RESUMEN
PURPOSE OF REVIEW: The optimal use of antimicrobials is necessary to slow resistance development and improve patient outcomes. Antimicrobial stewardship (AMS) is a bundle of interventions aimed at promoting the responsible use of antiinfectives. The ICU is an important field of activity for AMS because of high rates of antimicrobial use, high prevalence of resistant pathogens and complex pharmacology. This review discusses aims and interventions of AMS with special emphasis on the ICU. RECENT FINDINGS: AMS-interventions can improve the quality and quantity of antimicrobial prescribing in the ICU without compromising patient outcomes. The de-escalation of empiric therapy according to microbiology results and the limitation of treatment duration are important steps to reduce resistance pressure. Owing to the complex nature of critical illness, the pharmacological optimization of antimicrobial therapy is an important goal in the ICU. AMS-objectives and strategies are also applicable to patients with sepsis. This is reflected in the most recent guidelines by the Surviving Sepsis Campaign. AMS-interventions need to be adapted to their respective setting and be mindful of local prescribing cultures and prescribers' attitudes. SUMMARY: AMS in the ICU is effective and safe. Intensivists should be actively involved in AMS-programs and propagate responsible use of antimicrobials.
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Antiinfecciosos , Programas de Optimización del Uso de los Antimicrobianos , Sepsis , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Humanos , Sepsis/tratamiento farmacológicoRESUMEN
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 (eg, no shared electronic health record and no digital transfer of patient findings). OBJECTIVE: This study aims 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 multicenter, stepped-wedge cluster randomized trial (February 2017 to January 2020) to establish a telemedicine inpatient-outpatient network among university hospitals, hospitals, and outpatient physicians in North Rhine-Westphalia, Germany. Patients aged ≥18 years in the intensive care unit 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 respectively once per week to enhance treatment quality. The primary outcome was adherence to the 10 Choosing Wisely recommendations for infectious disease management. Guideline adherence was analyzed using binary logistic regression models. RESULTS: Overall, 159,424 patients (10,585 inpatients and 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 (odds ratio [OR] 4.00, 95% CI 1.83-9.20; P<.001) and in sepsis management in critically ill patients (OR 6.82, 95% CI 1.27-56.61; P=.04). There was a statistically nonsignificant decrease in sepsis-related mortality from 29% (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 participating 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<.001) and asymptomatic bacteriuria (OR 9.31, 95% CI 3.79-25.94; P<.001). For the other recommendations, we found no significant effects, or we had too few observations to generate models. The 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT03137589; https://clinicaltrials.gov/ct2/show/NCT03137589.
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Pacientes Ambulatorios , Telemedicina , Adolescente , Adulto , Cuidados Críticos , Enfermedad Crítica/terapia , Manejo de la Enfermedad , HumanosRESUMEN
BACKGROUND: The number of organs donated after brain death in Germany is far lower than the demand. This underlines the importance of providing the brain-dead donor with optimal medical care throughout the donation process to decrease the risk of graft dysfunction. Several international guidelines and national recommendations guide the intensivists in organ-protective intensive care management of the brain-dead donor. OBJECTIVE: The anesthetist is a key member during organ retrieval procedures and plays a crucial role in physiological donor management; however, evidence-based recommendations for the perioperative anesthetic management, drug treatment strategies and target values are lacking. Anesthesia literature about donor management is scarce and predominantly composed of reviews of practice, with little exploration of the scientific foundations. The aim of this review is to guide the anesthetist in the organ-protective perioperative therapy. The pathophysiological changes in patients who progress to brain death are briefly summarized. The available evidence, guidelines and expert opinions