Management of the infant born to a mother with tuberculosis: a systematic review and consensus practice guideline.

Infants born to mothers with tuberculosis disease are at increased risk of developing tuberculosis disease themselves. We reviewed published studies and guidelines on the management of these infants to inform the development of a consensus practice guideline. We searched MEDLINE, CINAHL, and Cochrane Library from database inception to Dec 1, 2022, for original studies reporting the management and outcome of infants born to mothers with tuberculosis. Of the 521 published papers identified, only three met inclusion criteria and no evidence-based conclusions could be drawn from these studies, given their narrow scope, variable aims, descriptive nature, inconsistent data collection, and high attrition rates. We also assessed a collection of national and international guidelines to inform a consensus practice guideline developed by an international panel of experts from different epidemiological contexts. The 16 guidelines reviewed had consistent features to inform the expert consultation process. Two management algorithms were developed-one for infants born to mothers considered potentially infectious at the time of delivery and another for mothers not considered infectious at the time of delivery-with different guidance for high and low tuberculosis incidence settings. This systematic review and consensus practice guideline should facilitate more consistent clinical management, support the collection of better data, and encourage the development of more studies to improve evidence-based care.

Etiologies of Mild and Moderate Diarrheal Illness among Children in Consuelo, Dominican Republic.

Since the rotavirus vaccine was included in the Dominican Republic's national immunization schedule in 2012, the microbiologic etiologies of acute gastroenteritis have not been described. This study aimed to determine the contribution of rotavirus as an etiology of acute gastroenteritis over a 12-month period in children under 5 years of age in both an inpatient and an outpatient setting in Consuelo, Dominican Republic. All children who were seen at Niños Primeros en Salud clinic or admitted to Hospital Municipal Dr. Angel Ponce Pinedo for acute gastroenteritis during January 2021-April 2022 were enrolled in the study. Stools were evaluated for rotavirus, enteric parasites, and pathogenic bacteria. Pathogen detection was compared between outpatients and inpatients and on the basis of child's vaccination status. From 181 children enrolled, 170 stool samples were collected, 28 (16.5%) from inpatients and 142 (83.5%) from outpatients. Rotavirus was the most commonly detected pathogen and was proportionately more common among hospitalized children, with nine (32.1%) cases among hospitalized children and 16 (11.3%) among outpatient children. (Pearson χ2 = 8.1, P = 0.004). Among patients with a positive rotavirus result, vaccination rate was lower among moderate (hospitalized) (three of six; 50%) compared with mild (outpatient) diarrhea patients (12 of 15; 80%). Giardia lamblia (10%) was the next most prevalent pathogen detected in both inpatients and outpatients using standard laboratory measures. Despite the availability of rotavirus vaccination, rotavirus remains a common cause of gastrointestinal illness among children under 5 years of age in our cohort. Incomplete vaccination status was associated with hospitalization for gastrointestinal illness.

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.

Genomic Analysis of Group B Streptococcus Carriage Isolates From Botswana Reveals Distinct Local Epidemiology and Identifies Novel Strains.

In pregnant people colonized with group B Streptococcus (GBS) in Botswana, we report the presence/expansion of sequence types 223 and 109, a low rate of erythromycin resistance, and 3 novel sequence types. These data highlight the importance of local epidemiologic studies of GBS, a significant source of neonatal disease.

Near-term pregnant women in the Dominican Republic experience high rates of Group B Streptococcus rectovaginal colonization with virulent strains.

