An Assessment of the Current Level of Implementation of the Core Elements of Antimicrobial Stewardship Programs in Public Hospitals in Ghana.

Introduction: Antimicrobial resistance (AMR) is becoming a threat to global public health. Antimicrobial stewardship (AMS) program (ASP) is one of the 5 strategic areas in the Ghana National Action Plan to fight this menace. Assessment of the core elements of ASP in a hospital setting has been identified as a pragmatic way of identifying the barriers and facilitators for its effective implementation. Method: The World Health Organization's toolkit for assessment of the 7 core elements of ASP in hospitals in low and middle income countries was used for this situational analysis of public hospitals in 2 regions of Ghana. The core elements included leadership commitment, accountability and responsibility, pharmacy expertize, AMS actions and interventions, education and training, and periodic monitoring and surveillance. Data collected using a checklist were imported into STATA version 14 for descriptive and bivariate analyses. Results: 15 public hospitals were assessed with the toolkit. Most of them were primary health care facilities (n = 12, 80.0%), had bed capacities between 100 and 199 beds, less than 50 medical doctors (n = 12, 80.0%), less than 5 pharmacists (n = 10, 66.7%), and between 100 and 199 nurses. Performances in 4 out of the 7 core elements were most deficient and they included leadership commitment, pharmacy expertize, AMS actions (interventions) implemented, monitoring and surveillance of antibiotic use, and bacteria resistance rates. Pharmacist-led ASPs were also found to be associated with their formal training on AMS. Key barriers identified included lack of skilled human resources, lack of available time for AMS-related duties and poor laboratory infrastructure. Conclusion: There was sub-optimal performance for almost all the core elements of ASP in the public hospitals in Ghana hampered mostly by lack of skilled human and financial resources. Pharmacists must be empowered through formal training and certificate programs in infectious disease management and AMS principles and strategies to enhance their contribution toward ASPs in hospitals. The results from this study should encourage nationwide assessment of ASPs across hospital settings in Ghana to better evaluate the level of their implementation and address potential barriers to guide AMS policies and ASP strategy development toward the fight against AMR.

Interprofessional education in antimicrobial stewardship, a collaborative effort.

Introduction: Antimicrobial stewardship (AMS) education and interprofessional collaboration are integral to the success of a stewardship programme. An interactive interprofessional AMS workshop, designed to encourage workplace interprofessional collaboration was piloted in a tertiary hospital. Objectives: To obtain feedback to determine the suitability and sustainability of the AMS workshop. Methods: Feedback was elicited through a predesigned questionnaire containing both open-ended and closed questions on the content and structure of the workshop. Results: The survey had a 70% (n = 16) overall response rate. All participants agreed that the goals of the workshop were met and that the knowledge and skills gained from the workshop would help them in their AMS roles. All participants indicated that the workshop content, and the level at which it was pitched, met their expectations and that it had improved their knowledge and skills. All agreed that they found it advantageous and enjoyed learning as an interprofessional group. Open feedback showed that the workshop was found to be useful and would potentially result in improved patient care, dissemination of knowledge, improved teamwork and organizational culture. Conclusions: The positive feedback and changes made following the workshop demonstrated that a targeted AMS educational workshop adds value to an antimicrobial stewardship programme.

A Multicenter Cross-Sectional Survey of Knowledge, Attitude, and Practices of Healthcare Professionals towards Antimicrobial Stewardship in Ghana: Findings and Implications.

