Antibiotic use in infants at risk of early-onset sepsis: results from a unicentric retrospective cohort study.

BACKGROUND: Antibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit. METHODS: Retrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy. RESULTS: We included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P < 0.001). The total days of therapy/1000 patient-days decreased from 63/1000 patient-days during the baseline period to 25.8/1000 patient-days in the postintervention period, representing a relative reduction of 59%. The antibiotic use rate decreased by more than half of the infants, from 3.2% during the baseline period to 1.3% in the postintervention period. CONCLUSIONS: The use of a departmental guideline to assess infants at risk of early-onset sepsis based on their clinical condition and prompt discontinuation of antibiotics, is a simple and low-cost measure that contributed to an important decrease in antibiotic use.

Exploring factors influencing delayed first antibiotic treatment for suspected early-onset sepsis in preterm newborns: a study before quality improvement initiative.

BACKGROUND: Early-onset sepsis (EOS) is a serious illness that affects preterm newborns, and delayed antibiotic initiation may increase the risk of adverse outcomes. PURPOSE: The objective of this study was to examine the present time of antibiotic administration in preterm infants with suspected EOS and the factors that contribute to delayed antibiotic initiation. METHODS: In this retrospective study in China, a total of 82 early preterm infants with suspected EOS between December 2021 and March 2023 were included. The study utilized a linear regression analytical approach to identify independent factors that contribute to delayed antibiotic administration. RESULTS: The mean gestational age and birth weight of the study population were 29.1 ± 1.4 weeks and 1265.7 ± 176.8 g, respectively. The median time of initial antibiotic administration was 3.8 (3.1-5.0) hours. Linear regression revealed that severe respiratory distress syndrome (RDS) (ß = 0.07, P = 0.013), penicillin skin test (PST) timing (ß = 0.06, P < 0.001) and medical order timing (ß = 0.04, P = 0.017) were significantly associated with the initial timing of antibiotic administration. CONCLUSIONS: There is an evident delay in antibiotic administration in preterm infants with suspected EOS in our unit. Severe RDS, PST postponement and delayed medical orders were found to be associated with the delayed use of antibiotics, which will be helpful for quality improvement efforts in the neonatal intensive care unit (NICU).

Early procalcitonin assays may reduce antibiotic exposure in premature newborn infants.

AIM: The diagnosis of early-onset neonatal sepsis (EOS) remains difficult. The main aim was to study the effect of a new algorithm for EOS, which includes the level of procalcitonin in umbilical cord blood, on the exposure to antibiotic therapy of premature newborn infants. METHODS: This was a monocentric, observational and retrospective study with before-and-after design. The duration and dose of antibiotic therapy provided as well as the morbidity and mortality were compared in two groups, one included 01 May 2015-30 November 2015 when procalcitonin was not used, and one after the change 01 November 2016-30 May 2017 when procalcitonin was used in a hospital setting in Nice, France. RESULTS: Sixty newborn infants were included in the before group and 54 in the after group. Antibiotic therapy was stopped after 24 h for 18 newborn infants in the after group and four in the before group, and after 48 h for 26 newborn infants in the after group and 10 in the before group. CONCLUSION: The implementation of a new decision-making algorithm including early procalcitonin assay of premature newborn infants significantly reduced exposure to antibiotics without modifying mortality or morbidity.

Umbilical cord blood hematological parameters in predicting early onset neonatal sepsis (EOS) - a prospective cohort study.

