Trends, seasonality and the association between outpatient antibiotic use and antimicrobial resistance among urinary bacteria in the Netherlands

Abstract

Objectives To determine trends, seasonality and the association between community antibiotic use and antimicrobial resistance (AMR) in Escherichia coli and Klebsiella pneumoniae in urinary tract infections. Methods We analysed Dutch national databases from January 2008 to December 2016 regarding antibiotic use and AMR for nitrofurantoin, trimethoprim, fosfomycin and ciprofloxacin. Antibiotic use was expressed as DDD/1000 inhabitant-days (DID) and AMR was expressed as the percentage of resistance from total tested isolates. Temporal trends and seasonality were analysed with autoregressive integrated moving average (ARIMA) models. Each antibiotic use–resistance combination was cross-correlated with a linear regression of the ARIMA residuals. Results The trends of DID increased for ciprofloxacin, fosfomycin and nitrofurantoin, but decreased for trimethoprim. Similar trends were found in E. coli and K. pneumoniae resistance to the same antibiotics, except for K. pneumoniae resistance to ciprofloxacin, which decreased. Resistance levels peaked in winter/spring, whereas antibiotic use peaked in summer/autumn. In univariate analysis, the strongest and most significant cross-correlations were approximately 0.20, and had a time delay of 3–6 months between changes in antibiotic use and changes in resistance. In multivariate analysis, significant effects of nitrofurantoin use and ciprofloxacin use on resistance to these antibiotics were found in E. coli and K. pneumoniae, respectively. There was a significant association of nitrofurantoin use with trimethoprim resistance in K. pneumoniae after adjusting for trimethoprim use. Conclusions We found a relatively low use of antibiotics and resistance levels over a 9 year period. Although the correlations were weak, variations in antibiotic use for these four antibiotics were associated with subsequent variations in AMR in urinary pathogens.

Large variation in the association between seasonal antibiotic use and resistance across multiple bacterial species and antibiotic classes

“…However, resistance to nitrofurantoin in all 3 species peaked in the winter/spring and lagged use by about 3 to 5.5 months. This was consistent with a previous finding that nitrofurantoin resistance lagged use by 3-6 months in E. coli and K. pneumoniae urinary tract isolates [11]. Quinolones, which are used to treat both respiratory infections and UTIs [27], showed both winter and summer peaks in use, but only a single winter/spring peak in ciprofloxacin resistance in all 3 species.…”

“…In contrast, a study from the Netherlands that analyzed antibiotics with summer/autumn peaks in use (e.g. Nitrofurantoin, Fosfomycin, Trimethoprim) found that resistance in E. coli and Klebsiella pneumoniae still peaked in the winter/spring and lagged use by 3-6 months [11], inconsistent with the Blanquart et al model. The authors of this study attribute the longer lag time to the weaker seasonal fluctuations and lower overall rates of antibiotic use in their study population.…”

Seasonal Patterns in Incidence and Antimicrobial Resistance of Common Bacterial Pathogens in Nursing Home Patients and Their Rooms

“…This trend that has been reported before for this organism ( 1 , 8 ), although this is the first time it has been found in the NH setting. Additionally, it is important to caution that although an association between resistance rates and antimicrobial use has been reported in some common gram-negative pathogens in various healthcare settings ( 15 , 16 ), such association may present with a lag, especially when infections are used as the endpoint rather than colonization, presumably at least in part due to the time elapsed between colonization, infection, and eventually collection of clinical samples ( 15 ).…”

Putative mobilized colistin resistance genes in the human gut microbiome

“…Still, its importance is often underestimated in community infections, as hospitalized infections gain the most attention [2]. Many previous studies have addressed the prevalence of AR in clinical environments [3][4][5], and more recently AR prevalence in non-hospitalized populations too [6,7]. Most of these studies were conducted on cultivable clinical strains using microbiological methods that involve cultivation and antibiogram tests.…”