regarding medical treatment strategies and therapeutic goals in organ-protective therapy are reviewed. The ethical and pathophysiological considerations regarding the performance of anesthesia during organ retrieval are discussed. METHODS: This review is based on a selective literature search in PubMed for publications regarding organ donation after brain death (keywords: "brain dead donor", "organ procurement", "organ protective therapy", "donor preconditioning", "perioperative donor management", "ethical considerations of brain dead donor"). International guidelines, national recommendations and expert opinions were given special consideration. RESULTS: Overall, the evidence for optimal perioperative organ-protective care of the brain-dead donor is limited. Most elements in the current recommendations and guidelines are based on pathophysiological reasoning, epidemiological observations or extrapolations from general organ-protective management strategies, and not on evidence from randomized controlled trials. National and international recommendations on treatment goals and drug therapy differ considerably in some aspects. The therapy concepts applied are very heterogeneous. Apart from medical challenges, the ethical circumstances are an additional burden for the entire treatment team. Whether anesthesia is reasonable during organ retrieval remains unclear. There is uncertainty about possible organ-protective effects of anesthetic drugs. Furthermore, ethical considerations raise the question of whether the determination of brain death and the use of anesthetic drugs during the procedure of organ retrieval are compatible with each other. CONCLUSION: Due to the lack of evidence, perioperative treatment should be guided by intensive care therapy strategies. The discussion about using anesthetic drugs during organ retrieval remains controversial. Pathophysiological considerations support the use of volatile anesthetics because of possible organ-protective effects. The use of neuromuscular blocking is justified to control any possible motor response resulting from spinal cord reflexes, whereas there is no evidence for a benefit from using opioids. Apart from that, it seems ethically problematic to anesthetise a brain-dead donor. Consequently, knowledge about the pathophysiological processes caused by brain death and about organ-protective therapy concepts are just as much a basic requirement as the consideration of ethical problems in organ donation after brain death. Only then are the caregivers able to do justice to both the organ recipient and the organ donor, as well as their relatives in this challenging situation.
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Anestesia , Anestésicos , Obtención de Tejidos y Órganos , Anestesia/métodos , Encéfalo , Muerte Encefálica , Humanos , Donantes de TejidosRESUMEN
AIMS: The purpose of this study was to explore pharmacokinetic and pharmacodynamic aspects of a contemporary dosing scheme of cefuroxime as perioperative prophylaxis in cardiac surgery using cardiopulmonary bypass (CPB). METHODS: Cefuroxime plasma concentrations were measured in 23 patients. A 1.5-g dose of cefuroxime was administered at start of surgery and CPB, followed by 3 additional doses every 6 hours postoperative. Drug levels were used to build a population pharmacokinetic model. Target attainment for Staphylococcus aureus (2-8 mg/L) and Escherichia coli (8-32 mg/L) were evaluated and dosing strategies for optimization were investigated. RESULTS: A dosing scheme of 1.5 g cefuroxime preoperatively with a repetition at start of CPB achieves plasma unbound concentrations of 8 mg/L in almost all patients during surgery. The second administration is critical to provide this level of coverage. Simulations indicate that higher unbound concentrations up to 32 mg/L are reached by a continuous infusion rate of 1 g/h after a bolus of 1 g. In the postoperative phase, most patients do not reach unbound concentrations above 2 mg/L. To improve target attainment up to 8 mg/L, the continuous application of cefuroxime with infusion rates of 0.125-0.25 g/h is simulated and shown to be an alternative to bolus dosing. CONCLUSION: Dosing recommendations for cefuroxime as perioperative antibiotic prophylaxis in cardiac surgery are sufficient to reach plasma unbound concentration to cover S. aureus during the operation. Target attainment is not achieved in the postoperative period. Continuous infusion of cefuroxime may optimize target attainment.
