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Bacterial Sepsis

Daniel C. Richter, Alexandra Heininger, Tatjana Brenner, M. Hochreiter, Michael Christian Bernhard, J. Briegel, Simon Dubler, Béatrice Grabein, Andreas Hecker, Wade A. Kruger, Konstantin Mayer, Mathias W Pletz, D. Storzinger, N. Pinder, Torsten Hoppe-Tichy, Sebastian Weiterer, S. Zimmermann, astrid. brinkmann, Markus A. Weigand, C Lichtenstern
Published 2017 · Medicine
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The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of β‑lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by “Free Access” [].)ZusammenfassungDie Sterblichkeit von Patienten mit Sepsis und septischem Schock ist weiterhin inakzeptabel hoch. Eine effektive, kalkulierte Antibiotikatherapie binnen der ersten Stunde nach Erkennen der Sepsis ist ein wichtiges Ziel der effektiven Sepsistherapie. Verzögerungen führen zum deutlichen Anstieg der Sterblichkeit. Daher bilden strukturierte Behandlungskonzepte eine rationale Grundlage unter Beachtung relevanter Diagnose- und Behandlungsschritte. Neben dem vermuteten Focus und individuellen Risiken einzelner Patienten müssen lokale Resistenzmuster und spezifische Problemerreger bei der Wahl der antiinfektiven Therapie berücksichtigt werden. Vielfältige pathophysiologische Veränderungen beeinflussen im Rahmen der Sepsis die substanzspezifische Pharmakokinetik (PK) vieler Antibiotika. Daher sollte das Prinzip der „Standarddosierung“ verlassen und durch einen individuelleren Therapieansatz mit stärkerer Gewichtung der Pharmakokinetik(PK)-/Pharmakodynamik(PD)-Indizes der Substanzgruppen ersetzt werden. Wenngleich dies noch nicht der klinische Standard ist, können Applikationsformen wie die prolongierte (oder kontinuierliche) Infusion von β‑Lactamen und ein therapeutisches Drugmonitoring (TDM) helfen, definierte PK-Ziele zu erreichen. Während die prolongierte Infusion auch ohne TDM auskommt, ist TDM bei kontinuierlicher Infusion grundsätzlich notwendig. Ein weiteres Argument für den individuellen, PK/PD-orientierten Antibiotikaeinsatz ist die Zunahme komplizierter Infektionen durch multiresistente Erreger (MRE) auf Intensivstationen. Zur effektiveren Behandlung etablieren sich dort zunehmend „antibiotic stewardship teams“ (ABS-Team). Die interprofessionelle Zusammenarbeit des Behandlungsteams mit Infektiologen/Mikrobiologen und klinischen Pharmazeuten führt nicht nur zum rationaleren Antibiotikaeinsatz, sondern beeinflusst das Behandlungsergebnis positiv. Den Goldstandard der Erregerdiagnostik stellen weiterhin der kulturbasierte Nachweis aus Probenmaterial und die mikrobiologische Resistenztestung auf die verschiedenen Antibiotikagruppen dar. Neue Polymerase-Kettenreaktion(PCR)-basierte Verfahren der Erregeridentifikation und Resistenzbestimmung ergänzen trotz hoher Untersuchungsgeschwindigkeit aufgrund der limitierten aktuellen Studienlage, der hohen Kosten und der eingeschränkten Verfügbarkeit derzeit die Sepsisroutinediagnostik lediglich. Bei komplizierten, septischen Krankheitsverläufen mit mehrfacher, antiinfektiver Vorbehandlung oder rekurrenter Sepsis können PCR-basierte Verfahren ergänzend zu Therapie-Monitoring und Diagnostik eingesetzt werden. Neue Antibiotika stellen potente Alternativen in der Behandlung von MRE-Infektionen dar. Aufgrund des oftmals definierten Erregerspektrums und der praktisch (noch) nicht vorhandenen Resistenzen sind diese zur gezielten Behandlung schwerer MRE-Infektionen geeignet (Therapieeskalation).
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Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study
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Time to Treatment and Mortality during Mandated Emergency Care for Sepsis
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Activity of Ceftazidime-Avibactam against Clinical and Isogenic Laboratory Pseudomonas aeruginosa Isolates Expressing Combinations of Most Relevant β-Lactam Resistance Mechanisms.
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How doweuse therapeuticdrugmonitoringto improve outcomes from severe infections in critically ill patients ? BMC InfectDis
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