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Probiotic sepsis in preterm neonates—a systematic review

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Abstract

Sepsis due to the administered probiotic strain/s is a barrier against adoption of prophylactic probiotic supplementation in preterm infants to reduce the risk of necrotising enterocolitis (NEC ≥ Stage II), all-cause mortality, late-onset sepsis, and feeding intolerance. We aimed to conduct a systematic review for reports of probiotic sepsis in preterm infants (gestation < 37 weeks). Databases including PubMed, Embase, Emcare, Cochrane Central library, and Google Scholar were searched in August 2021 and updated in Jan 2022. Probiotic sepsis was defined as positive blood/CSF culture isolating administered probiotic strain with symptoms suggestive of infection. Data collection included birth weight, gestation, comorbidities (e.g. gut surgery, NEC), presence of central venous catheters, treatment, and outcome. Literature search revealed 1569 studies. A total of 16 reports [randomised control trial (RCT): none; non-RCT: 1; case series: 8; case report: 7] involving 32 preterm infants with probiotic sepsis were included after exclusions for various reasons. Majority of the cases were born < 32 weeks’ gestation. Bifidobacterium (N = 19) was the most commonly isolated organism followed by Lactobacillus (N = 10), and Saccharomyces (N = 3). A total of 25/32 cases were confirmed to be due to the administered probiotic strain on full genomic analysis. Two studies reported one neonatal death each. Twelve neonates had comorbidities. Majority were treated with antibiotics (29/32) whereas others (3/32) required antifungal treatment.

Conclusion: Probiotics sepsis is relatively an uncommon event in preterm infants. Majority of the cases recovered after antibiotic or antifungal treatment. The importance of optimal surveillance and treatment of probiotic sepsis and research towards alternatives to probiotics (e.g. postbiotics) is emphasised.

What is Known:

• Probiotics have been shown to reduce necrotising enterocolitis, late-onset sepsis, all-cause mortality, and time to reach full enteral feeds in preterm infants.

• Despite the evidence, use of probiotics is not universal due to concerns regarding probiotic-associated sepsis in preterm infants.

What is New:

• This comprehensive systematic review showed that probiotic sepsis is a relatively rare phenomenon in preterm infants.

• All except one case where the diagnosis was uncertain recovered after antimicrobial therapy.

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Abbreviations

CSF:

Cerebrospinal fluid

LOS:

Late-onset sepsis

NEC:

Necrotising enterocolitis

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCT:

Randomised controlled trial

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Authors and Affiliations

  1. Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, WA, Australia

    Tithi Kulkarni & Sanjay Patole

  2. Department of Neonatology, Fiona Stanley Hospital, 11 Robin Warren Drive, Perth, WA, 6150, Australia

    Swati Majarikar & Mangesh Deshmukh

  3. Department of Neonatology, St. John of God Hospital Subiaco, Perth, WA, Australia

    Mangesh Deshmukh

  4. Department of Neonatology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India

    Anitha Ananthan

  5. Department of Neonatology, Surya Hospitals, Mumbai, Maharashtra, India

    Haribalakrishna Balasubramanian

  6. PathWest Laboratory Medicine Western Australia, Perth, WA, Australia

    Anthony Keil

  7. King Edward Memorial Hospital, Perth, WA, Australia

    Anthony Keil

  8. School of Medicine, University of Western Australia, Perth, WA, Australia

    Sanjay Patole

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  6. Anthony Keil
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Contributions

Tithi Kulkarni (TK): extraction of data, writing the first draft of the manuscript under supervision. Dr. Swati Majarikar (SM): independent literature search, extraction of data, addressed reviewer’s comments. Dr. Anita Ananthan (AA): independent literature search, interpretation of data, updating final draft of the manuscript. Dr. Haribalakrishna Balasubramanian (HB): independent literature search, interpretation of data, updating final draft of the manuscript. Associate Prof. Mangesh Deshmukh (MD): coordinated and supervised data extraction, and writing the first and final draft of the manuscript, addressed reviewer’s comments. Dr. Anthony Keil (AK): critically reviewed the manuscript for intellectual content as an expert microbiologist. Prof Sanjay Patole (SP): conceptualized and designed the study, interpretation of the data, critically reviewed the manuscript for intellectual content, addressed reviewer’s comments.

Corresponding author

Correspondence to Mangesh Deshmukh.

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Kulkarni, T., Majarikar, S., Deshmukh, M. et al. Probiotic sepsis in preterm neonates—a systematic review. Eur J Pediatr 181, 2249–2262 (2022). https://doi.org/10.1007/s00431-022-04452-5

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