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Antimicrobial resistance is a global threat in children, and the emergence of multi-drug-resistant organisms is of concern. This secondary analysis of an antimicrobial point prevalence survey (PPS) in children evaluates the impact of age on antimicrobial use. The mean antimicrobial prescriptions were assessed in neonates, infants, young children (1-5 years), school-going children (6-12 years), and adolescents (13-15 years) from a cross-sectional PPS at three academic hospitals between September 2021 and January 2022. Primary and secondary diagnoses, antibiotic type (World Health Organization AWaRe and Anatomical Therapeutic Chemical classifications), and the incidence of healthcare-associated infections (HAI) were evaluated per age category. Multiple regression models were used to analyse age-related risk factors for HAI. The number of antimicrobials per child (1.7-1.9 per patient) was higher in neonates and infants compared to children 6-12 years old (1.4 per patient). Watch antibiotics, especially carbapenems, were commonly prescribed in neonates (32.5%) and infants (42.2%). Reserve antimicrobial use was notable in neonates (4.7%) and infants (4.1%). The incidence risk ratio (IRR) of HAI was higher in neonates and infants (IRR 2.13; 95% CI 1.23-3.70, IRR 2.20; 95% CI 1.40-3.45, respectively) compared to 6- to 12-year-olds. On multivariate analysis of participants according to age, being HIV infected, length of stay >6 days, high McCabe severity score, having surgery and receipt of blood transfusion were associated with an increased risk of HAI (P < .001 for all) while on univariate analysis only, being premature and/or underweight was associated with an increased risk of HAI in infants (P < .001 for both). Infants with risk factors for HAI significantly influenced antimicrobial prescribing, underscoring the necessity for tailored antimicrobial stewardship and enhanced surveillance. The increased use of Watch antibiotics, particularly carbapenems, in infants warrants closer scrutiny. Further research is required to identify inappropriate antimicrobial use in high-risk hospitalized young children., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV., Methods: Two bNAbs, CAP256V2LS and VRC07-523LS, will be assessed in a sequential and randomized phase I, single-site, single-blind, dose-finding trial. We aim to investigate the 28-day safety and pharmacokinetics (PK) profile of incrementally higher doses of these bNAbs in breastfeeding HIV-1 exposed born without HIV neonates alongside standard of care antiretroviral (ARV) medication to prevent (infants) or treat (mothers) HIV infection. The trial design includes 3 steps and 7 arms (1, 2, 3, 4, 5, 6 and 6b) with 8 infants in each arm. The first step will evaluate the safety and PK profile of the bNAbs when given alone as a single subcutaneous (SC) administration at increasing mg/kg body weight doses within 96 h of birth: arms 1, 2 and 3 at doses of 5, 10, and 20 mg/kg of CAP256V2LS, respectively; arms 4 and 5 at doses of 20 and 30 mg/kg of VRC07-523LS, respectively. Step two will evaluate the safety and PK profile of a combination of the two bNAbs administered SC at fixed doses within 96 h of birth. Step three will evaluate the safety and PK profile of the two bNAbs administered SC in combination at fixed doses, after 3 months. Arms 1 and 6 will follow sequential recruitment, whereas randomization will occur sequentially between arms (a) 2 & 4 and (b) 3 & 5. Before each randomization, a safety pause will allow review of safety data of the preceding arms., Discussion: The results of this trial will guide further studies on bNAbs to prevent breast milk transmission of HIV., Protocol Version: Version 4.0 dated 15 March 2024., Trial Registration: Pan African Clinical Trial Registry (PACTR): PACTR202205715278722, 21 April 2022; South African National Clinical Trial Registry (SANCTR): DOH-27-062022-6058., (© 2024. The Author(s).)

