Episodes Of Late-onset Sepsis Research Articles

Predictors of Mortality in Late-Onset Sepsis in Very Low Birth Weight Newborns

Abstract Objective Late-onset sepsis (LOS) is a major public health burden globally. Newborns with very low birth weight (VLBW) are at high risk of mortality related to LOS. The protective effect of breast milk feeding against many infections has been studied but data on the effect of breast milk feeding on LOS mortality are limited. In this study, we aimed to evaluate the risk factors for LOS-related mortality. Methods This single-center, case–control study was conducted retrospectively from August 2013 to July 2018. VLBW newborns with ≤32 weeks of gestational age who had culture-proven LOS were included in the study. Demographics, clinical and laboratory data, and parenteral and enteral feeding details within 72 hours before LOS episodes were extracted from electronic and paper medical records. Results A total of 190 LOS episodes were identified in 168 VLBW newborns with a median birth weight of 888 (695–1,143) g. Lower birth weight (adjusted odds ratio [aOR] 0.81, 95% confidence interval [CI] [0.69–0.96], p = 0.01), C-section delivery (aOR 0.38, 95% CI [0.17–0.84], p = 0.02), gram-negative (aOR 4.97, 95% CI [2.01–12.28], p = 0.001) and polymicrobial sepsis (aOR 6.29, 95% CI [1.34–29.47], p = 0.03), and lower breast milk feeding 72 hours before LOS episodes (aOR 0.89, 95% CI [0.80–0.99], p = 0.03) were independently associated with higher odds of LOS related death. Conclusion Gram-negative sepsis was associated with higher odds of LOS mortality and C-section delivery was associated with lower odds of LOS mortality. Additionally, every 10 mL/kg/day increase in breast milk feeding was associated with 11% lower odds of LOS mortality although this finding should be interpreted cautiously as there may be unadjusted confounders due to the study design.

Stop in Time: How to Reduce Unnecessary Antibiotics in Newborns with Late-Onset Sepsis in Neonatal Intensive Care.

The fear of missing sepsis episodes in neonates frequently leads to indiscriminate use of antibiotics, and prescription program optimization is suggested for reducing this inappropriate usage. While different authors have studied how to reduce antibiotic overprescription in the case of early onset sepsis episodes, with different approaches being available, less is known about late-onset sepsis episodes. Biomarkers (such as C-reactive protein, procalcitonin, interleukin-6 and 8, and presepsin) can play a crucial role in the prompt diagnosis of late-onset sepsis, but their role in antimicrobial stewardship should be further studied, given that different factors can influence their levels and newborns can be subjected to prolonged therapy if their levels are expected to return to zero. To date, procalcitonin has the best evidence of performance in this sense, as extrapolated from research on early onset cases, but more studies and protocols for biomarker-guided antibiotic stewardship are needed. Blood cultures (BCs) are considered the gold standard for the diagnosis of sepsis: positive BC rates in neonatal sepsis workups have been reported as low, implying that the majority of treated neonates may receive unneeded drugs. New identification methods can increase the accuracy of BCs and guide antibiotic de-escalation. To date, after 36-48 h, if BCs are negative and the baby is clinically stable, antibiotics should be stopped. In this narrative review, we provide a summary of current knowledge on the optimum approach to reduce antibiotic pressure in late-onset sepsis in neonates.

Evaluation of the "Neonatal Sequential Organ Failure Assessment" to Predict Mortality in Late-Onset Sepsis in Very Preterm Infants.

We aimed to evaluate the use of "Neonatal Sequential Organ Failure Assessment" (nSOFA) scoring in predicting mortality, to compare the accuracy of nSOFA scores at different time points in very preterm infants with late-onset sepsis (LOS), and to investigate other possible parameters that would improve the prediction. This single-center, retrospective study included preterm infants born atS<32 weeks' gestation with culture-proven LOS. The nSOFA scores of non-fatal and fatal episodes were compared at nine time points. Of 120 culture-proven LOS episodes in 106 infants, 90 (75%) episodes were non-fatal and 30 (25%) episodes were fatal. The mean birth weight (BW) of the infants who died was lower than that of survivors (p=0.038). In the fatal LOS episodes, median nSOFA scores were higher at all time points measured before sepsis evaluation, at the time of evaluation, and at all time points measured after the evaluation (p<0.001). nSOFA scores before death and at 48 hours were higher in the fatal episodes (p<0.001). At the time of sepsis assessment, nSOFA score>4 was associated with a 7- to 16-fold increased risk of mortality. Adjustment for BW, lymphocyte and monocyte counts increased the risk to 9- to 18-fold. This study demonstrated that the use of nSOFA to predict mortality and morbidity in extremely preterm infants seems feasible. The scoring system could be improved by evaluating the other parameters.

