Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study.

BACKGROUND: Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the first postnatal week. METHODS: We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia. All late-preterm and term infants born between 2014 and 2018 who received intravenous antibiotics during the first postnatal week were classified as culture-negative cases treated for ≥5 days (CN ≥ 5d), culture-negative cases treated for <5 days (CN < 5d), or CP-EOS cases. RESULTS: Out of 757,979 infants, 21,703 (2.9%) received intravenous antibiotics. The number of infants classified as CN ≥ 5d, CN < 5d, and CP-EOS was 7996 (37%), 13,330 (61%), and 375 (1.7%). The incidence of CN ≥ 5d, CN < 5d, and CP-EOS was 10.6 (95% CI 10.3-10.8), 17.6 (95% CI 17.3-17.9), and 0.49 (95% CI 0.44-0.54) cases per 1000 livebirths. The median (IQR) number of antibiotic days administered for CN ≥ 5d, CN < 5d, and CP-EOS was 77 (77-78), 53 (52-53), and 5 (5-5) per 1000 livebirths. CONCLUSIONS: CN ≥ 5d substantially contributed to the overall antibiotic exposure, and was 21-fold more frequent than CP-EOS. Antimicrobial stewardship programs should focus on shortening antibiotic treatment for culture-negative cases. IMPACT: In a study of 757,979 infants born in high-income countries, we report a presumed culture-negative early-onset sepsis incidence of 10.6/1000 livebirths with an associated antibiotic exposure of 77 antibiotic days per 1000 livebirths. This study sheds light on the major contribution of presumed culture-negative early-onset sepsis to early-life antibiotic exposure. Given the diagnostic uncertainty surrounding culture-negative early-onset sepsis, the low mortality rate, and the disproportionate antibiotic exposure associated with this condition, our study emphasizes the importance of targeting culture-negative early-onset sepsis in antimicrobial stewardship programs.

Blood pressure in preterm infants with bronchopulmonary dysplasia in the first three months of life.

BACKGROUND: Neonatal hypertension is common in preterm infants with bronchopulmonary dysplasia (BPD). Our study aimed to examine blood pressure variation in the first three months of life in preterm BPD patients. METHODS: We conducted a retrospective, single-centre study at the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We collected blood pressure data from 26 preterm infants (born at < 30 weeks gestation) with moderate or severe BPD over three years (2019-2021). We calculated the BPD group's daily average blood pressure values and used previously defined normal blood pressure values from a preterm patient group born at < 30 weeks gestation as a reference. We used 19,481 systolic, diastolic and mean blood pressure measurement data separately to calculate daily average blood pressures. RESULTS: We found a statistically significant correlation between the blood pressure values of the BPD patient group and the reference data. The difference between the blood pressure curve of the group with BPD and that of the reference group was also statistically significant. We also analysed individual patients' daily average blood pressure values and found that 11 patients (42%) had hypertensive blood pressure values for three or more days within the first 90 days of life. Within this group, our statistical analysis showed a 25% chance of acute kidney injury. CONCLUSION: The blood pressure of the BPD group not only correlated with but also significantly differed from the reference data. Hypertension lasting three or more days occurred more frequently in patients with acute kidney injury accompanied by BPD.

[Abdominal and cranial ultrasound screenings in our Neonatal Intensive Care Unit]. / Hasi és agyi ultrahang-szurovizsgálatok Neonatális Intenzív Centrumunkban.

