SHEA NICU white paper series: Practical approaches for the prevention of viral respiratory infections.

This white paper provides clinicians and hospital leaders with practical guidance on the prevention and control of viral respiratory infections in the neonatal intensive care unit (NICU). This document serves as a companion to Centers for Disease Control and Prevention Healthcare Infection Control Practices Advisory Committee (HICPAC)'s "Prophylaxis and Screening for Prevention of Viral Respiratory Infections in Neonatal Intensive Care Unit Patients: A Systematic Review." It provides practical, expert opinion and/or evidence-based answers to frequently asked questions about viral respiratory detection and prevention in the NICU. It was developed by a writing panel of pediatric and pathogen-specific experts who collaborated with members of the HICPAC systematic review writing panel and the SHEA Pediatric Leadership Council to identify questions that should be addressed. The document has been endorsed by SHEA, the American Hospital Association (AHA), The Joint Commission, the Pediatric Infectious Diseases Society (PIDS), the Association for Professionals in Infection Control and Epidemiology (APIC), the Infectious Diseases Society of America (IDSA), and the National Association of Neonatal Nurses (NANN).

The Mortality of Congenital Syphilis.

OBJECTIVES: To document the case-fatality rate (CFR) of congenital syphilis diagnosed by molecular tools and rabbit infectivity testing (RIT) of clinical specimens in addition to standard evaluation and to compare that with the CFR using the Centers for Disease Control and Prevention (CDC) surveillance case definition. STUDY DESIGN: Prospective, single site, cohort study of all cases of syphilis among mothers and their infants from 1984 to 2002. The diagnosis of congenital syphilis was determined using IgM immunoblotting, polymerase chain reaction, and RIT of fetal or infant specimens in addition to clinical, laboratory, and radiographic criteria. Data were retrospectively reviewed to ascertain fetal and neonatal mortality. RESULTS: During the 18-year study, there were 191 cases of congenital syphilis confirmed by abnormalities on clinical, laboratory, or radiographic evaluation and/or positive serum IgM immunoblot, blood polymerase chain reaction, or blood/cerebrospinal fluid RIT. Of the 191 cases, 59 died for a CFR of 31%. Of the 59 deaths, 53 (90%) were stillborn and 6 (10%) died in the neonatal period. The majority (74%, 39/53) of stillbirths occurred in the third trimester. The CDC surveillance case definition correctly identified all infants with congenital syphilis, but the CDC CFR was 10% which underestimated the CFR by more than 300%. CONCLUSIONS: Our findings corroborate the high sensitivity of the CDC surveillance definition for congenital syphilis but highlight its poor estimation of its associated mortality. The CFR among infected progeny of pregnant women with syphilis was 31%, due mostly to demise in the third trimester and as such highlights the need for detection and appropriate treatment of syphilis during pregnancy.

Quality Improvement Through Nurse-initiated Kaiser Sepsis Calculator at a County Hospital.

BACKGROUND AND OBJECTIVES: Suspected early onset sepsis drives most antibiotic use in the newborn nursery. The Kaiser Sepsis Calculator (KSC) is a validated tool that safely decreases laboratory evaluation and antibiotic administration in infants aged ≥34 weeks. Our quality improvement aim was a nurse-initiated, KSC-based program to decrease blood cultures (BCx) and complete blood counts (CBC) by 10% from March 2021 to October 2021 among chorioamnionitis-exposed infants born ≥35 weeks' gestation. A secondary aim was to decrease antibiotic administration by 10%. METHODS: The KSC was implemented for infants at University Health, a county hospital affiliate of the University of Texas Health Science Center San Antonio, with a level I nursery and level IV NICU. The multidisciplinary project included pediatric hospitalists, neonatologists, family practitioners, maternal-fetal medicine physicians, fellows, residents, and nurses. All infants born 6 months before (August 2020-January 2021) and 7 months after protocol implementation (March 2021-September 2021) were analyzed. RESULTS: A total of 53 chorioamnionitis-exposed infants were included from the preintervention period and 51 from the postintervention period. CBC utilization decreased from 96% to 27%, BCx utilization decreased from 98% to 37%, and antibiotic utilization fell from 25% to 16%. In no cases were antibiotics prescribed against the KSC, and to our knowledge, no early onset sepsis diagnoses or infection-related hospital readmissions were missed. CONCLUSIONS: The multidisciplinary implementation of the KSC led to a reduction in testing, exceeding our initial goal. A nurse-initiated protocol reduced BCx, CBC, and antibiotic utilization among chorioamnionitis-exposed infants.

