An assessment of the current level of implementation of the core elements of antimicrobial stewardship programmes in public hospitals in Ghana

Introduction. Antimicrobial resistance (AMR) is becoming a threat to global public health. Antimicrobial stewardship (AMS) programme (ASP) is one of the five 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 seven core elements of ASP in hospitals in low- and middle-income countries was used for this situational analysis of public hospitals in two regions of Ghana. The core elements included leadership commitment, accountability and responsibility, pharmacy expertise, 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 to 199 beds, less than fifty medical doctors (n=12, 80.0%), less than five pharmacists (n=10, 66.7%), and between 100 to 199 nurses. Performances in four out of the seven core elements were most deficient and they included leadership commitment, pharmacy expertise, 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 towards 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 towards the fight against AMR

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

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

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

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

<div><p>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 (Δ<i>G</i>_bind) 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.</p></div

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&ndash;22.02; p-value = 0.001) and microbiological investigations prior to the commencement of antibiotics (aOR: 5.12; 95% CI: 1.08&ndash;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&ndash;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