OBJECTIVES: In low and middle income countries, there is a need for affordable and accurate biomarkers to identify neonates at risk of early onset neonatal sepsis (EOS). Cord blood hematological parameters if reliable and accurate for the detection of EOS are cost effective and can reduce the need for repeated venipuncture in the neonate. METHODS: In this prospective cohort study, the umbilical cord parameters of newborns with gestational age >34 weeks were collected. These neonates were followed up for 72 h and septic screen was employed in those babies who had risk factors or developed clinical features of sepsis. The cord blood parameters of the normal newborn and those who had sepsis were analyzed. RESULTS: A total of 513 neonates were enrolled for the study, 32 required septic screening of whom 13 neonates were found to meet the criteria for sepsis: either blood culture positive or sepsis screen positive with clinical features. Cord blood parameters were analyzed using independent t test. Red cell distribution width (RDW) and band cells were statistically significant (p 0.007 and 0.009 respectively) between the septic and normal neonates. Increased RDW had a sensitivity of 61.54 %, specificity of 54.60 %. Increased band cells with a cut off of >15 cells had a sensitivity of 7.7 % with specificity of 100 % with higher numbers in septic neonates. Increased RDW and band cells in combination had sensitivity of 61.54 % and specificity of 54.6 %. CONCLUSIONS: RDW and band cell can be potential markers of EOS in cord blood but require further study in a larger population.

Application of Advanced Molecular Methods to Study Early-Onset Neonatal Sepsis.

Early-onset sepsis (EOS) is a global health issue, considered one of the primary causes of neonatal mortality. Diagnosis of EOS is challenging because its clinical signs are nonspecific, and blood culture, which is the current gold-standard diagnostic tool, has low sensitivity. Commonly used biomarkers for sepsis diagnosis, including C-reactive protein, procalcitonin, and interleukin-6, lack specificity for infection. Due to the disadvantages of blood culture and other common biomarkers, ongoing efforts are directed towards identifying innovative molecular approaches to diagnose neonates at risk of sepsis. This review aims to gather knowledge and recent research on these emerging molecular methods. PCR-based techniques and unrestricted techniques based on 16S rRNA sequencing and 16S-23S rRNA gene interspace region sequencing offer several advantages. Despite their potential, these approaches are not able to replace blood cultures due to several limitations; however, they may prove valuable as complementary tests in neonatal sepsis diagnosis. Several microRNAs have been evaluated and have been proposed as diagnostic biomarkers in EOS. T2 magnetic resonance and bioinformatic analysis have proposed potential biomarkers of neonatal sepsis, though further studies are essential to validate these findings.

The histologic fetal inflammatory response and neonatal outcomes: systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the prognostic role of concomitant histological fetal inflammatory response with chorioamnionitis on neonatal outcomes through a systematic review and meta-analysis of existing literature. DATA SOURCES: The primary search was conducted on October 17, 2021, and it was updated on May 26, 2023, across 4 separate databases (MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and Scopus) without using any filters. STUDY ELIGIBILITY CRITERIA: Observational studies reporting obstetrical and neonatal outcomes of infant-mother dyads with histological chorioamnionitis and histological fetal inflammatory response vs infant-mother dyads with histological chorioamnionitis alone were eligible. Studies that enrolled only preterm neonates, studies on neonates born before 37 weeks of gestation, or studies on neonates with very low birthweight (birthweight <1500 g) were included. The protocol was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42021283448). METHODS: The records were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random-effect model-based pooled odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. RESULTS: Overall, 50 studies were identified. A quantitative analysis of 14 outcomes was performed. Subgroup analysis using the mean gestational age of the studies was performed, and a cutoff of 28 weeks of gestation was implemented. Among neonates with lower gestational ages, early-onset sepsis (pooled odds ratio, 2.23; 95% confidence interval, 1.76-2.84) and bronchopulmonary dysplasia (pooled odds ratio, 1.30; 95% confidence interval, 1.02-1.66) were associated with histological fetal inflammatory response. Our analysis showed that preterm neonates with a concomitant histological fetal inflammatory response are more likely to develop intraventricular hemorrhage (pooled odds ratio, 1.54; 95% confidence interval, 1.18-2.02) and retinopathy of prematurity (pooled odds ratio, 1.37; 95% confidence interval, 1.03-1.82). The odds of clinical chorioamnionitis were almost 3-fold higher among infant-mother dyads with histological fetal inflammatory response than among infant-mother dyads with histological chorioamnionitis alone (pooled odds ratio, 2.99; 95% confidence interval, 1.96-4.55). CONCLUSION: This study investigated multiple neonatal outcomes and found association in the case of 4 major morbidities: early-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity.