INTRODUCTION: Previously, all admitted neonates to our tertiary Neonatal Unit, University of Szeged, had a cranial and abdominal ultrasound performed as part of their care. OBJECTIVE: To analyze the findings and to evaluate the effectiveness of the universal ultrasound screening. METHOD: Results of cranial and abdominal ultrasound imaging performed in our Unit between 1st January 2014 and 31st December 2015 were analyzed retrospectively. Abnormalities found during the screening scans were studied further and assessed until discharge and during the first 2 years. All imagings were performed by a radiologist. RESULTS: During the examined 2 years, 579 neonates were admitted (gestational age mean 34.2 weeks [23-41, SD ± 4.04]), abdominal ultrasound was performed in 562 (97%) and cranial ultrasound in 560 (97%) babies, on the 3.6th day of life at an average (0-18, SD ± 2.24). Of all abdominal ultrasound scans, 87% (n = 488) was carried out as screening, and the found abnormalities in 140 (29%) of the cases: renal pelvic dilatation (n = 67 [47.9%]), free abdominal fluid (n = 17 [12.1%]), echogenic kidneys (n = 13 [9.3%]), congenital abnormalities of the kidney and urinary tract (n = 9 [6.4%]), abnormalities of the liver, bile system, adrenal gland [n = 14 [10%]). The screening identified 4 (0.8%) neonates with renal abnormilaties requiring surgical correction. In regards of renal abnormalities, we observed male (p = 0.18) and left sided (p = 0.54) predominance. Screening cranial ultrasound was performed in 65% (n = 362) of all neonates, discovering 51 (14%) anomalies: plexus chorioideus cyst (n = 21 [41%]), plexus chorioideus hemorrhage (n = 9 [17.6%]), mild ventricular asymmetry (n = 8 [15.7%]), subependymal hemorrhage (n = 5 [9.8%]), abnormalities of the periventricular area (n = 4 [7.8%]), colpocephaly, hydrocephalus externus, echogenic meninx and thalamic nodule [n = 1-1 (1.9-1.9%)]. CONCLUSION: Abdominal ultrasound screening discovered renal abnormalities and umbilical line complications as clinically relevant findings. However, a small number of renal abnormalities identified by screening required surgical intervention. Further studies are needed to identify possible risk groups to develop more efficient screening strategy to decrease the number of screened babies for 1 relevant finding (number to screen). Cranial ultrasound screening did not identify any abnormalities that needed intervention. We can not recommend universal cranial ultrasound screening based on our results. Orv Hetil. 2023; 164(31): 1222-1230.

Oscillometric arterial blood pressure in haemodynamically stable neonates in the first 2 weeks of life.

BACKGROUND: We aimed to provide data on the normal blood pressure of haemodynamically stable neonates. Our study uses retrospective, real-life oscillometric blood pressure measurement values to determine the expected blood pressure in different gestational age, chronological age and birth weight groups. We also investigated the effect of antenatal steroid on neonatal blood pressure. METHODS: Our retrospective study (2019-2021) was carried out in the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We involved 629 haemodynamically stable patients and analysed 134,938 blood pressure values. Data were collected from electronic hospital records of IntelliSpace Critical Care Anesthesia by Phillips. We used the PDAnalyser program for data handling and the IBM SPSS program for statistical analysis. RESULTS: We found a significant difference between the blood pressure of each gestational age group in the first 14 days of life. The systolic, diastolic and mean blood pressure rise are steeper in the preterm group than in the term group in the first 3 days of life. No significant blood pressure differences were found between the group with a complete antenatal steroid course and those who received incomplete steroid prophylaxis or did not receive antenatal steroids. CONCLUSION: We determined the average blood pressure of stable neonates and obtained normative data by percentiles. Our study provides additional data on how blood pressure varies with gestational age and birth weight. A higher resolution version of the Graphical abstract is available as Supplementary information.

Less is more: Antibiotics at the beginning of life.

Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.

Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia.

Importance: Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure. Objective: To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries. Design, Setting, and Participants: This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022. Exposures: Exposure to antibiotics started in the first postnatal week. Main Outcomes and Measures: The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality. Results: A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered. Conclusions and Relevance: The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.

Use of antibiotics in suspected early-onset neonatal sepsis / Antibiotikumhasználat korai szepszis gyanúja esetén újszülöttkorban.

