Research Interests: Causality, France, Causal Inference, Humans, INTENSIVE CARE, and 15 moreFemale, Confidence intervals, Disease Severity, American, Length of Stay, Clinical Sciences, Intensive Care Unit, Apache, Intensive Care Medicine, Intensive Care Units, Hospital Mortality, Logistic Models, Critical Illness, Confidence Interval, and Cross Infection
ABSTRACTDendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen... more
ABSTRACTDendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen storage sites synchronising DC maturation and antigen presentation. Maturation of DCs is accompanied by the induction of the ubiquitin-like modifier FAT10 (also known as UBD), which localises to aggresomes, structures that are similar to DALIS. FAT10 is conjugated to substrate proteins and serves as a signal for their rapid and irreversible degradation by the 26S proteasome similar to, yet independently of ubiquitin, thereby contributing to antigen presentation. Here, we have investigated whether FAT10 is involved in the formation and turnover of DALIS, and whether proteins accumulating in DALIS can be modified through conjunction to FAT10 (FAT10ylated). We found that FAT10 localises to DALIS in maturing DCs and that this localisation occurs independent...
Research Interests:
Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) improved ICU, hospital and 28-day survival in Intensive Care Units (ICU) with low levels of antibiotic resistance. Yet, it is unclear whether the... more
Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) improved ICU, hospital and 28-day survival in Intensive Care Units (ICU) with low levels of antibiotic resistance. Yet, it is unclear whether the effect differs between medical and surgical ICU patients. In an individual patient data meta-analysis we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16,528 hospital admissions and 17,884 ICU-admissions for complete case analysis. Compared to standard care or placebo the pooled adjusted odds ratios (aOR) for hospital mortality was 0·82 (95% Confidence Interval [CI] 0·72 - 0·93) for SDD and 0·84 (95%-CI 0·73 - 0·...
Research Interests:
... WA Krueger · M. Trick · TH Schroeder · KE Unertl ... Unsere Daten zeigen, dass die Verwen-dung von Prüfgasen mit Analysenzertifi-kat eine technisch einfach realisierbare Möglichkeit bietet, die Kalibrierung selbst-ständig mit hoher... more
... WA Krueger · M. Trick · TH Schroeder · KE Unertl ... Unsere Daten zeigen, dass die Verwen-dung von Prüfgasen mit Analysenzertifi-kat eine technisch einfach realisierbare Möglichkeit bietet, die Kalibrierung selbst-ständig mit hoher Präzision bei vertret-barem Arbeitsaufwand ...
Research Interests:
Research Interests: Microbiology, Treatment, Clinical Microbiology, Biological Sciences, Humans, and 13 moreEscherichia coli, Septic Shock, Female, Bacteria, Urinary Tract Infections, Recurrence, Anti-Bacterial Agents, Adult, Minocycline, Escherichia Coli Infections, Beta Lactamases, beta-Lactam Resistance, and Medical and Health Sciences
Research Interests:
Research Interests:
Research Interests:
Research Interests:
We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546... more
We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and strati- fied according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 � 400
Research Interests:
Enterococci are a common cause of serious infections, especially in newborns, severely immunocompromised patients, and patients requiring intensive care. To characterize enterococcal surface antigens that are targets of opsonic... more
Enterococci are a common cause of serious infections, especially in newborns, severely immunocompromised patients, and patients requiring intensive care. To characterize enterococcal surface antigens that are targets of opsonic antibodies, rabbits were immunized with various gentamicin-killed Enterococcus faecalis strains, and immune sera were tested in an opsonophagocytic assay against a selection of clinical isolates. Serum raised against one strain killed the homologous strain (12030) at a dilution of 1:5,120 and mediated opsonic killing of 33% of all strains tested. In addition, this serum killed two (28%) of seven vancomycin-resistant Enterococcus faecium strains. Adsorption of sera with the homologous strain eliminated killing activity. The adsorbing antigens were resistant to treatment with proteinase K and to boiling for 1 h, but were susceptible to treatment with sodium periodate, indicating that the antigen inducing opsonic activity is a polysaccharide. Antibodies in immun...