The impact of the early onset neonatal sepsis calculator on antibiotic initiation: a single center study in Israel.

To evaluate the effect of implementation of the Kaiser Permanente (KP) early onset sepsis (EOS) calculator in infants born at 34 week's gestation or more on antibiotic utilization and length of hospitalization. A single center, retrospective cohort study included all neonates born in Soroka Medical Center at 34 weeks gestation or more between January 1st, 2015, and January 1st, 2019, with a predefined maternal risk factor for EOS. Two cohorts of neonates were compared during two time periods, before and after the implementation of the KP calculator. Multivariable logistic and linear regressions were performed to assess the effect of the KP calculator on antibiotic treatment and length of hospitalization. Also, an interrupted time series (ITS) analysis was used to assess the time trends of the two periods. The study included 3858 neonates in the pre-implementation period and 3081 neonates in the post-implementation cohort. The use of the calculator resulted in a significant reduction (46%) in antibiotics treatment for suspected EOS (5.1 vs. 9.4%, P < 0.001). The ITS analysis demonstrated a sharp decline in the slope of antibiotic treatment in the post intervention period: (b = -0.14, p-value = 0.08). The length of hospitalization was significantly reduced in the post-implementation cohort from 62 to 60 h (p-value < 0.001) with no clinical significance. The incidence of EOS was similar in both groups.    Conclusion: A significant reduction in antibiotic treatment was demonstrated after the implementation of the KP calculator without an increase incidence of EOS. The calculator is a powerful accessory decision-making tool that can be used safely in combination with, but not replacing, thorough clinical assessment. What is Known: • The EOS calculator is a useful tool that leads to a significant reduction in preemptive antibiotic utilization. What is New: • The EOS calculator is sensitive when applied to the whole-nursery. • The calculator is useful in different populations, also when women are not routinely screened for GBS.

Trends and spatial distribution of neonatal sepsis, Uganda, 2016-2020.

BACKGROUND: In Uganda, sepsis is the third-leading cause of neonatal deaths. Neonatal sepsis can be early-onset sepsis (EOS), which occurs ≤ 7 days postpartum and is usually vertically transmitted from the mother to newborn during the intrapartum period, or late-onset sepsis (LOS), occurring 8-28 days postpartum and largely acquired from the hospital environment or community. We described trends and spatial distribution of neonatal sepsis in Uganda, 2016-2020. METHODS: We conducted a descriptive incidence study using routinely-reported surveillance data on in-patient neonatal sepsis from the District Health Information System version 2 (DHIS2) during 2016-2020. We calculated incidence of EOS, LOS, and total sepsis as cases per 1,000 live births (LB) at district (n = 136), regional (n = 4), and national levels, as well as total sepsis incidence by health facility level. We used logistic regression to evaluate national and regional trends and illustrated spatial distribution using choropleth maps. RESULTS: During 2016-2020, 95,983 neonatal sepsis cases were reported, of which 71,262 (74%) were EOS. Overall neonatal sepsis incidence was 17.4/1,000 LB. EOS increased from 11.7 to 13.4 cases/1,000 LB with an average yearly increase of 3% (p < 0.001); LOS declined from 5.7 to 4.3 cases/1,000 LB with an average yearly decrease of 7% (p < 0.001). Incidence was highest at referral hospitals (68/1,000 LB) and lowest at Health Center IIs (1.3/1,000 LB). Regionally, total sepsis increased in Central (15.5 to 23.0/1,000 LB, p < 0.001) and Northern regions (15.3 to 22.2/1,000 LB, p < 0.001) but decreased in Western (23.7 to 17.0/ 1,000 LB, p < 0.001) and Eastern (15.0 to 8.9/1,000, p < 0.001) regions. CONCLUSION: The high and increasing incidence of EOS in Uganda suggests a major gap in sepsis prevention and quality of care for pregnant women. The heterogenous distribution of neonatal sepsis incidence requires root cause analysis by health authorities in regions with consistently high incidence. Strengthening prevention and treatment interventions in Central and Northern regions, and in the most affected districts, could reduce neonatal sepsis. Employment of strategies which increase uptake of safe newborn care practices and prevent neonatal sepsis, such as community health worker (CHW) home visits for mothers and newborns, could reduce incidence.

