Risk Factors for Community Colonization With Extended-Spectrum Cephalosporin-Resistant Enterobacterales (ESCrE) in Botswana: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low- and middle-income countries (LMICs) is poorly described. Identifying risk factors for ESCrE colonization is critical to inform antibiotic resistance reduction strategies because colonization is typically a precursor to infection. METHODS: From 15 January 2020 to 4 September 2020, we surveyed a random sample of clinic patients at 6 sites in Botswana. We also invited each enrolled participant to refer up to 3 adults and children. All participants had rectal swabs collected that were inoculated onto chromogenic media followed by confirmatory testing. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Participants with ESCrE colonization (cases) were compared with noncolonized participants (controls) to identify risk factors for ESCrE colonization using bivariable, stratified, and multivariable analyses. RESULTS: A total of 2000 participants were enrolled. There were 959 (48.0%) clinic participants, 477 (23.9%) adult community participants, and 564 (28.2%) child community participants. The median (interquartile range) age was 30 (12-41) and 1463 (73%) were women. There were 555 cases and 1445 controls (ie, 27.8% of participants were ESCrE colonized). Independent risk factors (adjusted odds ratio [95% confidence interval]) for ESCrE included healthcare exposure (1.37 [1.08-1.73]), foreign travel [1.98 (1.04-3.77]), tending livestock (1.34 [1.03-1.73]), and presence of an ESCrE-colonized household member (1.57 [1.08-2.27]). CONCLUSIONS: Our results suggest healthcare exposure may be important in driving ESCrE. The strong links to livestock exposure and household member ESCrE colonization highlight the potential role of common exposure or household transmission. These findings are critical to inform strategies to curb further emergence of ESCrE in LMICs.

Performance of CHROMagar ESBL media for the surveillance of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) from rectal swabs in Botswana.

Introduction. Lack of laboratory capacity hampers consistent national antimicrobial resistance (AMR) surveillance. Chromogenic media may provide a practical screening tool for detection of individuals colonized by extended-spectrum beta-lactamase (ESBL)-producing organisms.Hypothesis. CHROMagar ESBL media represent an adequate screening method for the detection of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), isolated from rectal swabs.Aim. To evaluate the performance of CHROMagar ESBL media to accurately identify ESCrE isolates from rectal swab samples attained from hospitalized and community participants.Methodology. All participants provided informed consent prior to enrolment. Rectal swabs from 2469 hospital and community participants were inoculated onto CHROMagar ESBL. The performance of CHROMagar ESBL to differentiate Escherichia coli and Klebsiella spp., Enterobacter spp. and Citrobacter spp. (KEC spp.) as well as select for extended-spectrum cephalosporin resistance were compared to matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-TOF-MS) and VITEK-2 automated susceptibility testing.Results. CHROMagar ESBL had a positive and negative agreement of 91.2 % (95 % CI, 88.4-93.3) and 86.8 % (95 % CI, 82.0-90.7) for E. coli and 88.1 % (95 % CI 83.2-92.1) and 87.6 % (95 % CI 84.7-90.2) for KEC spp. differentiation, respectively, when compared to species ID by MALDI-TOF-MS. When evaluated for phenotypic susceptibilities (VITEK-2), 88.1 % (714/810) of the isolates recovered on the selective agar exhibited resistance to third-generation cephalosporins.Conclusion. The performance characteristics of CHROMagar ESBL media suggest that they may be a viable screening tool for the identification of ESCrE from hospitalized and community participants and could be used to inform infection prevention and control practices in Botswana and potentially other low-and middle-income countries (LMICs). Further studies are required to analyse the costs and the impact on time-to-result of the media in comparison with available laboratory methods for ESCrE surveillance in the country.

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.

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

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.

Colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) in healthcare and community settings in Botswana: an antibiotic resistance in communities and hospitals (ARCH) study.

OBJECTIVES: Although extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) are a global challenge, data on these organisms in low- and middle-income countries are limited. In this study, we sought to characterize colonization data critical for greater antibiotic resistance surveillance efforts. METHODS: This study was conducted in three hospitals and six clinics in Botswana. We conducted ongoing surveillance of adult patients in hospitals and clinics and adults and children in the community. All participants underwent rectal swab sampling to identify ESCrE and CRE. RESULTS: Enrollment occurred from January 15, 2020, to September 4, 2020, but paused from April 2, 2020, to May 21, 2020, because of a countrywide COVID-19 lockdown. Of 5088 individuals approached, 2469 (49%) participated. ESCrE colonization prevalence was 30.7% overall (43% for hospital participants, 31% for clinic participants, 24% for adult community participants, and 26% for child community participants) (P <0.001). A total of 42 (1.7%) participants were colonized with CRE. CRE colonization prevalence was 1.7% overall (6.8% for hospital participants, 0.7% for clinic participants, 0.2% for adult community participants, and 0.5% for child community participants) (P <0.001). ESCrE and CRE prevalence varied substantially across regions and was significantly higher prelockdown versus postlockdown. CONCLUSIONS: ESCrE colonization was high in all settings in Botswana. CRE prevalence in hospitals was also considerable. Colonization prevalence varied by region and clinical setting and decreased after a countrywide lockdown.