Antibiotic Treatment of Suspected and Confirmed Neonatal Sepsis Within 28 Days of Birth: A Retrospective Analysis

Neonatal sepsis causes significant mortality and morbidity worldwide. Diagnosis is usually confirmed via blood culture results. Blood culture sepsis confirmation can take days and suffer from contamination and false negatives. Empiric therapy with antibiotics is common. This study aims to retrospectively describe and compare treatments of blood culture-confirmed and unconfirmed, but suspected, sepsis within the University of Utah Hospital system. Electronic health records were obtained from 1,248 neonates from January 1, 2006, to December 31, 2017. Sepsis was categorized into early-onset (≤3 days of birth, EOS) and late-onset (\u3e3 and ≤28 days of birth, LOS) and categorized as culture-confirmed sepsis if a pathogen was cultured from the blood and unconfirmed if all blood cultures were negative with no potentially contaminated blood cultures. Of 1,010 neonates in the EOS cohort, 23 (2.3%) were culture-confirmed, most with Escherichia coli (42%). Treatment for unconfirmed EOS lasted an average of 6.1 days with primarily gentamicin and ampicillin while confirmed patients were treated for an average of 12.3 days with increased administration of cefotaxime. Of 311 neonates in the LOS cohort, 62 (20%) were culture-confirmed, most culturing coagulase negative staphylococci (46%). Treatment courses for unconfirmed LOS lasted an average of 7.8 days while confirmed patients were treated for an average of 11.4 days, these patients were primarily treated with vancomycin and gentamicin. The use of cefotaxime for unconfirmed EOS and LOS increased throughout the study period. Cefotaxime administration was associated with an increase in neonatal mortality, even when potential confounding factors were added to the logistic regression model (adjusted odds ratio 2.8, 95%CI [1.21, 6.88], p = 0.02). These results may not be generalized to all hospitals and the use of cefotaxime may be a surrogate for other factors. Given the low rate of blood culture positive diagnosis and the high exposure rate of empiric antibiotics, this patient population might benefit from improved diagnostics with reevaluation of antibiotic use guideline

Streetsport: Supporting and facilitating the development of enhanced graduate attributes.

Streetsport is a programme that aims to exercise social innovation by reducing instances of youth crime and anti-social behaviour; whilst promoting health and wellbeing through sport, physical activity and creative endeavour. As a vehicle for delivery the initiative facilitates work based educational experiences that are embedded within disadvantaged communities; supporting the development of enhanced graduate attributes by way of collaborative teaching and learning support. Adopting a collaborative partnership model, the programme brings together multiple courses, students and stakeholders to work within communities resulting in activities that react and respond to local needs, interests and demand

Master of Science

thesisMillions of neonates die each year worldwide with almost half of these deaths caused by severe infections resulting in sepsis. Preterm infants have higher rates of sepsis and may be at increased risk of severe complications, including death. The reports on frequency of early onset sepsis (EOS) and late onset sepsis (LOS) among neonates vary significantly depending on gestational age (GA), weight of newborn, and country of birth. There is no clearly established GA cutoff that separate neonates who are relatively resistant or susceptible to infection. It is thought that newborn susceptibility to infections is due to the immaturity of their immune system. However, recent discovery of residual levels of myeloid derived suppressor cells (MDSC) in the cord blood (CB) of term neonates suggested a potential role for MDSC in neonatal susceptibility to microbial infections. MDSC are best known for their negative role in the development of anti-cancer immune responses. Recently, it has been reported that elevated levels of MDSC are present in the peripheral blood of adult patients with sepsis. We hypothesize that residual MDSC present in the CB of newborns can serve as a biomarker of neonatal infection and specifically, LOS. The main purpose of this project was to establish a GA cutoff point that separates "resistant" and "susceptible" to LOS neonatal cohorts and to develop protocols for detection of various subsets of MDSC. Additionally, protocols for MDSC isolation using microbead technology were developed. Isolated MDSC will be used in future studies to establish iv mechanisms by which MDSC modulate immune responses in septic and healthy neonates. To identify GA cutoff for the selection of suitable participants for future study cohorts, medical record reviews of neonates hospitalized at the University of Utah Hospital from January 1, 2006-September 30, 2015 were conducted and etiologies of LOS were assessed. Lastly, this study collected CB samples from term neonates for MDSC isolation and phenotypic analysis of MDSC subsets. It was determined that GA of 30 weeks is the optimal cutoff point for selecting a cohort to study the association of susceptibility of neonates to LOS and presence of MDSC in their CB. Coagulase negative Staphylococcus (CoNS) was identified as the dominant bacterial strain causing LOS in neonates (47.4%). Vancomycin was found to be the most prescribed antibiotic for treatment of LOS. Evaluation of term neonatal CB identified 4 subsets of MDSC of neonates and a protocol was developed to guide future evaluations. The percentages of MDSC subsets among term neonates varied. The mean percentages were for granulocytic MDSC (G-MDSC) 6.4%, CD14low CD15hi 0.5%, CD14lowCD15low/inter 2.8%, and monocytic MDSC 0.4%. Additionally, an isolation protocol of MDSC and G-MDSC from CB using microbead technology was developed. The results of this research will provide a foundation for future study endeavors to use microbead isolation techniques to determine the suppressive functions of MDSC subsets in CB and provide a platform to explore ideas to differentiate MDSC or block their suppressive activity

Antibiotic Treatment of Suspected and Confirmed Neonatal Sepsis Within 28 Days of Birth: A Retrospective Analysis

Neonatal sepsis causes significant mortality and morbidity worldwide. Diagnosis is usually confirmed via blood culture results. Blood culture sepsis confirmation can take days and suffer from contamination and false negatives. Empiric therapy with antibiotics is common. This study aims to retrospectively describe and compare treatments of blood culture-confirmed and unconfirmed, but suspected, sepsis within the University of Utah Hospital system. Electronic health records were obtained from 1,248 neonates from January 1, 2006, to December 31, 2017. Sepsis was categorized into early-onset (≤3 days of birth, EOS) and late-onset (\u3e3 and ≤28 days of birth, LOS) and categorized as culture-confirmed sepsis if a pathogen was cultured from the blood and unconfirmed if all blood cultures were negative with no potentially contaminated blood cultures. Of 1,010 neonates in the EOS cohort, 23 (2.3%) were culture-confirmed, most with Escherichia coli (42%). Treatment for unconfirmed EOS lasted an average of 6.1 days with primarily gentamicin and ampicillin while confirmed patients were treated for an average of 12.3 days with increased administration of cefotaxime. Of 311 neonates in the LOS cohort, 62 (20%) were culture-confirmed, most culturing coagulase negative staphylococci (46%). Treatment courses for unconfirmed LOS lasted an average of 7.8 days while confirmed patients were treated for an average of 11.4 days, these patients were primarily treated with vancomycin and gentamicin. The use of cefotaxime for unconfirmed EOS and LOS increased throughout the study period. Cefotaxime administration was associated with an increase in neonatal mortality, even when potential confounding factors were added to the logistic regression model (adjusted odds ratio 2.8, 95%CI [1.21, 6.88], p = 0.02). These results may not be generalized to all hospitals and the use of cefotaxime may be a surrogate for other factors. Given the low rate of blood culture positive diagnosis and the high exposure rate of empiric antibiotics, this patient population might benefit from improved diagnostics with reevaluation of antibiotic use guideline