Antimicrobial resistance (AMR) poses a global threat, partly fueled by antimicrobial overuse. Paediatric inpatients are particularly vulnerable to infections, leading to high antimicrobial consumption. In low-to-middle income countries (LMICs) like South Africa, research on antimicrobial usage for neonatal and paediatric healthcare-associated infections (HAI) is limited. This cross-sectional study evaluated antimicrobial usage in three academic public sector hospitals in South Africa to improve appropriateness. 22.9% of hospitalised children received at least one prescribed antimicrobial, with neonates, infants, and adolescents having higher prescription rates for HAIs. Common antimicrobials prescribed included beta-lactamase sensitive penicillin, aminoglycosides, and carbapenems. Antimicrobial selection aligned with the WHO AWaRe classification system. HIV infection did not emerge as a risk factor for HAIs or excessive antimicrobial usage. The policy brief recommends several strategies, summarized by the acronym 'PRACTICE,' to optimize antimicrobial prescribing practices. These include implementing standardized policies for empiric antimicrobial use, routine review of antimicrobial therapy, age-specific antimicrobial stewardship programs, and continued collaborative efforts and research. Individualized treatment plans, improved infection prevention and control measures, ongoing surveillance, and exploring electronic technology for antimicrobial stewardship are also crucial. Addressing antimicrobial usage is imperative to combat the growing threat of AMR and improve patient outcomes in LMICs like South Africa.

Objectives: South Africa implemented a National Strategic Framework to optimise antimicrobial stewardship in 2014; however, there is limited data on how this has affected prescribing, especially to children treated in academic centres., Methods: We conducted a point prevalence survey using the World Health Organization (WHO) methodology to evaluate antibiotic and antifungal prescribing practices in paediatric departments at three academic hospitals in South Africa., Results: We recorded 1946 antimicrobial prescriptions in 1191 children, with 55.2% and 39.2% of the antibiotics classified as WHO AWaRe Access and Watch drugs, respectively. There were significant differences in prescription of Reserve antibiotics and antifungals between institutions. Receipt of WHO Watch and Reserve antibiotics was independently associated with infancy (<12 months) and adolescents (13-17 years) (adjusted relative risk [aRR]: 2.09-9.95); prolonged hospitalisation (aRR: 3.29-30.08); rapidly or ultimately fatal illness (aRR: 1.94 to 5.52); and blood transfusion (aRR: 3.28-5.70). Antifungal prescribing was associated with treatment of hospital-associated infection (aRR: 2.90), medical prophylaxis (aRR: 3.30), and treatment in intensive care units (aRR: 2.15-2.27)., Conclusions: Guidance on optimisation of infection prevention and control practice and strengthening of antimicrobial stewardship would impact positively on the care of sick children in our setting., Competing Interests: DPM was, in part, supported by a grant awarded by the Carnegie Corporation of New York. For the remaining authors none were declared., (© 2023 The Author(s).)

The South African National Department of Health developed a quality improvement (QI) programme to reduce maternal and neonatal mortality and still births. The programme was implemented between 2018 and 2022 in 21 purposively selected public health facilities. We conducted a process evaluation to describe the characteristics and skills of the QI team leaders of well-performing teams. The evaluation was conducted in 15 of the 21 facilities. Facilities were purposively selected and comprised semi-structured interviews with leaders at three time points; reviewing of QI documentation; and 37 intermittently conducted semi-structured interviews with the QI advisors, being QI technical experts who supported the teams. These interviews focused on participants' experiences and perceptions of how the teams performed, and performance barriers and enablers. Thematic data analysis was conducted using Atlas.ti. Variation in team performance was associated with leaders' attributes and skills. However, the COVID-19 pandemic also affected team functioning. Well-performing teams had leaders who effectively navigated COVID-19 and other challenges, who embraced QI and had sound QI skills. These leaders cultivated trust by taking responsibility for failures, correcting members' mistakes in encouraging ways, and setting high standards of care. Moreover, they promoted programme ownership among members by delegating tasks. Given the critical role leaders play in team performance and thus in the outcomes of QI programmes, efforts should focus on leader selection, training, and support., (© 2023. The Author(s).)

