Maternal and neonatal IgG against Klebsiella pneumoniae are associated with broad protection from neonatal sepsis: a case-control study of hospitalized neonates in Botswana.

Sepsis is the leading postnatal cause of neonatal mortality worldwide. Globally Klebsiella pneumoniae is the leading cause of sepsis in hospitalized neonates. This study reports development and evaluation of ELISA for anti-Klebsiella IgG using dried blood spot samples and evaluates the association of anti-Klebsiella IgG (anti-Kleb IgG) antibodies in maternal and neonatal samples and the risk of neonatal sepsis. Neonates and their mothers were enrolled at 0-96 hours of life in the neonatal unit of a tertiary referral hospital in Gaborone, Botswana and followed until death or discharge to assess for episodes of blood culture-confirmed neonatal sepsis. Neonates with sepsis had significantly lower levels of Kleb-IgG compared to neonates who did not develop sepsis (Mann-Whitney U, p=0.012). Similarly, samples from mothers of neonates who developed sepsis tended to have less Kleb-IgG compared to mothers of controls (p=0.06). The inverse correlation between Kleb-IgG levels and all-cause bacteremia suggests that maternal Kleb-IgG is broadly protective through cross-reactivity with common bacterial epitopes. These data support the continued use of immunoglobulin assays using DBS samples to explore the role of passive immunity on neonatal sepsis risk and reaffirm the critical need for research supporting the development of maternal vaccines for neonatal sepsis.

Antibiotic Use for Sepsis in Hospitalized Neonates in Botswana: Factors Associated with Guideline-Divergent Prescribing.

In low- and middle-income countries, where antimicrobial access may be erratic and neonatal sepsis pathogens are frequently multidrug-resistant, empiric antibiotic prescribing practices may diverge from the World Health Organization (WHO) guidelines. This study examined antibiotic prescribing for neonatal sepsis at a tertiary referral hospital neonatal unit in Gaborone, Botswana, using data from a prospective cohort of 467 neonates. We reviewed antibiotic prescriptions for the first episode of suspected sepsis, categorized as early-onset (EOS, days 0-3) or late-onset (LOS, >3 days). The WHO prescribing guidelines were used to determine whether antibiotics were "guideline-synchronous" or "guideline-divergent". Logistic regression models examined independent associations between the time of neonatal sepsis onset and estimated gestational age (EGA) with guideline-divergent antibiotic use. The majority (325/470, 69%) were prescribed one or more antibiotics, and 31 (10%) received guideline-divergent antibiotics. Risk factors for guideline-divergent prescribing included neonates with LOS, compared to EOS (aOR [95% CI]: 4.89 (1.81, 12.57)). Prematurity was a risk factor for guideline-divergent prescribing. Every 1-week decrease in EGA resulted in 11% increased odds of guideline-divergent antibiotics (OR [95% CI]: 0.89 (0.81, 0.97)). Premature infants with LOS had higher odds of guideline-divergent prescribing. Studies are needed to define the causes of this differential rate of guideline-divergent prescribing to guide future interventions.

County-Level Maternal Vulnerability and Preterm Birth in the US.

Importance: Appreciation for the effects of neighborhood conditions and community factors on perinatal health is increasing. However, community-level indices specific to maternal health and associations with preterm birth (PTB) have not been assessed. Objective: To examine the association of the Maternal Vulnerability Index (MVI), a novel county-level index designed to quantify maternal vulnerability to adverse health outcomes, with PTB. Design, Setting, and Participants: This retrospective cohort study used US Vital Statistics data from January 1 to December 31, 2018. Participants included 3 659 099 singleton births at 22 plus 0/7 to 44 plus 6/7 weeks of gestation born in the US. Analyses were conducted from December 1, 2021, through March 31, 2023. Exposure: The MVI, a composite measure of 43 area-level indicators, categorized into 6 themes reflecting physical, social, and health care landscapes. Overall MVI and theme were stratified by quintile (very low to very high) by maternal county of residence. Main Outcomes and Measures: The primary outcome was PTB (gestational age <37 weeks). Secondary outcomes were PTB categories: extreme (gestational age ≤28 weeks), very (gestational age 29-31 weeks), moderate (gestational age 32-33 weeks), and late (gestational age 34-36 weeks). Multivariable logistic regression quantified associations of MVI, overall and by theme, with PTB, overall and by PTB category. Results: Among 3 659 099 births, 298 847 (8.2%) were preterm (male, 51.1%; female, 48.9%). Maternal race and ethnicity included 0.8% American Indian or Alaska Native, 6.8% Asian or Pacific Islander, 23.6% Hispanic, 14.5% non-Hispanic Black, 52.1% non-Hispanic White, and 2.2% with more than 1 race. Compared with full-term births, MVI was higher for PTBs across all themes. Very high MVI was associated with increased PTB in unadjusted (odds ratio [OR], 1.50 [95% CI, 1.45-1.56]) and adjusted (OR, 1.07 [95% CI, 1.01-1.13]) analyses. In adjusted analyses of PTB categories, MVI had the largest association with extreme PTB (adjusted OR, 1.18 [95% CI, 1.07-1.29]). Higher MVI in the themes of physical health, mental health and substance abuse, and general health care remained associated with PTB overall in adjusted models. While the physical health and socioeconomic determinant themes were associated with extreme PTB, physical health, mental health and substance abuse, and general health care themes were associated with late PTB. Conclusions and Relevance: The findings of this cohort study suggest that MVI was associated with PTB even after adjustment for individual-level confounders. The MVI is a useful measure for county-level PTB risk that may have policy implications for counties working to lower preterm rates and improve perinatal outcomes.

