Defining neonatal sepsis Wynn, James L
Current opinion in pediatrics,
04/2016, Volume:
28, Issue:
2
Journal Article
Peer reviewed
Open access
Although infection rates have modestly decreased in the neonatal intensive care unit (NICU) as a result of ongoing quality improvement measures, neonatal sepsis remains a frequent and devastating ...problem among hospitalized preterm neonates. Despite multiple attempts to address this unmet need, there have been minimal advances in clinical management, outcomes, and accuracy of diagnostic testing options over the last 3 decades. One strong contributor to a lack of medical progress is a variable case definition of disease. The inability to agree on a precise definition greatly reduces the likelihood of aligning findings from epidemiologists, clinicians, and researchers, which, in turn, severely hinders progress toward improving outcomes.
Pediatric consensus definitions for sepsis are not accurate in term infants and are not appropriate for preterm infants. In contrast to the defined multistage criteria for other devastating diseases encountered in the NICU (e.g., bronchopulmonary dysplasia), there is significant variability in the criteria used by investigators to substantiate the diagnosis of neonatal sepsis.
The lack of an accepted consensus definition for neonatal sepsis impedes our efforts toward improved diagnostic and prognostic options, and accurate outcomes information for this vulnerable population.
One in 10 newborns will be born before completion of 36 weeks' gestation (premature birth). Infection and sepsis in preterm infants remain a significant clinical problem that represents a substantial ...financial burden on the healthcare system. Many factors predispose premature infants for having the greatest risk of developing and succumbing to infection as compared with all other age groups across the age spectrum. It is clear that the immune system of preterm infants exhibits distinct, rather than simply deficient, function as compared with more mature and older humans and that the immune function in preterm infants contributes to infection risk. While no single review can cover all aspects of immune function in this population, we will discuss key aspects of preterm neonatal innate and adaptive immune function that place them at high risk for developing infections and sepsis, as well as sepsis-associated morbidity and mortality.
An operational definition of organ dysfunction applicable to neonates that predicts mortality in the setting of infection is lacking. We determined the utility of an objective, electronic health ...record (EHR)-automated, neonatal sequential organ failure assessment (nSOFA) score to predict mortality from late-onset sepsis (LOS) in premature, very low birth weight (VLBW) infants.
Retrospective, single-center study of bacteremic preterm VLBW newborns admitted between 2012 and 2016. nSOFA scores were derived for patients with LOS at multiple time points surrounding the sepsis evaluation.
nSOFA scores at evaluation and at all points measured after evaluation were different between survivors and non-survivors. Among patients with an nSOFA score of >4, mortality was higher at evaluation (13% vs 67%, p < 0.001), +6 h (15% vs 64%, p = 0.002), and +12 h (7% vs 71%, p < 0.001) as compared to patients with a score of ≤4. Receiver operating characteristics area under the curve was 0.77 at evaluation (95% CI 0.62-0.92; p = 0.001), 0.78 at +6 h (0.66-0.92; p < 0.001), and 0.93 at +12 h (0.86-0.997; p < 0.001).
