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1.
Case Rep Crit Care ; 2021: 9937499, 2021.
Article in English | MEDLINE | ID: mdl-34650819

ABSTRACT

Accumulating evidence suggests that a patient subgroup with severe COVID-19 develops a cytokine release syndrome leading to capillary leakage and organ injury. Recent publications addressing therapy of cytokine storms recommended new extracorporeal therapies such as hemoadsorption. This case report describes a 59-year-old SARS-CoV-2-positive patient with severe ARDS. Due to severe hyperinflammation with concomitant hemodynamic instability and progressive renal failure, combination of continuous renal replacement and CytoSorb® hemoadsorption therapy was initiated. Treatment resulted immediately in a control of the hyperinflammatory response. Simultaneously, lung function continued to improve accompanied by profound hemodynamic stabilization. We report the successful utilization of CytoSorb® hemoadsorption in the treatment of a patient with SARS-CoV-2-induced cytokine storm syndrome.

2.
J Crit Care ; 67: 26-32, 2021 Oct 06.
Article in English | MEDLINE | ID: mdl-34628123

ABSTRACT

Beta-lactam dosing is challenging in critically ill patients with slow extended daily dialysis (SLEDD). This prospective observational study aimed to investigate meropenem and piperacillin concentrations and half-lives during SLEDD and in SLEDD-free intervals. Critically ill patients with SLEDD-therapy and meropenem or piperacillin therapy were included. Breakpoints of target attainment were defined as 2 and 20.8 mg/L for meropenem and piperacillin, respectively. Daily TDM was performed and therapies were adapted based on the measured concentrations. Elimination rate constants were determined by using nonlinear regression analysis. Seventeen patients were included (48 SLEDD intervals; median SLEDD-duration: 7.25 h). The median antibiotic trough concentrations and half-lives were significantly (p < 0.001) lower during and after the SLEDD-therapy compared to SLEDD-free intervals (median meropenem: 22.3 (IQR: 12.8, 25.6) vs. 28.3 mg/L (IQR: 16.9, 37.4); median piperacillin: 55.8 (IQR: 45.1, 84.9) vs. 130 mg/L (IQR: 91.5, 154.5); relative change: -48.0% each, IQR meropenem: -33.3, -58.5%; IQR piperacillin: -36.3, -52.1%). However, none of the measured trough concentrations were subtherapeutic during SLEDD. SLEDD leads to a reduction in meropenem and piperacillin concentrations of approximately 50% independently of the initial concentration. If the concentration is twice as high as the breakpoint of target attainment before SLEDD-therapy, subtherapeutic levels can be avoided.

3.
Antimicrob Agents Chemother ; 65(12): e0156421, 2021 11 17.
Article in English | MEDLINE | ID: mdl-34570645

ABSTRACT

Pneumonia is one of the most common infections in intensive care patients, and it is often treated with beta-lactam antibiotics. Even if therapeutic drug monitoring in blood is available, it is unclear whether sufficient concentrations are reached at the target site: the lung. The present study was initiated to fill this knowledge gap. Various compartments from 10 patients' explanted lungs were subjected to laboratory analysis. Meropenem was quantified in serum, bronchoalveolar lavage (BAL) fluid, microdialysate, and homogenized lung tissue with isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS). BAL fluid represents diluted epithelial lining fluid (ELF), and microdialysate represents interstitial fluid (IF). Differences between target site and blood concentrations were investigated. The median meropenem concentration in blood, ELF, IF, and tissue were 26.8, 18.0, 12.1, and 9.1 mg/liter, respectively. A total of 37.5% of the target site ELF and IF meropenem concentrations were below the clinical EUCAST breakpoint of 8 mg/liter. The median ELF/serum quotient was 61.8% (interquartile range [IQR], 24.8% to 87.6%), the median IF/serum quotient was 35.4% (IQR, 23.8% to 54.3%), and the median tissue/serum quotient was 34.2% (IQR, 28.3% to 38.2%). We observed a substantial interindividual variability between the blood and the compartments (ELF and IF), whereas the intraindividual variability was relatively low. Target site measurement in different lung compartments was feasible and successfully applied in a clinical setting. A relevant amount of 37.5% of the target site concentrations were below the clinical EUCAST breakpoint, indicating subtherapeutic dosing in high-risk patients receiving perioperative antibiotic prophylaxis in lung transplantation. (This study has been registered at ClinicalTrials.gov under identifier NCT03970265.).