Maternal colonization with Group B Streptococcus (GBS) is an important cause of stillbirth, prematurity, and serious infection and death in infants worldwide. Resource constraints limit prevention strategies in many regions. Maternal GBS vaccines in development could be a more accessible prevention strategy, but data on geographic variations in GBS clones are needed to guide development of a broadly effective vaccine. In the Dominican Republic (DR), limited data suggest that pregnant women experience GBS colonization at rates among the highest globally. We aimed to determine the prevalence of maternal rectovaginal GBS colonization and describe clonal characteristics of colonizing strains in the DR. A cross-sectional study assessed rectovaginal GBS colonization in 350 near-term pregnant women presenting for routine prenatal care at an urban tertiary center in the DR. Rectovaginal samples were tested with chromogenic Strep B Carrot Broth and cultured for confirmatory whole-genome sequencing. In a secondary analysis, participants' demographics and histories were assessed for association with GBS colonization. Rectovaginal GBS colonization occurred in 26.6% of women. Serotypes Ia, Ib, II, III, IV, and V were detected, with no one serotype predominating; serotype III was identified most frequently (21.5%). Virulent and emerging strains were common, including CC17 (15.1%) and ST1010 (17.2%). In this first characterization of maternal GBS serotypes in the DR, we found high rates of rectovaginal colonization including with virulent and emerging GBS strains. The serotypes observed here are all targeted by candidate hexavalent GBS vaccines, suggesting effective protection in the DR.

Factors Associated With Initiating Breastfeeding and Continuing it for At Least 4 Months in Consuelo, a Rural Town in the Dominican Republic.

Objective. We assessed the proportion of and factors associated with mothers initiating and continuing breastfeeding (BF) for ≥4 months in a rural town of the Dominican Republic. Methods. A survey was administered to 190 mothers of children cared for at a free clinic in Consuelo. Modified bivariate and multivariable Poisson regressions were utilized in data analysis. Results. BF was initiated in 89.5% of cases and continued ≥4 months in 81.7% of cases. Maternal education beyond secondary school [adjusted RR = 1.13, 95% CI: (1.04-1.24), 0.010], and visiting both public and private antenatal clinics [adjusted RR = 1.25; 95% CI: (1.10-1.37), 0.010] were associated with BF initiation. Public and private antenatal clinic attendance [adjusted RR = 1.01, 95% CI: (0.45-2.23), 0.020], Cesarean section [adjusted RR = 0.81, 95% CI: (0.68-0.98), 0.026], number of biological children [adjusted RR = 0.95, 95% CI: (0.90-1.00), 0.032] and maternal employment [adjusted RR = 0.89, 95% CI: (0.79-0.99), 0.048] were associated with BF continuation. Conclusions. These results provide valuable insights for targeting specific populations in future breastfeeding education interventions.

Under-Reporting of Tuberculosis Disease among Children and Adolescents in Low and Middle-Income Countries: A Systematic Review.

Under-reporting of tuberculosis (TB) disease in children and adolescents is a significant global concern, as many children are missing from TB notification data. A systematic literature review was conducted to understand the global reporting gap of child and adolescent TB as well as current interventions to close this gap in Low- and Middle- Income Countries (LMIC). Our study found large and variable gaps in child and adolescent TB reporting, due to various factors. Interventions to close this gap exist but are limited. Future studies are necessary to improve global surveillance systems to improve TB care delivery for children and adolescents.

Maternity care provider acceptance of a future Group B Streptococcus vaccine - A qualitative study in three countries.

INTRODUCTION: There are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). When approved, GBS vaccines will be intended for administration to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its' uptake in the population. Experience with prior maternal vaccines, e.g. influenza, Tdap and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women, and that provider recommendation is a key driver of vaccine uptake. METHODS: This study investigated attitudes of maternity care providers towards the introduction of a GBS vaccine in three countries (the United States (US), Ireland, and the Dominican Republic (DR)) with different GBS prevalence and prevention practices. Semi-structured interviews with maternity care providers were transcribed and coded for themes. The constant comparative method, and inductive theory building were used to develop conclusions. RESULTS: Thirty-eight obstetricians, 18 general practitioners and 14 midwives participated. There was variability in provider attitudes towards a hypothetical GBS vaccine. Responses ranged from enthusiasm to doubts over the need for a vaccine. Attitudes were influenced by perceived additional benefits of a vaccine over current strategy and confidence in the safety of vaccines during pregnancy. Knowledge, experience and approaches to GBS prevention differed geographically and according to provider type, and influenced how participants assessed the risks and benefits of a GBS vaccine. CONCLUSION: Maternity care providers are engaged in the topic of GBS management and there is opportunity to leverage attitudes and beliefs that will support a strong recommendation for a GBS vaccine. However, knowledge of GBS, and of the limitations of current prevention strategies vary among providers in different regions, and between different provider types. Targeted educational efforts with antenatal providers should focus on highlighting safety data the potential benefits of vaccination over current strategies.