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Profilaxis Antibiótica , Cefuroxima , Antibacterianos/uso terapéutico , Puente Cardiopulmonar , Cefuroxima/uso terapéutico , Humanos , Staphylococcus aureus , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
AIMS: Adequate plasma concentrations of antibiotics during surgery are essential for the prevention of surgical site infections. We examined the pharmacokinetics of 1.5 g cefuroxime administered during induction of anaesthesia with follow-up doses every 2.5 hours until the end of surgery. We built a physiologically based pharmacokinetic model with the aim to ensure adequate antibiotic plasma concentrations in a heterogeneous population. METHODS: A physiologically based pharmacokinetic model (PK-Sim® /MoBi® ) was developed to investigate unbound plasma concentrations of cefuroxime. Blood samples from 25 thoracic surgical patients were analysed with high-performance liquid chromatography. To evaluate optimized dosing regimens, physiologically based pharmacokinetic model simulations were conducted. RESULTS: Dosing simulations revealed that a standard dosing regimen of 1.5 g every 2.5 hours reached the pharmacokinetic/pharmacodynamic target for Staphylococcus aureus. However, for Escherichia coli, >50% of the study participants did not reach predefined targets. Effectiveness of cefuroxime against E. coli can be improved by administering a 1.5 g bolus immediately followed by a continuous infusion of 3 g cefuroxime over 3 hours. CONCLUSION: The use of cefuroxime for perioperative antibiotic prophylaxis to prevent staphylococcal surgical site infections appears to be effective with standard dosing of 1.5 g preoperatively and follow-up doses every 2.5 hours. In contrast, if E. coli is relevant in surgeries, this dosing regimen appears insufficient. With our derived dose recommendations, we provide a solution for this issue.
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Antibacterianos/sangre , Profilaxis Antibiótica/métodos , Cefuroxima/sangre , Modelos Biológicos , Atención Perioperativa/métodos , Infección de la Herida Quirúrgica/prevención & control , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Cefuroxima/administración & dosificación , Cefuroxima/uso terapéutico , Esquema de Medicación , Escherichia coli/efectos de los fármacos , Semivida , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , Staphylococcus aureus/efectos de los fármacosRESUMEN
BACKGROUND: Currently, there is an ongoing discussion about the question whether the emergence of multidrug-resistant microorganisms (MDRO) among humans is due to transfer of these bacteria from animals. OBJECTIVES: This review summarizes data on the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing enterobacteria in animals and humans, and describes knowledge about transmission pathways. MATERIAL AND METHODS: After a scientific literature analysis, relevant articles were identified by screening of titles and abstracts, amended by publications of infection control authorities and the respective reference lists. RESULTS: MDRO are both transmitted in the nosocomial setting and are increasingly detected as sources of infection outside healthcare facilities. CONCLUSIONS: Due to new transmission pathways of MDRO an inter-disciplinary approach towards prevention is necessary, involving medical, pharmaceutical and veterinary expertise.
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Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Zoonosis/epidemiología , Animales , Antibacterianos/uso terapéutico , Infecciones Bacterianas/microbiología , Infección Hospitalaria/microbiología , Medicina Basada en la Evidencia , Alemania/epidemiología , Instituciones de Salud/estadística & datos numéricos , Humanos , Prevalencia , Factores de Riesgo , Zoonosis/microbiología , Zoonosis/transmisiónRESUMEN
The adequate management of infections is an important task in critical care medicine which has an effect on patient outcome. As a result, the prevalence of antiinfective therapy is high in intensive care units. In the face of an unsettling development of worldwide microbial resistance, an optimization and reduction of antiinfective therapy is necessary. Antibiotic stewardship tries to improve antiinfective therapy with an interdisciplinary approach. One overall objective of antibiotic stewardship is the reduction of resistance induction in order to preserve the therapeutic efficiency of antibiotics. Intensive care units are important fields of action for antibiotic stewardship interventions. This article reviews available evidence and some practical aspects for antibiotic stewardship.
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Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/prevención & control , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/prevención & control , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Higiene/normas , Antibacterianos/administración & dosificación , Alemania , HumanosRESUMEN
A 65-year old woman presented with acute or chronic renal failure and signs of right heart failure. Renal replacement therapyusing a surgically placed dialysis catheter via the left jugular veinwas repeatedly complicated by altered flows of the dialysis unit, impaired consciousness, new onset of seizures and left-sided hemiparesis. The tip of the dialysis catheter was detected on transesophageal echocardiography within the lumen of the ascending aorta. Further imaging of the neck vessels demonstrated a primary placement of the catheter in the left common carotid artery. This incident underscores the value of ultrasound guidance for placement of intravascular catheters.
