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Volume 22, Number 9—September 2016
Letter

Bifidobacterium longum Subspecies infantis Bacteremia in 3 Extremely Preterm Infants Receiving Probiotics

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To the Editor: Metaanalysis of randomized trials that tested different probiotics showed a reduction of ≈50% in necrotizing enterocolitis and all-cause deaths in preterm infants (1). Use of probiotics is increasing worldwide (2,3), and cases of probiotic sepsis were not reported among >5,000 infants in an updated review (1).

In Norway, a consensus-based protocol recommending prophylactic probiotic supplementation for preterm infants at highest risk for necrotizing enterocolitis (gestational age <28 weeks, birthweight <1,000 g) was introduced in 2014. After considering the safety profile, we investigated use in preterm infants of a widely used combination of oral probiotics (Infloran; Laboratorio Farmacéutico Specialità Igienico Terapeutiche, Mede, Italy) that contained 109 Lactobacillus acidophilus (ATCC 4356) and 109 Bifidobacterium longum subspecies infantis (ATCC 15697).

B. longum is a microaerotolerant, anaerobic bacterium susceptible to many antimicrobial drugs (Table). This bacterium is a rare cause of neonatal infections; until 2015, only 2 Bifidobacterium bacteremia cases in premature newborns had been reported (4,5).

A total of 290 extremely preterm infants received oral probiotics during April 2014–August 2015 in Norway. Three patients were given a diagnosis of B. longum bacteremia: 2 patients in a neonatal unit in which 17 patients were given oral probiotics and 1 patient in a neonatal unit in which 31 patients were given oral probiotics (Table).

All 3 infants had respiratory distress syndrome and received mechanical ventilation after birth. Enteral feeding with human milk was begun on day 1. Oral probiotics (½ capsule, 1×/d) were given during the first week of life and increased to 1 capsule/day after 4–7 days.

We identified B. longum in blood cultures by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (Bruker Daltonics, Billerica, MA, USA). Whole-genome sequencing (MiSeq, Illumina, San Diego, CA, USA) and comparative analysis of nucleotide-level variation by using variant cell format in SAMtools (http://samtools.sourceforge.net) showed that all 3 blood culture isolates and a B. longum strain cultured from an oral probiotic capsule were identical.

Patient 1 had sepsis and severe hypotension 8 days after birth. A blood culture was prepared, and the patient was given antimicrobial drugs and vasoactive support. Abdominal distention, gastric residuals, and feed intolerance developed the next day, but the patient was cardiorespiratory stable. On day 12, abdominal radiographs showed pneumoperitoneum. Surgery showed multiple ileal perforations and bowel necrosis. Histologic analysis showed classical features of necrotizing enterocolitis. The patient received an ileostoma and improved after treatment with antimicrobial drugs. Blood culture was positive for gram-positive rods, which were identified as B. longum. Subsequent clinical course was uneventful.

Patient 2 had apnea, bradycardia, and temperature instability 12 days after birth. A blood culture was prepared, and the patient was given antimicrobial drugs. Blood culture was positive for gram-positive rods, which were identified as B. longum. Use of oral probiotics was discontinued. The patient recovered rapidly, and subsequent clinical course was uneventful.

Patient 3 had sepsis and necrotizing enterocolitis 9 days after birth. Ultrasound showed free abdominal fluid. A blood culture was prepared, and the patient was given antimicrobial drugs. Surgery showed 2 separate bowel perforations, and the patient received an ileostoma and colostoma. Histologic analysis did not show necrosis or inflammation. Enterococcus faecalis grew in the blood culture obtained on day 9. The patient had a complicated clinical course and received prolonged mechanical ventilation. However, the patient gradually tolerated full feeds. Use of oral probiotics was continued.

On day 46, the condition of patient 3 suddenly deteriorated; hypotension and metabolic acidosis developed, and the patient was again given antimicrobial drugs. A blood culture was positive for B. longum. Supplementation with oral probiotics was discontinued. The patient recovered from the infection, but secondary ileus developed. The patient had a complicated clinical course until discharge.

