First name
Tonya
Last name
Arscott-Mills

Title

Assessing antibiotic utilization among pediatric patients in Gaborone, Botswana.

Year of Publication

2022

Number of Pages

20503121221104437

Date Published

12/2022

ISSN Number

2050-3121

Abstract

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.

DOI

10.1177/20503121221104437

Alternate Title

SAGE Open Med

PMID

36814934
Featured Publication
No

Title

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

Year of Publication

2023

Number of Pages

20503121221149356

Date Published

12/2023

ISSN Number

2050-3121

Abstract

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,  = 0.020) and high inpatient triage, assessment, and treatment score (adjusted odds ratio 5.0,  = 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.

DOI

10.1177/20503121221149356

Alternate Title

SAGE Open Med

PMID

36741934

Title

Risk factors for mortality in a hospitalised neonatal cohort in Botswana.

Year of Publication

2022

Number of Pages

e062776

Date Published

09/2022

ISSN Number

2044-6055

Abstract

OBJECTIVES: A disproportionate number of neonatal deaths occur in low/middle-income countries, with sepsis a leading contributor of mortality. In this study, we investigate risk factors for mortality in a cohort of high-risk hospitalised neonates in Botswana. Independent predictors for mortality for infants experiencing either a sepsis or a non-sepsis-related death are described.

METHODS: This is a prospective observational cohort study with infants enrolled from July to October 2018 at the neonatal unit (NNU) of Princess Marina Hospital (PMH) in Gaborone, Botswana. Data on demographic, clinical and unit-specific variables were obtained. Neonates were followed to death or discharge, including transfer to another hospital. Death was determined to be infectious versus non-infectious based on primary diagnosis listed on day of death by lead clinician on duty.

RESULTS: Our full cohort consisted of 229 patients. The overall death rate was 227 per 1000 live births, with cumulative proportion of deaths of 22.7% (n=47). Univariate analysis revealed that sepsis, extremely low birth weight (ELBW) status, hypoxic ischaemic encephalopathy, critical illness and infants born at home were associated with an increased risk of all-cause mortality. Our multivariate model revealed that critical illness (HR 3.07, 95% CI 1.56 to 6.03) and being born at home (HR 4.82, 95% CI 1.76 to 13.19) were independently associated with all-cause mortality. Low birth weight status was independently associated with a decreased risk of mortality (HR 0.24, 95% CI 0.11 to 0.53). There was a high burden of infection in the cohort with more than half of infants (140, 61.14%) diagnosed with sepsis at least once during their NNU admission. Approximately 20% (n=25) of infants with sepsis died before discharge. Our univariate subanalysis of the sepsis cohort revealed that ELBW and critical illness were associated with an increased risk of death. These findings persisted in the multivariate model with HR 3.60 (95% CI 1.11 to 11.71) and HR 2.39 (95% CI 1 to 5.77), respectively.

CONCLUSIONS: High rates of neonatal mortality were noted. Urgent interventions are needed to improve survival rates at PMH NNU and to prioritise care for critically ill infants at time of NNU admission, particularly those born at home and/or of ELBW.

DOI

10.1136/bmjopen-2022-062776

Alternate Title

BMJ Open

PMID

36691117

Title

'That's when I struggle' … Exploring challenges faced by care givers of children with tuberculosis in Botswana.

Year of Publication

2016

Number of Pages

1314-1319

Date Published

2016 Oct

ISSN Number

1815-7920

Abstract

SETTING: Government-funded public health clinics in and around Gaborone, Botswana.

OBJECTIVE: To explore the challenges faced by care givers of children on treatment for tuberculosis (TB) to inform a more child-friendly approach to Botswana's National TB Programme (NTP) strategy.

DESIGN: Qualitative study using 28 in-depth interviews with care givers of children receiving anti-tuberculosis treatment.

RESULTS: Care givers identified five main challenges: long delays in their child's diagnosis, difficulty attending clinic for daily treatment, difficulty administering TB medications, stock-outs of TB medications leading to treatment interruptions, and inadequate TB education. Care givers prioritized these same five areas to improve the overall management of their child's TB.