Background: The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals., Methods: This cross-sectional study included hospitalized neonates and children (0-15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site., Results: Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5-32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6-12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06-2.53], infants (aRR: 1.57; 95% CI: 1.12-2.21) and adolescents (aRR: 2.18; 95% CI: 1.45-3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04-1.70) and underweight (aRR: 1.25; 95% CI: 1.01-1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI., Conclusions: The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite progress, maternal and neonatal mortality and still births remain high in South Africa. The South African National Department of Health implemented a quality improvement (QI) programme, called Mphatlalatsane, to reduce maternal and neonatal mortality and still births. It was implemented in 21 public health facilities, seven per participating province, between 2018 and 2022., Methods: We conducted a qualitative process evaluation of the contextual and implementation process factors' influence on implementation uptake amongst the QI teams in 15 purposively selected facilities. Data collection included three interview rounds with the leaders and members of the QI teams in each facility; intermittent interviews with the QI advisors; programme documentation review; observation of programme management meetings; and keeping a fieldwork journal. All data were thematically analysed in Atlas.ti. Implementation uptake varied across the three provinces and between facilities within provinces., Results: Between March and August 2020, the COVID-19 pandemic disrupted uptake in all provinces but affected QI teams in one province more severely than others, because they received limited pre-pandemic training. Better uptake among other sites was attributed to receiving more QI training pre-COVID-19, having an experienced QI advisor, and good teamwork. Uptake was more challenging amongst hospital teams which had more staff and more complicated MNH services, versus the primary healthcare facilities. We also attributed better uptake to greater district management support. A key factor shaping uptake was leaders' intrinsic motivation to apply QI methodology. We found that, across sites, organic adaptations to the QI methodology were made by teams, started during COVID-19. Teams did away with rapid testing of change ideas and keeping a paper trail of the steps followed. Though still using data to identify service problems, they used self-developed audit tools to record intervention effectiveness, and not the prescribed tools., Conclusions: Our study underscores the critical role of intrinsic motivation of team leaders, support from experienced technical QI advisors, and context-sensitive adaptations to maximise QI uptake when traditionally recognised QI steps cannot be followed., (© 2023. The Author(s).)

Background: The COVID-19 pandemic undermined gains in reducing maternal and perinatal mortality in South Africa. The Mphatlalatsane Initiative is a health system intervention to reduce mortality and morbidity in women and newborns to desired levels., Objective: Our evaluation aims to determine the effect of various exposures, including the COVID-19 pandemic, and a system-level, complex, patient-centered quality improvement (QI) intervention (the Mphatlalatsane Initiative) on maternal and neonatal health services at 21 selected South African facilities. The objectives are to determine whether Mphatlalatsane reduces the institutional maternal mortality ratio, neonatal mortality rate, and stillbirth rate (objective 1) and improves patients' experiences (objective 2) and quality of care (objective 3). Objective 4 assesses the contextual and implementation process factors, including the COVID-19 pandemic, that shape Mphatlalatsane uptake and variation., Methods: This study is an implementation science type 2 hybrid effectiveness, controlled before-and-after design with quantitative and qualitative components. The Mphatlalatsane intervention commenced at the end of 2019. For objective 1, intervention and control facility-level data from the District Health Information System are compared for changes in institutional maternal and neonatal mortality and stillbirth rates and associations with QI, the COVID-19 pandemic, and both. This first analysis includes data from 18 facilities, regardless of their allocation to intervention or comparison, to obtain a general idea of the effect of the COVID-19 pandemic. For objectives 2 to 3, data collectors abstract data from maternal and neonatal records, interview participants, and conduct neonatal facility assessments. For objective 4, interviews, program documentation, surveys, and observations are used to assess how contextual factors at the macro-, meso-, and microlevels explain variation in intervention uptake and outcome. The intervention dose is measured at the microlevel only in the intervention facilities. The study assesses the Mphatlalatsane Initiative from 2020 to 2022., Results: From preliminary analysis, across the 3 provinces, maternal and neonatal deaths increased during the COVID-19 pandemic, whereas stillbirths remained unchanged. Maternal satisfaction with quality of care was >90%. The COVID-19 pandemic severely disrupted the QI teams functioning. However, the QI teams regained their pre-COVID-19 momentum by adapting the QI model, with advisers providing mentoring and support. Variation in adoption at the mesolevel was related to stable and motivated leadership (particularly at the facility level), poor integration into routine processes, and buy-in from senior district managers who were affected by competing priorities. Varying referral and specialist outreach systems, staff availability and development, and service delivery infrastructure are plausible factors in variable outcomes., Conclusions: Few evaluations rigorously evaluated the effect of health system interventions on improving health services and outcomes. Results will inform the scaling up of successful intervention components and strategies to mitigate the effects of the COVID-19 pandemic or similar emerging epidemics on maternal and neonatal mortality., International Registered Report Identifier (irrid): DERR1-10.2196/42041., (©Terusha Chetty, Yages Singh, Willem Odendaal, Solange Mianda, Nada Abdelatif, Samuel Manda, Helen Schneider, Ameena Goga. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.06.2023.)