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Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/etiología , Cateterismo Periférico/efectos adversos , Ecocardiografía/métodos , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Enfermedades del Sistema Nervioso/etiología , Diálisis Renal/efectos adversos , Anciano , Estenosis Carotídea/prevención & control , Femenino , Humanos , Enfermedades del Sistema Nervioso/prevención & controlRESUMEN
Necrotizing soft tissue infections are a heterogeneous group of severe infections of the skin, connective tissue and muscles in which necrotic destruction of the tissue occurs at the site of infection. Various bacteria are known as "typical" triggering pathogens and the infection can occur on the entire surface of the body. Necrotizing soft tissue infections are always a time-sensitive emergency associated with high mortality. Many affected patients are critically ill and require treatment in an intensive care unit. The rapid and radical surgical treatment is an essential part of management and in addition an adequate and timely antimicrobial treatment is of great importance. The health consequences for surviving patients are often severe, as extensive soft tissue damage leads to functional impairments. In many cases extensive plastic surgery follow-up is necessary. Therefore, necrotizing soft tissue infections are "complicated" in every phase of the disease and require interprofessional treatment. This review article provides a current overview of various aspects of the diagnostics, treatment and aftercare of necrotizing soft tissue infections.
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Necrosis , Infecciones de los Tejidos Blandos , Humanos , Infecciones de los Tejidos Blandos/terapia , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/patología , Necrosis/microbiología , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/terapia , Fascitis Necrotizante/microbiología , Fascitis Necrotizante/patología , Antibacterianos/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: A significant proportion of critically ill patients with acute kidney injury require continuous renal replacement therapy (CRRT). This article summarizes current evidence on the diagnosis and treatment of acute kidney injury. Regional citrate anticoagulation (RCA) is an emerging but complex technique. A variety of solutions and systems are currently used for RCA. Descriptions of the dosage and methods differ significantly and may cause confusion in everyday practice. This article reviews important scientific findings and highlights pharmacological and pathophysiological aspects of RCA, with a special emphasis on practical clinical issues regarding dosage and available citrate solutions. RECENT FINDINGS: RCA provides a similar or even longer circuit run, with manageable metabolic complications. Although large-scale multicentre trials are needed, there is increasing evidence for the benefits of citrate solutions in CRRT. International guidelines recommend using citrate anticoagulation rather than heparin in patients without contraindications against citrate. SUMMARY: RCA-CRRT is a technique that can be safely used in the majority of intensive care patients with severe multiple-organ failure. The range of citrate solutions available, the different methods in use--continuous venovenous haemofiltration, continuous venovenous haemodialysis and continuous venovenous haemodiafiltration--and the lack of a generally accepted complete CRRT 'set' have impeded implementation of the technique in clinical practice. Unresolved questions regarding dosage and assessment preclude evidence-based comparison in prospective, multicentre studies. For the moment, each institution has to develop a local working protocol. In clinical practice, detailed staff training and monitoring of possible metabolic disturbances for this complex intervention is essential.
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Anticoagulantes/uso terapéutico , Ácido Cítrico/uso terapéutico , Terapia de Reemplazo Renal , Cuidados Críticos , HumanosRESUMEN
BACKGROUND AND OBJECTIVE: Resistance to antibacterial substances is a huge and still emerging issue, especially with regard to Gram-negative bacteria and in critically ill patients. We report a study in six patients infected with extensively drug-resistant Gram-negative bacteria in a limited outbreak who were successfully managed with a quasi-continuous infusion of cefiderocol. METHODS: Patients were initially treated with prolonged infusions of cefiderocol over 3 h every 8 h, and the application mode was then switched to a quasi-continuous infusion of 2 g over 8 h, i.e. 6 g in 24 h. Therapeutic drug monitoring (TDM) was established using an in-house liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: Determined trough plasma concentrations were a median of 50.00 mg/L [95% confidence interval (CI) 27.20, 74.60] and steady-state plasma concentrations were a median of 90.96 mg/L [95% CI 37.80, 124]. No significant differences were detected with respect to acute kidney injury/continuous renal replacement therapy. Plasma concentrations determined from different modes of storage were almost equal when frozen or cooled, but markedly reduced when stored at room temperature. CONCLUSIONS: (Quasi) continuous application of cefiderocol 6 g/24 h in conjunction with TDM is a feasible mode of application; the sample for TDM should either be immediately analyzed, cooled, or frozen prior to analysis.
