Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
PLoS Comput Biol. 2021 Jan 29;17(1):e1008446. doi: 10.1371/journal.pcbi.1008446. eCollection 2021 Jan.
Beta-lactam- and in particular carbapenem-resistant Enterobacteriaceae represent a major public health threat. Despite strong variation of resistance across geographical settings, there is limited understanding of the underlying drivers. To assess these drivers, we developed a transmission model of cephalosporin- and carbapenem-resistant Klebsiella pneumoniae. The model is parameterized using antibiotic consumption and demographic data from eleven European countries and fitted to the resistance rates for Klebsiella pneumoniae for these settings. The impact of potential drivers of resistance is then assessed in counterfactual analyses. Based on reported consumption data, the model could simultaneously fit the prevalence of extended-spectrum beta-lactamase-producing and carbapenem-resistant Klebsiella pneumoniae (ESBL and CRK) across eleven European countries over eleven years. The fit could explain the large between-country variability of resistance in terms of consumption patterns and fitted differences in hospital transmission rates. Based on this fit, a counterfactual analysis found that reducing nosocomial transmission and antibiotic consumption in the hospital had the strongest impact on ESBL and CRK prevalence. Antibiotic consumption in the community also affected ESBL prevalence but its relative impact was weaker than inpatient consumption. Finally, we used the model to estimate a moderate fitness cost of CRK and ESBL at the population level. This work highlights the disproportionate role of antibiotic consumption in the hospital and of nosocomial transmission for resistance in gram-negative bacteria at a European level. This indicates that infection control and antibiotic stewardship measures should play a major role in limiting resistance even at the national or regional level.
β-内酰胺类药物，特别是碳青霉烯类耐药肠杆菌科细菌，对公共健康构成重大威胁。尽管在地理环境上存在耐药性的巨大差异，但对于潜在驱动因素的了解有限。为了评估这些驱动因素，我们开发了一种头孢菌素和碳青霉烯类耐药肺炎克雷伯菌的传播模型。该模型使用来自 11 个欧洲国家的抗生素消费和人口数据进行参数化，并根据这些环境下的肺炎克雷伯菌耐药率对模型进行拟合。然后，在反事实分析中评估耐药性的潜在驱动因素的影响。根据报告的消费数据，该模型可以同时拟合 11 个欧洲国家 11 年来产超广谱β-内酰胺酶和碳青霉烯类耐药肺炎克雷伯菌（ESBL 和 CRK）的流行率。拟合可以解释耐药性在消费模式和医院传播率方面的巨大国家间差异。基于该拟合，反事实分析发现，减少医院内的医院传播和抗生素消费对 ESBL 和 CRK 流行率的影响最大。社区内的抗生素消费也会影响 ESBL 的流行率，但相对影响比住院消费弱。最后，我们使用该模型估计了 CRK 和 ESBL 在人群水平上的中度适应成本。这项工作强调了抗生素消费在医院和医院内传播对欧洲水平下革兰氏阴性菌耐药性的不成比例作用。这表明，即使在国家或地区层面，感染控制和抗生素管理措施也应在限制耐药性方面发挥重要作用。
