Microbial prevalence and antibiotic susceptibility pattern in hospitalized patients in a tertiary care hospital

Background: Antimicrobial resistance is among the top ten global threats as declared by WHO in 2019. Irrational use of antibiotics has led to the evolution of resistant microbes. There is limited data in our setting regarding microbes and their antibiotic susceptibility patterns. This study determines predominant bacterial isolates, their susceptibility pattern and current practices among prescribers regarding change of empirical to definitive treatment following antibiotic susceptibility test (AST) results. Method: A retrospective observational study involving 171 culture and AST reports of inpatients admitted between Jan-Dec 2020 in a tertiary-care hospital in Dar-es-Salaam. Results: Of 171 specimens, 52.6% were culture-positive. The frequently isolated organisms included Klebsiella species (21.1%), Escherichia coli (18.9%) and Staphylococcus aureus (14.4%). Of these, Gram-negative isolates showed high rates of resistance against third-generation cephalosporins (71.7%) whereas Gram-positive isolates showed high rates of resistance against penicillins (100%). More than half (58.1%) of the patients with positive culture had changes in antibiotics from empirical to definitive treatment that did not match the AST results. Conclusion: Varied rates of resistance to fourth-generation cephalosporin by the majority of bacterial isolates are alarming. This calls for the establishment of antimicrobial stewardship programs to cater for optimal and rational use of antibiotics by consumers and prescribers

Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche

Macrophages are fundamental cells of the innate immune system that support normal haematopoiesis and play roles in both anti-cancer immunity and tumour progression. Here we use a chimeric mouse model of chronic myeloid leukaemia (CML) and human bone marrow (BM) derived macrophages to study the impact of the dysregulated BM microenvironment on bystander macrophages. Utilising single-cell RNA sequencing (scRNA-seq) of Philadelphia chromosome (Ph) negative macrophages we reveal unique subpopulations of immature macrophages residing in the CML BM microenvironment. CML exposed macrophages separate from their normal counterparts by reduced expression of the surface marker CD36, which significantly reduces clearance of apoptotic cells. We uncover aberrant production of CML-secreted factors, including the immune modulatory protein lactotransferrin (LTF), that suppresses efferocytosis, phagocytosis, and CD36 surface expression in BM macrophages, indicating that the elevated secretion of LTF is, at least partially responsible for the supressed clearance function of Ph- macrophages