Multiple pneumatoceles and lung abscesses caused by early-onset E. coli sepsis in a preterm neonate.

Early-onset sepsis (EOS) is a serious and fatal illness in neonates, Group B Streptococcus and Escherichia coli are major causative pathogens. We report a case of EOS and pneumonia caused by E. coli in a preterm neonate with multiple pneumatoceles and lung abscesses. A male neonate weighing 1670g was delivered at 33 6/7 weeks' gestation by a mother with clinical chorioamnionitis. He showed respiratory distress soon after birth and developed septic shock. He was intubated and mechanical ventilation was started. E.coli was detected in blood culture obtained from both the patient and his mother. He developed multiple pneumatoceles and lung abscesses. Surgical drainage was complicated, cefotaxime was thus continued until day 74. Pneumatoceles and lung abscesses are complications of neonatal pneumonia, rarely reported by E. coli. Multiple lung abscesses in our patient are distinct from single abscesses in previous case studies of neonatal lung abscesses. We speculate that bacteremia along with pneumatoceles led to multiple lung abscesses in our patient. These complications require long-term antibiotic therapy, to minimize morbidity and mortality, and should thus be considered when managing EOS caused by E. coli.

Prevalence and determinants of early onset neonatal sepsis at two selected public referral hospitals in the Northwest Ethiopia: a cross-sectional study.

INTRODUCTION: Globally, neonatal mortality is decreasing, and road maps such as the Early Newborn Action Plan set ambitious targets for 2030. Despite this, deaths in the first weeks of life continue to rise as a percentage of total child mortality. Neonatal sepsis with early onset continues to be a significant cause of death and illness. The majority of sepsis-related deaths occur in developing nations, where the prevalence and causes of newborn sepsis are yet unknown. As a result, the goal of this study was to determine the prevalence of early-onset sepsis and identify determinant factors. METHODS: A cross-sectional study was conducted on 368 study participants in referral hospitals of East and West Gojjam Zones from March 1st to April 30th, 2019. Study participants were selected at random using lottery method. Face-to-face interviews with index mothers for maternal variables and neonatal record review for neonatal variables were used to collect data using a structured pretested questionnaire. Data were entered into Epidata 3.1 and then exported to STATA/SE software version 14. Finally, the logistic regression model was used for analysis. Statistical significance was declared at P < 0.05 after multivariable logistic regression. RESULTS: A total of 368 newborns and their index mothers took part in this study. The mean age of the newborns was 4.69 days (± 1.93SD). Early-onset neonatal sepsis was seen in 34% of the babies. Nulliparity (AOR: 3.3, 95% CI: 1.1-9.5), duration of labor > 18 h after rupture of membranes (AOR: 11.3, 95% CI: 3.0-41.8), gestational age of 32-37 weeks (AOR: 3.2, 95% CI: 1.2-8.5), and neonates who require resuscitation at birth (AOR: 4, 95% CI: 1.4 -11.8) were all found to be significantly associated with early-onset neonatal sepsis. CONCLUSION AND RECOMMENDATION: Early-onset neonatal sepsis was found to be high in this study. Early-onset neonatal sepsis was found to be associated with maternal, obstetric, and neonatal variables. Comprehensive prevention strategies that target the identified risk factors should be implemented right away.

Biochemical surveillance versus clinical observation of term infants born after prolonged rupture of membranes - A quality assurance initiative.