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Monitoreo de Drogas , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida , Estudios de Factibilidad , Antibacterianos/uso terapéutico , Bacterias Gramnegativas , CefiderocolRESUMEN
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 COVID-19 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.
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Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Tratamiento Farmacológico de COVID-19 , Infección Hospitalaria/diagnóstico , Antibacterianos/farmacocinética , Programas de Optimización del Uso de los Antimicrobianos/organización & administración , Biomarcadores/análisis , Coinfección/tratamiento farmacológico , Coinfección/microbiología , Infección Hospitalaria/tratamiento farmacológico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/virología , Humanos , Unidades de Cuidados Intensivos , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Activación Viral/efectos de los fármacosRESUMEN
BACKGROUND: Due to high pharmacokinetic variability, standard doses of meropenem are frequently inadequate in septic patients. Therapeutic drug monitoring of meropenem is not widely available; therefore, improved empiric dosing recommendations are needed. OBJECTIVES: This study aimed to compare the attainment of pharmacologic targets for two common empirical dosing regimens for meropenem in patients with septic shock. METHODS: Two empiric dosing schemes for meropenem were compared using extended infusions (120 minutes) in 32 patients with septic shock in the intensive care units at two different hospitals. One regimen was 3 × 2 g meropenem/24 h for two days, followed by 3 × 1 g meropenem/24 h; the other regimen was 4 × 1 g meropenem/24 h. Serum meropenem concentrations were measured for the first 72 h of therapy, and pharmacokinetic modelling was performed to define the percentage of time the free drug concentration was above various target MICs for each regimen (%fT>MIC). RESULTS: Both regimens led to a sufficiently high %fT>MIC for pathogens with target MICs < 4 mg/L. When higher MICs were targeted, the %fT>MIC of 4 × 1 g meropenem decreased faster than that of 3 × 2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide appropriate drug concentrations. Renal function was a significant covariate of target attainment. CONCLUSIONS: The results of this study can guide clinicians in their choice of an empirical dosing regimen for meropenem. If pathogens with low MICs (< 4 mg/L) are targeted, both dosing regimens are adequate, whereas more resistant strains require higher doses.
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Meropenem/farmacocinética , Meropenem/uso terapéutico , Choque Séptico/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/sangre , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Meropenem/sangre , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Método de Montecarlo , Proyectos Piloto , Resultado del TratamientoRESUMEN
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.
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Anticoagulantes/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/terapia , Anestesia General , Anticoagulantes/uso terapéutico , Reanimación Cardiopulmonar , Angiografía Coronaria , Resultado Fatal , Femenino , Fracturas del Fémur/cirugía , Heparina/uso terapéutico , Humanos , Hipertensión Intraabdominal/complicaciones , Hipertensión Intraabdominal/terapia , Persona de Mediana Edad , Infarto del Miocardio/terapia , Transfusión de Plaquetas , Choque Cardiogénico/terapiaRESUMEN
We investigated covariates of pharmacokinetics of micafungin in critically ill patients. After application of micafungin, plasma samples were collected. Non-linear mixed effects modelling (NONMEM 7.3) was used to develop the pharmacokinetic model. Using this model, the adequacy of a fixed 100 mg dosing regimen was evaluated in the study cohort. A two-compartment model with linear elimination was found to describe the obtained data. SOFA score was identified as a significant covariate on both clearance and central volume of distribution, respectively. Patients in highly critical condition, represented by a SOFA above 10 showed a 30.8% lower central volume of distribution than the less critically ill patients. For patients with bilirubin levels above 4 mg/dl, clearance was decreased by 21.1%. Renal replacement therapy (RRT) did not influence micafungin clearance or the volumes of distribution. In a posthoc evaluation of the modeled population, 100 mg micafungin was suitable when assessing the PKPD targets (AUC/MIC) for C. albicans and C. glabrata, with insufficient target attainment for C. parapsilosis. Micafungin pharmacokinetics appear not to be influenced by the status of RRT. A dose of 100 mg micafungin is suitable for infections with C. albicans and C. glabrata in critically ill patients.
