Lactobacillus rhamnosus sepsis associated with probiotic therapy in an extremely preterm infant: Pathogenesis and a review for clinicians
Open accessAbstract
BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most serious complications in preterm infants. Probiotics have been used to prevent NEC. Safety is a major concern for this practice. METHODS: We reported a female preterm infant who received oral Lactobacillus rhamnosus GG but developed sepsis 12 days after the treatment. Cultures of blood and the catheter tip yielded L. rhamnosus. Next-generation sequencing was performed to analyze isolates from blood, stool, catheter, and product capsules. We also determined the capacities of these isolates to form biofilms. A literature review was performed. RESULTS: The patient was treated with ampicillin and piperacillin/tazobactam, and she subsequently recovered without complications. The analysis of genome sequences indicated that all the isolates belonged to the clone of L. rhamnosus GG (ATCC 53103), suggesting that sepsis was a catheter-related infection caused by the oral probiotic. L. rhamnosus GG (ATCC 53103) and the probiotic strain tested formed biofilms under all growth conditions. Isolates from the blood and catheter tip also formed biofilms, but the stool isolate did not. The capacity of intrinsic biofilm formation in L. rhamnosus GG depended on environmental factors and the type of culture medium. Literature review of L. rhamnosus GG sepsis in preterm and young infants found that nearly 60% of the patients had a suspected or confirmed infected catheter. CONCLUSION: The study showed that the capacity of L. rhamnosus GG to form biofilms, especially in the presence of glucose, is a critical factor leading to the probiotic-related sepsis in preterm infants.
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In the reported Chiang et al. case, the patient developed sepsis and necrotizing enterocolitis on day 28.
“On day 28, she developed sepsis and NEC and was treated with vancomycin, cefotaxime, and metronidazole.”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [62]
In the reported Chiang et al. case, Lcb. rhamnosus GG was begun on day 14 to prevent necrotizing enterocolitis.
“To prevent the development of NEC, Lcb. rhamnosus GG was begun on day 14.”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [62]
Chiang et al. reported one case of a preterm female who had low birthweight (749 g) and had respiratory distress syndrome.
“Chiang et al. reported one case of a preterm female who had low birthweight (749 g) and had respiratory distress syndrome [62].”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [62]
In the reported Chiang et al. case, the blood isolate and the PICC catheter tip isolate were confirmed by genomic sequencing to be identical to the probiotic Lcb. rhamnosus GG strain.
“The blood isolate and the isolate from the PICC catheter tip were confirmed by genomic sequencing assay to be to identical to the probiotic Lcb. rhamnosus GG strain.”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [62]
Cites
Lactobacillus species: Taxonomic complexity and controversial susceptibilities
Goldstein, E. J. C., Tyrrell, K. L., & Citron, D. M. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/civ072 · Cited by 392 · see citing works
Two cases of Lactobacillus bacteremia during probiotic treatment of short gut syndrome
Kunz, A. N., Noel, J. M., & Fairchok, M. P. (2004) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200404000-00017 · Cited by 319 · see citing works
Lactobacillus Sepsis and Probiotic Therapy in Newborns: Two New Cases and Literature Review
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Brecht, M., Garg, A., Longstaff, K., Cooper, C., & Andersen, C. (2016) · Neonatology · doi:10.1159/000441965 · Cited by 38 · see citing works
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Lactobacillus Bacteremia and Probiotics: A Review
Kullar, R., Goldstein, E. J. C., Johnson, S., & McFarland, L. V. (2023) · Microorganisms · doi:10.3390/microorganisms11040896 · Cited by 156 · see citing works
“reported one case of a preterm female who had low birthweight (749 g) and had respiratory distress syndrome [62].”
BackgroundProbiotic sepsis in preterm neonates-a systematic review
Kulkarni, T., Majarikar, S., Deshmukh, M., Ananthan, A., Balasubramanian, H., Keil, A., & Patole, S. (2022) · European Journal of Pediatrics · doi:10.1007/s00431-022-04452-5 · Cited by 71 · see citing works
Mikucka, A., Deptuła, A., Bogiel, T., Chmielarczyk, A., Nurczyńska, E., & Gospodarek-Komkowska, E. (2022) · Pathogens · doi:10.3390/pathogens11090977 · Cited by 38 · see citing works
Lactobacilli Infection Case Reports in the Last Three Years and Safety Implications
Rossi, F., Amadoro, C., & Colavita, G. (2022) · doi:10.20944/preprints202202.0248.v1 · Cited by 65 · see citing works
- Authors
- Chiang, M.-C., Chen, C.-L., Feng, Y., Chen, C.-C., Lien, R., & Chiu, C.-H.
- Affiliations
- Chang Gung University (TW)
- Sir Run Run Shaw Hospital (CN)
- Corresponding author
- Chiu, Cheng-Hsun
- Venue
- Journal of Microbiology, Immunology and Infection
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 54
- Issue
- 4
- Pages
- 575-580
- ISSN
- 1684-1182 (ISSN-L)
- OpenAlex
- W3014822828
- Cited by
- 79
- References
- 4
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 12 · 2023: 13 · 2022: 17 · 2021: 11 · 2020: 2
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Microbiology Immunology and Infection (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chang Gung Memorial Hospital
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Neonatal and Maternal Infections
- Keywords
- Lactobacillus rhamnosus GG, probiotic safety, preterm infants, catheter-related infection, biofilm formation, necrotizing enterocolitis prevention
- MeSH terms
- Administration, Oral, Anti-Bacterial Agents, Humans, Infant, Newborn, Biofilms, Sepsis, Probiotics, Enterocolitis, Necrotizing, Lacticaseibacillus rhamnosus, Infant, Extremely Premature
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