Diebner Hans H, Wallrafen A Melina, Timmesfeld Nina, Rahmel Tim, Nowak Hartmuth
Abteilung für Medizinische Informatik, Biometrie und Epidemiologie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.
Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, D-44892 Bochum, Germany.
Antibiotics (Basel). 2025 May 30;14(6):561. doi: 10.3390/antibiotics14060561.
Antimicrobial resistance is one of the 10 most pressing health problems worldwide. First steps toward harnessing the complex dynamics of antibiotic resistance are presented. To accomplish this, we first shift down a gear and try to understand the actual driving dynamics behind the development of resistance in a specific clinical department. Analyses are based on the clinical and microbiological data of a German hospital over an observation period of more than 7 years, which we evaluate descriptively and semi-quantitatively in order to obtain a basis for informed and intelligent action in terms of antibiotic stewardship. The specific results include the observed increase in the resistance rate with increasing overall consumption, while increases over time independent of consumption are fairly moderate. Vancocymin and refoximin are an exception in the development of resistance, as resistance to these substances appears to decrease with increasing consumption. However, there have been substantial dose adjustments for these substances, which are likely to be decisive here. An intra-host increase in resistance due to treatment time on the one hand and repeated treatments on the other is observed. Within the sub-cohort of ineffectively treated patients, i.e., with resistance to the antibiotic, mortality increases on average, but with ampicillin/sulbactam as a striking exception. Patients with infections caused by ampicillin-resistant bacteria have a lower mortality rate. The observed resistance rates of the eight most frequently administered antibiotics show a temporal variability that includes random fluctuations as well as decidedly regular cycles. The time series associated with the various antibiotics show pairwise time lag correlations, which indicates the existence of retardedly mediated cross-resistance. We conclude with an outlook on upcoming further analyses and a draft action plan on how to control and harness the complex dynamics observed by means of successful, informed, and intelligent antibiotic stewardship.
抗菌药物耐药性是全球十大最紧迫的健康问题之一。本文介绍了应对抗生素耐药性复杂动态的初步措施。为此，我们首先放缓节奏，试图了解特定临床科室耐药性发展背后的实际驱动因素。分析基于一家德国医院超过7年观察期的临床和微生物数据，我们对其进行描述性和半定量评估，以便为抗生素管理方面的明智行动提供依据。具体结果包括，随着总体消耗量增加，耐药率上升，而与消耗量无关的随时间增加幅度较为适中。万古霉素和瑞伐沙星在耐药性发展方面是个例外，因为随着消耗量增加，对这些药物的耐药性似乎有所下降。然而，这些药物已经进行了大幅剂量调整，这可能在此起决定性作用。一方面观察到由于治疗时间以及另一方面重复治疗导致宿主内耐药性增加。在治疗无效患者亚组中，即对抗生素耐药的患者中，死亡率平均上升，但氨苄西林/舒巴坦是一个显著例外。由耐氨苄西林细菌引起感染的患者死亡率较低。八种最常用抗生素的观察到的耐药率呈现出时间变异性，包括随机波动以及明显的周期性。与各种抗生素相关的时间序列显示出成对的时间滞后相关性，这表明存在延迟介导的交叉耐药性。我们最后展望了即将进行的进一步分析以及关于如何通过成功、明智和智能的抗生素管理来控制和应对所观察到的复杂动态的行动计划草案。