Severity of illness and mortality among children admitted to a tertiary referral hospital in Botswana: A secondary data analysis of a prospective cohort study.

Objectives: Data on triage practices of children admitted to Princess Marina Hospital in Gaborone, Botswana is limited. The inpatient triage, assessment, and treatment score was developed for low resource settings to predict mortality in children. We assess its performance among children admitted to Princess Marina Hospital and their demographic, clinical, and risk factors for death. Methods: This was a secondary data analysis of a prospective cohort study comprising 299 children ages 1 month to 13 years admitted June to September 2018. Descriptive statistics, bivariate analysis, and multivariate logistic regression were used. Sensitivity and specificity data were generated for the inpatient triage, assessment, and treatment score. Results: Thirteen children died (13/284, 4.6%). Comorbidity (adjusted odds ratio 4.0, p = 0.020) and high inpatient triage, assessment, and treatment score (adjusted odds ratio 5.0, p = 0.017) increased odds of death. The area under the receiver operating characteristic curve was 0.81. Using inpatient triage, assessment, and treatment cutoff of 4, the sensitivity, specificity, and likelihood ratio were 31%, 94%, and 5.0, respectively. Conclusion: Implementing the inpatient triage, assessment, and treatment score in low resource settings may improve identification, treatment, and evaluation of the sickest children.

Kinetics of pneumococcal antibodies among HIV-exposed, uninfected infants in Botswana.

BACKGROUND: Streptococcus pneumoniae is a leading cause of severe infections among children. Despite vaccination, HIV-exposed, uninfected (HEU) children have a higher incidence of invasive pneumococcal disease than HIV-unexposed, uninfected (HUU) children. We sought to compare the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV-13) in HEU and HUU infants. METHODS: We conducted a prospective cohort study of 134 mother-infant dyads in Botswana. Infants received PCV-13 doses at 2, 3, and 4 months through routine clinical care. We measured IgG antibodies specific to vaccine serotypes in sera collected from infants at 0, 5, and 12 months of age. We calculated the proportion of infants with protective IgG levels (≥0.35 µg/mL) to specific pneumococcal serotypes. RESULTS: At birth, fewer than half of infants had protective IgG levels to serotypes 1 (38%), 3 (46%), 4 (33%), 5 (23%), 6B (40%), 7F (44%), 9 V (44%), and 23F (46%). Compared to HUU infants (n = 97), HEU infants (n = 37) had lower antibody concentrations at birth to serotypes 5 (p = 0.046) and 19A (p = 0.008) after adjustment for maternal age and infant birth weight. More than 80% of HEU and HUU infants developed protective antibody levels to each of the 13 vaccine serotypes following PCV-13 vaccination. Median concentrations of antibodies to pneumococcal serotypes declined by 55-93% between 5 and 12 months of age, with fewer than half of infants having protective antibody levels to serotypes 1 (47%), 3 (28%), 9 V (44%), 18C (24%), and 23F (49%) at 12 months of age. CONCLUSIONS: Both HEU and HUU infants developed protective antibody responses to PCV-13 administered in a 3 + 0 schedule. However, antibody concentrations to many pneumococcal serotypes waned substantially by 12 months of age, suggesting that a PCV-13 booster dose in the second year of life may be needed to maintain protective pneumococcal antibody levels in older infants and young children.

Skin conditions among pediatric dermatology outpatients in Botswana.

