Feasibility of synchronized high flow nasal cannula.

BACKGROUND: A high-flow nasal cannula (cHFNC) delivers flow continuously (during inspiration and expiration). Using the diaphragm electrical activity (Edi), synchronizing HFNC could be an alternative (cycling high/low flow on inspiration/expiration, respectively). The objective of this study was to demonstrate the feasibility of synchronized HFNC (sHFNC) and compare it to cHFNC. METHODS: Different levels of cHFNC and sHFNC (4, 6, 8, and 10 liters per minute [LPM], with 2 LPM on expiration for sHFNC) were compared in eight rabbits (mean weight 3.16 kg), before and after acute lung injury (pre-ALI and post-ALI). Edi, tracheal pressure (Ptr), esophageal pressure (Pes), flow, and arterial CO2 were measured. In addition to the animal study, one 3.52 kg infant received sHFNC and cHFNC using a Servo-U ventilator. RESULTS: In the animal study, there were more pronounced decreases in Edi, reduced Pes swings and reduced PaCO2 at comparable flows during sHFNC compared to cHFNC both pre and post-ALI (p < .05). Baseline (pre-inspiratory) Ptr was 2-7 cmH2O greater during cHFNC (p < .05) indicating more dynamic hyperinflation. In one infant, the ventilator performed as expected, delivering Edi-synchronized high/low flow. CONCLUSION: Synchronizing high flow unloaded breathing, decreased Edi, and reduced PaCO2 in an animal model and is feasible in infants.

Transcatheter patent ductus arteriosus closure in premature infants requiring high-frequency ventilation.

Transcatheter closure has become a common treatment method for patent ductus arteriosus in premature infants at many centres; however, many remain uncertain about the ability to perform the procedure in the catheterisation laboratory for infants requiring high-frequency ventilation. This study presents our centre's experience following the implementation of neonatal ventilatory guidelines, which resulted in 100% procedural success without any procedural or respiratory adverse events.

Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial: study protocol for a randomized controlled trial comparing rates of extubation failure in extremely premature infants undergoing extubation to non-invasive neurally adjusted ventilatory assist versus non-synchronized nasal intermittent positive pressure ventilation.

BACKGROUND: Invasive mechanical ventilation contributes to bronchopulmonary dysplasia (BPD), the most common complication of prematurity and the leading respiratory cause of childhood morbidity. Non-invasive ventilation (NIV) may limit invasive ventilation exposure and can be either synchronized or non-synchronized (NS). Pooled data suggest synchronized forms may be superior. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) delivers NIV synchronized to the neural signal for breathing, which is detected with a specialized catheter. The DIVA (Diaphragmatic Initiated Ventilatory Assist) trial aims to determine in infants born 240/7-276/7 weeks' gestation undergoing extubation whether NIV-NAVA compared to non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV) reduces the incidence of extubation failure within 5 days of extubation. METHODS: This is a prospective, unblinded, pragmatic, multicenter phase III randomized clinical trial. Inclusion criteria are preterm infants 24-276/7 weeks gestational age who were intubated within the first 7 days of life for at least 12 h and are undergoing extubation in the first 28 postnatal days. All sites will enter an initial run-in phase, where all infants are allocated to NIV-NAVA, and an independent technical committee assesses site performance. Subsequently, all enrolled infants are randomized to NIV-NAVA or NS-NIPPV at extubation. The primary outcome is extubation failure within 5 days of extubation, defined as any of the following: (1) rise in FiO2 at least 20% from pre-extubation for > 2 h, (2) pH ≤ 7.20 or pCO2 ≥ 70 mmHg; (3) > 1 apnea requiring positive pressure ventilation (PPV) or ≥ 6 apneas requiring stimulation within 6 h; (4) emergent intubation for cardiovascular instability or surgery. Our sample size of 478 provides 90% power to detect a 15% absolute reduction in the primary outcome. Enrolled infants will be followed for safety and secondary outcomes through 36 weeks' postmenstrual age, discharge, death, or transfer. DISCUSSION: The DIVA trial is the first large multicenter trial designed to assess the impact of NIV-NAVA on relevant clinical outcomes for preterm infants. The DIVA trial design incorporates input from clinical NAVA experts and includes innovative features, such as a run-in phase, to ensure consistent technical performance across sites. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , trial identifier NCT05446272 , registered July 6, 2022.

