["Drug Interaction Stewardship" (DIS) and Therapeutic Drug Monitoring for Anti-infective Treatment in Intensive Care, a Single Centre Observational Study]. / "Drug Interaction Stewardship" (DIS) und therapeutisches Drug-Monitoring (TDM) für die antiinfektive Therapie in der operativen Intensivmedizin, eine monozentrische Beobachtungsstudie.

INTRODUCTION: Appropriate medication of intensive care patients is complicated by disturbed organ functions and organ failure, pathophysiological changes in severely ill patients as well as possible sepsis, ongoing haemodialysis for renal and hepatic insufficiency, varying pharmacokinetics/-dynamics (PK/PD) of drugs as well as numerous drug interactions. AIM: Illustration of an interdisciplinary approach in daily clinical practice to optimise regular "polymedication" as well as the ongoing medication of patients prior to surgical interventions as indicated and as part of the appropriate peri- and postoperative intensive care management. METHOD: A so-called "drug interaction stewardship" (DIS) is very similar to the already established "antibiotic stewardship" (ABS) during daily clinical routine of an intensive care unit and has been implemented. In addition, therapeutic drug monitoring (TDM) has been extended to antibiotics/antimycotics (such as meropenem, piperacillin-tazobactam, ceftazidime, linezolide, voriconazole, fluconazole, caspofungin), for which TDM had not yet been established. This was in a consecutive cohort of patients with abdominal surgery over a defined time period and was part of a systematic clinical single centre observational study (tertiary centre). RESULTS: From 01 - 2012 to 08 - 2016, 1,454 single drug patient consultations led to 385 (26.5%) changes in medical treatment, which had been previously initiated by an experienced intensive care physician. Most frequently in 156 cases (10.7%) this was due to newly calculated PK/PD. Analysis of 2,333 TDM samples resulted in a minimum serum level within the adequate range in 1,130 cases (48.4%). In 427 cases (18.3%), the drug serum level was too low and in 776 subjects (33.3%), prompting a change in the type, dose, dose interval and application route. CONCLUSION: DIS and TDM provide a high rate of detection of unwanted drug interactions and inappropriate drug levels in surgical intensive care patients and help to assure targeted therapy changes.

Recharge contribution to the Guarani Aquifer System estimated from the water balance method in a representative watershed.

The contribution of recharge to regional groundwater flow systems is essential information required to establish sustainable water resources management. The objective of this work was to determine the groundwater outflow in the Ribeirão da Onça Basin using a water balance model of the saturated soil zone. The basin is located in the outcrop region of the Guarani Aquifer System (GAS). The water balance method involved the determination of direct recharge values, groundwater storage variation and base flow. The direct recharge was determined by the water table fluctuation method (WTF). The base flow was calculated by the hydrograph separation method, which was generated by a rain-flow model supported by biweekly streamflow measurements in the control section. Undisturbed soil samples were collected at depths corresponding to the variation zone of the groundwater level to determine the specific yield of the soil (drainable porosity). Water balances were performed in the saturated zone for the hydrological years from February 2004 to January 2007. The direct recharge ranged from 14.0% to 38.0%, and groundwater outflow from 0.4% to 2.4% of the respective rainfall during the same period.

Observational clinical study on the effects of different dosing regimens on vancomycin target levels in critically ill patients: Continuous versus intermittent application.

Different dosing regimens for vancomycin are in clinical use: intermittent infusion and continuous administration. The intention of using these different dosing regimens is to reduce toxicity, to achieve target levels faster and to avoid treatment failure. The aim of this phase IV study was to compare safety and effectiveness in both administration regimens. The study was conducted in 2010 and 2011 in three postoperative intensive care units (ICUs) in a tertiary care university hospital in Berlin, Germany. Adult patients with vancomycin therapy and therapeutic drug monitoring were included. Out of 675 patients screened, 125 received vancomycin therapy, 39% with intermittent and 61% with continuous administration. Patients with continuous administration achieved target serum levels significantly earlier (median day 3 versus 4, p=0.022) and showed fewer sub-therapeutic serum levels (41% versus 11%, p<0.001). ICU mortality rate, duration of ICU stay and duration of ventilation did not differ between groups. Acute renal failure during the ICU stay occurred in 35% of patients with intermittent infusion versus 26% of patients with continuous application (p=0.324). In conclusion, continuous administration of vancomycin allowed more rapid achievement of targeted drug levels with fewer sub-therapeutic vancomycin levels observed. This might indicate that patients with more severe infections or higher variability in renal function could benefit from this form of administration.