Zinc Supplementation in Very Low Birth Weight Infants: A Randomized Controlled Trial.

Preterm infants have high zinc (Zn) requirements and are generally believed to be in a negative Zn balance in the early period of life. In this study, we aimed to investigate the effect of high-dose Zn supplementation in very low birth weight (VLBW: infants with birth weight < 1.5 kg) infants on feeding intolerance and development of mortality and/or morbidities including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS). This is a prospective randomized trial. VLBW preterm infants with gestational age of <32 weeks were randomly allocated on the seventh day of life to receive extra amount of supplemental Zn along with the enteral feedings (9 + 3 mg), besides regular low-dose supplementation (3 mg), from enrollment until discharge. Outcome measures were feeding intolerance, NEC (stage ≥ 2), LOS, and mortality. A total of 195 infants (97 from study group and 98 from control group) were analyzed. A total of 46 (47.4%) infants in the study group and 64 (65.3%) infants in the control group ended up with feeding intolerance (p = 0.012). NEC was observed in 11 infants (11.2%) in the control group and only 1 infant (1%) in the study group (p = 0.003). There was a negative correlation between high-dose Zn supplementation and number of culture-proven LOS episodes (p = 0.041). This significance was also present for clinical sepsis, being higher in the control group (p = 0.029). No relationship between high-dose Zn supplementation and mortality and other morbidities (hemodynamically significant patent ductus arteriosus, bronchopulmonary dysplasia, retinopathy of prematurity, and severe intraventricular hemorrhage) was observed. Zn supplementation for VLBW infants is found to be effective to decrease feeding intolerance, NEC, and LOS episodes in this vulnerable population. Current data support the supplementation of VLBW infants with higher than regular dose of Zn. · Higher dose of Zn supplementation is shown to be a beneficial intervention in VLBW infants.. · Zn may decrease feeding intolerance, sepsis or NEC.. · Higher than regular dose of Zn seems to be safe..

Carboxyhemoglobin as biomarker of late-onset sepsis in preterm infants

Carboxyhemoglobin (COHb) is considered a biomarker of oxidative stress and previous studies reported an increase in COHb levels in preterm infants who develop late-onset sepsis (LOS). Our aim was to assess the correlation between COHb levels and the risk for LOS development. We retrospectively studied 100 preterm infants, 50 in the LOS and 50 in the no LOS group. COHb levels were measured on the day of diagnosis of the first episode of LOS, 3, 2, and 1 days before and 1 and 4 days after the onset of LOS. Logistic regression analysis showed that a higher level of COHb 2 days before the diagnosis of LOS increases the risk for LOS development (OR 12.150, 95% Cl 1.311–12.605; P = 0.028). A COHb level of 1.55% measured 2 days before the diagnosis of LOS is the best predictive threshold for LOS with a sensitivity of 70% and a specificity of 70%. Conclusion: Increased levels of COHb may predict the diagnosis of LOS in very preterm infants with a good accuracy. If further studies confirm our findings, this easy-to-measure biomarker could provide neonatologists with another tool for monitoring and early diagnosis of sepsis in high-risk patients.What is Known:• Carboxyhemoglobin (COHb) is a biomarker of oxidative stress.• Previous studies reported an increase in COHb levels in preterm infants who develop late-onset sepsis (LOS).What is New:• COHb levels increased two days before the diagnosis of LOS and this increase was associated with the risk for developing LOS.• ROC curve analysis for COHb measured two days before the diagnosis of LOS showed that 1.55% is the best predictive threshold for LOS with a sensitivity of 70% and a specificity of 70%.

Carboxyhemoglobin Levels in Preterm Neonatal Late-Onset Sepsis: to Predict or not to Predict.