Remote Stewardship for Medically Underserved Nurseries: A Stepped-Wedge, Cluster Randomized Study.

BACKGROUND AND OBJECTIVES: Antibiotic overuse is associated with adverse neonatal outcomes. Many medically underserved centers lack pediatric antibiotic stewardship program (ASP) support. Telestewardship may mitigate this disparity. Authors of this study aimed to determine the effectiveness and safety of a nursery-specific ASP delivered remotely. METHODS: Remote ASP was implemented in 8 medically underserved newborn nurseries using a stepped-wedge, cluster-randomized design over 3 years. This included a 15-month baseline period, a 9-month "step-in" period using random nursery order, and a 12-month postintervention period. The program consisted of education, audit, and feedback; and 24/7 infectious diseases provider-to-provider phone consultation availability. Outcomes included each center's volume of antibiotic use and the proportion of infants exposed to any antibiotics. Safety measures included length of stay, transfer to another facility, sepsis, and mortality. RESULTS: During the study period, there were 9277 infants born (4586 preintervention, 4691 postintervention). Infants exposed to antibiotics declined from 6.2% pre-ASP to 4.2% post-ASP (relative risk 0.68 [95% confidence interval, 0.63% to 0.75%]). Total antibiotic use declined from 117 to 84.1 days of therapy per 1000 patient-days (-28% [95% confidence interval -22% to -34%]. No safety signals were observed. Most provider-to-provider consultations were <5 minutes in duration and occurred during normal business hours. CONCLUSIONS: The number of infants exposed to antibiotics and total antibiotic use declined in medically underserved nurseries after implementing a remote ASP. No adverse safety events were seen, and the remote ASP time demands were manageable. Remote stewardship may be a safe and effective strategy for optimizing antibiotic use in medically underserved newborn nurseries.

Neonatal bloodstream infections.

PURPOSE OF REVIEW: Neonatal bloodstream infections (BSI) are a major contributor to morbidity and mortality within neonatal intensive care units. BSI, including central line-associated BSI, have decreased over the past 15 years but remain common in extremely preterm infants. The purpose of this review is to highlight recent advances in the causes, diagnosis, management, and prevention of neonatal BSI. RECENT FINDINGS: Continued quality improvement efforts and bundles have reduced BSI incidence, and novel approaches are highlighted. An update of emerging pathogens as well as traditional pathogens with novel antimicrobial resistance, which are an increasingly common cause of neonatal BSI, is included. Finally, current and future investigations into serum or noninvasive biomarkers for neonatal BSI are reviewed. SUMMARY: Neonatal BSIs continue to decrease due to enhanced infection control and prevention techniques. However, many challenges remain, including emerging bacterial and fungal resistance and the continued need for novel diagnostics that hasten time to pathogen identification and effective treatment. This review of the past 18 months highlights the rapid changes in this area. Ongoing efforts to reduce the morbidity and mortality caused by neonatal BSI must remain a priority.

Biomarkers for the Diagnosis of Neonatal Sepsis.

Neonatal sepsis is a major cause of morbidity and mortality in neonates and is challenging to diagnose. Infants manifest nonspecific clinical signs in response to sepsis; these signs may be caused by noninfectious conditions. Time to antibiotics affects neonatal sepsis outcome, so clinicians need to identify and treat neonates with sepsis expeditiously. Clinicians use serum biomarkers to measure inflammation and infection and assess the infant's risk of sepsis. However, current biomarkers lack sufficient sensitivity or specificity to be consider useful diagnostic tools. Continued research to identify novel biomarkers as well as novel ways of measuring them is sorely needed.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

Antibiotic exposure and growth patterns in preterm, very low birth weight infants.

