Antimicrobial stewardship, therapeutic drug monitoring and infection management in the ICU: results from the international A- TEAMICU survey

Abstract: Background: Severe infections and multidrug-resistant pathogens are common in critically ill patients. Antimicrobial stewardship (AMS) and therapeutic drug monitoring (TDM) are contemporary tools to optimize the use of antimicrobials. The A-TEAMICU survey was initiated to gain contemporary insights into dissemination and structure of AMS programs and TDM practices in intensive care units. Methods: This study involved online survey of members of ESICM and six national professional intensive care societies. Results: Data of 812 respondents from mostly European high- and middle-income countries were available for analysis. 63% had AMS rounds available in their ICU, where 78% performed rounds weekly or more often. While 82% had local guidelines for treatment of infections, only 70% had cumulative antimicrobial susceptibility reports and 56% monitored the quantity of antimicrobials administered. A restriction of antimicrobials was reported by 62%. TDM of antimicrobial agents was used in 61% of ICUs, mostly glycopeptides (89%), aminoglycosides (77%), carbapenems (32%), penicillins (30%), azole antifungals (27%), cephalosporins (17%), and linezolid (16%). 76% of respondents used prolonged/continuous infusion of antimicrobials. The availability of an AMS had a significant association with the use of TDM. Conclusions: Many respondents of the survey have AMS in their ICUs. TDM of antimicrobials and optimized administration of antibiotics are broadly used among respondents. The availability of antimicrobial susceptibility reports and a surveillance of antimicrobial use should be actively sought by intensivists where unavailable. Results of this survey may inform further research and educational activities

Genexpressionsanalysen an myxoid/rundzelligen Liposarkomen

Myxoid/rundzellige Liposarkome gehören zu den häufigsten Malignomen des Weichgewebes. Für diese Arbeit wurden mit DNA-Mikroarrays (Affymetrix) Genexpressionsanalysen an vier myxoid/rundzelligen Liposarkomen und vier normalen Fettgewebsproben angefertigt. Es wurde eine Liste von Genen erstellt, die in den Tumoren wenigstens 2-fach überexprimiert waren. Einige Gene wurden experimentell weiter bearbeitet: $\textit {ret, cdk4, cyclin D2, N-ras, c-myc}$. Für $\textit {cdk4, cyclin D2}$ und $\it {c-myc}$ konnte die Überexpression im Northern Blotting bestätigt werden. Es wurden immunhistochemische Analysen an Gewebeschnitten von 36 myxoid/rundzelligen Liposarkomen durchgeführt, um die Expression der genannten Gene auf Proteinebene zu untersuchen. Hierbei zeigten sich positive Befunde für $\it cdk4$ (94%), $\it {cyclin D2}$ (92%), $\it {c-myc}$ (66%) und $\it ret$ (69%). Ein interessanter Befund war eine starke Lokalisierung von $\it ret$-Protein in den Kapillarendothelien der intratumoralen Gefäße

Netzwerkgründung Antibiotic Stewardship in Westfalen-Lippe

Der Begriff „Antibiotic Stewardship“ (ABS) fasst Maßnahmen zum rationalen und hinsichtlich der Resistenzentwicklung verantwortungsvollen Einsatz von Antibiotika zusammen. ABS-Programme entstanden zunächst im stationären, später auch im ambulanten Sektor. Nicht zuletzt hat der öffentliche Gesundheitsdienst die Bedeutung von ABS erkannt und es erscheint naheliegend, die bestehenden ABS-Ansätze nicht nur vor Ort fach- und sektorübergreifend zu verknüpfen, sondern sich auch überregional zu vernetzen und verfügbares Wissen und Erfahrungen mit einem größeren Kreis zu teilen. Der Beitrag stellt die Ideen und Konzepte des neugegründeten ABS-Netzwerkes in Westfalen-Lippe sowie Teilnehmende, Diskussionspunkte und Ablauf der Netzwerkgründung vor.Peer Reviewe

