Abstract
BackgroundClostridium perfringens forms part of the human gut microbiota and has been associated with life-threatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains.MethodsC. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis.Results29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC.ConclusionsApproximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC.Trial registrationclinicaltrials.govNCT01102738, registered 13th April 2010.
Highlights
Clostridium perfringens forms part of the human gut microbiota and has been associated with lifethreatening necrotising enterocolitis (NEC) in premature infants
C. perfringens incidence and clinical factors associated with its colonisation Faecal samples and complete clinical notes were available for 333 infants
We have found that just under a third of infants (29.4%) in our premature neonatal cohort were colonised with C. perfringens in their gut at some time during their stay in the neonatal intensive care unit (NICU), with duration of maternal milk feeds, antibiotic therapy, and continuous positive airway pressure with supplemental oxygen (CPAP oxygen) treatment exerting the strongest influence over probability of carriage
Summary
Clostridium perfringens forms part of the human gut microbiota and has been associated with lifethreatening necrotising enterocolitis (NEC) in premature infants. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains. Clostridium perfringens is an archetypal pathosymbiont, forming part of the gut commensal microbiota in humans and animals, and capable of producing devastating disease by way of its toxin arsenal. This anaerobic, Gram-positive spore-former is the leading cause of traumatic gas gangrene in humans [1] and one of the. We have gone on to relate this to perinatal factors which we hypothesise will influence rates of carriage
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