BACKGROUND: Antibiotic exposure in term infants has been associated with later obesity. Premature, very-low-birth-weight (birth weight ≤ 1500 g) infants in the neonatal intensive care unit frequently are exposed to antibiotics. Our hypothesis was that in preterm infants, there is a positive linear and dose-dependent relationship between antibiotic exposure and growth from birth through 12 months' corrected age. METHODS: Retrospective analysis of prospectively collected data of all antibiotic use among inborn, preterm (≤32 weeks' gestation), very-low-birth-weight infants admitted to the neonatal intensive care unit at Parkland Memorial Hospital and followed in the Low Birth Weight Clinic at Children's Medical Center, Dallas, TX. Antibiotic use was quantified by days of therapy which was compared with weight and length parameters at birth, 36 weeks' postmenstrual age, and 2, 4, 6, and 12 months' corrected age. The change in weight and length z-scores from birth to all subsequent age points was calculated. Stepwise multivariate regression analysis was performed to determine predictors of weight, length, and weight-for-length delta z-scores from birth to each subsequent age point. RESULTS: During the 18-month study, 161 infants received a median of 11 (IQR, 5.5-19.5) antibiotic days of therapy which was not associated with weight or length delta z-scores from birth through 12 months' corrected age. CONCLUSION: Association of prolonged antibiotic use and neonatal morbidities and mortality may override the potential association with increased weight gain in the NICU and beyond.

Short-Term Complications Associated with Surgical Ligation of Patent Ductus Arteriosus in ELBW Infants: A 25-Year Cohort Study.

OBJECTIVE: This article aims to determine the incidence of short-term complications of surgical patent ductus arteriosus (PDA) ligations, the factors associated with those complications, and whether complications are associated with poor long-term outcomes. STUDY DESIGN: Retrospective cohort study of all extremely low birth weight (ELBW, < 1,000 g) infants who underwent surgical PDA ligation at a single-center neonatal intensive care unit from 1989 to 2015. Demographic, clinical, and laboratory data were reviewed. The primary outcome was development of a short-term (< 2 weeks from ligation) surgical complication. Secondary outcomes include bronchopulmonary dysplasia (BPD), length of stay, and mortality. RESULTS: A total of 180 ELBW infants were included; median gestational age and birth weight was 24 weeks and 683 g, respectively, and 44% of infants had at least one short-term complication. Need for vasopressors (33%) was the most common medical complication and vocal cord paralysis (9%) was the most common surgical complication. Younger corrected gestational age at time of repair was associated with increased risk for complications. Mortality, length of stay, and BPD rates were similar between infants with and without complications. CONCLUSION: Serious complications were seen in a minority of infants. Additional research is needed to determine if short-term complications are associated with long-term adverse outcomes.

The impact of isolation precautions on caregiver-infant interactions in the neonatal intensive care unit: A case-control study.

This case-control study investigated the association between isolation precautions and the frequency of infant-caregiver interaction in the NICU. Interactions were discretely counted; cases and controls were matched by isolation status. Cases had fewer interactions than controls (median, 4 vs 8; P < .0001). Further research is needed to determine whether this reduction impacts patient outcomes.

Antibiotic Utilization and Infection Among Infants with Abdominal Wall Defects.

BACKGROUND: Neonates with abdominal wall defects are at an increased infection risk because of the defect itself and prolonged neonatal intensive care unit (NICU) stays. Antibiotic prophylaxis until closure of the defect is common. However, infection risk and antibiotic use have not been well quantified in these infants. METHODS: A retrospective cohort study of infants with abdominal wall defects (gastroschisis and omphalocele) admitted to a single-center NICU from 2007 to 2018. Demographic and clinical information, including microbiologic studies, antibiotic dosing and surgical care, were collected. Antibiotic use was quantified using days of therapy (DOT) per 1000 patient-days. Sepsis was defined as culture of a pathogen from a normally sterile site. RESULTS: Seventy-four infants were included; 64 (86%) with gastroschisis and 10 (14%) with omphalocele. Median day of closure was 8 days [interquartile range (IQR) 6-10, range 0-31]. All infants received ≥1 course of antibiotics; median antibiotic DOT/infant was 24.5 (IQR 18-36) for an average of 416.5 DOT per 1000 patient-days. Most antibiotic use was preclosure prophylaxis (44%) and treatment of small intestinal bowel overgrowth (24%). Suspected and proven infection accounted for 26% of all antibiotic use. Skin and soft tissue infection (13/74, 18%) and late-onset sepsis (11/74, 15%) were the most common infections; 2 infants had sepsis while on antibiotic prophylaxis. All infants survived to discharge. CONCLUSIONS: Most antibiotic use among infants with abdominal wall defects was prophylactic. Infection on prophylaxis was rare, but 35% of infants had infection after prophylaxis. Improved stewardship strategies are needed for these high-risk infants.