BACKGROUND: An understanding of the prevalence patterns of skin diseases in children in Botswana is needed to guide national dermatological policy development, training, and resource allocation to improve patient care. OBJECTIVE: To describe local skin disease patterns in children aged 0-18 years presenting for dermatologic care in Botswana. METHODS: A retrospective review of records from 1st January 2011 to 31st December 2016 was conducted at the outpatient dermatology clinic of Princess Marina Hospital (PMH) in Gaborone, Botswana and outreach clinic sites. RESULTS: There were 4413 pediatric visits constituting 18.6% of all dermatology visits. There was a slight male predominance of 1.2:1. The majority of disorders were noninfectious 80.1% (3537/4413) versus infectious 14.6% (645/4413), with 5.2% (231/4413) unclassified. In the noninfectious category, two-thirds were inflammatory, followed by disorders of nails, skin appendages, and pigmentary disorders. Atopic dermatitis was the most common inflammatory disorder. Over half of infectious skin diseases were viral, followed by fungal and bacterial disorders. In the HIV-related disorders, the majority were verrucae 94% (108/115) followed by Kaposi sarcoma. The nine most common skin diagnoses accounted for close to 70% of all skin diseases seen at the clinic, and these included atopic dermatitis (almost half of all cases), followed by verruca, acne, and vitiligo. CONCLUSION: There is a high burden of skin disorders in children in Botswana. In our cohort, a small number of skin conditions made up the vast majority of pediatric diagnoses. This information can be used to guide dermatology training and resource allocation to better manage these common diseases.

Optimising the management of childhood acute diarrhoeal disease using a rapid test-and- treat strategy and/or Lactobacillus reuteri DSM 17938: a multicentre, randomised, controlled, factorial trial in Botswana.

INTRODUCTION: The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy ('test-and-treat') and/or Lactobacillus reuteri DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis. METHODS: This was a multicentre, randomised, factorial, controlled, trial. Children aged 2-60 months admitted for acute non-bloody diarrhoea to four hospitals in southern Botswana were eligible. Participants were assigned to treatment groups by web-based block randomisation. Test-and-treat results were not blinded, but participants and research staff were blinded to L. reuteri/placebo assignment; this was dosed as 1×108 cfu/mL by mouth daily and continued for 60 days. The primary outcome was 60-day age-standardised height (HAZ) adjusted for baseline HAZ. All analyses were by intention to treat. The trial was registered at Clinicaltrials.gov. RESULTS: Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus L. reuteri group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus L. reuteri group and 69 to the standard care plus placebo group. There was no demonstrable impact of the test-and-treat intervention (mean increase of 0.01 SD, 95% CI -0.14 to 0.16 SD) or the L. reuteri intervention (mean decrease of 0.07 SD, 95% CI -0.22 to 0.08 SD) on adjusted HAZ at 60 days. CONCLUSIONS: In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of L. reuteri DSM 17938, were found to markedly impact linear growth or other important outcomes. We cannot exclude the possibility that test-and-treat will improve the care of children with significant enteropathogens (such as Shigella) in their stool. TRIAL REGISTRATION NUMBER: NCT02803827.

The perceptions and practices of parents and children on acute pain management among hospitalized children in two Botswana referral hospitals.

BACKGROUND: Perceptions and practices of parties in pediatric pain are critical in children's access to adequate acute pain management. The personal factors of the child and parents have been shown to be central to pediatric pain management by the Symptom Management Theory. AIM: To describe children and parents/guardians' perceptions (knowledge, attitudes and beliefs) and practices regarding pediatric acute pain management and explain the influence of socio-cultural and environmental factors on those perceptions and practices. METHODS: Descriptive cross-sectional survey using modified versions of the American Pain Society Patient Outcome Questionnaire-Revised among parents/guardians and children. RESULTS: A convenience sample of 275 parents/guardians and 42 children aged 8 to 13 years admitted between date November 2018 and February 2019 to two Botswana tertiary hospitals completed the surveys. Forty-seven percent (n = 129) of parents/guardians reported the child to be in moderate-severe pain, while 38% (n = 16) of children reported pain as moderate-severe at the time of the survey. The children mean scores for cm-APS-POQ-R were 113(33) while parents/guardian's guardians for m-APS-POQ-R were 123(26). The subscales except for the parents/'guardians' pain interference (p = .96) were statistically significant (p = .000), showing adequate knowledge, positive attitudes and high pain intensity for both parents/guardians and children. CONCLUSION: Parent/guardians and children reported a high incidence of acute pain, were content with pain management services, and showed adequate knowledge of pediatric pain and its management. The incongruence between the intensity of pain, satisfaction on the adequacy of pain management and knowledge and attitudes demonstrated in this study need further inquiry.