Antimicrobial stewardship (AMS) programs are part of the key activities that contribute to reducing antimicrobial resistance (AMR). Good knowledge, attitudes, and practices (KAP) among healthcare professionals (HCPs) are essential to improving future antimicrobial use and reducing AMR, which is a priority in Ghana. A multicenter cross-sectional survey was conducted in six public hospitals in Ghana among key HCPs to assess their level of KAP towards AMS using a validated self-administered electronic questionnaire. Data analyses included descriptive and inferential statistics using STATA version 14. Overall, 339 out of 355 HCPs responded to the questionnaire, giving a response rate of 95.5%. Most responders were nurses (n = 256, 78.2%), followed by medical doctors (n = 45, 13.3%). The study recorded both poor knowledge (8.9%) and practice levels (35.4%), as well as a good attitude (78.8%) towards AMS. Ongoing exposure to AMS structured training, exposure to continuous professional development training on AMS in the previous year, and the number of years of working experience were predictors of the HCPs' level of knowledge (aOR = 3.02 C.I = 1.12-8.11), attitude (aOR = 0.37 C.I = 0.20-0.69) and practice (aOR = 2.09 C.I =1.09-3.99), respectively. Consequently, concentrated efforts must be made to address current low levels of knowledge and poor practices regarding AMS among HCPs in Ghana as part of ongoing strategies in the National Action Plan to reduce AMR.

Progestins in the symptomatic management of endometriosis: a meta-analysis on their effectiveness and safety.

BACKGROUND: Endometriosis is a complex chronic disease that affects approximately 10% of women of reproductive age worldwide and commonly presents with pelvic pain and infertility. METHOD & OUTCOME MEASURES: A systematic review of the literature was carried out using the databases Pubmed, Scopus, Cochrane and ClinicalTrials.gov in women with a confirmed laparoscopic diagnosis of endometriosis receiving progestins to determine a reduction in pain symptoms and the occurrence of adverse effects. RESULTS: Eighteen studies were included in the meta-analysis. Progestins improved painful symptoms compared to placebo (SMD = -0.61, 95% CI (-0.77, -0.45), P < 0.00001) with no comparable differences between the type of progestin. After median study durations of 6-12 months, the median discontinuation rate due to adverse effects was 0.3% (range: 0 - 37.1%) with mild adverse effects reported. CONCLUSION: The meta-analysis revealed that pain improvement significantly increased with the use of progestins with low adverse effects. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021285026.

Antimicrobial Stewardship in Public-Sector Hospitals in KwaZulu-Natal, South Africa.

Antimicrobial resistance (AMR) is a serious global public-health threat. Evidence suggests that antimicrobial stewardship (AMS) is a valuable tool to facilitate rational antibiotic use within healthcare facilities. A cross-sectional situational analysis using a questionnaire was conducted to determine the current status of antimicrobial stewardship (AMS) activities in all public-sector hospitals in KwaZulu-Natal (KZN). The survey had a 79% (57, N = 72) response rate. A total of 75% of hospitals had an antimicrobial stewardship committee (AMSC), 47% (20, N = 43) had a formal written statement of support from leadership, and 7% (3, N = 43) had budgeted financial support. Only 37% (16, N = 43) had on-site or off-site support from a clinical microbiologist, and 5% (2, N = 43) had an on-site infectious disease (ID) physician. Microbiologist input on pathogen surveillance data (aOR: 5.12; 95% CI: 4.08-22.02; p-value = 0.001) and microbiological investigations prior to the commencement of antibiotics (aOR: 5.12; 95% CI: 1.08-42.01; p-value = 0.041) were significantly associated with having either on- or off-site microbiology support. Respondents that had a representative from microbiology on the AMSC were significantly associated with having and interrogating facility-specific antibiograms (P = 0.051 and P = 0.036, respectively). Those facilities that had access to a microbiologist were significantly associated with producing an antibiogram (aOR: 4.80; 95% CI: 1.25-18.42; p-value = 0.022). Facilities with an ID physician were significantly associated with having a current antibiogram distributed to prescribers within the facility (P = 0.010) and significantly associated with sending prescribers personalized communication regarding improving prescribing (P = 0.044). Common challenges reported by the facilities included suboptimal hospital management support; a lack of clinicians, pharmacists, nurses, microbiologists, and dedicated time; the lack of a multidisciplinary approach; low clinician buy-in; inadequate training; a lack of printed antibiotic guidelines; and financial restrictions for microbiological investigations. The survey identified the need for financial, IT, and management support. Microbiology and infectious disease physicians were recognized as scarce human resources.