Összefoglaló. Bevezetés: Az újszülöttkori szepszis ritka, de magas mortalitással járó állapot. Az Egészségügyi Szakmai Kollégium Neonatológiai Tagozata 2017-ben bevezette a korai szepszisrol szóló állásfoglalást, meghatározva a kezelés indikációját a túlzott mértéku antibiotikumadás elkerülése céljából. Célkituzés: Retrospektív analízissel vizsgáltuk az állásfoglalás elotti és utáni idoszak antibiotikumhasználatát klinikánk beteganyagán. Módszer: Az intézményünkben 2014. 01. 01. és 2018. 12. 31. között született, a 34. gestatiós hetet betöltött újszülöttek adatait vizsgáltuk a következo kimenetelekre koncentrálva: szepszisre utaló klinikai tünetek jelenléte, az antibiotikummal kezelt újszülöttek száma, koraiszepszis-incidencia, mortalitás. A statisztikai analízis az RStudio programmal történt (szignifikancia: p<0,05). Eredmények: A vizsgált 5 évben összesen 12 347 újszülött jött a világra, közülük antibiotikumot kapott 1502 (12,16%); évekre lebontva: 2014-ben 517 (21,10%), 2015-ben 401 (16,63%), 2016-ban 459 (17,96%), 2017-ben 61 (2,39%), 2018-ban 64 (2,69%). Az antibiotikumterápiában részesültek (n = 1502) közül 239 (15,91%) újszülöttnek volt fertozésre utaló tünete. A klinikai tüneteket mutató újszülöttek száma nem növekedett szignifikánsan (p = 0,285); 2014-ben 52 (2,12%), 2015-ben 42 (1,74%), 2016-ban 42 (1,64%), 2017-ben 46 (1,80%), 2018-ban 57 (2,40%). Hemokultúra-pozitív szepszis összesen: 4; koraiszepszis-incidencia: 0,324/1000. Szepszishez kötheto haláleset nem volt. Megbeszélés: A protokollváltást megelozoen az újszülöttek csupán rizikófaktorok alapján is részesültek antibiotikumterápiában, 2017 óta azonban elsosorban a fertozés klinikai tüneteit mutató újszülötteket kezeljük, ami az antibiotikumhasználat szignifikáns csökkenéséhez vezetett. A korábbi, rizikófaktorok alapján adott antibiotikumterápia megszüntetését követoen nem emelkedett a tünetet mutató szeptikus újszülöttek száma, sem a korai szepszis okozta mortalitás. Következtetés: A 34. gestatiós hetet betöltött újszülötteknél a korai szepszis gyanúja miatti antibiotikumhasználat biztonsággal csökkentheto volt, ezzel megelozve a felesleges antibiotikumkezelés rövid és hosszú távú mellékhatásait. Orv Hetil. 2022; 163(11): 431-437. INTRODUCTION: Early-onset neonatal sepsis is a rare, but life-threatening condition. In 2017, the Hungarian Neonatal Society issued a national guideline to rationalize the use of antibiotic use in neonatal sepsis. OBJECTIVE: To retrospectively determine the frequency of prescribed antibiotics before and after the introduction of national guidance. METHOD: Data of neonates (>34. gestational weeks) delivered in our hospital between 1st January 2014 and 31st December 2018 were analysed with focusing on signs of sepsis, number of neonates treated with antibiotics, incidence of early-onset neonatal sepsis, sepsis-related mortality. Statistical analysis was performed with RStudio software (significance: p<0.05). RESULTS: During the analysed time period, 12 347 neonates were born, 1502 (12.16%) neonates were given antibiotics, showing a significant decrease after 2017: 517 (21.10%) in 2014, 401 (16.63%) in 2015, 459 (17.96%) in 2016, 61 (2.39%) in 2017, 64 (2.69%) in 2018, respectively. Out of the group of neonates treated with antibiotics (n = 1502), only 239 (15.91%) neonates showed the clinical signs of sepsis. No significant change was observed in the number of symptomatic newborns during the study period: 52 (2.12%) in 2014, 42 (1.74%) in 2015, 42 (1.64%) in 2016, 46 (1.80%) in 2017, 57 (2.40%) in 2018, p = 0.285. Blood culture confirmed neonatal sepsis was observed in 4 babies, incidence of early-onset neonatal sepsis was 0.324/1000, sepsis-related mortality was zero. DISCUSSION: Before the introduction of the national guideline, most of the neonates were prescribed antibiotics based on risk factors. Since 2017, antibiotics have been mainly preserved for newborns with clinical signs of sepsis. Despite cessation of antiobiotic treatment indicated by risk factors, the number of symptomatic babies and sepsis-related mortality have not increased. CONCLUSION: The use of antibiotics for neonates >34th gestational week can be safely reduced, entailing a decrease in short- and long-term complications of early antibiotic use. Orv Hetil. 2022; 163(11): 431-437.