Neonatal high frequency ventilation: Current trends and future directions.

High frequency ventilation (HFV) in neonates has been in use for over forty years. Some early HFV ventilators are no longer available, but high frequency oscillatory ventilation (HFOV) and jet ventilators (HFJV) continue to be commonly employed. Advanced HFOV models available outside of the United States are much quieter and easier to use, and are available as options on many conventional ventilators, providing important improvements such as tidal volume measurement and targeting. HFJV excels in treating air leak and non-homogenous lung disease and is often used for other diseases as well. High frequency non-invasive ventilation (hfNIV) is a novel application of HFV that remains under investigation. Similar to bubble CPAP, hfNIV has been applied with a variety of high-frequency ventilators. Efficacy and safety of hfNIV with any device have not yet been established. This article describes the current approaches to these HFV therapies and stresses the importance of understanding how each device works and what disease processes may respond best to the technology employed.

The effect of bethanechol on tracheobronchomalacia in preterm infants with bronchopulmonary dysplasia: a retrospective cohort study.

OBJECTIVE: Bethanechol has demonstrated improvement in trachealis tone in animal models, but no trials have studied efficacy in infants. This study aimed to examine if bethanechol improves a standardized pulmonary severity score (PSS) in infants with severe bronchopulmonary dysplasia with a diagnosis of tracheobronchomalacia (TBM). STUDY DESIGN: This retrospective cohort study evaluated cases treated with bethanechol matched with controls who did not receive bethanechol. TBM was diagnosed by dynamic computography. Daily PSS was recorded for each infant from 40 to 55 weeks post-menstrual age. RESULTS: Cases' mean PSS change was 21% lower than the controls' mean PSS change pre- and post-bethanechol (95% CI -40%, -2%) by paired t-test (p = 0.03). Matched differences (controls' PSS - cases' PSS) demonstrated greater mean PSS difference post-bethanechol compared to pre-bethanechol 0.17, (95% CI 0.05, 0.29) by paired t-test (p = 0.009). CONCLUSION: Infants with TBM treated with bethanechol compared to those not treated had a lower PSS reflecting improved respiratory status.

Tidal volume delivery during nasal intermittent positive pressure ventilation: infant cannula vs. nasal continuous positive airway pressure prongs.

OBJECTIVE: To measure tidal volume delivery during nasal intermittent positive pressure ventilation with two nasal interfaces: infant cannula and nasal prongs. STUDY DESIGN: A single-center crossover study of neonates with mild respiratory distress. Fifteen preterm neonates were randomized to initial interface of infant cannula or nasal prongs and monitored on a sequence of pressure settings first on the initial interface, then repeated on the alternate interface. We compared relative tidal volumes between the two interfaces with two-way repeated measures ANOVA during three breath types: synchronized (I), patient effort without ventilator breaths (II), and ventilator breaths without patient effort (III). Clinical trial #NCT04326270. RESULTS: Type III breaths delivered no significant tidal volume. No significant difference was measured in relative tidal volume delivery between the interfaces when breath types were matched. CONCLUSIONS: Nasal intermittent positive pressure ventilation delivers neither clinically nor statistically significant tidal volume with either infant cannula or nasal prongs.

Zinc Deficiency: A Potential Hidden Driver of the Detrimental Cycle of Chronic Kidney Disease and Hypertension.

Globally, over 103 million individuals are afflicted by CKD, a silent killer claiming the lives of 1.2 million people annually. CKD is characterized by five progressive stages, in which dialysis and kidney transplant are life-saving routes for patients with end stage kidney failure. While kidney damage impairs kidney function and derails BP regulation, uncontrolled hypertension accelerates the development and progression of CKD. Zinc (Zn) deficiency has emerged as a potential hidden driver within this detrimental cycle of CKD and hypertension. This review article will (1) highlight mechanisms of Zn procurement and trafficking, (2) provide evidence that urinary Zn wasting can fuel Zn deficiency in CKD, (3) discuss how Zn deficiency can accelerate the progression of hypertension and kidney damage in CKD, and (4) consider Zn supplementation as an exit strategy with the potential to rectify the course of hypertension and CKD progression.