The nSOFA scoring system predicted mortality in VLBW infants with LOS and this automated system was integrated into our EHR. Prediction of LOS mortality is a critical step toward improvements in neonatal sepsis outcomes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The risk of infant meningitis has been dramatically reduced by successful vaccination programs over the past several decades.1 A study of 931 infants ≤28 days old (nearly all ≥36 weeks at birth) with ...a history of fever presenting for evaluation to the emergency room between 2006 and 2017 found just 5 cases (0.54% of febrile infants) of bacterial meningitis (BM).2 Compared to the risk in term infants, BM is only slightly more common among preterm infants cared for in the Neonatal Intensive Care Unit (NICU).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Since 1992, professional societies or public health agencies in the United States
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–
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and elsewhere
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–
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have issued several generations of recommendations for prevention or management of ...early-onset neonatal sepsis (EOS). Despite those efforts, recommendations remain inconsistent, clarifications are necessary
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, local adaptations are common
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, and compliance rates are low
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. We postulate that lack of consensus, especially regarding postnatal management of the neonate, is largely a result of two sets of factors. First, obstetrical prevention strategies have substantially reduced incidence of EOS, potentially changing the utility of predictive strategies based on risk factors. Second, recent data better delineate relationships among risk factors, clinical signs, and EOS, suggesting that risk predictors may have different utilities in different groups. The purpose of this commentary is to explore these questions and to suggest new approaches to management of newborns who may be at risk for EOS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Increased endothelial permeability is central to the pathogenesis of sepsis and leads to organ dysfunction and death but the endogenous mechanisms that drive increased endothelial permeability are ...not completely understood. We previously reported that cell-free hemoglobin (CFH), elevated in 80% of patients with sepsis, increases lung microvascular permeability in an ex vivo human lung model and cultured endothelial cells. In this study, we augmented a murine model of polymicrobial sepsis with elevated circulating CFH to test the hypothesis that CFH increases microvascular endothelial permeability by inducing endothelial apoptosis. Mice were treated with an intraperitoneal injection of cecal slurry with or without a single intravenous injection of CFH. Severity of illness, mortality, systemic and lung inflammation, endothelial injury and dysfunction and lung apoptosis were measured at selected time points. We found that CFH added to CS increased sepsis mortality, plasma inflammatory cytokines as well as lung apoptosis, edema and inflammation without affecting large vessel reactivity or vascular injury marker concentrations. These results suggest that CFH is an endogenous mediator of increased endothelial permeability and apoptosis in sepsis and may be a promising therapeutic target.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this issue of Pediatric Research, Greenberg and colleagues3 examined a cohort of 5730 ELBW, 22–28-week gestation infants cared for in the Eunice Kennedy Shriver NICHD NRN from 2008 to 2014 with ...the intent to: (1) describe changes over time in prolonged early antibiotic therapy among infants without culture-confirmed (blood or CSF) infection or an intra-abdominal inflammatory process spontaneous intestinal perforation (SIP)/ NEC, and (2) describe associations of prolonged early antibiotic therapy with adverse outcomes on a more contemporary cohort.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Extremely low birth weight (ELBW) infants have high morbidity and mortality, frequently due to invasive infections from bacteria, fungi, and viruses. The microbial communities present in the ...gastrointestinal tracts of preterm infants may serve as a reservoir for invasive organisms and remain poorly characterized. We used deep pyrosequencing to examine the gut-associated microbiome of 11 ELBW infants in the first postnatal month, with a first time determination of the eukaryote microbiota such as fungi and nematodes, including bacteria and viruses that have not been previously described. Among the fungi observed, Candida sp. and Clavispora sp. dominated the sequences, but a range of environmental molds were also observed. Surprisingly, seventy-one percent of the infant fecal samples tested contained ribosomal sequences corresponding to the parasitic organism Trichinella. Ribosomal DNA sequences for the roundworm symbiont Xenorhabdus accompanied these sequences in the infant with the greatest proportion of Trichinella sequences. When examining ribosomal DNA sequences in aggregate, Enterobacteriales, Pseudomonas, Staphylococcus, and Enterococcus were the most abundant bacterial taxa in a low diversity bacterial community (mean Shannon-Weaver Index of 1.02 ± 0.69), with relatively little change within individual infants through time. To supplement the ribosomal sequence data, shotgun sequencing was performed on DNA from multiple displacement amplification (MDA) of total fecal genomic DNA from two infants. In addition to the organisms mentioned previously, the metagenome also revealed sequences for gram positive and gram negative bacteriophages, as well as human adenovirus C. Together, these data reveal surprising eukaryotic and viral microbial diversity in ELBW enteric microbiota dominated bytypes of bacteria known to cause invasive disease in these infants.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK