Impact of discontinuing contact precautions and enforcement of basic hygiene measures on nosocomial vancomycin-resistant Enterococcus faecium transmission.

OBJECTIVES: Vancomycin-resistant Enterococcus faecium (VREfm) has emerged as a pathogen of major concern for public health. Although definitive evidence is lacking, contact precautions have been a crucial element in infection prevention and control (IPC) strategies designed to limit nosocomial VRE transmission. This study investigated the effect of discontinuing contact precautions while enforcing basic hygiene measures, including hand hygiene, environmental cleaning and antiseptic body washing, for patients with VRE in intensive care units (ICUs) on the prevention of nosocomial VRE transmission causing bacteraemia. METHODS: Contact precautions were discontinued in January 2018. In total, 96 VREfm isolates from 61 patients with VREfm bacteraemia and/or colonization hospitalized in eight ICUs in a tertiary care hospital in 2016 and 2019 in were characterized by whole-genome sequencing. VRE transmission was investigated using patient movement data and admission screening for reliable identification of nosocomial acquisition. RESULTS: Discontinuation of contact precautions did not increase VREfm transmission events (eight in 2016 vs one in 2019). While the rate of endogenous VREfm was similar in both years (38% vs 31%), the number of non-colonized patients prior to VREfm bacteraemia was 16 (16/29, 55%) in 2019, which was significantly higher than in 2016 (8/32, 25%). The mean incidence density for VREfm bacteraemia was similar for both years (0.26 vs 0.31 per 1000 patient-days in 2016 and 2019, respectively). CONCLUSION: Discontinuation of contact precautions while enforcing basic hygiene measures did not lead to an increase in nosocomial bloodstream infection rates due to VREfm transmission in a hyperendemic ICU setting.

[Urology in the corona-virus pandemic-a guideline 4/20]. / Urologie in der Corona-Virus-Pandemie ­ Leitfaden 4/20.

The coronavirus pandemic is a major challenge for healthcare systems worldwide. For urology, the expansion of the health-care structures for the treatment of patients suffering from COVID-19 should be supported as best as possible. At the same time, one should aim to ensure adequate care for urological emergencies and urgent urological treatments as far as possible, even during the pandemic. For this, patients must be prioritized individually, alternative therapy concepts must be considered and regional and supraregional cooperation must be used. Outpatient departments are of great importance in the care, examination and coordination of urological emergencies and urgent treatment. Urological clinics must prepare themselves to perform urgent operations and interventions on SARS-CoV­2-positive patients. Here, the creation of a separate, appropriately equipped emergency operating room to perform operations and interventions on SARS-CoV­2 patients should be considered. Furthermore strictly defined hygiene measures to protect employees in various clinical scenarios should be set up.

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.

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 ].).

Tigecycline in critically ill patients on continuous renal replacement therapy: a population pharmacokinetic study.

BACKGROUND: Tigecycline is a vital antibiotic treatment option for infections caused by multiresistant bacteria in the intensive care unit (ICU). Acute kidney injury (AKI) is a common complication in the ICU requiring continuous renal replacement therapy (CRRT), but pharmacokinetic data for tigecycline in patients receiving CRRT are lacking. METHODS: Eleven patients mainly with intra-abdominal infections receiving either continuous veno-venous hemodialysis (CVVHD, n = 8) or hemodiafiltration (CVVHDF, n = 3) were enrolled, and plasma as well as effluent samples were collected according to a rich sampling schedule. Total and free tigecycline was determined by ultrafiltration and high-performance liquid chromatography (HPLC)-UV. Population pharmacokinetic modeling using NONMEM® 7.4 was used to determine the pharmacokinetic parameters as well as the clearance of CVVHD and CVVHDF. Pharmacokinetic/pharmacodynamic target attainment analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT. RESULTS: A two-compartment population pharmacokinetic (PK) model was suitable to simultaneously describe the plasma PK and effluent measurements of tigecycline. Tigecycline dialysability was high, as indicated by the high mean saturation coefficients of 0.79 and 0.90 for CVVHD and CVVHDF, respectively, and in range of the concentration-dependent unbound fraction of tigecycline (45-94%). However, the contribution of CRRT to tigecycline clearance (CL) was only moderate (CLCVVHD: 1.69 L/h, CLCVVHDF: 2.71 L/h) in comparison with CLbody (physiological part of the total clearance) of 18.3 L/h. Bilirubin was identified as a covariate on CLbody in our collective, reducing the observed interindividual variability on CLbody from 58.6% to 43.6%. The probability of target attainment under CRRT for abdominal infections was ≥ 0.88 for minimal inhibitory concentration (MIC) values ≤ 0.5 mg/L and similar to patients without AKI. CONCLUSIONS: Despite high dialysability, dialysis clearance displayed only a minor contribution to tigecycline elimination, being in the range of renal elimination in patients without AKI. No dose adjustment of tigecycline seems necessary in CRRT. TRIAL REGISTRATION: EudraCT, 2012-005617-39 . Registered on 7 August 2013.

