Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study.

BACKGROUND: The relevance of vancomycin resistance in enterococcal blood stream infections (BSI) is still controversial. Aim of this study was to outline the effect of vancomycin resistance of Enterococcus faecium on the outcome of patients with BSI after orthotopic liver transplantation (OLT). METHODS: The outcome of OLT recipients developing BSI with vancomycin-resistant (VRE) versus vancomycin-susceptible Enterococcus faecium (VSE) was compared based on data extraction from medical records. Multivariate regression analyses identified risk factors for mortality and unfavourable outcomes (defined as death or prolonged intensive care stay) after 30 and 90 days. RESULTS: Mortality was similar between VRE- (n = 39) and VSE- (n = 138) group after 30 (p = 0.44) or 90 days (p = 0.39). Comparable results occurred regarding unfavourable outcomes. Mean SOFANon-GCS score during the 7-day-period before BSI onset was the independent predictor for mortality at both timepoints (HR 1.32; CI 1.14-1.53; and HR 1.18; CI 1.08-1.28). Timely appropriate antibiotic therapy, recent ICU stay and vancomycin resistance did not affect outcome after adjusting for confounders. CONCLUSION: Vancomycin resistance did not influence outcome among patients with Enterococcus faecium bacteraemia after OLT. Only underlying severity of disease predicted poor outcome among this homogenous patient population. TRIAL REGISTRATION: This study was registered at the German clinical trials register (DRKS-ID: DRKS00013285).

[New antibiotics for severe infections due to multidrug-resistant pathogens : Definitive treatment and escalation]. / Neue Antibiotika bei schweren Infektionen durch multiresistente Erreger : Definitive Therapie und Eskalation.

Multidrug-resistant pathogens often lead to treatment failure of antimicrobial regimens. After a period of imbalance between the occurrence/spread of resistance mechanisms and the development of new substances, some new substances have meanwhile been approved and many more are currently undergoing clinical testing. They are particularly effective against specific resistance mechanisms/pathogens and should be preserved for definitive treatment of an isolated pathogen. In the absence of alternatives reserve antibiotics, such as aztreonam and colistin have experienced a renaissance. They are again used in special infection scenarios and clinically tested in combination with new substances. Despite the introduction and development of new substances the building of resistance will at some time also render these (at least partially) ineffective. Therefore, their implementation must be carried out according to the antibiotic or infectious diseases stewardship.

[Infections due to multidrug-resistant pathogens : Pathogens, resistance mechanisms and established treatment options]. / Infektionen durch multiresistente Erreger : Erreger, Resistenzmechanismen und etablierte Therapieoptionen.

The increase in resistant pathogens has long been a global problem. Complicated life-threatening infections due to multidrug-resistant pathogens (MRD) meanwhile occur regularly in intensive care medicine. An important and also potentially modifiable factor of the rapid spread of resistance is the irrational use of broad spectrum antibiotics in human medicine. In addition to many other resistance mechanisms, beta-lactamases play an important role in Gram-negative pathogens. They are not uncommonly the leading reason of difficult to treat infections and the failure of known routinely used broad spectrum antibiotics, such as cephalosporins, (acylamino)penicillins and carbapenems. Strategies for containment of MRDs primaríly target the rational use of antibiotics. In this respect interdisciplinary treatment teams, e.g. antibiotic stewardship (ABS) and infectious diseases stewardship (IDS) play a major role.

[Evidence-based interdisciplinary treatment of abdominal sepsis]. / Evidenzbasierte, interdisziplinäre Behandlung der abdominellen Sepsis.

Abdominal sepsis is the most severe form of abdominal infection. It is characterized by a dysregulated host response to infection leading to life-threatening organ failure or septic shock. The latter has a mortality of >40%. This article reviews the evidence on the strategic approach to treatment of patients with abdominal sepsis and septic shock. The focus is on the time-critical elements of diagnosis, anti-infective treatment and hemodynamic stabilization.

Bacterial sepsis : Diagnostics and calculated antibiotic therapy.

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 ß­lactam 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" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).

[S2k guidelines of the PEG on calculated parenteral initial treatment of bacterial diseases in adults : Focussed summary and supplementary information on antibiotic treatment of critically ill patients]. / S2k-Leitlinie der PEG zur kalkulierten parenteralen Initialtherapie bakterieller Erkrankungen bei Erwachsenen : Fokussierte Zusammenfassung und ergänzende Informationen zur Antibiotikatherapie kritisch kranker Patienten.

In January 2018 the recent revision of the S2k guidelines on calculated parenteral initial treatment of bacterial diseases in adults-update 2018 (Editor: Paul Ehrlich Society for Chemotherapy, PEG) was realized. It is a helpful tool for the complex infectious disease setting in an intensive care unit. The present summary of the guidelines focuses on the topics of anti-infective agents, including new substances, pharmacokinetics and pharmacodynamics as well as on microbiology, resistance development and recommendations for calculated drug therapy in septic patients. As in past revisions the recent resistance situation and results of new clinical studies are considered and anti-infective agents are summarized in a table.

[Bacterial sepsis : Diagnostics and calculated antibiotic therapy]. / Bakterielle Sepsis : Diagnostik und kalkulierte Antibiotikatherapie.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective 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 focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics 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 beta-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 basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological 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 treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy 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 absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).