荷兰门诊抗生素使用与尿路细菌耐药性之间的趋势、季节性及关联

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

作者信息

Martínez Evelyn Pamela, van Rosmalen Joost, Bustillos Roberto, Natsch Stephanie, Mouton Johan W, Verbon Annelies

机构信息

Facultad de Medicina Veterinaria y Zootecnia, Universidad Central del Ecuador, Quito, Ecuador.

Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.

出版信息

J Antimicrob Chemother. 2020 Aug 1;75(8):2314-2325. doi: 10.1093/jac/dkaa165.

DOI:10.1093/jac/dkaa165

PMID:32417922

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.

摘要

目的

确定尿路感染中社区抗生素使用与大肠埃希菌和肺炎克雷伯菌耐药性（AMR）之间的趋势、季节性及关联。

方法

我们分析了2008年1月至2016年12月荷兰国家数据库中关于呋喃妥因、甲氧苄啶、磷霉素和环丙沙星的抗生素使用及AMR情况。抗生素使用以限定日剂量/1000居民日（DDD/1000 inhabitant-days，DID）表示，AMR以耐药分离株占总检测分离株的百分比表示。使用自回归积分移动平均（ARIMA）模型分析时间趋势和季节性。每种抗生素使用-耐药组合与ARIMA残差的线性回归进行交叉相关分析。

结果

环丙沙星、磷霉素和呋喃妥因的DID呈上升趋势，而甲氧苄啶的DID呈下降趋势。在大肠埃希菌和肺炎克雷伯菌对相同抗生素的耐药性方面也发现了类似趋势，但肺炎克雷伯菌对环丙沙星的耐药性呈下降趋势。耐药水平在冬季/春季达到峰值，而抗生素使用在夏季/秋季达到峰值。单因素分析中，最强且最显著的交叉相关性约为0.20，抗生素使用变化与耐药性变化之间的时间延迟为3 - 6个月。多因素分析中，在大肠埃希菌和肺炎克雷伯菌中分别发现呋喃妥因使用和环丙沙星使用对这些抗生素耐药性有显著影响。在调整甲氧苄啶使用后，呋喃妥因使用与肺炎克雷伯菌对甲氧苄啶的耐药性存在显著关联。