[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).

Heart transplantation as salvage therapy for progressive prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis (MRSE).

BACKGROUND: Prosthetic valve endocarditis (PVE) has the highest in-hospital mortality among all cases of infective endocarditis (IE), it is estimated at about 40 %. Orthotopic heart transplantation (OHT) as a measure of last resort, may be considered in selected cases where repeated surgical procedures and conservative efforts have failed to eradicate persistent or recurrent IE. Only few clinical data are available regarding this rare indication for OHT, since active IE has traditionally been considered as a contraindication for OHT. CASE PRESENTATION: We report on a 55 year old male patient who underwent prosthetic valve replacement with a mechanical valved conduit ten years ago and developed now persistent PVE with severe complications due to methicillin-resistant Staphylococcus epidermidis (MRSE). Repeated surgical procedures and conservative efforts have failed to eradicate the pathogen. Regarding the lack of curative options, salvage OHT was discussed as a measure of last resort. 28 months after the first diagnosis of PVE, the patient was successfully transplanted and is now doing well under close follow-up (6 months post-OHT). CONCLUSIONS: PVE remains a challenging condition regarding diagnosis and treatment. The presented case underscores the urgent need for an integrated and multidisciplinary approach to patients with suspected and definitive IE - especially in PVE. OHT might be a feasible measure of last resort in selected patients with IE. Our case report adds published clinical experience to this rarely performed procedure and consolidates previous findings.

Bacterial and viral contamination of breathing circuits after extended use - an aspect of patient safety?

BACKGROUND: In the past, anaesthetic breathing circuits were identified as a source of pathogen transmission. It is still debated, whether breathing circuits combined with breathing system filters can be safely used for more than 1 day. The aim of this study was to evaluate the transmission risk of bacteria and also viruses via breathing circuits after extended use. METHODS: The inner and outer surface of 102 breathing circuits used for 1 day and of 101 circuits used for 7 days were examined for bacteria and viruses. Additionally, 10 and 20 breathing circuits each were examined after use on patients with pulmonary virus infection and with multidrug-resistant organism (MDRO) colonisation/infection respectively. Bacteria were detected by standard microbiological procedures; PCR techniques were applied for herpes simplex virus, cytomegalovirus, influenza, parainfluenza and respiratory syncytial virus. RESULTS: Endoluminal bacterial contamination of breathing circuits remained unchanged after 7-day vs. 1-day use (5.9% vs. 7.8%) [CI95%: -0.0886-0.0506, pnon-inferiority 0.0260]. Only outside surface contamination with bacteria belonging to environmental species or human flora increased (16.8 vs. 6.9%) [CI 95%: 0.0118 - 0.1876, pnon-inferiority 0.8660]. Viruses occurred on the patient side, but not in breathing circuits. No MDRO occurred in the 20 circuits after use on patients harbouring such germs. CONCLUSION: Endoluminal contamination of breathing circuits with bacteria did not increase after extended use. No viruses were detected in the breathing circuits using filters. Based on our results, the extended use of ABC without exceptions appears safe, if a high level of anaesthesia workplace cleaning is secured.

[Strategies for antifungal treatment failure in intensive care units]. / Strategien bei Versagen einer antimykotischen Therapie auf Intensivstation.

Recent epidemiologic studies reveal both an increasing incidence and an escalation in resistance of invasive fungal infections in intensive care units. Primary therapy fails in 70 % of cases, depending on the underlying pathogens and diseases. The purpose of this review is to raise awareness for the topic of antifungal therapy failure, describe the clinical conditions in which it occurs, and suggest a possible algorithm for handling the situation of suspected primary therapy failure.

Successful ganciclovir treatment of primary cytomegalovirus infection containing the UL97 mutation N510S in an intestinal graft recipient.