Research Interests:
Research Interests:
Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, which might help to prevent inflammatory injury to the organism. However, if host defense mechanisms are affected similarly, the ability to... more
Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, which might help to prevent inflammatory injury to the organism. However, if host defense mechanisms are affected similarly, the ability to eliminate bacteria might be reduced. We hypothesized that local anesthetics have time-dependent effects on phagocytosis of S. aureus, oxidative burst, and CD11b expression by human neutrophils. To test this hypothesis, we reanalyzed data from a previous study. Blood samples from 11 healthy volunteers were incubated with lidocaine (1,846 mumol/L), bupivacaine (770 mumol/L) or ropivacaine (801 mumol/L) for 30 minutes. Thereafter, bacteria were added, either fluorescently labeled for determination of phagocytosis, or unstained for determination of oxidative burst and CD11b expression. After an additional incubation for 0, 10, 30, or 60 minutes, phagocytosis was stopped and neutrophils were stained with monoclonal antibodies for flow cytometric analysis. Data were analyzed by analysis of variance for repeated measurements. Lidocaine and bupivacaine inhibited neutrophil functions in a time-dependent manner (P < .05). Prolonged local anesthetic exposure reduced the fraction of ingesting neutrophils by 20% +/- 12% (mean +/- SD) and 7% +/- 7%, bacterial uptake by 19% +/- 16% and 14% +/- 12%, oxidative burst by 29% +/- 23% and 28% +/- 25%, and CD11b expression by 66% +/- 24% and 25% +/- 21% for lidocaine and bupivacaine, respectively. Ropivacaine exerted a time-dependent effect on CD11b expression only (24% +/- 34%; P < .05). Our results indicate that in a whole blood model, time-dependent effects of local anesthetics affect key neutrophil functions necessary for bacterial elimination. However, these effects only occur at concentrations that are unlikely to be routinely attained in the clinical setting, and concern about interfering with the host defense is likely unwarranted.
Research Interests:
Research Interests:
Research Interests: Microbiology, Treatment, Clinical Microbiology, Biological Sciences, Humans, and 14 moreEscherichia coli, Septic Shock, Female, Bacteria, Urinary Tract Infections, Recurrence, Spectrum, Anti-Bacterial Agents, Adult, Minocycline, Escherichia Coli Infections, Beta Lactamases, beta-Lactam Resistance, and Medical and Health Sciences
Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinal fluid is poor, especially in... more
Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinal fluid is poor, especially in cases without severe meningeal inflammation. We successfully used linezolid to treat a case of posttraumatic MRSE meningitis with a low-level inflammatory response. Therapeutic effectiveness was documented microbiologically and by the simultaneous measurement of linezolid levels in serum and cerebrospinal fluid.
Research Interests: Computed Tomography, Adolescent, Clinical Microbiology, Biological Sciences, Cerebrospinal Fluid, and 15 moreCase Report, Humans, Operating Room, Female, Clinical, Glasgow Coma Scale, Staphylococcus epidermidis, Methicillin Resistance, Central Venous Catheter, Intracranial Pressure, Oxazolidinones, Acetamides, Inflammatory response, Medical and Health Sciences, and Accidents Traffic
Research Interests: Multivariate Analysis, Prospective studies, Humans, Europe, Female, and 14 moreMale, Microbial genetic and drug resistance, Risk factors, Clinical Sciences, Middle Aged, Public health systems and services research, Bacteremia, Intensive Care Medicine, Risk Factors, Intensive Care Units, Hospital Mortality, Logistic Models, fungemia, and Cross Infection
Research Interests: Prospective studies, Humans, INTENSIVE CARE, Female, Male, and 15 moreAntimicrobial resistance, Clinical Sciences, Intensive Care Unit, Digestive System, Colistin, Methicillin Resistance, Microbial Sensitivity Tests, Intensive Care Medicine, Pseudomonas Aeruginosa, Intensive Care Units, Observational Study, Methicillin Resistant Staphylococcus Aureus, Coagulase Negative Staphylococci, Cross Infection, and Population surveillance(Antimicrobial resistance, Clinical Sciences, Intensive Care Unit, Digestive System, Colistin, Methicillin Resistance, Microbial Sensitivity Tests, Intensive Care Medicine, Pseudomonas Aeruginosa, Intensive Care Units, Observational Study, Methicillin Resistant Staphylococcus Aureus, Coagulase Negative Staphylococci, Cross Infection, and Population surveillance)