In this study, we aimed to evaluate carboxyhemoglobin (COHb) levels in diagnosing late-onset sepsis (LOS) in preterm neonates. The records of culture-positive LOS in preterm neonates hospitalized in NICU from January 2017 to July 2022 were reviewed. COHb levels, C-reactive protein, procalcitonin, and neutrophil to lymphocyte ratio of septic preterm infants were compared to controls. In addition, serial COHb levels measured within six hours before or 24h after blood culture sampling, three to seven days prior, and three to five days after starting antimicrobial therapy were retrieved from patient records. The study included 77 blood-culture-positive preterm infants and 77 non-septic controls. During the LOS episode, the COHb values were found to be significantly increased (median: 1.8, IQR: 1.4-2.5) when compared to the control group (median: 1.2, IQR: 0.8-1.6) (p < 0.001). ROC analysis yielded an AUC of 0.714 for COHb (95% CI: 0.631-0.796, p<0.001). At an optimal cut-off of >1.5%, the test's sensitivity was 64.94%, the specificity was 72.73%, the positive predictive value was 70.42%, and the negative predictive value was 67.47%. LOS led to a dramatic rise followed by a decrease after the initiation of the antimicrobial therapy [1.8 (1.4-2.5)] vs. [1.45 (0.2-4)] p<0.001. COHb levels increased at the beginning of LOS, decreasing in response to antibiotics. When used in conjunction with other sepsis biomarkers, the variation of COHb can be important in evaluating late-onset sepsis episodes in preterm infants.

Late-Onset Sepsis Mortality among Preterm Infants: Beyond Time to First Antibiotics.

Objective: To investigate the impact of timing, in vitro activity and appropriateness of empirical antimicrobials on the outcome of late-onset sepsis among preterm very low birth weight infants that are at high risk of developing meningitis. Study design: This retrospective study included 83 LOS episodes in 73 very low birth weight infants born at ≤32 weeks' gestation with positive blood and/or cerebrospinal fluid culture or polymerase chain reaction at >72 h of age. To define the appropriateness of empirical antimicrobials we considered both their in vitro activity and their ideal delivery through the blood-brain barrier when meningitis was confirmed or not ruled out through a lumbar puncture. The primary outcome was sepsis-related mortality. The secondary outcome was the development of brain lesions. Timing, in vitro activity and appropriateness of empirical antimicrobials, were compared between fatal and non-fatal episodes. Uni- and multi-variable analyses were carried out for the primary outcome. Results: Time to antibiotics and in vitro activity of empirical antimicrobials were similar between fatal and non-fatal cases. By contrast, empirical antimicrobials were appropriate in a lower proportion of fatal episodes of late-onset sepsis (4/17, 24%) compared to non-fatal episodes (39/66, 59%). After adjusting for Gram-negative vs. Gram-positive pathogen and for other supportive measures (time to volume administration), inappropriate empirical antimicrobials remained associated with mortality (aOR, 10.3; 95% CI, 1.4-76.8, p = 0.023), while timing to first antibiotics was not (aOR 0.9; 95% CI, 0.7-1.2, p = 0.408; AUC = 0.88). The association between appropriate antimicrobials and brain sequelae was also significant (p = 0.024). Conclusions: The risk of sepsis-related mortality and brain sequelae in preterm very low birth weight infants is significantly associated with the appropriateness (rather than the timing and the in vitro activity) of empirical antimicrobials. Until meningitis is ruled out through lumbar puncture, septic very low birth weight infants at high risk of mortality should receive empiric antimicrobials with high delivery through the blood-brain barrier.

Late-onset sepsis in very preterm infants in Norway in 2009–2018: a population-based study

ObjectiveTo evaluate epidemiology and outcomes among very preterm infants (<32 weeks’ gestation) with culture-positive and culture-negative late-onset sepsis (LOS).DesignCohort study using a nationwide, population-based registry.Setting21 neonatal units in Norway.ParticipantsAll very...

Use of an electronic medical record to optimize a neonatal sepsis score for mortality prediction.

Late-onset sepsis (LOS) is a significant cause of mortality in preterm infants. The neonatal sequential organ failure assessment (nSOFA) provides an objective assessment of sepsis risk but requires manual calculation. We developed an EMR pipeline to automate nSOFA calculation for more granular analysis of score performance and to identify optimal alerting thresholds. Infants born <33 weeks of gestation with LOS were included. A SQL-based pipeline calculated hourly nSOFA scores 48 h before/after sepsis evaluation. Sensitivity analysis identified the optimal timing and threshold of nSOFA for LOS mortality. Eighty episodes of LOS were identified (67 survivors, 13 non-survivor). Non-survivors had persistently elevated nSOFA scores, markedly increasing 12 h prior to culture. At sepsis evaluation, the AUC for nSOFA >2 was 0.744 (p = 0.0047); thresholds of >3 and >4 produced lower AUCs. nSOFA is persistently elevated for infants with LOS mortality compared to survivors with an optimal alert threshold >2.

