Isaac Raplee1, Lacey Walker1, Lei Xu1, Anil Surathu1, Ashok Chockalingam1, Sharron Stewart1, Xiaomei Han1, Rodney Rouse1, Zhihua Li2. 1. Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 2. Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Zhihua.Li@fda.hhs.gov.
Abstract
INTRODUCTION: According to the Centers for Disease Control's 2015 Hospital Acquired Infection Hospital Prevalence Survey, 1 in 31 hospital patients was infected with at least one nosocomial pathogen while being treated for unrelated issues. Many studies associate antibiotic administration with nosocomial infection occurrence. However, to our knowledge, there is little to no direct evidence of antibiotic administration selecting for nosocomial opportunistic pathogens. AIM: This study aims to confirm gut microbiota shifts in an animal model of antibiotic treatment to determine whether antibiotic use favors pathogenic bacteria. METHODOLOGY: We utilized next-generation sequencing and in-house metagenomic assembly and taxonomic assignment pipelines on the fecal microbiota of a urinary tract infection mouse model with and without antibiotic treatment. RESULTS: Antibiotic therapy decreased the number of detectable species of bacteria by at least 20-fold. Furthermore, the gut microbiota of antibiotic treated mice had a significant increase of opportunistic pathogens that have been implicated in nosocomial infections, like Acinetobacter calcoaceticus/baumannii complex, Chlamydia abortus, Bacteroides fragilis, and Bacteroides thetaiotaomicron. Moreover, antibiotic treatment selected for antibiotic resistant gene enriched subpopulations for many of these opportunistic pathogens. CONCLUSIONS: Oral antibiotic therapy may select for common opportunistic pathogens responsible for nosocomial infections. In this study opportunistic pathogens present after antibiotic therapy harbored more antibiotic resistant genes than populations of opportunistic pathogens before treatment. Our results demonstrate the effects of antibiotic therapy on induced dysbiosis and expansion of opportunistic pathogen populations and antibiotic resistant subpopulations of those pathogens. Follow-up studies with larger samples sizes and potentially controlled clinical investigations should be performed to confirm our findings.
INTRODUCTION: According to the Centers for Disease Control's 2015 Hospital Acquired Infection Hospital Prevalence Survey, 1 in 31 hospital patients was infected with at least one nosocomial pathogen while being treated for unrelated issues. Many studies associate antibiotic administration with nosocomial infection occurrence. However, to our knowledge, there is little to no direct evidence of antibiotic administration selecting for nosocomial opportunistic pathogens. AIM: This study aims to confirm gut microbiota shifts in an animal model of antibiotic treatment to determine whether antibiotic use favors pathogenic bacteria. METHODOLOGY: We utilized next-generation sequencing and in-house metagenomic assembly and taxonomic assignment pipelines on the fecal microbiota of a urinary tract infectionmouse model with and without antibiotic treatment. RESULTS: Antibiotic therapy decreased the number of detectable species of bacteria by at least 20-fold. Furthermore, the gut microbiota of antibiotic treated mice had a significant increase of opportunistic pathogens that have been implicated in nosocomial infections, like Acinetobacter calcoaceticus/baumannii complex, Chlamydia abortus, Bacteroides fragilis, and Bacteroides thetaiotaomicron. Moreover, antibiotic treatment selected for antibiotic resistant gene enriched subpopulations for many of these opportunistic pathogens. CONCLUSIONS: Oral antibiotic therapy may select for common opportunistic pathogens responsible for nosocomial infections. In this study opportunistic pathogens present after antibiotic therapy harbored more antibiotic resistant genes than populations of opportunistic pathogens before treatment. Our results demonstrate the effects of antibiotic therapy on induced dysbiosis and expansion of opportunistic pathogen populations and antibiotic resistant subpopulations of those pathogens. Follow-up studies with larger samples sizes and potentially controlled clinical investigations should be performed to confirm our findings.
Authors: Janiece S Glover; Brittney D Browning; Taylor D Ticer; Amy C Engevik; Melinda A Engevik Journal: Front Physiol Date: 2022-05-24 Impact factor: 4.755