(Antimicrobial resistance, Clinical Sciences, Intensive Care Unit, Digestive System, Colistin, Methicillin Resistance, Microbial Sensitivity Tests, Intensive Care Medicine, Pseudomonas Aeruginosa, Intensive Care Units, Observational Study, Methicillin Resistant Staphylococcus Aureus, Coagulase Negative Staphylococci, Cross Infection, and Population surveillance)
Research Interests: Clinical Trial, Germany, Humans, Female, Infection, and 15 moreMale, Economic Impact, Cost effectiveness, Length of Stay, Clinical Sciences, Health Care System, Analytical Model, Economic Models, Cost Benefit Analysis, Drug Costs, Methicillin Resistant Staphylococcus Aureus, Oxazolidinones, Acetamides, Decision Support Techniques, and Cross Infection
Intravenously administered ciprofloxacin is partially secreted into the intestinal lumen and thereby eliminates fecal Enterobacteriaceae. Sucralfate inhibits the antimicrobial activity of ciprofloxacin by chelate binding. In a prospective... more
Intravenously administered ciprofloxacin is partially secreted into the intestinal lumen and thereby eliminates fecal Enterobacteriaceae. Sucralfate inhibits the antimicrobial activity of ciprofloxacin by chelate binding. In a prospective study, we investigated the impact of intravenous ciprofloxacin on the intestinal microflora during oral administration of sucralfate. A total of 45 stool specimens were analyzed in 20 hospitalized patients who were treated with 200 mg of ciprofloxacin i.v. bid. Ten patients concomitantly received 1 g sucralfate p.o. tid (group A). After more than 3 days of i.v. ciprofloxacin, the mean fecal ciprofloxacin concentration was 185.3 +/- 158.7 micrograms/g in patients of group A and 108.7 +/- 76.9 micrograms/g in patients without concurrent sucralfate (group B). There was no significant difference in mean fecal ciprofloxacin levels between both groups (Wilcoxon's test). Enterobacteriaceae were below the threshold of detection (10(2) cfu/g) in all patients of group B after 3 days of treatment whereas small numbers were found in only 2 samples of patients of group A (10(4) cfu/g). Intravenous ciprofloxacin eliminates or largely reduces intestinal Enterobacteriaceae irrespective of concurrent administration of sucralfate.
Research Interests:
Barbiturates and propofol are used for deep sedation of patients with elevated intracranial pressure refractory to standard therapeutic regimens. Such patients often suffer from bacterial infections, which are most commonly caused by... more
Barbiturates and propofol are used for deep sedation of patients with elevated intracranial pressure refractory to standard therapeutic regimens. Such patients often suffer from bacterial infections, which are most commonly caused by Staphylococcus aureus. Various interactions of anesthetics with components of the host defense have been documented, but very little is known about the influence on monocytes, which are a first-line defense against bacterial invasion. Therefore, we studied the effects of thiopental, methohexital, and propofol on monocyte phagocytosis using an in vitro whole blood model of viable S. aureus. Whole blood samples were preincubated with different concentrations of thiopental, methohexital, and propofol. Phagocytosis was stopped at different time points after addition of viable S. aureus. Monocytes then were stained with monoclonal antibodies for flow cytometric analysis of monocyte recruitment (ratio of ingesting monocytes). Furthermore, the fluorescence intensity of ingested bacteria served as semiquantitative measurement of phagocytosis activity. Both barbiturates inhibited monocyte recruitment and phagocytosis activity concentration-dependently, whereas propofol did not affect any of the investigated parameters. At concentrations of 7.6 x10(-3) M thiopental or 1.1 x 10(-3) M methohexital and greater, monocyte recruitment and phagocytosis activity were significantly inhibited. The calculated half-maximum inhibitory concentration (IC50) of thiopental was 8.4 x 10(-3) M for monocyte recruitment and 8.6 x 10(-3) M for phagocytosis activity. The corresponding values for methohexital were 4.1 x 10(-3) M and 1.1 x 10(-3) M, respectively. The two barbiturates induce concentration-dependent inhibition of monocyte phagocytosis, whereas propofol is without effect. In combination with previously described effects on granulocyte function, these findings suggest that defense against bacterial infection might be reduced by barbiturates.