Antibiotika-resistente Erreger in Deutschland

Hintergrund: Die Frage, ob die zunehmende Verbreitung von Erregern mit Antibiotika-Multiresistenzen (MRE) beim Menschen durch Übertragungen von Tieren erklärbar ist, wird öffentlich diskutiert. Ziel der Arbeit: Diese Übersichtsarbeit trägt Daten zum Vorkommen von Methicillin-resistenten Staphylococcus aureus (MRSA) und Extended-Spectrum Beta-Lactamase (ESBL) bildenden Enterobakterien bei Mensch und Tier zusammen und beschreibt die Erkenntnisse zur zoonotischen Transmission. Material und Methoden: Es wurde eine Literaturrecherche durchgeführt. Relevante Literatur wurde durch Screening von Überschriften und Abstracts identifiziert und ergänzt durch Publikationen von Infektionsschutzbehörden bzw. die dort zitierten Originalarbeiten. Ergebnisse: Es zeigte sich eine Vielzahl nosokomialer Verbreitungswege von MRE sowie eine zunehmende Relevanz von außerhalb des Gesundheitswesens gelegenen Infektionsquellen. Diskussion: Für eine effektive Prävention von MRE ist ein interdisziplinärer Ansatz notwendig, der sowohl die Grenzen medizinischer und pharmazeutischer Fachgebiete als auch die Grenzen zwischen Human- und Veterinärmedizin überschreitet

Continuous Glucose Monitoring in Patients Undergoing Extracorporeal Ventricular Assist Therapy

<div><p>Background</p><p>Dysregulations of blood glucose (BG) are associated with adverse outcome in critical illness; controlling BG to target appears to improve outcome. Since BG-control is challenging in daily intensive care practice BG-control remains poor especially in patients with rapidly fluctuating BG. To improve BG-control and to avoid deleterious hypoglycemia, automated online-measurement tools are advocated. We thus evaluated the point-accuracy of the subcutaneous Sentrino^® Continuous Glucose Monitoring System (CGM, Medtronic Diabetes, Northridge, California) in patients undergoing extracorporeal cardiac life support (ECLS) for cardiogenic shock.</p><p>Methods</p><p>Management of BG was performed according to institute’s standard aiming at BG-levels between 100–145 mg/dl. CGM-values were recorded without taking measures into therapeutic account. Point-accuracy in comparison to intermittent BG-measurement by the ABL-blood-gas analyzer was determined.</p><p>Results</p><p>CGM (n = 25 patients) correlated significantly with ABL-values (r = 0.733, p<0.001). Mean error from standard was 15.0 mg/dl (11.9%). 44.2% of the readings were outside a 15% range around ABL-values. In one of 635 paired data-points, ABL revealed hypoglycemia (BG 32 mg/dl) whereas CGM did not show hypoglycemic values (132mg/dl).</p><p>Conclusions</p><p>CGM reveals minimally invasive BG-values in critically ill adults with dynamically impaired tissue perfusion. Because of potential deviations from standard, CGM-readings must be interpreted with caution in specific ICU-populations.</p></div

Demographic data.

<p>Demographic data.</p

Regression analysis, Pearson correlation: 0.733398, significance (2-tailed), p = 0.000.

<p>Regression analysis, Pearson correlation: 0.733398, significance (2-tailed), p = 0.000.</p

Clarke Error Grid Analysis.

<p>Zone A: Clinically accurate, Zone B: Benign, Zone C: Overcorrected, Zone D: Failure to detect, Zone E: Erroneus.</p

