There is a growing concern about the role of the environment in the dissemination of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this systematic review, we summarize evidence for increases of ARG in the natural environment associated with potential sources of ARB and ARG such as agricultural facilities and wastewater treatment plants. A total of 5247 citations were identified, including studies that ascertained both ARG and ARB outcomes. All studies were screened for relevance to the question and methodology. This paper summarizes the evidence only for those studies with ARG outcomes (n = 24). Sixteen studies were at high (n = 3) or at unclear (n = 13) risk of bias in the estimation of source effects due to lack of information or failure to control for confounders. Statistical methods were used in nine studies; three studies assessed the effect of multiple sources using modeling approaches, and none reported effect measures. Most studies reported higher ARG concentration downstream/near the source, but heterogeneous findings hindered making any sound conclusions. To quantify increases of ARG in the environment due to specific point sources, there is a need for studies that emphasize analytic or design control of confounding, and that provide effect measure estimates.

Herein we describe a protocol for a systematic review of the evidence on whether point sources of anthropogenic effluent are associated with an increase in antibiotic resistance in the adjacent environment. The review question was based on the Population, Exposure, Comparator, Outcome, Study Design (PECOS) framework as follows: Is the prevalence or concentration of antibiotic resistant bacteria or resistance genes (O) in soil, water, air or free-living wildlife (P) higher in close proximity to, or downstream from, known or suspected sources of anthropogenic effluent (E) compared to areas more distant from or upstream from these sources (C)? A comprehensive search strategy was created to capture all relevant, published literature. Criteria for two stages of eligibility screening were developed to exclude publications that were not relevant to the question, and determine if the study used a design that permitted estimation of an association between a source and levels of resistance. A decision matrix was created for assessment of risk of bias to internal validity due to sample selection bias, information bias, and confounding. The goal of this protocol is to provide a method for determining the state of knowledge about the effect of point sources on antibiotic resistance in the environment.

Evolution of cell populations can be described with dissipative particle dynamics, whereeach cell moves according to the balance of forces acting on it, or with partialdifferential equations, where cell population is considered as a continuous medium. Wecompare these two approaches for some model examples