AIM: To examine whether biochemical surveillance vs clinical observation of term infants with prolonged rupture of membranes as a risk factor for early-onset sepsis is associated with differences in patient trajectories in maternity and neonatal intensive care units. METHODS: A retrospective study of live-born infants with gestational age ≥ 37 + 0 weeks born after prolonged rupture of membranes (≥24 h) in four Norwegian hospitals 2017-2019. Two hospitals used biochemical surveillance, and two used predominantly clinical observation to identify early-onset sepsis cases. RESULTS: The biochemical surveillance hospitals had more C-reactive protein measurements (p < 0.001), neonatal intensive care unit admissions (p < 0.001) and antibiotic treatment (p < 0.001). Hospitals using predominantly clinical observation initiated antibiotic treatment earlier in infants with suspected early-onset sepsis (p = 0.04) but not in infants fulfilling early-onset sepsis diagnostic criteria (p = 0.09). There was no difference in antibiotic treatment duration (p = 0.59), fraction of infants fulfilling early-onset sepsis diagnostic criteria (p = 0.49) or length of hospitalisation (p = 0.30), and no early-onset sepsis-related adverse outcomes. CONCLUSION: The biochemical surveillance hospitals had more C-reactive protein measurements, but there was no difference in antibiotic treatment duration, early-onset sepsis cases, length of hospitalisation or adverse outcomes. Personnel resources needed for clinical surveillance should be weighed against the limitation of potentially painful procedures.

The full blood count in screening asymptomatic infants for early-onset sepsis: A cross-sectional study.

AIM: The full blood count (FBC) is commonly measured as part of a partial septic work-up in asymptomatic infants at increased risk of early-onset neonatal sepsis (EOS). To determine the impact of FBC parameters on infants' subsequent management a retrospective cross-sectional study was performed. METHODS: Infants, born at ≥34 weeks gestation, asymptomatic at birth, undergoing a partial septic work-up and receiving prophylactic antibiotics due to increased risk of EOS in a single centre over a 2-year period, were included. The primary outcome measure was frequency of FBC result impacting on duration of antibiotic therapy. Secondary outcome measures included frequency of FBC parameters outside of the reference range and incidental diagnoses. RESULTS: In total, 16 726 live-born infants were delivered during the study period. A total of 802 (4.8%) were included. Thirteen infants (1.6%) received a prolonged course of antibiotics due to suspicion for EOS. Two of these infants had elevated white cell counts. All had normal neutrophil counts. In no case did the FBC result influence the decision to prolong the antibiotic course. CONCLUSION: In a cohort of 802 infants, asymptomatic at birth and at increased risk of EOS, the FBC result did not impact on the decision to prolong the course of antibiotics for suspicion of EOS.

[Establishment of a nomogram model for predicting the risk of early-onset sepsis in very preterm infants]. / 预测极早产儿早发型败血症发生风险的列线图模型的构建.

OBJECTIVES: To identify risk factors associated with early-onset sepsis (EOS) in very preterm infants and develop a nomogram model for predicting the risk of EOS. METHODS: A retrospective analysis was conducted on 344 very preterm infants delivered at the First Affiliated Hospital of Zhengzhou University and admitted to the Department of Neonatology between January 2020 and December 2022. These infants were randomly divided into a training set (241 infants) and a validating set (103 infants) in a 7:3 ratio. The training set was further divided into two groups based on the presence or absence of EOS: EOS (n=64) and non-EOS (n=177). Multivariate logistic regression analysis was performed to identify risk factors for EOS in the very preterm infants. The nomogram model was developed using R language and validated using the validating set. The discriminative ability, calibration, and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. RESULTS: The multivariate logistic regression analysis revealed that gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis were risk factors for EOS in very preterm infants (P<0.05). The area under the ROC curve for the training set was 0.925 (95%CI: 0.888-0.963), and that for the validating set was 0.796 (95%CI: 0.694-0.898), confirming the model's good discrimination. The Hosmer-Lemeshow goodness-of-fit test suggested that the model was well-fitting (P=0.621). The calibration curve analysis and decision curve analysis demonstrated that the model had high predictive efficacy and clinical applicability. CONCLUSIONS: Gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis are significantly associated with the development of EOS in very preterm infants.The nomogram model for predicting the risk of EOS in very preterm infants, constructed based on these factors, has high predictive efficacy and clinical applicability.

