AbstractThough wastewater and sewage systems are known to be a significant reservoir of antibiotic resistant bacterial populations and periodic outbreaks of drug resistant infection, there is little quantitative understanding of the drivers behind resistant population growth in these settings. In order to fill this gap in quantitative understanding of outbreaks of antibiotic resistant infections in wastewater, we have developed a mathematic model synthesizing many of the known drivers of antibiotic resistance in these settings in order to predict the growth of resistant populations in different environmental scenarios. A number of these drivers of drug resistant infection outbreak including antibiotic residue concentration, antibiotic interaction and synergy, chromosomal mutation and horizontal gene transfer, have not previously been integrated into a single computational model. Our integrated model shows that low levels of antibiotic residues present in wastewater can lead to the increased development of resistant populations, and the dominant mechanism of resistance acquisition in these populations is horizontal gene transfer rather than chromosomal mutations. Additionally, we found that synergistic antibiotic interactions can cause increased resistant population growth. Our study shows that the effects of antibiotic interaction are observable even at the low antibiotic concentrations present in wastewater settings. These findings, consistent with recent experimental and field studies, provide new quantitative knowledge on the evolution of antibiotic resistant bacterial reservoirs, and the model developed herein can be adapted for use as a prediction tool in public health policy making, particularly in low income settings where water sanitation issues remain widespread and disease outbreaks continue to undermine public health efforts.SignificanceThe rate at which antimicrobial resistance (AMR) has developed and spread throughout the world has increased in recent years, and it is suggested that at the current rate, several million people may die by 2050 due to AMR. One major reservoir of resistant bacterial populations that has been linked to outbreaks of drug resistant bacterial infections, but is not well understood, is in wastewater settings, where antibiotic pollution is often present. Using ordinary differential equations incorporating several known drivers of resistance in wastewater, we find that interactions between antibiotic residues and horizontal gene transfer significantly affect the growth of resistant bacterial reservoirs.
Recent Advances in the Detection of Antibiotic and Multi-Drug Resistant Salmonella: An Update