Renal oximetry for early acute kidney injury detection in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia are at high risk of acute kidney injury (AKI). METHODS: We performed a two-site prospective observational study from 2018 to 2019 to evaluate the utility of renal near-infrared spectroscopy (NIRS) in detecting AKI in 38 neonates with HIE receiving therapeutic hypothermia. AKI was defined by a delayed rate of serum creatinine decline (< 33% on day 3 of life, < 40% on day 5, and < 46% on day 7). Renal saturation (Rsat) and systemic oxygen saturation (SpO2) were continuously measured for the first 96 h of life (HOL). Renal fractional tissue oxygen extraction (RFTOE) was calculated as (SpO2 - Rsat)/(SpO2). Using renal NIRS, urine biomarkers, and perinatal factors, logistic regression was performed to develop a model that predicted AKI. RESULTS: AKI occurred in 20 of 38 neonates (53%). During the first 96 HOL, Rsat was higher, and RFTOE was lower in the AKI group vs. the no AKI group (P < 0.001). Rsat > 70% had a fair predictive performance for AKI at 48-84 HOL (AUC 0.71-0.79). RFTOE ≤ 25 had a good predictive performance for AKI at 42-66 HOL (AUC 0.8-0.83). The final statistical model with the best fit to predict AKI (AUC = 0.88) included RFTOE at 48 HOL (P = 0.012) and pH of the infants' first postnatal blood gas (P = 0.025). CONCLUSIONS: Lower RFTOE on renal NIRS and pH on infant first blood gas may be early predictors for AKI in neonates with HIE receiving therapeutic hypothermia. A higher resolution version of the Graphical abstract is available as Supplementary information.

Approaches to Interdisciplinary Care for Infants with Severe Bronchopulmonary Dysplasia: A Survey of the Bronchopulmonary Dysplasia Collaborative.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) remains the most common late morbidity for extremely premature infants. Care of infants with BPD requires a longitudinal approach from the neonatal intensive care unit to ambulatory care though interdisciplinary programs. Current approaches for the development of optimal programs vary among centers. STUDY DESIGN: We conducted a survey of 18 academic centers that are members of the BPD Collaborative, a consortium of institutions with an established interdisciplinary BPD program. We aimed to characterize the approach, composition, and current practices of the interdisciplinary teams in inpatient and outpatient domains. RESULTS: Variations exist among centers, including composition of the interdisciplinary team, whether the team is the primary or consult service, timing of the first team assessment of the patient, frequency and nature of rounds during the hospitalization, and the timing of ambulatory visits postdischarge. CONCLUSION: Further studies to assess long-term outcomes are needed to optimize interdisciplinary care of infants with severe BPD. KEY POINTS: · Care of infants with BPD requires a longitudinal approach from the NICU to ambulatory care.. · Benefits of interdisciplinary care for children have been observed in other chronic conditions.. · Current approaches for the development of optimal interdisciplinary BPD programs vary among centers..

The Relationship Between Follower Affect for President Trump and the Adoption of COVID-19 Personal Protective Behaviors.

In the current series of studies, we draw upon implicit leadership theories, social learning theory, and research on decision making to investigate whether affect toward President Trump explains U.S. residents' evaluations of his leadership during the COVID-19 crisis, as well as the likelihood that that residents engage in personal protective behaviors. A meta-analysis using 17 nationally representative datasets with a total of 26,876 participants indicated that participants who approve of President Trump tend to approve of his leadership regarding the COVID-19 pandemic and were less likely to engage in personal protective behavior (PPBs; i.e., hand washing, wearing a mask or other face covering in public, and social distancing). On the other hand, those disapproving of President Trump also tended to disapprove of his leadership during the COVID-19 crisis and were more likely to engage in PPBs. In a second study, using an established measure of leader affect (leader affect questionnaire) and controlling for political party, we replicated and extended these results by demonstrating that expending cognitive effort toward understanding the COVID-19 crisis attenuated the relationship between affect toward President Trump and (1) approval of his leadership during the COVID-19 crisis and (2) engagement in some, but not all, PPBs.

Epidemiology of Neonatal Acute Respiratory Distress Syndrome: Prospective, Multicenter, International Cohort Study.