Neonatal sepsis in alloimmune hemolytic disease of the fetus and newborn: A retrospective cohort study of 260 neonates.

Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and suspected sepsis, including antibiotic treatment over a 10-year surveillance period. All neonates with HDFN admitted to our neonatal intensive care unit between January 2012 and December 2021 were included in this retrospective, cohort study. Annual proportions of infants with a central-line and central-line-associated bloodstream infection (CLABSI) rates (per 1000 central-line days and per 100 infants) were evaluated. Numbers of confirmed and suspected early- and late-onset sepsis episodes were assessed over the entire study period. Of the 260 included infants, 25 (9.6%) were evaluated for suspected sepsis, with 16 (6.2%) having ≥1 confirmed sepsis episode. A total of 123 central-lines were placed in 98 (37.7%) neonates, with impending exchange transfusion (ET) being the most frequent indication. Of the 34 (34.7%) neonates in whom a central-line was placed due to impending ET, 11 (32.4%) received no ET. Overall CLABSI incidence was 13.58 per 1000 central-line days. Neonates with a central-line had a higher risk for confirmed late-onset infection (RR 1.11, 95% CI: 1.04-1.20) and sepsis work-up (RR 1.10, 95% CI: 1.03-1.17) compared to infants without a central-line. Sepsis incidence among neonates with HDFN remains high, in particular in those with a central-line. Considering the substantial proportion of neonates with a central-line without eventual ET, central-line placement should be delayed until the likelihood of ET is high.

Recurrent Late-Onset Sepsis in Extremely Low Birth Weight Infants Is Associated with Motor Deficits in Early School Age

Introduction: Sepsis is regarded as a risk factor for brain injury in preterm infants. We herein hypothesize that extremely low birth weight infants (ELBWI, birth weight <1,000 g) having survived recurrent blood culture-proven late-onset sepsis (LOS) episodes are more likely to have an adverse long-term neurologic outcome. Methods: In a large multicenter observational study of ELBWI ≤28 6/7 weeks, we evaluated the impact of recurrent LOS (blood culture-proven, after day 7 of life) on development at 5–6 years. Neurodevelopment, behavior, and motor qualities were tested by blinded investigators. Univariate and logistic regression analyses were performed. Results: The cohort consisted of 1343 ELBWI including 1,080 infants without LOS, 186 infants with one LOS, and 77 with recurrent LOS, i.e., 55 infants with two and 22 infants with three LOS episodes. After Bonferroni-Holm correction, multiple logistic regression analysis revealed recurrent sepsis to be significantly associated with adverse motor development (critical MABC-2 testing: 3.3 [1.5–7.3], p = 0.003, p_B = 0.012), whereas no significant impact of recurrent LOS was found on intelligence quotient and behavioral difficulties. Odds of having critical motor testing results for infants with recurrent LOS were 1.7 times (95% confidence interval 1.4–2.3) that of infants with one LOS. Conclusion: Recurrent sepsis in preterm infants is associated with adverse long-term motor development. However, infants with recurrent infections are also more likely to have preterm-related complications, and reasons for a worse neurodevelopmental outcome remain to be elucidated.

The ecology and antimicrobial resistance of Staphylococci colonising neonates

Coagulase Negative Staphylococci (CoNS) are common commensals of human skin, account for nearly 20% of the microbiota in infants and are thought to promote early immune responses in healthy babies. However, CoNS are opportunistic pathogens and in the UK between 2005 and 2014 were responsible for 57% of episodes of Late Onset Sepsis (LOS). In neonatal intensive care units (NICUs) this is a major concern and antiseptics are used to prevent vascular catheter infections. Chlorhexidine (CHX) and Octenidine (OCT) are the most common agents used for skin antisepsis, but evidence is emerging of antiseptic tolerance amongst CoNS. We undertook a longitudinal survey of CoNS from skin and rectal swabs isolated from babies in two NICUs from countries with different antiseptic regimens (UK and Germany). Over 1000 isolates were characterised for antimicrobial susceptibility and sequenced. The most frequent species isolated were S. epidermidis and S. haemolyticus with similar strain types present in both units. Reduced susceptibility to CHX and OCT was observed in UK isolates (where CHX is used), compared to German isolates (where OCT is used). Analysis of genome data using GWAS and clustering techniques has identified loci associated with antimicrobial susceptibility. Comparison of isolates taken on admission and thereafter, demonstrated that babies acquired isolates with decreased antiseptic tolerance after admission. This data provides new information about the phylogeny of CoNS in NICUs and suggest different potentials for selection of resistance between antiseptics commonly used in neonatal care.

