The Actual Clinical Situation Ruthlessly Exposes the Challenge of Rational Care for Nosocomial and Community-Acquired Infections and Requires Even More Efforts for Satisfactory Antibiotic Stewardship.

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.