Residency training on the frontlines of the COVID-19 pandemic - a qualitative study from Tanzania

Introduction: the Coronavirus Disease 2019 pandemic has affected residency training globally. The aim of this study was to understand how the pandemic affected teaching and learning in residency programs in low resource settings where residents and faculty were working on the front line treating patients with the disease. Methods: this qualitative study enrolled residents and faculty from the Aga Khan University in Tanzania who were providing front line care during the pandemic. Purposeful sampling was used and data was collected using focus group discussions and in-depth interviews between August and September 2020. Analysis was done using qualitative content analysis. Results: twelve residents and six faculty members participated in this study. Two main themes emerged. The first was: New and unfamiliar teaching and learning experiences. Residents and faculty had to adapt to changes in the learning environment and the academic program. Residents had increased responsibilities, including providing front line care and working with reduced supervision. The second theme was: Learning opportunities amidst crisis. There were opportunities to improve critical care and procedural skills. They also had opportunities to improve non-technical skills like teamwork and communication. Conclusion: residents and faculty had to adapt to changes in teaching and learning. Residents also had to take up additional responsibilities. Support systems are required to help them adapt to the changes and settle in their new roles. There were opportunities to learn new skills, and training should be restructured to maximize the use of these opportunities

Untargeted metabolomics analysis reveals key pathways responsible for the synergistic killing of colistin and doripenem combination against Acinetobacter baumannii

Combination therapy is deployed for the treatment of multidrug-resistant Acinetobacter baumannii, as it can rapidly develop resistance to current antibiotics. This is the first study to investigate the synergistic effect of colistin/doripenem combination on the metabolome of A. baumannii. The metabolite levels were measured using LC-MS following treatment with colistin (2 mg/L) or doripenem (25 mg/L) alone, and their combination at 15 min, 1 hr and 4 hr (n = 4). Colistin caused early (15 min and 1 hr) disruption of the bacterial outer membrane and cell wall, as demonstrated by perturbation of glycerophospholipids and fatty acids. Concentrations of peptidoglycan biosynthesis metabolites decreased at 4 hr by doripenem alone, reflecting its mechanism of action. The combination induced significant changes to more key metabolic pathways relative to either monotherapy. Down-regulation of cell wall biosynthesis (via D-sedoheptulose 7-phosphate) and nucleotide metabolism (via D-ribose 5-phosphate) was associated with perturbations in the pentose phosphate pathway induced initially by colistin (15 min and 1 hr) and later by doripenem (4 hr). We discovered that the combination synergistically killed A. baumannii via time-dependent inhibition of different key metabolic pathways. Our study highlights the significant potential of systems pharmacology in elucidating the mechanism of synergy and optimizing antibiotic pharmacokinetics/pharmacodynamics