Does acute funisitis predict worse neonatal outcomes among term newborns?

BACKGROUND: Acute funisitis-the histologic diagnosis of inflammation within the umbilical cord-represents a fetal inflammatory response to infection. Although acute funisitis has been associated with an increased risk of adverse outcomes among preterm neonates, there are limited and conflicting data with term deliveries. OBJECTIVE: This study aimed to evaluate the association between acute funisitis and neonatal morbidity in neonates born at term to pregnant patients with a clinical diagnosis of intraamniotic infection. STUDY DESIGN: This was a retrospective cohort study of pregnant patients who had clinically diagnosed intraamniotic infection at term, delivered vaginally at a single tertiary institution from 2013 to 2019, and had histologic chorioamnionitis on placental pathology. Patients with intrauterine fetal demise or missing neonatal/placental pathology data were excluded. The primary outcome was a neonatal sepsis composite, defined as culture-positive bacteremia, neutropenia (absolute neutrophil count<3500/µL), or immature-to-total neutrophil ratio>0.2. The secondary outcomes included composite neonatal morbidity, defined as neonatal intensive care unit admission, 5-minute Apgar score <7, bacteremia, endotracheal intubation or need for continuous positive airway pressure, intraventricular hemorrhage (grade 3 or 4), necrotizing enterocolitis (stage 3 or 4), umbilical artery pH<7.1, umbilical artery base excess>12, and neonatal mortality. The components of these composites, neonatal intensive care unit length of stay, and Kaiser early-onset sepsis score were also measured. Neonates with acute funisitis on pathology were compared with those without acute funisitis using bivariate statistics. Regression was used to estimate the relative risk of outcomes. RESULTS: Of 184 neonates with deliveries complicated by intraamniotic infection, acute funisitis was present in 109 (59%) placental specimens. Composite neonatal sepsis was significantly higher among neonates with acute funisitis (relative risk, 1.85; 95% confidence interval, 1.13-3.03) than in those without acute funisitis. As a marker for sepsis, acute funisitis has a sensitivity of 39.4%, negative predictive value of 47.2%, specificity of 78.7%, and positive predictive value of 72.9%. An immature-to-total neutrophil ratio>0.2 (relative risk, 1.83; 95% confidence interval, 1.09-3.08) was also significantly associated with acute funisitis. Neonatal morbidity composite, intraventricular hemorrhage, necrotizing enterocolitis, neonatal intensive care unit admission, higher Kaiser early-onset sepsis scores, and other examined outcomes were not statistically associated with acute funisitis. CONCLUSION: In term deliveries complicated by intraamniotic infection, acute funisitis was associated with increased neonatal sepsis. Current approaches for estimating neonatal sepsis risk are limited by their reliance on indirect maternal factors such as maximum maternal temperature and intrapartum antibiotic use. This study suggests that acute funisitis may serve as a marker that could be utilized to augment risk stratification at birth if a protocol for evaluating the umbilical cord in real-time were widely adopted.

Clinical utiliy of a model-based piperacillin dose in neonates with early-onset sepsis.

AIMS: Early-onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model-based dosing regimen of piperacillin/tazobactam in EOS patients. METHODS: A prospective, single-centre, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg-1 , q8h) was determined based on a previous piperacillin PPK model in young infants using NONMEM v7.4. The pharmacodynamics (PD) target (70%fT > MIC, free drug concentration above MIC during 70% of the dosing interval) attainment was calculated using NONMEM combined with an opportunistic sampling design. The clinical treatment data were collected. RESULTS: A total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14-41.29) weeks. Forty-seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2-305.8) hours and 31 (30, 5-123) days. There were no obvious adverse events and no infection-related deaths occurred in the first month of life. CONCLUSIONS: A model-based dosing regimen of piperacillin/tazobactam was evaluated clinically, was tolerated well and was determined to be effective for EOS treatment.

Clinical utility of a model-based amoxicillin dosage regimen in neonates with early-onset sepsis.