Sepsis treatment options identified by 10-year study of microbial isolates and antibiotic susceptibility in a level-four neonatal intensive care unit.

This observational study investigated the microbiology of blood culture-positive sepsis episodes and susceptibility to empiric antibiotics in early-onset sepsis (EOS) and late-onset sepsis (LOS) in a level-four neonatal intensive care unit (NICU) from 2010 to 2019. It was based on patient records and data that Oslo University Hospital, Norway, routinely submitted to the Norwegian Neonatal Network database. Clinical data were merged with blood culture results, including antibiotic susceptibility. We studied 5249 infants admitted to the NICU 6321 times and identified 324 positive blood cultures from 287 infants, with 30 EOS and 305 LOS episodes. Frequent causative agents for EOS were group B streptococci (33.3%), Escherichia coli (20.0%) and Staphylococcus aureus (16.7%). All were susceptible to empiric ampicillin and gentamicin. LOS was most frequently caused by coagulase-negative staphylococci (CONS) (73.8%), Staphylococcus aureus (15.7%) and Enterococci (6.9%). CONS, Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella and Enterobacter represented 91.9% of LOS episodes and were susceptible to vancomycin and cefotaxime (96.1%), vancomycin and gentamicin (97.0%) and cloxacillin and gentamicin (38.1%). Empiric treatment with ampicillin and gentamicin was adequate for EOS. Combining vancomycin and gentamicin may be a safer alternative to cefotaxime for LOS, as this reduces exposure to broad-spectrum antibiotics.

Incidence and microbiological characteristics of neonatal late onset sepsis in a neonatal intensive care unit in Peru

ObjectivesOur study aimed to determine the incidence of late onset sepsis and the most frequent microorganisms causing it in the neonatal unit at Hospital Cayetano Heredia in Lima, Peru. MethodsDescriptive and retrospective study. We reviewed all positive blood cultures and cultures of cerebrospinal fluid drawn from inborn patients beyond 72 h of life, admitted to the neonatal unit from January 2015 to December 2019. ResultsThe incidence of late onset sepsis was 7.4% of admitted patients and 10.04 per 1000 live births. During our study period, 234 episodes of late onset sepsis occurred in 204 patients. The incidence was higher in very low birth weight infants, reaching 36.2% and even higher in extremely low birth weight infants (40.7%). Coagulase-negative Staphylococcus and then Klebsiella spp. were the most frequent causative microorganisms. The most frequent cause of late onset sepsis in very low birth weight infants was gram-negative bacteria (Klebsiella spp., was the most frequent causative microorganism). ConclusionsLate onset neonatal sepsis is prevalent in our neonatal unit. It is important to know which are the most prevalent causative microorganisms to be able to choose adequate antibiotic coverage and to design strategies to prevent infection.

The association between clinical and biochemical characteristics of late-onset sepsis and bronchopulmonary dysplasia in preterm infants

Studies in preterm infants have shown an association between late-onset sepsis (LOS) and the development of bronchopulmonary dysplasia (BPD). It is unknown whether clinical or biochemical characteristics during sepsis modulate the risk for BPD. This single-center retrospective cohort study included all patients with a gestational age < 30 weeks, born between 2009 and 2015, in whom empiric antimicrobial treatment was initiated > 72 h after birth and continued for at least 5 days, independent on microbiological results. The association between clinical and biochemical characteristics of LOS and the development of BPD in survivors were assessed with multivariate logistic regression analysis adjusted for early-onset sepsis, small for gestational age, and gestational age. Of the 756 admitted infants, 256 infants (mean GA: 27.0 weeks; birthweight: 924 grams) had at least one LOS episode, of whom 79 (30.9%) developed BPD. Analyses showed that only the need for and duration of mechanical ventilation during LOS were independently associated with an increased risk for BPD (adjusted OR 2.62, 95% CI 1.38, 4.96, p value 0.003, and OR 1.004, 95% CI 1.00, 1.007, p value 0.045, respectively).Conclusion: During a LOS, the need for and duration of mechanical ventilation are independently associated with the risk of developing BPD in preterm infants.What is Known:• Premature infants diagnosed with a late-onset sepsis are at higher risk of developing bronchopulmonary dysplasia• This association is mainly shown in infants with a positive blood cultureWhat is New:• This study investigates the clinical and biochemical characteristics of late-onset sepsis and the development of bronchopulmonary dysplasia• The need for mechanical ventilation and duration of mechanical ventilation during late-onset sepsis are associated with an increased risk of developing bronchopulmonary dysplasia.