4.
Ann Intensive Care ; 11(1): 115, 2021 Jul 22.
Article in English | MEDLINE | ID: mdl-34292421

ABSTRACT

BACKGROUND: A cytokine storm is life threatening for critically ill patients and is mainly caused by sepsis or severe trauma. In combination with supportive therapy, the cytokine adsorber Cytosorb® (CS) is increasingly used for the treatment of cytokine storm. However, it is questionable whether its use is actually beneficial in these patients. METHODS: Patients with an interleukin-6 (IL-6) > 10,000 pg/ml were retrospectively included between October 2014 and May 2020 and were divided into two groups (group 1: CS therapy; group 2: no CS therapy). Inclusion criteria were a regularly measured IL-6 and, for patients allocated to group 1, CS therapy for at least 90 min. A propensity score (PS) matching analysis with significant baseline differences as predictors (Simplified Acute Physiology Score (SAPS) II, extracorporeal membrane oxygenation, renal replacement therapy, IL-6, lactate and norepinephrine demand) was performed to compare both groups (adjustment tolerance: < 0.05; standardization tolerance: < 10%). U-test and Fisher's-test were used for independent variables and the Wilcoxon test was used for dependent variables. RESULTS: In total, 143 patients were included in the initial evaluation (group 1: 38; group 2: 105). Nineteen comparable pairings could be formed (mean initial IL-6: 58,385 vs. 59,812 pg/ml; mean SAPS II: 77 vs. 75). There was a significant reduction in IL-6 in patients with (p < 0.001) and without CS treatment (p = 0.005). However, there was no significant difference (p = 0.708) in the median relative reduction in both groups (89% vs. 80%). Furthermore, there was no significant difference in the relative change in C-reactive protein, lactate, or norepinephrine demand in either group and the in-hospital mortality was similar between groups (73.7%). CONCLUSION: Our study showed no difference in IL-6 reduction, hemodynamic stabilization, or mortality in patients with Cytosorb® treatment compared to a matched patient population.

5.
Infection ; 49(6): 1347-1353, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34195950

ABSTRACT

BACKGROUND: Increasing incidence of invasive infections caused by rare fungi was observed over the recent years. CASE: Here, we describe the first reported case of an infection caused by the thermophilic mold Talaromyces thermophilus. Cultivation and, hence, identification of this fastidious organism is challenging since standard incubation conditions are not sufficient. Retrospective analysis of patient samples and in vitro experiments demonstrated that testing for fungal antigens, i.e., the cell wall components galactomannan and ß-1,3-D-glucan, is a promising tool.


Subject(s)
Antigens, Fungal , Fungi , Eurotiales , Humans , Retrospective Studies
6.
Transpl Infect Dis ; 23(4): e13675, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34166573

ABSTRACT

BACKGROUND: Posaconazole and itraconazole are commonly used for systemic antifungal prophylaxis after lung transplantation. The aim of this study on critically ill lung transplant recipients was to assess the rate of adequate plasma concentrations and the frequency of fungal-induced transitions from antifungal prophylaxis to therapy after the administration of either posaconazole or itraconazole for systemic prophylaxis. METHODS: Critically ill lung transplant recipients with postoperative posaconazole or itraconazole prophylaxis and therapeutic drug monitoring from February 2016 to November 2019 were retrospectively included in the study. Positive fungal cultures or Aspergillus antigen tests resulting in a transition from antifungal prophylaxis to therapy were analyzed from the first day of prophylaxis until 7 days after the last sample for each patient. Adequate plasma concentrations were defined as ≥500 µg/L for itraconazole and ≥700 µg/L for posaconazole. RESULTS: Two hundred seventy-five samples from 73 patients were included in the analysis. Overall, 60% of the posaconazole and 55% of the itraconazole concentrations were subtherapeutic. Administration of posaconazole suspension resulted significantly (P < .01) more often in subtherapeutic concentrations than tablets (68% vs 10%). Patients treated with posaconazole showed less positive fungal records resulting in a transition from prophylaxis to therapy than patients treated with itraconazole (10% vs 33%, P-value: .029). The detection of a fungal pathogen was not associated with the measured plasma concentrations or the achievement of the target concentrations. CONCLUSION: Our findings suggest that posaconazole should be used instead of itraconazole for systemic prophylaxis in critically ill lung transplant recipients.