Lessons from COVID-19 in South Africa: Keeping our environment clean should be the first law of health.

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, the links between poor hygiene, unclean environments and human health cannot be overemphasised, particularly in South Africa with its high incidence of infectious diseases and overburdened health system. One very controllable factor that is often overlooked is the poor disposal of litter and waste management and its adverse effects on public health. By wearing masks, regular handwashing and sanitising, as well as making sure that neighbourhoods and public spaces are clean and safe, the spread of COVID-19 and other diseases can be prevented.

New InhA Inhibitors Based on Expanded Triclosan and Di-Triclosan Analogues to Develop a New Treatment for Tuberculosis.

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has reinforced the need for the development of new anti-TB drugs. The first line drug isoniazid inhibits InhA. This is a prodrug requiring activation by the enzyme KatG. Mutations in KatG have largely contributed to clinical isoniazid resistance. We aimed to design new 'direct' InhA inhibitors that obviate the need for activation by KatG, circumventing pre-existing resistance. In silico molecular modelling was used as part of a rational structure-based drug-design approach involving inspection of protein crystal structures of InhA:inhibitor complexes, including the broad spectrum antibiotic triclosan (TCS). One crystal structure exhibited the unusual presence of two triclosan molecules within the Mycobacterium tuberculosis InhA binding site. This became the basis of a strategy for the synthesis of novel inhibitors. A series of new, flexible ligands were designed and synthesised, expanding on the triclosan structure. Low Minimum Inhibitory Concentrations (MICs) were obtained for benzylphenyl compounds (12, 43 and 44) and di-triclosan derivative (39), against Mycobacterium bovis BCG although these may also be inhibiting other enzymes. The ether linked di-triclosan derivative (38) displayed excellent in vitro isolated enzyme inhibition results comparable with triclosan, but at a higher MIC (125 µg mL-1). These compounds offer good opportunities as leads for further optimisation.

Interprofessional collaborative learning in the workplace: a qualitative study at a non-governmental organisation in Durban, South Africa.

BACKGROUND: The rapid progression of diseases and the complex, changing landscape of healthcare has increased the awareness that interprofessional collaboration is essential in ensuring safe and effective healthcare delivery. However, to develop a "collaborative practice-ready" workforce, organisations need to invest in the application of alternative approaches to the training of healthcare professionals. PURPOSE OF THE STUDY: To describe the perceptions of healthcare professionals attending an HIV interprofessional collaborative initiative at a non-governmental organization research site in South Africa and to provide suggestions regarding the improvement of this educational programme. METHODS: Focus group discussions (December 2018 to January 2019), were conducted on a purposeful sample (N = 21) consisting of healthcare professionals (clinicians, pharmacists, pharmacy assistants, and nurses), and clinical trial staff (recruiters, administrators, QC officers, psychologists, counsellors) based at a research site, who were invited to attend a continuing medical education initiative on the pathogenesis and treatment of HIV. Qualitative content analysis was carried out to identify meaning units, which were then condensed and labelled with a code. This was further grouped to form categories. RESULTS: Five categories emerged: learning something new, acquiring from each other, promoting company culture, needing company buy-in and teaching methods matter. Interprofessional collaborative learning improved technical capacity, work relationships and company culture. The diversity in learning needs of the different professionals requires a structuring of a curriculum to meet the needs of all. The success of this initiative requires company buy-in/investment and recognition from leaders and higher management with regards to time and resources. Suggestions for improvement included: formalizing the training, introducing more lectures and pitching each topic at different levels i.e. basic, intermediate or advanced, thus ensuring maximum benefit for all. CONCLUSION: Inter-professional learning was perceived as highly valuable. This initiative has the potential to develop further but requires resources and company buy-in. All staff working (clinical and non-clinical) at the NGO site were represented in the interviews, thus ensuring a richer understanding of all perspectives relevant to the study site. The small sample size confined to a single research site, however, prevents these findings from being generalized and limits the applicability of its findings.