Early-onset sepsis (EOS) is one of the most significant causes of morbidity and mortality in neonates. Currently, amoxicillin is empirically used to treat neonates with EOS. However, data on its effectiveness in neonates with EOS are still limited. Therefore, we aimed to evaluate the pharmacodynamics (PD) target attainment and effectiveness of a model-based amoxicillin dosage regimen in these neonates. We used a previously developed model and collected additional clinical data from the EOS neonates who used the model-based dosage regimen (25 mg/kg every 12 h). The primary outcomes were PD target attainment (free drug concentration above minimum inhibitory concentration during 70% of the dosing interval) and treatment failure rate. The secondary endpoints were length of amoxicillin treatment, duration of hospitalization etc. Seventy-five neonates (postmenstrual age 28.4-41.6 wk) were enrolled. A total of 70 (93.3%) neonates reached their PD target using 1 mg/L as the minimum inhibitory concentration breakpoint. The treatment failure rate was 10.7%.

Presepsin levels in neonatal cord blood are not influenced by maternal SARS-CoV-2 infection.

OBJECTIVES: Coronavirus disease (COVID-19) can present with various symptoms and can involve multiple organs. Women infected during pregnancy have a higher incidence of obstetrical complications and infants born to "positive" mothers may get the infection with different manifestations. Presepsin seems to be a promising sepsis biomarker in adults and neonates. The aim of this study was to assess if presepsin levels in neonatal cord blood could be influenced by maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A total of 119 neonates born from women with a confirmed diagnosis of SARS-CoV-2 infection were enrolled and presepsin levels of cord blood samples were collected. All neonates were tested for SARS-CoV-2 infection at birth and after 48-72 h. RESULTS: The median presepsin value in umbilical cord blood samples collected after birth was 455 pg/mL. Presepsin levels were not influenced by maternal symptoms of COVID-19, weight for gestational age, or delivery mode, and did not significantly differ between infants with and without adverse neonatal outcomes. Infants hospitalized for more than 5 days had a significantly higher presepsin level at birth rather than those discharged up to 4 days of life. Three infants with positive nasopharyngeal swab at birth had higher Presepsin levels than two infants tested positive at 48 h. CONCLUSIONS: This is the first study reporting cord presepsin levels in term and preterm infants born to mothers with COVID-19, that appeared to be not influenced by maternal clinical presentation. However, further studies are needed to explain the mechanisms of P-SEP increase in neonates exposed to perinatal maternal SARS-CoV-2 infection or with an indeterminate/possible SARS-CoV-2 infection in the same neonates.

Potential benefit from the implementation of the Kaiser Permanente neonatal early-onset sepsis calculator on clinical management of neonates with presumed sepsis.

To assess the potential benefit from the implementation of the Kaiser Permanente early-onset sepsis calculator (EOS-C), in terms of antibiotic use and requested laboratory tests, in a network of neonatal intensive care units (NICUs) in Greece, and to determine the incidence of early-onset sepsis (EOS) in Greek NICUs, a prospective surveillance study was conducted in 7 NICUs between April 2018 and June 2019. Data were collected for all newborns ≥ 34 weeks' gestation receiving empiric antibiotic therapy within the first 3 days of life. The number of live births and positive blood or cerebrospinal fluid cultures within the first 3 days of life were used for calculation of EOS incidence. Evaluation of possible impact of implementing the calculator was done by comparing the clinicians' recorded management to the calculator's suggested course of action. The unit-specific incidence of culture-proven EOS ranged between 0 and 2.99/1000 live births. The weighted incidence rate for all 7 units was 1.8/1000 live births. Management of EOS guided by the calculator could lead to a reduction of empiric antibiotic initiation up to 100% for the group of "well-appearing" neonates and 86% for "equivocal," lowering exposure to antibiotics by 4.2 and 3.8 days per neonate, respectively. Laboratory tests for blood cultures drawn could be reduced by up to 100% and 68%, respectively. Sensitivity of the EOS-C in identifying neonates with positive blood cultures was high.Conclusion: Management strategies based on the Kaiser Permanente neonatal sepsis calculator may significantly reduce antibiotic exposure, invasive diagnostic procedures, and hospitalizations in late preterm and term neonates. What is Known: • Neonates are frequently exposed to antibiotics for presumed EOS. • The Kaiser Permanente sepsis calculator can reduce antibiotic exposure in neonates.. What is New: • EOS calculator can be an effective antibiotic stewardship tool in a high prescribing country and can reduce invasive diagnostic procedures and mother-baby separation. • Incidence of EOS in Greece is higher compared to other European countries.