Subject(s)
Antifungal Agents , Itraconazole , Antifungal Agents/therapeutic use , Critical Illness , Humans , Itraconazole/therapeutic use , Lung , Retrospective Studies , Transplant Recipients , Triazoles
7.
Sci Rep ; 11(1): 10190, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33986443

ABSTRACT

There are different methods of artificial liver support for patients with acute liver dysfunction (ALD). However, CytoSorb (CS) might be a new approved option for those patients. Question of interest is whether the elimination performance of CS was comparable to that of advanced organ support (ADVOS). Patients, treated with CS (integrated into high-flux dialysis) or ADVOS and a total bilirubin > 10 mg/dl were included. Laboratory parameters were evaluated before starting therapy (d0) and 12-24 h thereafter (d1). The Wilcoxon-test with associated samples was used for statistical analysis. Thirty-nine patients (33 CS, 6 ADVOS) were included. The median bilirubin at d0 was 16.9 and 17.7 mg/dl and at d1 was 13.2 and 15.9 mg/dl, in the CS and ADVOS group, respectively. There was a significant bilirubin reduction as well in the CS group (p < 0.001, median relative reduction: 22.5%) as in the ADVOS group (p = 0.028, median relative reduction: 22.8%). There was no significant difference in the relative bilirubin reduction between CS and ADVOS therapies. The use of CytoSorb and ADVOS in patients with ALD led to a significant and comparable decrease in total bilirubin. The easy use of CS might be an advantage compared to other procedures.


Subject(s)
Bilirubin/isolation & purification , Liver Diseases/therapy , Renal Dialysis/methods , Adsorption , Adult , Aged , Aged, 80 and over , Albumins/metabolism , Bilirubin/chemistry , Critical Illness , Cytokines/blood , Cytokines/metabolism , Female , Germany , Humans , Liver Diseases/metabolism , Liver Diseases/physiopathology , Male , Middle Aged , Pilot Projects , Retrospective Studies , Serum Albumin/metabolism
8.
Antibiotics (Basel) ; 10(4)2021 Apr 20.
Article in English | MEDLINE | ID: mdl-33924047

ABSTRACT

BACKGROUND: The MeroRisk-calculator, an easy-to-use tool to determine the risk of meropenem target non-attainment after standard dosing (1000 mg; q8h), uses a patient's creatinine clearance and the minimum inhibitory concentration (MIC) of the pathogen. In clinical practice, however, the MIC is rarely available. The objectives were to evaluate the MeroRisk-calculator and to extend risk assessment by including general pathogen sensitivity data. METHODS: Using a clinical routine dataset (155 patients, 891 samples), a direct data-based evaluation was not feasible. Thus, in step 1, the performance of a pharmacokinetic model was determined for predicting the measured concentrations. In step 2, the PK model was used for a model-based evaluation of the MeroRisk-calculator: risk of target non-attainment was calculated using the PK model and agreement with the MeroRisk-calculator was determined by a visual and statistical (Lin's concordance correlation coefficient (CCC)) analysis for MIC values 0.125-16 mg/L. The MeroRisk-calculator was extended to include risk assessment based on EUCAST-MIC distributions and cumulative-fraction-of-response analysis. RESULTS: Step 1 showed a negligible bias of the PK model to underpredict concentrations (-0.84 mg/L). Step 2 revealed a high level of agreement between risk of target non-attainment predictions for creatinine clearances >50 mL/min (CCC = 0.990), but considerable deviations for patients <50 mL/min. For 27% of EUCAST-listed pathogens the median cumulative-fraction-of-response for the observed patients receiving standard dosing was < 90%. CONCLUSIONS: The MeroRisk-calculator was successfully evaluated: For patients with maintained renal function it allows a reliable and user-friendly risk assessment. The integration of pathogen-based risk assessment substantially increases the applicability of the tool.