OBJECTIVES: Age-specific definitions for acute respiratory distress syndrome (ARDS) are available, including a specific definition for neonates (the "Montreux definition"). The epidemiology of neonatal ARDS is unknown. The objective of this study was to describe the epidemiology, clinical course, treatment, and outcomes of neonatal ARDS. DESIGN: Prospective, international, observational, cohort study. SETTING: Fifteen academic neonatal ICUs. PATIENTS: Consecutive sample of neonates of any gestational age admitted to participating sites who met the neonatal ARDS Montreux definition criteria. MEASUREMENTS AND MAIN RESULTS: Neonatal ARDS was classified as direct or indirect, infectious or noninfectious, and perinatal (≤ 72 hr after birth) or late in onset. Primary outcomes were: 1) survival at 30 days from diagnosis, 2) inhospital survival, and 3) extracorporeal membrane oxygenation (ECMO)-free survival at 30 days from diagnosis. Secondary outcomes included respiratory complications and common neonatal extrapulmonary morbidities. A total of 239 neonates met criteria for the diagnosis of neonatal ARDS. The median prevalence was 1.5% of neonatal ICU admissions with male/female ratio of 1.5. Respiratory treatments were similar across gestational ages. Direct neonatal ARDS (51.5% of neonates) was more common in term neonates and the perinatal period. Indirect neonatal ARDS was often triggered by an infection and was more common in preterm neonates. Thirty-day, inhospital, and 30-day ECMO-free survival were 83.3%, 76.2%, and 79.5%, respectively. Direct neonatal ARDS was associated with better survival outcomes than indirect neonatal ARDS. Direct and noninfectious neonatal ARDS were associated with the poorest respiratory outcomes at 36 and 40 weeks' postmenstrual age. Gestational age was not associated with any primary outcome on multivariate analyses. CONCLUSIONS: Prevalence and survival of neonatal ARDS are similar to those of pediatric ARDS. The neonatal ARDS subtypes used in the current definition may be associated with distinct clinical outcomes and a different distribution for term and preterm neonates.

Injury Prevention Activities in US Schools, School Health Policies and Practices Survey 2014.

BACKGROUND: Exposure to injury and violence early in life increases the risk of experiencing injury and violence later in life. In 2019, the top 3 leading causes of death among 15- to 18-year-olds in the United States were unintentional injury, suicide, and homicide. This study examines the extent to which schools promote injury and violence prevention. METHODS: This study examined injury- and violence-related school policies and practices using nationally representative data from the 2014 School Health Policies and Practices Study. The social ecological model served as the theoretical framework to identify level of impact. RESULTS: For many injury-related topics, more than 75% of schools nationwide had relevant policies and practices to address those topics. However, this study showed differences in schools' injury-related policies and practices by urbanicity. CONCLUSIONS: Understanding and identifying gaps in school policies and practices is essential for reducing and preventing the injury and violence children experience. Collecting data on school policies and practices allows for better monitoring and evaluation to determine which are efficacious and aligned with the best available evidence.

Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia.

OBJECTIVE: To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. RESULTS: AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. CONCLUSIONS: Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.

Ventilatory Strategies in Infants with Established Severe Bronchopulmonary Dysplasia: A Multicenter Point Prevalence Study.

We performed a point prevalence study on infants with severe bronchopulmonary dysplasia (BPD), collecting data on type and settings of ventilatory support; 187 infants, 51% of whom were on invasive positive-pressure ventilation (IPPV), from 15 centers were included. We found a significant center-specific variation in ventilator modes.

Use of inhaled nitric oxide in preterm vs term/near-term neonates with pulmonary hypertension: results of the PaTTerN registry study.

OBJECTIVE: To evaluate inhaled nitric oxide (iNO) in preterm (PT) vs term/near-term (TNT) neonates with hypoxic respiratory failure (HRF) and pulmonary hypertension (PH) in an observational registry (PaTTerN). STUDY DESIGN: Non-inferiority study comparing PT neonates of GA ≥ 27 to <34 weeks vs TNT neonates of GA ≥ 34 to ≤40 weeks with HRF associated with PH, who received iNO for 24-96 h during the first 0-7 days after birth. Primary endpoint: Achieving ≥25% decrease in oxygenation index/surrogate oxygenation index during iNO treatment. RESULTS: Of 140 neonates (PT, n = 55; TNT, n = 85), the primary endpoint was achieved in 50 (90.9%) PT vs 75 (88.2%) TNT neonates (difference [95% CI]: 0.027 [-0.033, 0.087]); PT neonates achieved non-inferiority interval, and the study was stopped early based on prespecified criteria. CONCLUSIONS: Use of iNO for improving oxygenation in PT neonates with HRF associated with PH is at least as effective as in TNT neonates. CLINICAL TRIAL REGISTRATION: #NCT03132428, registered April 27, 2017.