Malassezia Hepatic Abscess in a Neonate.

Malassezia sp. require exogenous lipid for growth and can cause disseminated infection in neonates requiring intravenous lipid infusions. Usually, Malassezia infection in neonates presents as fungemia or hematogenous dissemination into bone or lungs. We present a presumed case of Malassezia liver abscess associated with lipid infusion via a mispositioned umbilical venous catheter.

Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection.

OBJECTIVE: To determine the frequency of abnormal findings on evaluation of neonates with congenital CMV infection who have a normal physical examination STUDY DESIGN: Retrospective, 2-center study (1996-2017) that reviewed results of complete blood cell count and platelets, serum alanine aminotransferase (ALT) and bilirubin concentrations, eye examination, cranial ultrasonography or other neuroimaging, and brainstem evoked responses performed on neonates with congenital CMV infection and a normal physical examination RESULTS: Of 34 infants with congenital CMV infection and a normal physical examination, 56% (19/34) had ≥1 abnormality: 39%, elevated ALT concentration; 45%, abnormal neuroimaging (five, lenticulostriate vasculopathy; six, intraventricular hemorrhage; four, calcifications); 12%, anemia; 16%, thrombocytopenia; and 3%, chorioretinitis. Seven (21%) infants had sensorineural hearing loss, and 18 infants received antiviral therapy. CONCLUSION: Some infants with congenital CMV infection and a normal physical examination had abnormalities on laboratory or neuroimaging evaluation, which in some cases prompted antiviral treatment.

Hospital-level Antibiotic Use and Complexity of Care Among Neonates.

BACKGROUND: Despite increasing neonatal antibiotic stewardship efforts, understanding of interhospital variation in neonatal antibiotic use is limited. METHODS: A retrospective cohort study was conducted among primarily academically affiliated hospitals participating in the Vizient Clinical Database/Resource Manager. Neonatal discharges were identified by admission age <1 month, excluding nonviable neonates and normal newborns. Hospitals with ≥100 neonatal discharges and complete data for January-December 2016 were included. Antibiotic use was measured in days of therapy per 1000 patient-days (DOT/1000 pd). A composite measure of neonatal care complexity (NCC; low, medium, high) was based on the volume of very low-birth-weight neonates and neonates undergoing surgical procedures, cardiac surgery, or extracorporeal membranous oxygenation. RESULTS: The 118 included hospitals represented 184 716 neonatal discharges; 22 hospitals with low NCC, 56 with medium NCC, and 40 with high NCC. Mean antibiotic DOT/1000 pd was 363 (standard deviation [SD], 94) in high NCC hospitals, 243 (SD, 88) in medium NCC hospitals, and 184 (SD, 122) in low NCC hospitals. Increasing NCC was associated with higher antibiotic use, with an incidence rate ratio (IRR) of 1.95 (95% confidence interval [CI], 1.55 to 2.47) for high vs low NCC and IRR 1.31 (95% CI, 1.05 to 1.64) for medium vs low NCC. Increasing case mix index was associated with higher antibiotic use (IRR 1.86 per unit increase; 95% CI, 1.50 to 2.31). CONCLUSIONS: Aggregate antibiotic use among hospitalized neonates varies based on care complexity. Substantial variation despite stratification by complexity suggests incomplete risk adjustment and/or avoidable variation in care.