Carbapenemase producing Acinetobacter infections mostly occur in critically ill hospitalized patients, immunocompromised patients and patients administered with carbapenems. This poses an important problem as carbapenems are the drugs of choice for treatment of Acinetobacter infections. Therefore, studies understanding antibiotic resistance mechanisms in Acinetobacter is of paramount importance. With high resolution data available from whole genome sequencing (WGS) and our ability to perform both sequencing and bioinformatic analysis in house, we aim to identify the Acinetobacter resistance genes present in both the chromosomal and plasmid DNA. Our long-term goal is to understand the emergence and spread of resistance genes of Acinetobacter and how it contributes to patient outcomes. We hypothesize that patients with Acinetobacter infections can have different patient outcomes based on the resistance genes they harbor. The objective of this pilot research is to identify the different resistance genes or its variants in Acinetobacter that contribute to adverse patient outcomes such as prolonged infection leading to increased duration of stay and mortality. The central hypothesis will be addressed by the following specific aims 1) Identify all chromosomal or plasmid derived antibiotic-resistance genes harbored by the carbapenem-resistant Acinetobacter baumannii (CRAb) isolates via whole genome sequencing (WGS) and computational analysis 2) Determine if any resistance genes or variants of these genes in the CRAb isolates act as a predictor of adverse clinical outcomes. In addition to the above-mentioned goals, this study will provide a unique opportunity to understand the epidemiology of Acinetobacter infections using whole genome multilocus sequence typing MLST (wgMLST) in a clinical setting. This integrated approach with whole genome DNA sequencing, plasmid sequencing, epidemiologic surveillance and patient outcome data in a non-outbreak situation will allow us to comprehensively evaluate the high-risk Acinetobacter clades and prioritize treatment options for those patients. The findings from the proposed research will advance our understanding of the epidemiology and implications of resistance mechanisms that contribute to adverse patient outcomes to improve resource prioritization in healthcare facilities.
The proposed project is relevant to public health because carbapenem resistance mainly among gram-negative bacteria such as Acinetobacter is a global threat. We will employ high resolution whole genome sequencing methodology to identify the different resistance gene/s and determine what role they play in patient outcomes. Findings from the proposed research will lead to better understanding of the relevant resistance gene/s that contribute to adverse patient outcomes.
