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.

Keeping It Real: Infection Prevention and Control Problems and Solutions in Low- and Middle-income Countries.

Infection prevention challenges are ubiquitous in healthcare, but some are unique to or more prevalent in low-and middle-income country settings. Despite limited resources, innovative and committed paediatric healthcare providers and infection preventionists have found creative solutions to address the very real and pressing risks their patients face every day. We gathered examples of infection prevention and control challenges faced by clinicians in resource-limited healthcare facilities, and the real-world infection prevention and control solutions they implemented, with the goal of learning broader lessons applicable to low-and middle-income countrie.

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.

Psychological Reactance is a Novel Risk Factor for Adolescent Antiretroviral Treatment Failure.

Psychological reactance is an aversive response to perceived threats against personal agency. For adolescents receiving HIV treatment in Botswana, we utilized a two-question, medication-specific reactance tool to assess whether: (1) verbal reminders to take medicines made adolescents want to avoid taking them, and, (2) whether adolescents felt anger when reminded to take medicines. Reactant adolescents had 2.05-fold (95% CI 1.23, 3.41) greater odds of treatment failure than non-reactant adolescents (p = 0.03). Adjusted risk of treatment failure was 14% (95% CI 3%, 28%) greater for each point elevation in reactance score (p = 0.016). Autonomy over medication-taking did not modify the association between reactance and treatment failure. Psychological reactance may be a useful interventional target for improving adolescent adherence.