ReviewGut bacteria and late-onset neonatal bloodstream infections in preterm infants
Introduction
Late-onset neonatal bloodstream infections in preterm infants are illnesses (i) in which a credible pathogen is recovered from the blood, and (ii) that occur after the first 72 h of age [1], [2], [3], [4], [5]. The Gram-negative bacilli, Gram-positive cocci, and fungi that represent the majority of infections have differing pre-invasion habitats in the body, control strategies, treatments, and prognoses when they cause extraintestinal infections.
Infants who have had culture-proven late-onset neonatal bloodstream infections have higher mortality than those who have not had these infections [1], [6]. Late-onset neonatal bloodstream infections in very low birth weight infants bestow independent risks to long-term child development, in addition to the well-recognized risks bestowed by brain injury, bronchopulmonary dysplasia, and retinopathy of prematurity [2]. Indeed, it has been calculated that a single late-onset neonatal bloodstream infection in a preterm infant approximately quadruples the likelihood of cerebral palsy, independent of intracranial structural abnormalities [7]. Neonatal infections are also associated with lower Bayley Scale of Infant Development II scores, worse psychomotor development, abnormal vision, and lesser occipital frontal circumferences, among those infants who survive their episode of late-onset neonatal bloodstream infections and who are discharged to home [3].
Our understanding of late-onset neonatal bloodstream infections is severely limited by their unpredictable onset in infants at risk. In this review, we emphasize data from human cohorts, and cite animal data only if they might illuminate human biology relevant to late-onset neonatal bloodstream infections.
Section snippets
Prospects for preventing late-onset neonatal bloodstream infections beyond line care and hand hygiene
Lessons can be learned from attempts to control early-onset (occurring <72 h after birth) infection with Streptococcus agalactiae (Group B streptococcus (GBS)). Screening for maternal colonization with GBS, and the treatment of mothers and their newborns with parenteral antibiotics (usually β-lactam agents), have reduced the incidence of early-onset bloodstream infections with GBS [8], [9]. In contrast, the incidence of late-onset neonatal bloodstream infections caused by GBS is increasing [10]
The gut as the pre-invasion habitat/reservoir of bacterial bloodstream invaders
Several observations support the concept that the gut is the reservoir of Gram-negative pathogens before late-onset neonatal bloodstream infections are clinically apparent. Though it is intuitive that increased gut permeability would permit the extra-intestinal dissemination (translocation) of bacteria harbored by this organ, it was not until Graham et al. demonstrated that, among 20 episodes of bloodstream infections in 15 infants caused by Gram-negative bacilli, 19 of the bloodstream isolates
Probiotics to prevent late-onset neonatal bloodstream infections
Probiotics offer a possible intervention to prevent late-onset neonatal bloodstream infections, especially those of gut origin. Two recent meta-analyses have addressed the efficacy of probiotics in preventing late-onset neonatal bloodstream infections. Zhang et al. [46] proposed that probiotics might prevent bloodstream infections in low birthweight infants, but no effect was seen in children weighing <1000 g at birth. Rao et al. also concluded that probiotics had a preventive effect [47] and
The future
Worldwide, neonatologists approach late-onset neonatal bloodstream infections in a reactive “rule out sepsis” mode. It is critical that neonatologists remain vigilant and respond to the earliest signs of bloodstream infections in all preterm infants, as these are not normal hosts. However, in many cases, the specific pathogens that subsequently invade the bloodstream may be found in the stool prior to clinical signs of systemic infection. Moreover, accumulating data suggest that colonization
Acknowledgements
We are grateful to Ms Maida Redzic for assistance with manuscript preparation, Drs Michael Carl and Carey-Ann Burnham for helpful conversations, and to Dr Chrisoph Haertel for critical reading of the manuscript.
References (50)
- et al.
Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis
J Pediatr
(2011) - et al.
Enteric gram-negative bacilli bloodstream infections: 17 years' experience in a neonatal intensive care unit
Am J Infect Control
(2004) - et al.
Compliance with prevention practices and their association with central line-associated bloodstream infections in neonatal intensive care units
Am J Infect Control
(2014) - et al.
Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis
Lancet Infect Dis
(2013) - et al.
Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network
J Pediatr
(1996) - et al.
Outbreak of late-onset group B Streptococcus in a neonatal intensive care unit
Am J Infect Control
(2010) - et al.
Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial
Lancet
(2016) - et al.
Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications
Acta Paediatr
(2014) - et al.
Using a count of neonatal morbidities to predict poor outcome in extremely low birth weight infants: added role of neonatal infection
Pediatrics
(2009) - et al.
Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months
Pediatrics
(2006)
Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants
Pediatrics
Outcome of early-onset sepsis in a national cohort of very low birth weight infants
Pediatrics
Sepsis as a risk factor for neonatal morbidity in extremely preterm infants
Acta Paediatr
Perinatal infection is an important risk factor for cerebral palsy in very-low-birthweight infants
Dev Med Child Neurol
Epidemiology of invasive group B streptococcal disease in the United States, 1999–2005
JAMA
Group B Streptococcus and Escherichia coli infections in the intensive care nursery in the era of intrapartum antibiotic prophylaxis
Pediatr Infect Dis J
Stable rates of neonatal sepsis in a tertiary neonatal unit
J Paediatr Child Health
Sepsis from the gut: the enteric habitat of bacteria that cause late-onset neonatal bloodstream infections
Clin Infect Dis
Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births
J Pediatr
Risk factors associated with laboratory-confirmed bloodstream infections in a tertiary neonatal intensive care unit
Pediatr Infect Dis J
Ohio statewide quality-improvement collaborative to reduce late-onset sepsis in preterm infants
Pediatrics
Statewide NICU central-line-associated bloodstream infection rates decline after bundles and checklists
Pediatrics
Risk factors for colonization with extended-spectrum beta-lactamase-producing bacteria and intensive care unit admission
Emerg Infect Dis
Colonization status and appropriate antibiotic therapy for nosocomial bacteremia caused by antibiotic-resistant gram-negative bacteria in an intensive care unit
Infect Control Hosp Epidemiol
Screening for extended-spectrum beta-lactamase-producing Enterobacteriaceae among high-risk patients and rates of subsequent bacteremia
Clin Infect Dis
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