International consensus is needed on premedication for non-emergency neonatal intubation after survey found wide-ranging policies and practices in 70 countries.

AIM: This study evaluated whether practitioners from 70 countries used premedication for non-emergency neonatal intubation and identified attitudes and experience regarding the safety, side effects and efficiency of neonatal intubation. METHODS: Invitations to take part in the survey were issued between December 18, 2018 and February 4, 2019 to the users of neonatal-based websites and Facebook groups, members of professional societies and the authors of relevant publications in the last five years. RESULTS: We analysed 718 completed questionnaires from 40 European and 30 non-European countries. Most of the responses were from neonatologists (69.6%) and paediatric or neonatal trainees (10.3%). In units without a protocol (31.6%), more than half of the practitioners (60.4%) chose premedication according to personal preference and 37.0%-11.9% of the overall respondents did not use any drugs for non-emergency intubation. The most frequently reported drug combination was fentanyl, atropine and succinylcholine (6.8%). Most of the practitioners (78.5%) use the same drugs for term and preterm infants. Only 24.8% of the physicians were fully satisfied with their premedication practices. CONCLUSION: Nearly 12% of the respondents did not use premedication for non-emergency neonatal intubation. The wide-ranging policies and practices found among the respondents highlight the need for international consensus guidelines.

Pediatric localized intestinal lymphangiectasia treated with resection.

INTRODUCTION: Primary intestinal lymphangiectasia (PIL) is a very rare disorder usually diagnosed before the third year of life or later in adulthood, presenting with pitting edema, hypoproteinemia and low immunoglobulin levels. The location and the extent of the affected bowel greatly influence the clinical manifestation. The localized or segmental form of PIL is extremely rare with only five pediatric cases reported worldwide. CASE PRESENTATION: A 10 year-old Caucasian boy presented with 3 months history of recurrent abdominal pain and a 1 month history of diarrhea. An ultrasound scan was performed on two separate occasions 10 days apart, revealing a growing cystic mass on the right side of the abdomen, in front of the psoas muscle. Subsequently an MRI scan confirmed that the mass originated from the mesenteries and infiltrates a short segment of the small bowel. Surgical resection of the affected segment was performed. Histopathological examination of the removed segment of ileum was consistent with intestinal lymphangiectasia. We could not identify any associated genetic syndromes or any other conditions that could have caused secondary intestinal lymphangiectasia. The patient's recovery from surgery was uneventful and no recurrence was observed in the following 4 years. CONCLUSION: Despite being a benign condition, mortality of PIL can be as high as 13% due to the difficulties associated with the management of the disease. PIL should be considered as a rare but potential cause for an abdominal mass, even in the older child, when cystic mesenterial involvement might be seen on ultrasound or MRI. In selected cases of PIL affecting only a short segment of the bowel or following unsuccessful conservative treatment, surgical resection of the affected bowel segment can be curative.