9.
Infection ; 49(3): 491-500, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33515390

ABSTRACT

PURPOSE: SARS-COV-2 infection can develop into a multi-organ disease. Although pathophysiological mechanisms of COVID-19-associated myocardial injury have been studied throughout the pandemic course in 2019, its morphological characterisation is still unclear. With this study, we aimed to characterise echocardiographic patterns of ventricular function in patients with COVID-19-associated myocardial injury. METHODS: We prospectively assessed 32 patients hospitalised with COVID-19 and presence or absence of elevated high sensitive troponin T (hsTNT+ vs. hsTNT-) by comprehensive three-dimensional (3D) and strain echocardiography. RESULTS: A minority (34.3%) of patients had normal ventricular function, whereas 65.7% had left and/or right ventricular dysfunction defined by impaired left and/or right ventricular ejection fraction and strain measurements. Concomitant biventricular dysfunction was common in hsTNT+ patients. We observed impaired left ventricular (LV) global longitudinal strain (GLS) in patients with myocardial injury (-13.9% vs. -17.7% for hsTNT+ vs. hsTNT-, p = 0.005) but preserved LV ejection fraction (52% vs. 59%, p = 0.074). Further, in these patients, right ventricular (RV) systolic function was impaired with lower RV ejection fraction (40% vs. 49%, p = 0.001) and reduced RV free wall strain (-18.5% vs. -28.3%, p = 0.003). Myocardial dysfunction partially recovered in hsTNT + patients after 52 days of follow-up. In particular, LV-GLS and RV-FWS significantly improved from baseline to follow-up (LV-GLS: -13.9% to -16.5%, p = 0.013; RV-FWS: -18.5% to -22.3%, p = 0.037). CONCLUSION: In patients with COVID-19-associated myocardial injury, comprehensive 3D and strain echocardiography revealed LV dysfunction by GLS and RV dysfunction, which partially resolved at 2-month follow-up. TRIAL REGISTRATION: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.


Subject(s)
COVID-19/physiopathology , Ventricular Dysfunction/physiopathology , Aged , COVID-19/complications , COVID-19/diagnostic imaging , COVID-19/pathology , Echocardiography, Three-Dimensional , Female , Follow-Up Studies , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Stroke Volume , Troponin T/blood , Ventricular Dysfunction/diagnostic imaging , Ventricular Dysfunction/etiology , Ventricular Dysfunction/pathology
10.
Crit Care ; 25(1): 41, 2021 01 28.
Article in English | MEDLINE | ID: mdl-33509234

ABSTRACT

BACKGROUND: Rhabdomyolysis is frequently occurring in critically ill patients, resulting in a high risk of acute kidney injury (AKI) and potentially permanent kidney damage due to increased myoglobin levels. The extracorporeal elimination of myoglobin might be an approach to prevent AKI, but its molecular weight of 17 kDa complicates an elimination with conventional dialysis membranes. Question of interest is, if myoglobin can be successfully eliminated with the cytokine adsorber Cytosorb® (CS) integrated in a high-flux dialysis system. METHODS: Patients were included between 10/2014 and 05/2020 in the study population if they had an anuric renal failure with the need of renal replacement therapy, if CS therapy was longer than 90 min and if myoglobin level was > 5.000 ng/ml before treatment. The measurement times of the laboratory values were: d-1 = 24-36 h before CS, d0 = shortly before starting CS and d1 = 12-24 h after starting CS treatment. Statistical analysis were performed with Spearman's correlation coefficient, Wilcoxon test with associated samples and linear regression analysis. RESULTS: Forty-three patients were included in the evaluation (median age: 56 years, 77% male patients, 32.6% ECMO therapy, median SAPS II: 80 points and in-hospital mortality: 67%). There was a significant equilateral correlation between creatine kinase (CK) and myoglobin at all measurement points. Furthermore, there was a significant reduction of myoglobin (p = 0.03, 95% confidence interval (CI): - 9030, - 908 ng/ml) during CS treatment, with a median relative reduction of 29%. A higher median reduction of 38% was seen in patients without ongoing rhabdomyolysis (CK decreased during CS treatment, n = 21). In contrast, myoglobin levels did not relevantly change in patients with increasing CK and therefore ongoing rhabdomyolysis (n = 22, median relative reduction 4%). Moreover, there was no significant difference in myoglobin elimination in patients with and without ECMO therapy. CONCLUSION: Blood purification with Cytosorb® during high-flux dialysis led to a significant reduction of myoglobin in patients with severe rhabdomyolysis. The effect might be obscured by sustained rhabdomyolysis, which was seen in patients with rising CK during treatment. Prospective clinical trials would be useful in investigating its benefits in avoiding permanent kidney damage.