Cause of preterm birth and late-onset sepsis in very preterm infants: the EPIPAGE-2 cohort study.

BackgroundThe pathogenesis of late-onset sepsis (LOS) in preterm infants is poorly understood and knowledge about risk factors, especially prenatal risk factors, is limited. This study aimed to assess the association between the cause of preterm birth and LOS in very preterm infants.Methods2052 very preterm singletons from a national population-based cohort study alive at 72 h of life were included. Survival without LOS was compared by cause of preterm birth using survival analysis and Cox regression models.Results437 (20.1%) had at least one episode of LOS. The frequency of LOS varied by cause of preterm birth: 17.1% for infants born after preterm labor, 17.9% after preterm premature rupture of membranes, 20.3% after a placental abruption, 20.3% after isolated hypertensive disorders, 27.5% after hypertensive disorders with fetal growth restriction (FGR), and 29.4% after isolated FGR. In multivariate analysis, when compared to infants born after preterm labor, the risk remained higher for infants born after hypertensive disorders (hazard ratio HR = 1.7, 95% CI = 1.2–2.5), hypertensive disorders with FGR (HR = 2.6, 95% CI = 1.9–3.6) and isolated FGR (HR = 2.9, 95% CI = 1.9–4.4).ConclusionVery preterm infants born after hypertensive disorders or born after FGR had an increased risk of LOS compared to those born after preterm labor.Impact Late-onset sepsis risk differs according to the cause of preterm birth.Compared with those born after preterm labor, infants born very preterm because of hypertensive disorders of pregnancy and/or fetal growth restriction display an increased risk for late-onset sepsis.Antenatal factors, in particular the full spectrum of causes leading to preterm birth, should be taken into consideration to better prevent and manage neonatal infectious morbidity and inform the parents.

Acute Kidney Injury Associated with Late-Onset Neonatal Sepsis: A Matched Cohort Study

To determine incidence and severity of acute kidney injury (AKI) within 7days of sepsis evaluation and to assess AKI duration and the association between AKI and 30-day mortality. Retrospective, matched cohort study in a single-center level IV neonatal intensive care unit. Eligible infants underwent sepsis evaluations at ≥72hours of age during calendar years 2013-2018. Exposed infants (cases) were those with culture-proven sepsis and antimicrobial duration ≥5days. Nonexposed infants (controls) were matched 1:1 to exposed infants based on gestational and corrected gestational age, and had negative sepsis evaluations with antibiotic durations <48hours. AKI was defined by modified neonatal Kidney Disease Improving Global Outcomes criteria. Statistical analysis included Mann-Whitney and χ2 tests, multivariable logistic regression, and Kaplan-Meier time-to-event analysis. Among 203 episodes of late-onset sepsis, 40 (20%) developed AKI within 7days after evaluation, and among 193 episodes with negative cultures, 16 (8%) resulted in AKI (P=.001). Episodes of sepsis also led to greater AKI severity, compared with nonseptic episodes (P=.007). The timing of AKI onset and AKI duration did not differ between groups. Sepsis was associated with increased odds of developing AKI (aOR, 3.0; 95% CI, 1.5-6.2; P=.002). AKI was associated with increased 30-day mortality (aOR, 4.5; 95% CI, 1.3-15.6; P=.017). Infants with late-onset sepsis had increased odds of AKI and greater AKI severity within 7days of sepsis evaluation, compared with age-matched infants without sepsis. AKI was independently associated with increased 30-day mortality. Strategies to mitigate AKI in critically ill neonates with sepsis may improve outcomes.