Recently, 5 other B. longum bacteremia cases among 5 preterm infants at 26–31 weeks gestation were reported (6,7). All 5 infants had received oral probiotics; 3 had severe gastrointestinal complications, similar to patient 1 in our report, and 2 patients were moderately compromised, similar to patient 2 (6,7).

We do not know whether Bifidobacterium organisms in blood culture for patient 1 were a consequence of intestinal necrosis and bacterial translocation or the cause of necrotizing enterocolitis. Patient 3 probably had a leaky gut that predisposed this patient to bacterial translocation. All 3 patients were extremely premature (23–24 weeks gestation) and had impaired immune systems, which predisposed them to infections with bacteria with low virulence. A recently published case of Bifidobacterium bacteremia in a 2-year old boy with leukemia highlights impaired immunity as a risk factor (8).

Only aerobic blood cultures are prepared for neonates. We detected Bifidobacterium bacteremia by using 2 automated blood culture systems and aerobic bottles. However, the sensitivity of these systems for detecting Bifidobacterium bacteremia is unknown. Thus, the incidence of Bifidobacterium bacteremia is theoretically underestimated. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry improves species detection and its use might be 1 reason for the apparently recent increase in probiotic-associated bacteremia.

We report that systemic infection with probiotic bacteremia might have a severe clinical course in extremely preterm infants. Clinical suspicion and appropriate blood culture conditions are essential for proper diagnosis and management.

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Eirin EsaiassenComments to Author , Pauline Cavanagh, Erik Hjerde, Gunnar S. Simonsen, Ragnhild Støen, and Claus Klingenberg
Author affiliations: University Hospital of North Norway, Tromsø, Norway (E. Esaiassen, P. Cavanagh, G.S. Simonsen, C. Klingenberg); Arctic University of Norway, Tromsø (E. Esaiassen, E. Hjerde, G.S. Simonsen, C. Klingenberg); St. Olavs Hospital, Trondheim, Norway (R. Støen); Norwegian University of Science and Technology, Trondheim (R. Støen)

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References

  1. AlFaleh  K, Anabrees  J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2014;4:CD005496.PubMed
  2. Janvier  A, Malo  J, Barrington  KJ. Cohort study of probiotics in a North American neonatal intensive care unit. J Pediatr. 2014;164:9805. DOIPubMed
  3. Härtel  C, Pagel  J, Rupp  J, Bendiks  M, Guthmann  F, Rieger-Fackeldey  E, Prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics and outcome in very low birth weight infants. J Pediatr. 2014;165:2859. DOIPubMed
  4. Jenke  A, Ruf  EM, Hoppe  T, Heldmann  M, Wirth  S. Bifidobacterium septicaemia in an extremely low-birthweight infant under probiotic therapy. Arch Dis Child Fetal Neonatal Ed. 2012;97:F2178. DOIPubMed
  5. Ohishi  A, Takahashi  S, Ito  Y, Ohishi  Y, Tsukamoto  K, Nanba  Y, Bifidobacterium septicemia associated with postoperative probiotic therapy in a neonate with omphalocele. J Pediatr. 2010;156:67981. DOIPubMed
  6. Zbinden  A, Zbinden  R, Berger  C, Arlettaz  R. Case series of Bifidobacterium longum bacteremia in three preterm infants on probiotic therapy. Neonatology. 2015;107:569. DOIPubMed
  7. Bertelli  C, Pillonel  T, Torregrossa  A, Prod’hom  G, Fischer  CJ, Greub  G, Bifidobacterium longum bacteremia in preterm infants receiving probiotics. Clin Infect Dis. 2015;60:9247. DOIPubMed
  8. Avcin  SL, Pokorn  M, Kitanovski  L, Premru  MM, Jazbec  J. Bifidobacterium breve sepsis in child with high-risk acute lymphoblastic leukemia. Emerg Infect Dis. 2015;21:16745. DOIPubMed

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DOI: 10.3201/eid2209.160033

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Table of Contents – Volume 22, Number 9—September 2016

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Erin Esaiassen, University Hospital of North Norway, Box 53, N-9038, Tromsø, Norway

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Page created: August 16, 2016
Page updated: August 16, 2016
Page reviewed: August 16, 2016
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