Research Interests:
Enterococci are important nosocomial pathogens that are increasingly difficult to treat due to intrinsic and acquired resistance to antibiotics, including vancomycin. A recently described capsular polysaccharide (CP) isolated from... more
Enterococci are important nosocomial pathogens that are increasingly difficult to treat due to intrinsic and acquired resistance to antibiotics, including vancomycin. A recently described capsular polysaccharide (CP) isolated from Enterococcus faecalis 12030 was used to evaluate the potential efficacy of active or passive immunotherapy regimens as adjunctive treatments. Evaluation of protective efficacy was carried out in immunocompetent mice challenged intravenously (i.v.) with live enterococci. In nonimmune mice, i.v. inoculations resulted in high levels of bacteria in kidneys, spleens, and livers 5 days after challenge. Mice immunized with four 10-μg doses of CP antigen/mouse were protected against challenge with the homologous E. faecalis strain. High-titer opsonic immunoglobulin G was also induced by immunizing rabbits with the purified CP, and passive transfer of this antiserum to mice produced significantly lower bacterial counts in organs than did normal rabbit serum or ster...
Research Interests: Electron Microscopy, Biological Sciences, Spleen, Kidney, Liver, and 15 moreMice, Multidrug Resistance, Female, Animals, Staphylococcus aureus, Urinary tract infection, Sterilization, Vaccination, Intensive Care Unit, Surveillance System, Enterococcus faecalis, Coronary Care Unit, immunoglobulin G, Nosocomial infection, and Medical and Health Sciences
The development of acute renal failure (ARF) in critically ill patients is associated with an increase in hospital mortality. Recently, it was shown that starting renal replacement therapy early and using high-filtrate flow rates can... more
The development of acute renal failure (ARF) in critically ill patients is associated with an increase in hospital mortality. Recently, it was shown that starting renal replacement therapy early and using high-filtrate flow rates can improve the outcome, but this could not be confirmed in later investigations. Studying selected patient subgroups could provide a useful basis for patient selection in future trials evaluating the outcome of renal replacement therapies. We, therefore, investigated the impact of the underlying disease on the outcome of patients with ARF. We retrospectively analysed 306 patients with ARF who were treated with renal replacement therapy. Patients were classified according to six initial diagnosis groups: haemorrhagic shock, post-cardiac surgery, post-liver transplantation, trauma, severe sepsis and miscellaneous. Univariate and multivariate multiple logistic regression analysis was used to determine which factors influenced the outcome. Underlying disease proved to be the only independent risk factor for mortality that was present at intensive care unit (ICU) admission (P = 0.047). Patients with severe sepsis had a significantly higher mortality rate (68%) than ARF patients as a whole (51%) (P = 0.02). Length of stay in the ICU, the use of catecholamines, the delay before ARF onset, and the correlation between APACHE II score and ICU length of stay proved to be additional independent predictors of outcome. Patient selection and subgroup definition according to the underlying disease could augment the usefulness of future trials evaluating the outcome of ARF.
