Development of the first edition of African treatment guidelines for common bacterial infections and syndromes

Standard treatment guidelines (STGs) are an important tool for ensuring high quality clinical care and prudent antimicrobial use (AMU) and stewardship (AMS). In 2018, African Union (AU) member state representatives recognized the lack of STGs as a barrier to AMS at national and facility levels. Previous research reported that only 17 of 55 (31%) member states had STGs that provided disease- or pathogen-specific antimicrobial treatment recommendations, excluding those that covered only treatment of HIV, malaria, and tuberculosis). The Africa Centres for Disease Control and Prevention convened expert panels to develop first edition antibiotic treatment guidelines for priority infectious diseases and clinical syndromes for pediatric and adult patient populations in Africa. The purpose of the guidelines is to provide healthcare workers with treatment guidance by harmonising existing national STGs, filling gaps where existing STGs are not available, and serving as a model for future guidelines. Two expert panels of 28 total clinicians, pharmacists, and other relevant stakeholders from 14 AU member states representing each continental region convened to develop consensus treatment recommendations for select priority bacterial infections and clinical syndromes. In developing recommendations, the panels considered treatment recommendations from existing STGs, drug availability, clinical experience, and available antimicrobial resistance data. The guidelines underwent an external review process where clinical stakeholders who did not serve on either panel were invited to submit feedback prior to their publication. The guidelines provide empiric antibiotic therapy guidelines – including drug selection, route of administration, formulation, dosage, and therapy duration – and principles of stewardship for 28 bacterial infections or clinical syndromes. The first edition guidelines for the treatment of common infectious diseases and clinical syndromes in Africa aims to improve clinical treatment and antimicrobial stewardship and will serve as a template for future regional guidelines.

Emerging non-invasive neuroplastic-targeting therapies for substance use disorder treatment

Context: America is in the midst of a substance use disorder (SUD) epidemic, which has only worsened in the current COVID-19 pandemic. SUD is a public health crisis that affects an everincreasing proportion of the population and is extraordinarily difficult to treat. Misused substances induce neuroplastic changes that not only predispose individuals to relapse but also persist after completing treatment recommendations.

Trends in the epidemiology of urinary tract infections in pregnancy at a tertiary hospital in Johannesburg: Are contemporary treatment recommendations appropriate?

Background: Urinary tract infections (UTIs) are common during pregnancy and are associated with maternal and foetal complications. Empiric antibiotic choices in pregnancy require consideration of efficacy and safety, resulting in limited oral options. With rapidly evolving antibiotic resistance, surveillance to guide empiric treatment recommendations is essential.Methods: A retrospective analysis of urine culture isolates from the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) Obstetrics Department for 1 January 2015 to 31 December 2020 was performed.Results: The top 3 pathogens were Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae. For E. coli susceptibility to cefuroxime declined (95% to 81%, p 0.0001). Similarly, the E. coli extended spectrum beta-lactamase rate increased from 5% to 10% (p = 0.04). E. coli susceptibility to nitrofurantoin (93%) and fosfomycin (96%) remained high. In 2019, carbapenem-resistant K. pneumoniae emerged. Ampicillin susceptibility was high amongst the E. faecalis isolates. Amoxicillin-clavulanate demonstrated high levels of activity against the top 3 uropathogens.Conclusion: The Essential Drug List recommended antibiotics for lower UTIs, nitrofurantoin and fosfomycin, are appropriate empiric options for E. coli, the most common uropathogen in the CMJAH obstetric population. The high rate of E. faecalis susceptibility to nitrofurantoin reported from other Gauteng tertiary obstetric patients, suggests that nitrofurantoin will provide adequate empiric cover for a large proportion of UTIs. However, the determination of the E. faecalis nitrofurantoin and fosfomycin susceptibility rates in the CMJAH obstetric population will provide useful data. Periodic surveillance at the various levels of antenatal care in different regions of South Africa and the determination of risk factors for infections with resistant uropathogens is needed.

Sample Preparation Approach Influences PAM50 Risk of Recurrence Score in Early Breast Cancer

The PAM50 gene expression subtypes and the associated risk of recurrence (ROR) score are used to predict the risk of recurrence and the benefits of adjuvant therapy in early-stage breast cancer. The Prosigna assay includes the PAM50 subtypes along with their clinicopathological features, and is approved for treatment recommendations for adjuvant hormonal therapy and chemotherapy in hormone-receptor-positive early breast cancer. The Prosigna test utilizes RNA extracted from macrodissected tumor cells obtained from formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, RNA extracted from fresh-frozen (FF) bulk tissue without macrodissection is widely used for research purposes, and yields high-quality RNA for downstream analyses. To investigate the impact of the sample preparation approach on ROR scores, we analyzed 94 breast carcinomas included in an observational study that had available gene expression data from macrodissected FFPE tissue and FF bulk tumor tissue, along with the clinically approved Prosigna scores for the node-negative, hormone-receptor-positive, HER2-negative cases (n = 54). ROR scores were calculated in R; the resulting two sets of scores from FFPE and FF samples were compared, and treatment recommendations were evaluated. Overall, ROR scores calculated based on the macrodissected FFPE tissue were consistent with the Prosigna scores. However, analyses from bulk tissue yielded a higher proportion of cases classified as normal-like; these were samples with relatively low tumor cellularity, leading to lower ROR scores. When comparing ROR scores (low, intermediate, and high), discordant cases between the two preparation approaches were revealed among the luminal tumors; the recommended treatment would have changed in a minority of cases.