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Antifúngicos/farmacocinética , Micafungina/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Candida albicans/efectos de los fármacos , Candida glabrata/efectos de los fármacos , Candida parapsilosis/efectos de los fármacos , Candidiasis/sangre , Candidiasis/tratamiento farmacológico , Enfermedad Crítica , Monitoreo de Drogas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
UNLABELLED: Macrophages play an important role during the development and progression of atherosclerotic plaques. alphavbeta3 integrins are highly expressed by macrophages; thus, targeting alphavbeta3 may allow targeting of culprit macrophage-loaded atherosclerotic lesions in vivo. METHODS: An alphavbeta3-targeted Arg-Gly-Asp (RGD) peptide was labeled with the cyanine 5.5 (Cy 5.5) dye and applied to image atherosclerotic plaques in apolipoprotein E-deficient mice. RESULTS: The peptide-dye conjugate binds to alphavbeta3 integrin-positive RAW264.7 macrophages with high affinity. Competition experiments confirmed binding specificity of the probe. A significant fluorochrome accumulation in atherosclerotic plaques was demonstrated 24 h after injection by fluorescence reflectance imaging, which was blocked with high efficiency by competition with the unlabeled peptide. Conversely, the nonconjugated dye revealed only a minor fluorescence signal in the plaques. Fluorescence microscopy revealed colocalization of the probe with macrophages in the plaque of a mouse model for accelerated atherosclerosis, which was corroborated in human carotid artery specimens. In addition to macrophage-associated signals, binding of the probe to the neointima or elastica of the arteries was observed. CONCLUSION: RGD-Cy 5.5, combined with near-infrared optical imaging methods, allows the specific imaging of alphavbeta3-integrin expression on macrophages recruited to vascular lesions and may serve to estimate macrophage-bound inflammatory activity of atherosclerotic lesions.
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Aterosclerosis/metabolismo , Aterosclerosis/patología , Fluorescencia , Colorantes Fluorescentes/metabolismo , Integrina alfaVbeta3/metabolismo , Macrófagos/metabolismo , Animales , Apolipoproteínas E/deficiencia , Carbocianinas/metabolismo , Línea Celular , Citometría de Flujo , Humanos , Rayos Infrarrojos , Ratones , Ratones Noqueados , Microscopía Fluorescente , Péptidos Cíclicos/metabolismo , Unión Proteica , Especificidad por SustratoRESUMEN
BACKGROUND: Results of blood culture (BC) diagnostics should be swiftly available to guide treatment of critically ill patients. Conventional BC diagnostics usually performs species identification of microorganisms from mature solid medium colonies. Species identification might be speed up by using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) of biomass from shortly incubated solid media. METHODS: This single-center analysis compared the applicability of MALDI-TOF-based species identification from shortly incubated cultures in laboratory routine vs. conventional diagnostics and assessed its effects of on empiric antibiotic therapy. RESULTS: Median time between detection of BCs as "positive" by incubators and further processing (e.g. microscopy) was 6 h 21 min. Median time between microscopy and result reporting to the ward was 15 min. Including 193 BCs, MALDI-TOF from shortly incubated biomass resulted in significantly faster (p > 0.001) species identification. Species results became available for clinicians after a median of 188 min (231 min for Gram-positive bacteria, 151 min for Gram-negative bacteria) compared to 909 min (n = 192 BCs) when conventional diagnostics was used. For 152/179 bacteremia episodes (85%) empiric antibiotic therapy had already been started when the microscopy result was reported to the ward; microscopy led to changes of therapies in 14/179 (8%). In contrast, reporting the bacterial species (without antibiogram) resulted in therapeutic adjustments in 36/179 (20%). Evaluating these changes revealed improved therapies in 26/36 cases (72%). CONCLUSIONS: Species identification by MALDI-TOF MS from shortly incubated subcultures resulted in adjustments of empiric antibiotic therapies and might improve the clinical outcome of septic patients.