Research Interests: Acute kidney injury, Acute renal failure, Humans, Female, Male, and 15 moreRisk factors, ROC Curve, Length of Stay, Clinical Sciences, Aged, Middle Aged, Adult, Odds ratio, Retrospective Studies, Risk Factors, Catecholamines, Predictive value of tests, Renal Replacement Therapy, Critical Illness, and Patient selection
Research Interests:
Research Interests:
Research Interests:
Ventilator-associated pneumonia is the most serious infectious complication in critically ill patients, associated with increased length of intensive care unit treatment and high mortality rates. Investigations focused on outcome... more
Ventilator-associated pneumonia is the most serious infectious complication in critically ill patients, associated with increased length of intensive care unit treatment and high mortality rates. Investigations focused on outcome variables have improved the database to estimate diagnostic and therapeutic management strategies. This knowledge has diminished the importance of the discussion on how to diagnose the pneumonia. This review summarizes recent data on epidemiology and mortality, risk factors and prevention, diagnosis, microbiology and antimicrobial treatment of ventilator-associated pneumonia.
Research Interests:
We investigated the epidemiology of ventilator-associated pneumonia in elderly ICU patients. More precisely, we assessed prevalence, risk factors, signs and symptoms, causative bacterial pathogens, and associated outcomes. Secondary... more
We investigated the epidemiology of ventilator-associated pneumonia in elderly ICU patients. More precisely, we assessed prevalence, risk factors, signs and symptoms, causative bacterial pathogens, and associated outcomes. Secondary analysis of a multicenter prospective cohort (EU-VAP project). Twenty-seven European ICUs. Patients who were mechanically ventilated for greater than or equal to 48 hours. We compared middle-aged (45-64 yr; n = 670), old (65-74 yr; n = 549), and very old patients (≥ 75 yr; n= 516). Ventilator-associated pneumonia occurred in 103 middle-aged (14.6%), 104 old (17.0%), and 73 very old patients (12.8%). The prevalence (n ventilator-associated pneumonia/1,000 ventilation days) was 13.7 in middle-aged patients, 16.6 in old patients, and 13.0 in very old patients. Logistic regression analysis could not demonstrate older age as a risk factor for ventilator-associated pneumonia. Ventilator-associated pneumonia in elderly patients was more frequently caused by Enterobacteriaceae (24% in middle-aged, 32% in old, and 43% in very old patients; p = 0.042). Regarding clinical signs and symptoms at ventilator-associated pneumonia onset, new temperature rise was less frequent among very old patients (59% vs 76% and 74% for middle-aged and old patients, respectively; p = 0.035). Mortality among patients with ventilator-associated pneumonia was higher among elderly patients: 35% in middle-aged patients versus 51% in old and very old patients (p = 0.036). Logistic regression analysis confirmed the importance of older age in the risk of death (adjusted odds ratio for old age, 2.1; 95% CI, 1.2-3.9 and adjusted odds ratio for very old age, 2.3; 95% CI, 1.2-4.4). Other risk factors for mortality in ventilator-associated pneumonia were diabetes mellitus, septic shock, and a high-risk pathogen as causative agent. In this multicenter cohort study, ventilator-associated pneumonia did not occur more frequently among elderly, but the associated mortality in these patients was higher. New temperature rise was less common in elderly patients with ventilator-associated pneumonia, whereas more episodes among elderly patients were caused by Enterobacteriaceae.