Effect of bovine lactoferrin on prevention of late-onset sepsis in infants &lt;1500 g: a pooled analysis of individual patient data from two randomized controlled trials

We previously conducted two randomized controlled trials with bovine lactoferrin (bLF) for the prevention of late-onset sepsis (LOS) in infants with a birth weight <2500 g (Study 1) and <2000 g (Study 2). The aim of this study was to determine the preventative effects of bLF on culture-proven or probable LOS in infants with a birth weight <1500 g from both studies, and to determine the effect of bLF in relation to intake of human milk. Both trial designs had similar inclusion and exclusion criteria, the same dose of bLF [200 mg·(kg body mass)-1·day-1], and used the same control (maltodextrin). We fitted multivariate Cox regression models to estimate the effect of bLF on the risk of development of the composite outcome, adjusting for covariates. We included 335 neonates with a mean birth weight of 1162 ± 244 g; 27.5% were <1000 g. There were 33 first episodes of LOS in the bLF treatment group and 48 in the control group (19.5% vs. 28.9%). bLF had a protective effect on the risk of development of LOS [hazard ratio (HR) = 0.64; %95 CI = 0.41-0.99; p= 0.048]; particularly among infants weighing <1000 g [HR = 0.46; %95 CI = 0.22-0.96; p= 0.039] and infants with a low intake of human milk [HR = 0.40; %95 CI = 0.19-0.84; p= 0.015]. Therefore, bLF supplementation protects infants <1500 g from LOS, particularly those infants not receiving human milk.

Red cell distribution width as a predictor of late-onset Gram-negative sepsis.

Late-onset sepsis (LOS) remains an important cause of morbidity and mortality in preterm infants. In this study, our aim was to investigate the red-cell distribution width (RDW) levels during a LOS episode, and its association with the type of growing microorganism and mortality. Preterm infants with culture-proven sepsis during their neonatal intensive care unit stay were enrolled. Red-cell distribution width levels were obtained in the first 4h of postnatal life and at the onset of the LOS episode, and compared for these time frames. The study cohort was divided into two groups according to the type of the growing microorganism. The RDW levels were then assessed in intra- and inter-group analyses. Eighty-six infants were included in the final analysis. RDW levels were increased in the study cohort after a LOS attack (P < 0.001). Infants with Gram-negative sepsis showed a significant increase in their RDW levels, but they remained unchanged in infants with Gram-positive sepsis (P < 0.001 and P = 0.4, respectively). An RDW cut-off of >19.50% was related with a sensitivity of 87% and a specificity of 81% for predicting late-onset Gram-negative sepsis (P < 0.001). Logistic regression analysis showed a positive association of RDW with mortality when adjusted for covariants (adjusted odds ratio: 1.40; 95% confidence interval: 1.02-1.80; P = 0.03). Our findings show that RDW levels increased during a LOS episode in preterm infants, which was especially evident in Gram-negative infections. We believe that these findings may be of importance in the early diagnosis and prognosis of LOS in preterm infants.

Randomized Controlled Trial of Bovine Lactoferrin for Prevention of Sepsis and Neurodevelopment Impairment in Infants Weighing Less Than 2000 Grams

To determine the effect of bovine lactoferrin on prevention of late-onset sepsis (LOS) and neurodevelopment delay. Randomized, double-blind, controlled trial in neonates with a birth weight of 500-2000 g in 3 neonatal units in Lima, Peru, comparing bovine lactoferrin 200mg/kg/day with placebo administered for 8weeks. The primary outcome was the first episode of culture-proven LOS or sepsis-associated death. Neurodevelopment delay was assessed by the Mullen Scales at 24months corrected age. Of the 414 infants enrolled, 209 received bovine lactoferrin and 205 received placebo. LOS or sepsis-associated death occurred in 22 infants (10.5%) in the bovine lactoferrin group vs 30 (14.6%) in the placebo group; there was no difference after adjusting for hospital and birth weight; hazard ratio 0.73 (95% CI, 0.42-1.26). For infants with birth weights of <1500g the hazard ratio was 0.69 (95% CI, 0.39-1.25). The mean age-adjusted normalized Mullen composite score at 24months was 83.3±13.6 in the bovine lactoferrin group vs 82.6±13.1 in the placebo group. Growth outcomes and rehospitalization rates during the 2-year follow-up were similar in both groups, except for significantly less bronchiolitis in the bovine lactoferrin group (rate ratio, 0.34; 95% CI, 0.14-0.86). Supplementation with bovine lactoferrin did not decrease the incidence of sepsis in infants with birth weights of <2000 g. Growth and neurodevelopment outcomes at 24months of age were similar. Neonatal bovine lactoferrin supplementation had no adverse effects. ClinicalTrials.gov: NCT01525316.