Evolution of pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

The Prevalence, Intensity, Assessment, and Management of Acute Pain in Hospitalized Children in Botswana.

BACKGROUND: There is very limited clinical and observational data on acute pain experienced by children in sub-Saharan Africa. AIMS: To report the prevalence and intensity of acute pain, pain management practices, and describe associations between acute pain outcomes, children's and parents or guardian's demographics in hospitalized children aged 2 months to 13 years in Botswana. DESIGN: A descriptive correlational prospective observational study using five repeated cross-sectional samples. SETTINGS: Two referral hospitals in Botswana. PARTICIPANTS: The sample size included 308 children and 226 parents or guardians. Data were collected between November 2018 and February 2019 from children, their parents or guardians (<7 years child), and the health record for pain documentation and treatment. MEASURES: Pain was measured using Faces Pain Scale-Revised for children ≥7 years, revised Face, Legs, Activity, Cry, Consolability scale for children <7 years and numeric rating scale for parents or guardians. RESULTS: There are 1,290 data points for children of which 1,000 were children <7 years and 999 data points for parents or guardians of children <7 years were used in analysis. Fifty percent of children <7 years were in pain using the revised Face, Legs, Activity, Cry, Consolability scale, whereas parents indicated 46% to be in pain. The pain prevalence for children ≥7 years was estimated at 54%. Pain was documentated at a rate of 54 % on the health records. Acetaminophen was most common analgesic across all age groups. Univariate associations of child <7 years pain intensity was statistically significant (p ≤ .05) for weight, diagnosis, residence, and parent relationship. Parents reported pain intensity was statistically significant (p ≤ .05) for child sex, weight, diagnosis, residence, surgery, parent or guardian age and education. Only age and surgery were significant for children ≥7 years. CONCLUSIONS: Acute pain prevalence and intensity among hospitalized children in Botswana is low.

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.

Assessing antibiotic utilization among pediatric patients in Gaborone, Botswana.

Objectives: Over the past decade, concerning trends in antimicrobial resistance have emerged in Southern Africa. Given a paucity of pediatric data, our objectives were to (1) describe antibiotic utilization trends at a national referral center in Southern Africa and (2) assess the proportion of patients receiving antibiotics appropriately. In addition, risk factors for inappropriate use were explored. Methods: We performed a prospective cohort study on medical and surgical pediatric patients aged below 13 years admitted to the country's tertiary care referral hospital in Gaborone, Botswana. We collected demographics, clinical, laboratory, and microbiology details, in addition to information on antibiotic use. We separately categorized antibiotic prescriptions using the World Health Organization AWaRe Classification of Access, Watch, and Restrict. Results: Our final cohort of 299 patients was 44% female and 27% HIV-exposed; most (68%) were admitted to the General Pediatrics ward. Infections were a common cause of hospitalization in 29% of the cohort. Almost half of our cohort were prescribed at least one antibiotic during their stay, including 40% on admission; almost half (47%) of these prescriptions were deemed appropriate. At the time of discharge, 52 (21%) patients were prescribed an antibiotic, of which 37% were appropriate. Of all antibiotics prescribed, 42% were from the World Health Organization Access antibiotic list, 58% were from the Watch antibiotic list, and 0% were prescribed antibiotics from the Restrict antibiotic list. Univariate analyses revealed that surgical patients were significantly more likely to have inappropriate antibiotics prescribed on admission. Patients who were treated for diseases for which there was a clinical pathway, or who had blood cultures sent at the time of admission were less likely to have inappropriate antibiotics prescribed. On multivariate analysis, apart from admission to the surgical unit, there were no independent predictors for inappropriate antibiotic use, although there was a trend for critically ill patients to receive inappropriate antibiotics. Conclusion: Our study reveals high rates of antibiotic consumption, much of which was inappropriate. Promising areas for antimicrobial stewardship interventions include (1) standardization of management approaches in the pediatric surgical population and (2) the implementation of feasible and generalizable clinical pathways in this tertiary care facility.

Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy.

Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0-6 months of age) or bimonthly (6-12 months of age) from 179 mother-infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.