Research Interests: Nursing, Critical Care Medicine, Humans, Europe, Female, and 15 moreMale, Clinical Sciences, Aged, Prevalence, Middle Aged, Odds ratio, Prognosis, Geriatric Assessment, Intensive Care Units, Hospital Mortality, Proportional Hazards Models, Logistic Models, Critical Illness, Cohort Studies, and Cause of death
To study the relative contribution of antibiotics and bacterial virulence factors in the process of translocation of Enterococcus faecalis from the gut to extraintestinal organs. Prospective controlled animal study. Animal experimental... more
To study the relative contribution of antibiotics and bacterial virulence factors in the process of translocation of Enterococcus faecalis from the gut to extraintestinal organs. Prospective controlled animal study. Animal experimental laboratory at a university medical center. Fifty-two female Balb/c mice. We developed a mouse model to study the translocation of Enterococcus faecalis from the intestinal tract. Balb/c mice received sterile drinking water or antibiotic combinations to deplete their indigenous intestinal microflora. The animals subsequently were fed genetically engineered enterococci expressing different combinations of the putative enterococcal virulence factors aggregation substance and binding substance. Animals were killed, and their livers, spleens, and mesenteric lymph nodes were aseptically removed and cultured along with fecal samples for enumeration of bacteria. All animals were colonized with the test strains at 2-6 x 109 colony forming units/g of feces; in the antibiotic-treated animals, feces were free from anaerobes and Enterobacteriaceae. In animals fed the identical bacterial mutant, the colony counts in mesenteric lymph nodes were significantly lower in mice not treated with antibiotics than in those treated with antibiotics (p =.016). Multigroup analysis of variance revealed no significant differences of the translocation frequencies for the different mutant strains; however, the differences were statistically significant for all groups receiving antibiotics vs. the group not receiving antibiotics (p <.05-.01). There was a trend (although not statistically significant) for a higher proportion of positive cultures from either spleen or liver in mice that had enterococci recovered from their mesenteric lymph nodes (28%) relative to those that did not have enterococci isolated from the lymph nodes (12%; rate ratio 2.39, p =.30 by logistic regression analysis). Oral antibiotics can select for extraintestinal translocation of Enterococcus faecalis, and neither aggregation substance nor binding substance seems to be required for this process. The experiments encourage further exploration of host and microbial factors contributing to translocation and may provide a better understanding of the pathogenesis of enterococcal infections in patients in intensive care units.
Research Interests:
Deep sedation with barbiturates or propofol is a standard therapy for patients with critically elevated intracranial pressure. Such patients are prone to infectious complications, especially to pneumonias, which are most commonly caused... more
Deep sedation with barbiturates or propofol is a standard therapy for patients with critically elevated intracranial pressure. Such patients are prone to infectious complications, especially to pneumonias, which are most commonly caused by Staphylococcus aureus. Although various immunomodulatory effects of barbiturates have been described in vitro, their influence on the phagocytosis of viable S. aureus has yet to be investigated. Therefore, we examined the effects of thiopentone, methohexitone, and propofol on the phagocytosis of viable S. aureus. Laboratory study. University laboratory. Ten healthy volunteers aged 32.5 +/- 7 yrs. Blood sampling. Whole blood samples were preincubated with different concentrations of thiopentone, methohexitone, and propofol, which is an isopropylphenol derivate. After viable S. aureus was added, phagocytosis was stopped at different time points. Leukocytes were then stained with monoclonal antibodies for flow cytometric analysis of granulocyte recruitment (ratio of ingesting granulocytes) and phagocytosis activity (fluorescence intensity of ingested bacteria). Both barbiturates inhibited granulocyte recruitment and phagocytosis activity in a dose-dependent manner, whereas propofol did not affect any of the investigated variables. At concentrations higher than 7.6 x 10(-3) M (for thiopentone, p < .008) and 1.1 x 10(-3) M (for methohexitone, p < .04), granulocyte recruitment and phagocytosis activity were significantly inhibited. The calculated inhibitory concentrations (IC50) of thiopentone for granulocyte recruitment and for phagocytosis activity were 1.3 x 10(-2) M and 1.1 x 10(-2) M, respectively. The corresponding values for methohexitone were 3.6 x 10(-3) M and 1.1 x 10(-3) M. Our in vitro model points at substantially different effects of barbiturates and propofol on phagocytosis of S. aureus, which is one of the most important pathogens in patients who need neuroprotective therapy. The inhibitory effects of both barbiturates demonstrate a strong dose-dependency, with more pronounced effects for methohexitone. Impairment of phagocytosis activity was more pronounced than granulocyte recruitment.
