiotic translocation from the intestinal mucosa. The presence of a central venous catheter is also a frequent finding and is considered as a possible source of sepsis. Studies with athymic neonatal mice have shown that the colonization with probiotics can lead to increased mortality.8 This finding suggests that the immaturity of the immune system in preterm infants put them at particularly high risk for probiotic-associated sepsis. The present case report should prompt a discussion of pros and cons of probiotic use. Additional systematical investigations and well organized clinical studies are needed to clarify risk factors for the development of septic complications after a treatment with probiotics. Katrin Guenther, MD Eberhardt Straube, MD Wolfgang Pfister, MD Albrecht Guenther, MD Axel Huebler, MD Department of Pediatrics Friedrich-Schiller University Jena, Germany