Early-onset neonatal sepsis and antibiotic use in Indonesia: a descriptive, cross-sectional study.

BACKGROUND: Early diagnosis and prompt antibiotic treatment are crucial to reducing morbidity and mortality of early-onset sepsis (EOS) in neonates. However, this strategy remains challenging due to non-specific clinical findings and limited facilities. Inappropriate antibiotics use is associated with ineffective therapy and adverse outcomes. This study aims to determine the characteristics of EOS and use of antibiotics in the neonatal-intensive care units (NICUs) in Indonesia, informing efforts to drive improvements in the prevention, diagnosis, and treatment of EOS. METHODS: A descriptive study was conducted based on pre-intervention data of the South East Asia-Using Research for Change in Hospital-acquired Infection in Neonates project. Our study population consisted of neonates admitted within 72 h of life to the three participating NICUs. Neonates who presented with three or more clinical signs or laboratory results consistent with sepsis and who received antibiotics for 5 consecutive days were considered to have EOS. Culture-proven EOS was defined as positive blood or cerebrospinal fluid culture. Type and duration of antibiotics used were also documented. RESULTS: Of 2,509 neonates, 242 cases were suspected of having EOS (9.6%) with culture-proven sepsis in 83 cases (5.0% of neonatal admissions in hospitals with culture facilities). The causative organisms were mostly gram-negative bacteria (85/94; 90.4%). Ampicillin / amoxicillin and amikacin were the most frequently prescribed antibiotics in hospitals with culture facilities, while a third-generation cephalosporin was mostly administered in hospital without culture facilities. The median durations of antibiotic therapy were 19 and 9 days in culture-proven and culture-negative EOS groups, respectively. CONCLUSIONS: The overall incidence of EOS and culture-proven EOS was high in Indonesia, with diverse and prolonged use of antibiotics. Prospective antibiotic surveillance and stewardship interventions are required.

Restrictive prescription of antibiotics in preterm infants with premature rupture of membranes.

BACKGROUND: In preterm infants with premature rupture of membranes, antibiotic treatment is frequently started but rates of early onset sepsis are lower. In line with national guidelines, a stratified approach in the decision to start antibiotic treatment using maternal history, clinical impression and biomarkers has been implemented in our level III neonatal center and its results are evaluated. METHODS: Retrospective cohort study of all preterm newborns with rupture of membranes at least 1 h prior to delivery admitted to our tertiary neonatal intensive care unit. Data on antibiotic exposure, mortality and major neonatal complications were extracted from the electronic patient charts to evaluate the effects and safety of our stratified approach. RESULTS: Four hundred fifty-six infants met the inclusion criteria. 120 (26%) received primary antibiotics whereas 336 (74%) did not. Of those receiving primary antibiotics, 13 (11%) had a blood culture positive sepsis, 46 (38%) met the criteria of clinical sepsis and in 61 (51%) sepsis was ruled out and antibiotics were stopped after 48-96 h. All infants with blood culture positive sepsis were identified and treated within the first 24 h of life using this approach. None of the 336 infants who were not started on antibiotics primarily needed antibiotic therapy within the first 5 days of life. There were no deaths or major neonatal complications in the group that did not receive empiric antibiotics. CONCLUSIONS: Our stratified approach for preterm infants with premature rupture of membranes allows a safe reduction of antibiotic exposure even in this high risk population. As a result, only 25% of high risk preterm newborns are treated with antibiotics of which more than half receive less than 5 days of treatment. To treat one infant with blood culture positive sepsis, only 9 infants receive empiric antibiotics.