STEM the bullying: An empirical investigation of abusive supervision in academic science.

BACKGROUND: Academic bullying is a topic of significant interest of late, with high profile cases featured in scientific journals. Our aim is to document the nature and extent of academic bullying behaviors, examining who are the primary targets and perpetrators as well as the responses to and outcomes of bullying. METHODS: We developed a cross-sectional global survey aimed primarily at those in academic science institutions. The survey was administered via Qualtrics and data were collected (between November 2019 and July 2021) from 2006 individuals whose participation was solicited through various means including advertisements in Science and Nature magazines and the American Chemical Society. FINDINGS: Among the 2006 survey participants, the majority of targets were graduate students or postdocs. An overwhelming proportion of participants reported either experiencing (84%) or witnessing (59%) abusive supervision, or both (49%). While a majority of perpetrators were male, they were proportionately no more likely to abuse than females. Perpetrators were more likely from the highest-ranked institutions and they were most likely PIs. Females were more likely to report being bullied but their scores on the Tepper abusive supervision scale and the contextual behavior checklist we developed were not greater than male targets. Male targets actually reported higher levels of certain bullying behaviors. While international scholars were no more likely to report being bullied, the severity of the behaviors they reported was significantly greater. Targets (64%) were most likely to use avoidant tactics (not reporting and relying on family/friends for support) in response to bullying due to fear of retaliation (61%). The small percentage that did report the abuse (29%) overwhelmingly reported unfair and biased (58%) outcomes. Additional qualitative analysis of open-ended comments revealed similar patterns. We also noticed that the COVID-19 pandemic has exacerbated academic bullying and changed the patterns of behaviors possibly due to the remote nature of interactions. Open-ended responses from targets are analyzed with examples provided. INTERPRETATION: Our results elucidated the various forms of abuse, the most likely perpetrators and targets, as well as the typical reactions of targets and witnesses. We investigated the results of targets' actions following chronic bullying. Our findings highlight the domain, extent, and dynamics of academic bullying to hopefully motivate the scientific community to take action.

A closer look at the spreaders of COVID-19 in Wisconsin and the US.

In this study, we design and use a mathematical model to primarily address the question of who are the main drivers of COVID-19 - the symptomatic infectious or the pre-symptomatic and asymptomatic infectious in the state of Wisconsin and the entire United States. To set the stage, we first briefly simulate and illustrate the benefit of lockdown. With these lockdown scenarios, and in general, the more dominant influence of the the pre-symptomatic and asymptomatic infectious over the symptomatic infectious, is shown in various ways. Numerical simulations for the U.S. show that an increase in testing and isolating for the pre-symptomatic and asymptomatic infectious group has up to 4 times more impact than an increase in testing for the symptomatic infectious in terms of cumulative deaths. An increase in testing for the pre-symptomatic and asymptomatic infectious group also has significantly more impact (on the order of twice as much) on reducing the control reproduction number than testing for symptomatic infectious. Lastly, we use our model to simulate an implementation of a natural herd immunity strategy for the entire U.S. and for the state of Wisconsin (once an epicenter for COVID-19). These simulations provide specific examples confirming that such a strategy requires a significant number of deaths before immunity is achieved, and as such, this strategy is certainly questionable in terms of success.

Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections.

BACKGROUND: In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population. METHODS: Infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3) at doses stratified by postmenstrual age. Due to slow enrollment, a protocol amendment allowed eligible infants already receiving study regimens to enroll without randomization. The primary outcome was mortality within 30 days of study drug completion. Secondary outcomes included adverse events, outcomes of special interest, and therapeutic success (absence of death, negative cultures, and clinical cure score >4) 30 days after study drug completion. RESULTS: One hundred eighty infants [128 randomized (R), 52 nonrandomized (NR)] were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 [95% confidence interval (CI): 1.39-12.13], 4.53 (95% CI: 1.21-15.50), and 4.07 (95% CI: 1.22-12.70) for groups 1, 2, and 3, respectively. CONCLUSIONS: Each of the antibiotic regimens are safe in premature infants with cIAI. CLINICAL TRIAL REGISTRATION: NCT0199499.