In solid organ transplantation, human cytomegalovirus (HCMV) is considered to be the most important viral pathogen. We report a case of a CMV R-/D+ small intestine transplant recipient with a primary CMV infection on valganciclovir prophylaxis. Sequencing of the HCMV DNA for drug resistance-associated mutations revealed the UL97 mutation N510S. This mutation has been initially reported to confer ganciclovir resistance. Based on in vitro recombinant phenotyping, this assumption has recently been questioned. Switching the antiviral treatment to an intravenous regimen of ganciclovir eliminated HCMV DNAemia, showing the in vivo efficacy of ganciclovir for the UL97 mutation N510S. Hence, knowledge of drug efficacy is crucial for an adequate choice of antiviral medication, carefully balancing antiviral potency versus the risk of harmful side effects.

Spontaneous hepatic rupture in amyloidosis - report of a case.

In systemic amyloidosis spontaneous rupture of the liver is a rare complication. Here we report on a patient with unrecognized systemic amyloidosis who presented to an outside hospital with unspecific abdominal pain. Under the signs of a hemorrhagic shock, distended abdomen and intraabdominal bleeding a laparotomy was performed. Due to uncontrollable hemorrhage of the ruptured right liver lobe a packing was performed. After being transferred to the reporting institution a CT scan was performed showing a grade IV laceration of the right liver. Therefore a transarterial embolization of the right hepatic artery was carried out. The following day an infection of the abdominal cavity and the abdominal wall with gas-producing bacteria was noticed and a relaparotomy, necrectomy and repacking due to diffuse bleeding were performed. The situation deteriorated and at the second relaparotomy the following day an almost completely necrotic liver was found. The patient deceased the following day. Life-threatening spontaneous liver rupture due to systemic amyloidosis might only successfully be cured by high urgency liver transplantation as presented in the literature. However, in two published cases interventional therapy by embolization of bleeding vessels has saved patients' life.

[Current aspects of sepsis caused by bacterial translocation]. / Neue Erkenntnisse zur Sepsis durch bakterielle Translokation.

Bacterial translocation has been put forward as a concept to explain sepsis without an infectious focus, but it has been difficult to prove in humans. Dysfunction of the intestinal barrier, which is composed of physical, biochemical and immunological factors, is the pathophysiological prerequisite for bacterial translocation. Recent findings indicate that not only viable bacteria but also pathogen associated molecular patterns may translocate and cause sepsis. Molecular detection methods for bacteria or their components have been developed to address these new concepts, but they have not yet become widely available. Specific therapeutic interventions within the sepsis cascades and signaling pathways of the innate and specific immune system so far have not been successful. Selective oral decontamination (SOD) und selective digestive tract decontamination (SDD) are efficacious prophylactic measures against nosocomial septic complications. An increased incidence of resistant pathogens has not been encountered. The use of probiotics as prophylaxis against septic complications is controversial and has led in some studies to a worse prognosis.

Donor heparinization is not a contraindication to liver transplantation even in recipients with acute heparin-induced thrombocytopenia type II: a case report and review of the literature.

Heparin-induced thrombocytopenia (HIT) type II is caused by an immune-mediated side effect of heparin anticoagulation resulting in a clotting disorder. In the setting of urgent liver transplantation, the question arises whether a graft from a heparinized donor can be safely transplantated in a recipient with even acute heparin-induced thrombocytopenia type II. We report on a patient with end-stage liver disease and acute HIT II waiting for liver transplantation. Despite the risk of life-threatening complications, an organ procured from a heparinized donor was accepted. Assuming heparin residuals within the graft, the donor organ was flushed backtable with increased amounts of Wisconsin solution. The subsequent transplantation and the postoperative course were uneventful; neither thromboses nor graft dysfunction occurred. Even in acute episode of HIT II with circulating antibodies, a patient may receive an organ from a heparin-treated donor, if adequate precautions during organ preparation are observed.

Emergence of increasing linezolid-resistance in enterococci in a post-outbreak situation with vancomycin-resistant Enterococcus faecium.

During 2004 and at the start of 2005 a university hospital in Southwest Germany was affected by an extensive outbreak of vancomycin-resistant Enterococcus faecium (VRE). Although the outbreak was contained, linezolid-resistant enterococci emerged during and after the outbreak as the usage of linezolid became more common. Linezolid resistance was no longer limited to VRE. Nosocomial spread of linezolid-resistant but vancomycin-susceptible E. faecium was detected and these strains also emerged in patients without prior drug exposure. Linezolid should therefore be used with caution and the susceptibility of isolates monitored over time. Isolation precautions and screening of contacts should be considered to avoid spread of resistant isolates.