CONCLUSION: Our findings suggest that despite accessing care through an NTP that adheres to World Health Organization guidelines, care givers for children on treatment in Botswana continue to encounter significant challenges. While each of these represents a potential threat to successful treatment, they can be addressed with relatively small systematic and programmatic adjustments. These results will inform the next version of the Botswana NTP guidelines towards a more child- and care giver-centered approach.

DOI

10.5588/ijtld.15.0989

Alternate Title

Int. J. Tuberc. Lung Dis.

PMID

27725041

Title

Evaluation of Anatomically Designed Flocked Rectal Swabs for Use with the Biofire FilmArray™ Gastrointestinal Panel for Detection of Enteric Pathogens in Children Admitted to Hospital with Severe Gastroenteritis.

Year of Publication

2019

Date Published

2019 Sep 11

ISSN Number

1098-660X

Abstract

Diagnosing diarrheal disease is difficult in part due to challenges in obtaining and transporting a bulk stool specimen, particularly in resource-limited settings. We compared the performance of flocked rectal swabs to that of traditional bulk stool samples for enteric pathogen detection using the BioFire™ FilmArray Gastrointestinal panel in children admitted to 4 hospitals in Botswana with community onset severe gastroenteritis. Of the 117-matched flocked rectal swab/stool pairs, we found no significant difference in pathogen detection rates between the flocked rectal swab samples and traditional bulk stool sampling methods for any bacterial (168 versus 167, respectively), viral (94 versus 92, respectively), or protozoan (18 versus 18, respectively) targets. The combination of flocked rectal swab samples with FilmArray testing allows for the rapid diagnosis of infectious gastroenteritis, facilitating a test and treat approach for infections that are life-threatening in many resource-limited settings. Culture recovery rates for bacterial pathogens utilizing this approach need to be assessed.

DOI

10.1128/JCM.00962-19

Alternate Title

J. Clin. Microbiol.

PMID

31511336

Title

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.

Year of Publication

2022

Date Published

2022 Apr

ISSN Number

2059-7908

Abstract

<p><strong>INTRODUCTION: </strong>The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy ('test-and-treat') and/or&nbsp;<em>Lactobacillus reuteri</em> DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis.</p>

<p><strong>METHODS: </strong>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 <em>L. reuteri</em>/placebo assignment; this was dosed as 1×10<sup>8</sup> 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.</p>

<p><strong>RESULTS: </strong>Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus <em>L. reuteri&nbsp;</em>group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus <em>L. reuteri&nbsp;</em>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&nbsp;<em>L. reuteri</em> intervention (mean decrease of 0.07 SD, 95% CI -0.22 to 0.08 SD) on adjusted HAZ at 60 days.</p>

<p><strong>CONCLUSIONS: </strong>In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of <em>L. reuteri&nbsp;</em>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 <em>Shigella</em>) in their stool.</p>

<p><strong>TRIAL REGISTRATION NUMBER: </strong>NCT02803827.</p>

DOI

10.1136/bmjgh-2021-007826

Alternate Title

BMJ Glob Health

PMID

35418412

Title

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

Year of Publication

2022

Number of Pages

14

Date Published

2022 01 24

ISSN Number

2047-2994

Abstract

<p><strong>INTRODUCTION: </strong>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.</p>

<p><strong>METHODS: </strong>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 &amp; templates (flat surfaces); 2) sterile syringe &amp; tubing (water aspiration); and 3) structured swabbing techniques (hands &amp; 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.</p>

<p><strong>RESULTS: </strong>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&nbsp;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.</p>

<p><strong>CONCLUSIONS: </strong>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, &amp; 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.</p>

DOI

10.1186/s13756-021-01042-2

Alternate Title

Antimicrob Resist Infect Control

PMID

35074019

Title

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

Year of Publication

2022

Number of Pages

e0262225

Date Published

2022

ISSN Number

1932-6203

Abstract

<p>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.</p>

DOI

10.1371/journal.pone.0262225

Alternate Title

PLoS One

PMID

34986196

Title

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

Year of Publication

2021

Date Published

2021 Sep 11

ISSN Number

1751-7370

Abstract

<p>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.</p>

DOI

10.1038/s41396-021-01108-4

Alternate Title

ISME J

PMID

34511605

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