Research Interests:
Research Interests:
Research Interests:
In patients with acute renal failure, the pharmacokinetics of meropenem depend on the operational characteristics of the renal replacement therapy. Dosage recommendations are based on the correlation of plasma levels with pharmacodynamic... more
In patients with acute renal failure, the pharmacokinetics of meropenem depend on the operational characteristics of the renal replacement therapy. Dosage recommendations are based on the correlation of plasma levels with pharmacodynamic requirements. Eight critically ill patients with acute renal failure were treated by continuous veno-venous hemofiltration with a filtrate flow of 1,600 ml/h and received 500 mg of meropenem every 12 h. Plasma and hemofiltrate concentrations of meropenem at steady state were determined by HPLC. Peak levels in plasma amounted to 39.5 +/- 10.5 mg/l (mean +/- SD) and trough levels were 2.4 +/- 1.5 mg/l. The minimal inhibitory concentration (MIC) for susceptible bacteria (4 mg/l) was covered for 40% of the dosing interval or longer in all patients. The MIC for intermediately susceptible organisms (8 mg/l) was covered for 33% in 6 of the 8 patients. The elimination half-life was prolonged to 3.63 +/- 0.77 h. The sieving coefficient of meropenem was 0.91 +/- 0.10 and the recovery in hemofiltrate amounted to 30.9 +/- 11.5% of the dose. A dosage of 500 mg twice daily provides appropriate serum levels for the treatment of infections caused by susceptible bacteria. A higher dosage is adequate for infections by intermediately susceptible bacteria or for renal replacement therapies with markedly higher filtrate flow rates.
Research Interests: Acute kidney injury, Chemotherapy, Acute renal failure, Humans, Female, and 15 moreMale, Steady state, Antibiotics, Shell Half-Life, Aged, Middle Aged, Microbial Sensitivity Tests, Bacterial infections, Flow Rate, Multiple Organ Failure, Renal Replacement Therapy, Critical Illness, kidney failure, minimal inhibitory concentration, and Pharmacology and pharmaceutical sciences
Research Interests:
Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two... more
Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two groups, each comprising eight healthy volunteers who received the following doses: 500 mg as an intravenous infusion over 30 min three times a day (t.i.d.) versus a 250-mg loading dose followed by a 1,500 mg continuous infusion over 24 h for group A and 1,000 mg as an intravenous infusion over 30 min t.i.d. versus a 500-mg loading dose followed by a 3,000-mg continuous infusion over 24 h for group B. Meropenem concentrations in plasma and urine were determined by liquid chromatography-mass spectrometry/mass spectrometry and high-performance liquid chromatography with UV detection, respectively. Pharmacokinetic calculations were done by use of a two-compartment open model, and the data were extrapolated by Monte Carlo simulations for 10,000 simulate...
Research Interests: Microbiology, Monte Carlo Simulation, Clinical Trial, Mass Spectrometry, Medical Microbiology, and 15 moreMonte Carlo, Adolescent, Humans, Computer Simulation, Low Dose, Female, Male, High Performance Liquid Chromatography, Adult, Liquid Chromatography, Pseudomonas Aeruginosa, Antibacterial Agent, Monte Carlo Method, Klebsiella pneumoniae, and Pharmacology and pharmaceutical sciences
Background With invasion of bacteria, the host defense system is activated by a complex cascade of various mechanisms. Local anesthetics previously were shown to interact with diverse components of the immune response, such as leukocyte... more
Background With invasion of bacteria, the host defense system is activated by a complex cascade of various mechanisms. Local anesthetics previously were shown to interact with diverse components of the immune response, such as leukocyte adherence on endothelial monolayers, oxidative burst, or crosstalk within lymphocyte subset populations. However, effects of newer local anesthetics like bupivacaine and ropivacaine on antibacterial host defense-primarily phagocytosis activity, oxidative burst, or CD11b expression-still remain unclear. Methods Whole blood samples were preincubated with local anesthetics (lidocaine, 9.2, 92.2, and 1,846 microm bupivacaine, 6.1, 61, and 770 microm; ropivacaine, 6.4, 64, and 801 microm). For the oxidative burst and CD11b assay, dihydroethidium was added to the probes. After viable Staphylococcus aureus was added in a 5 to 1 ratio following leukocyte count, phagocytosis was stopped at different times, and staining with monoclonal antibodies was performed...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinare Vereinigung fur Int...more