Estimation of multidrug resistance variability in the National Antimicrobial Monitoring System

Multidrug resistance is a serious problem raising the specter of infections for which there is no treatment. One of the most important tools in combating multidrug resistance is large scale monitoring programs, because they track resistance over large geographic areas and time scales. This large scope, however, can also introduce variability into the data. The primary monitoring program in the United States is the National Antimicrobial Resistance Monitoring System (NARMS). This study examines the variability of a previously identified resistance pattern in Escherichia coli among ampicillin, gentamicin, sulfisoxazole, and tetracycline using samples isolated from chicken during the years 2004 to 2006 and 2008 to 2012. 2007 is excluded because sulfisozaxole resistance was not measured at slaughter that year. To assess variability in this resistance pattern susceptibility/resistance contingency tables were constructed for each of the 15 combinations of the 4 drugs for each of the years. For each table, variability across the years was assessed at the full table multinomial level as a measure of general variability of the resistance pattern and at the level of the highest order interaction term in a log-linear model of the table as a measure of variability in that particular component of the resistance pattern. A power analysis using the traditional asymptotic normal approximation and one using a Dirichlet-multinomial simulation were carried out to determine the effect of variation on ability to detect nonzero highest order loglinear model terms and the validity of the normal approximation in carrying out such tests. All tables exhibit overdispersion at the multinomial level and in their highest order model parameters. The normal approximation performs well for large sample sizes, low levels of dispersion, and small log-linear model parameters. The approximation breaks down as dispersion or the log linear model parameter grows or sample size shrinks. Taken together these analyses indicate that the level of variability in the NARMS dataset makes it difficult to detect multidrug resistance patterns at the current level of sample collection. In order to better control this dispersion NARMS could collect more variables on each of the samples.