Antimicrobial stewardship in South Africa: a scoping review of the published literature.

OBJECTIVES: To map published data of antimicrobial stewardship (AMS) interventions that are currently being carried out in hospitals and clinics in the public and private health sectors of South Africa in line with the antimicrobial resistance (AMR) strategy of South Africa. METHODS: A systematic scoping review was conducted to identify AMS initiatives in the public and private health sectors of South Africa for the period 1 January 2000 to 31 March 2019. An electronic search of databases was made including PubMed, Scopus, a key medical journal (South African Medical Journal), University of KwaZulu-Natal (UKZN) WorldCat iCatalogue and AMR networks: Federation of Infectious Diseases Societies in South Africa (FIDSSA). Reference lists of published articles were also reviewed for inclusion. Keywords included 'antimicrobial antibiotic stewardship South Africa'. FINDINGS: Of a total of 411 articles, using a stepwise screening process, 18 articles were selected for inclusion in the review. The interventions/initiatives were divided into four broad categories: (i) AMS intervention: prescription audits and usage; (ii) AMS intervention: education and its impact; (iii) other AMS interventions; and (iv) the role of different healthcare professionals in AMS. CONCLUSIONS: The data identifies a need for and the value of AMS in both the public and private health sectors of South Africa. Initiatives are carried out across both sectors but more attention needs to be focused on AMS implementation in line with the National AMR Strategy of South Africa. Collaboration between the different sectors will aid in overcoming the AMR challenge.

Recent advancements in the development of anti-tuberculosis drugs.

Modern chemotherapy has significantly improved patient outcomes against drug-sensitive tuberculosis. However, the rapid emergence of drug-resistant tuberculosis, together with the bacterium's ability to persist and remain latent present a major public health challenge. To overcome this problem, research into novel anti-tuberculosis targets and drug candidates is thus of paramount importance. This review article provides an overview of tuberculosis highlighting the recent advances and tools that are employed in the field of anti-tuberculosis drug discovery. The predominant focus is on anti-tuberculosis agents that are currently in the pipeline, i.e. clinical trials.

Multi-drug resistance profile of PR20 HIV-1 protease is attributed to distorted conformational and drug binding landscape: molecular dynamics insights.

The PR20 HIV-1 protease, a variant with 20 mutations, exhibits high levels of multi-drug resistance; however, to date, there has been no report detailing the impact of these 20 mutations on the conformational and drug binding landscape at a molecular level. In this report, we demonstrate the first account of a comprehensive study designed to elaborate on the impact of these mutations on the dynamic features as well as drug binding and resistance profile, using extensive molecular dynamics analyses. Comparative MD simulations for the wild-type and PR20 HIV proteases, starting from bound and unbound conformations in each case, were performed. Results showed that the apo conformation of the PR20 variant of the HIV protease displayed a tendency to remain in the open conformation for a longer period of time when compared to the wild type. This led to a phenomena in which the inhibitor seated at the active site of PR20 tends to diffuse away from the binding site leading to a significant change in inhibitor-protein association. Calculating the per-residue fluctuation (RMSF) and radius of gyration, further validated these findings. MM/GBSA showed that the occurrence of 20 mutations led to a drop in the calculated binding free energies (ΔGbind) by ~25.17 kcal/mol and ~5 kcal/mol for p2-NC, a natural peptide substrate, and darunavir, respectively, when compared to wild type. Furthermore, the residue interaction network showed a diminished inter-residue hydrogen bond network and changes in inter-residue connections as a result of these mutations. The increased conformational flexibility in PR20 as a result of loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces led to a loss of protease grip on ligand. It is interesting to note that the difference in conformational flexibility between PR20 and WT conformations was much higher in the case of substrate-bound conformation as compared to DRV. Thus, developing analogues of DRV by retaining its key pharmacophore features will be the way forward in the search for novel protease inhibitors against multi-drug resistant strains.