Characterizing the bioburden of ESBL-producing organisms in a neonatal unit using chromogenic culture media: a feasible and efficient environmental sampling method.

INTRODUCTION: Infections due to extended spectrum beta-lactamase producing organisms (ESBL) have emerged as the leading cause of sepsis among hospitalized neonates in Botswana and much of sub-Saharan Africa and south Asia. Yet, ESBL reservoirs and transmission dynamics within the neonatal intensive care unit (NICU) environment are not well-understood. This study aimed to assess the efficiency and feasibility of a chromogenic-culture-media-based environmental sampling approach to characterize the ESBL bioburden within a NICU. METHODS: A series of four point-prevalence surveys were conducted at a 36-bed NICU at a public tertiary referral hospital in Botswana from January-June 2021. Samples were collected on 4 occasions under semi-sterile technique using 1) flocked swabs & templates (flat surfaces); 2) sterile syringe & tubing (water aspiration); and 3) structured swabbing techniques (hands & equipment). Swabs were transported in physiological saline-containing tubes, vortexed, and 10 µL was inoculated onto chromogenic-agar that was selective and differential for ESBL (CHROMagar™ ESBL, Paris, France), and streaking plates to isolate individual colonies. Bacterial colonies were quantified and phenotypically characterized using biochemical identification tests. RESULTS: In total, 567 samples were collected, 248 (44%) of which grew ESBL. Dense and consistent ESBL contamination was detected in and around sinks and certain high-touch surfaces, while transient contamination was demonstrated on medical equipment, caregivers/healthcare worker hands, insects, and feeding stations (including formula powder). Results were available within 24-72 h of collection. To collect, plate, and analyse 50 samples, we estimated a total expenditure of $269.40 USD for materials and 13.5 cumulative work hours among all personnel. CONCLUSIONS: Using basic environmental sampling and laboratory techniques aided by chromogenic culture media, we identified ESBL reservoirs (sinks) and plausible transmission vehicles (medical equipment, infant formula, hands of caregivers/healthcare workers, & insects) in this NICU environment. This strategy was a simple and cost-efficient method to assess ESBL bioburden and may be feasible for use in other settings to support ongoing infection control assessments and outbreak investigations.

Pediatric Palliative Care Education Model in Low Resource Settings: A Mixed-Methods Evaluation.

CONTEXT: Globally, approximately 21.6 million children need pediatric palliative care (PPC). The greatest burden lies in low- and middle-income countries, where the demand for PPC exceeds available resources. OBJECTIVES: The objective of this study was to assess the impact of a PPC workshop on healthcare providers' self-efficacy, comfort and confidence related to the provision of PPC in a Bhutanese referral-level hospital. METHODS: This mixed-methods study included a one-and-a-half day PPC workshop with surveys administered to participants at three time points (before, immediately after, and six months after the workshop) to evaluate changes in self-efficacy, comfort and confidence. The study was conducted in January 2017 with healthcare providers at the Jigme Dorji Wangchuck National Referral Hospital in Thimphu, Bhutan. RESULTS: Forty-one providers participated in the workshop; 38 completed the post-workshop survey and 27 completed the six months post-workshop survey. Results showed statistically significant increases in comfort levels from pre- to post-workshop surveys across nearly all areas. Qualitative results supported these findings. CONCLUSION: The results of this study suggest that a short, interactive and interdisciplinary workshop, originally designed for the United States setting but adapted to a low resource context, is an effective way to improve providers' self-efficacy, comfort and confidence in the provision of PPC in resource-limited settings.