Antimicrobial stewardship in the ICU in COVID-19 times : the known unknowns

Since the start of the COVID-19 pandemic, there has been concern about the concomitant rise of antimicrobial resistance. While bacterial co-infections seem rare in COVID-19 patients admitted to hospital wards and intensive care units (ICUs), an increase in empirical antibiotic use has been described. In the ICU setting, where antibiotics are already abundantly-and often inappropriately-prescribed, the need for an ICU-specific antimicrobial stewardship programme is widely advocated. Apart from essentially warning against the use of antibacterial drugs for the treatment of a viral infection, other aspects of ICU antimicrobial stewardship need to be considered in view of the clinical course and characteristics of COVID-19. First, the distinction between infectious and non-infectious (inflammatory) causes of respiratory deterioration during an ICU stay is difficult, and the much-debated relevance of fungal and viral co-infections adds to the complexity of empirical antimicrobial prescribing. Biomarkers such as procalcitonin for the decision to start antibacterial therapy for ICU nosocomial infections seem to be more promising in COVID19 than non-COVID-19 patients. In COVID-19 patients, cytomegalovirus reactivation is an important factor to consider when assessing patients infected with SARS-CoV-2 as it may have a role in modulating the patient immune response. The diagnosis of COVID-19-associated invasive aspergillosis is challenging because of the lack of sensitivity and specificity of the available tests. Furthermore, altered pharmacokinetic/pharmacodynamic properties need to be taken into account when prescribing antimicrobial therapy. Future research should now further explore the 'known unknowns', ideally with robust prospective study designs. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/

An innovative telemedical network to improve infectious disease management in critically ill patients and outpatients: a stepped-wedge, cluster randomized controlled trial (TELnet@NRW)

Marx G, Greiner W, Juhra C, et al. An innovative telemedical network to improve infectious disease management in critically ill patients and outpatients: a stepped-wedge, cluster randomized controlled trial (TELnet@NRW). Journal of Medical Internet Research . 2022.BACKGROUND: Evidence-based infectious disease and intensive care management is more relevant than ever. Medical expertise in the two disciplines is often geographically limited to university institutions. In addition, the interconnection between inpatient and outpatient care is often insufficient (e.g., no shared electronic health record, no digital transfer of patient findings).; OBJECTIVE: To establish and evaluate a telemedical inpatient-outpatient network based on expert teleconsultations to increase treatment quality in intensive care medicine and infectious diseases.; METHODS: We performed a multicentre, stepped-wedge cluster randomised trial (Feb 2017 - Jan 2020) to establish a telemedicine inpatient-outpatient network among university hospitals, hospitals, and outpatient physicians in North Rhine Westphalia, Germany. Patients ≥ 18 years of age in the intensive care unit (ICU) or consulting with a physician in the outpatient setting were eligible. We provided expert knowledge from intensivists and infectious disease specialists through advanced training courses and expert teleconsultations with 24/7/365 availability on demand resp. once per week to enhance treatment quality. The primary outcome was adherence to the ten Choosing Wisely recommendations for infectious disease management. Guideline adherence was analysed using binary logistic regression models.; RESULTS: Overall, 159,424 patients (10,585 inpatients, 148,839 outpatients) from 17 hospitals and 103 outpatient physicians were included. There was a significant increase in guideline adherence in the management of Staphylococcus aureus infections (OR 4.00 [95% CI 1.83, 9.20], P<.01) and in sepsis management in critically ill patients (OR 6.82 [95% CI 1.27, 56.61], P=.04). There was a statistically non-significant decrease in sepsis related mortality from 28.8% (19/66) in the control group to 23.8% (50/210) in the intervention group. Furthermore, the extension of treatment with prophylactic antibiotics after surgery was significantly less likely (OR 9.37 [95% CI 1.52, 111.47], P=.04). Patients treated by outpatient physicians, who were regularly taking part in expert teleconsultations, were also more likely to be treated according to guideline recommendations regarding antibiotic therapy for uncomplicated upper respiratory tract infections (OR 1.34 [95% CI 1.16, 1.56], P<.01) and asymptomatic bacteriuria (OR 9.31 [95% CI 3.79, 25.94], P<.01). For the other recommendations, we found no significant effects, or we had too few observations to generate models. Key limitations of our study include selection effects due to the applied on-site triage of patients as well as the limited possibilities to control for secular effects.; CONCLUSIONS: Telemedicine facilitates a direct round-the-clock interaction over broad distances between intensivists or infectious disease experts and physicians who care for patients in hospitals without ready access to these experts. Expert teleconsultations increase guideline adherence and treatment quality in infectious disease and intensive care management creating added value for critically ill patients.; CLINICALTRIAL: ClinicalTrials.gov, NCT03137589, https://clinicaltrials.gov/ct2/show/NCT03137589