Subject(s)
Cytokines/metabolism , Myoglobin/metabolism , Renal Reabsorption , Rhabdomyolysis/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Critical Illness/therapy , Female , Germany , Humans , Male , Middle Aged , Myoglobin/adverse effects , Prospective Studies , Renal Replacement Therapy/methods , Retrospective Studies , Rhabdomyolysis/physiopathology
11.
Circ Cardiovasc Imaging ; 14(1): e012220, 2021 01.
Article in English | MEDLINE | ID: mdl-33463366

ABSTRACT

BACKGROUND: Myocardial injury, defined by elevated troponin levels, is associated with adverse outcome in patients with coronavirus disease 2019 (COVID-19). The frequency of cardiac injury remains highly uncertain and confounded in current publications; myocarditis is one of several mechanisms that have been proposed. METHODS: We prospectively assessed patients with myocardial injury hospitalized for COVID-19 using transthoracic echocardiography, cardiac magnetic resonance imaging, and endomyocardial biopsy. RESULTS: Eighteen patients with COVID-19 and myocardial injury were included in this study. Echocardiography revealed normal to mildly reduced left ventricular ejection fraction of 52.5% (46.5%-60.5%) but moderately to severely reduced left ventricular global longitudinal strain of -11.2% (-7.6% to -15.1%). Cardiac magnetic resonance showed any myocardial tissue injury defined by elevated T1, extracellular volume, or late gadolinium enhancement with a nonischemic pattern in 16 patients (83.3%). Seven patients (38.9%) demonstrated myocardial edema in addition to tissue injury fulfilling the Lake-Louise criteria for myocarditis. Combining cardiac magnetic resonance with speckle tracking echocardiography demonstrated functional or morphological cardiac changes in 100% of investigated patients. Endomyocardial biopsy was conducted in 5 patients and revealed enhanced macrophage numbers in all 5 patients in addition to lymphocytic myocarditis in 1 patient. SARS-CoV-2 RNA was not detected in any biopsy by quantitative real-time polymerase chain reaction. Finally, follow-up measurements of left ventricular global longitudinal strain revealed significant improvement after a median of 52.0 days (-11.2% [-9.2% to -14.7%] versus -15.6% [-12.5% to -19.6%] at follow-up; P=0.041). CONCLUSIONS: In this small cohort of COVID-19 patients with elevated troponin levels, myocardial injury was evidenced by reduced echocardiographic left ventricular strain, myocarditis patterns on cardiac magnetic resonance, and enhanced macrophage numbers but not predominantly lymphocytic myocarditis in endomyocardial biopsies.


Subject(s)
COVID-19/complications , COVID-19/pathology , Myocarditis/etiology , Myocarditis/pathology , Myocardium/pathology , Aged , Biopsy , COVID-19/blood , Cohort Studies , Echocardiography/methods , Female , Germany , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Myocarditis/diagnostic imaging , Prospective Studies , SARS-CoV-2 , Troponin/blood
12.
Anaesthesist ; 70(7): 573-581, 2021 07.
Article in German | MEDLINE | ID: mdl-33369696

ABSTRACT

BACKGROUND: In a pandemic situation the overall mortality rate is of considerable interest; however, these data must always be seen in relation to the given healthcare system and the availability of local level of care. A recently published German data evaluation of more than 10,000 COVID-19 patients treated in 920 hospitals showed a high mortality rate of 22% in hospitalized patients and of more than 50% in patients requiring invasive ventilation. Because of the high infection rates in Bavaria, a large number of COVID-19 patients with considerable severity of disease were treated at the intensive care units of the LMU hospital. The LMU hospital is a university hospital and a specialized referral center for the treatment of patients with acute respiratory distress syndrome (ARDS). OBJECTIVE: Data of LMU intensive care unit (ICU) patients were systematically evaluated and compared with the recently published German data. METHODS: Data of all COVID-19 patients with invasive and noninvasive ventilation and with completed admission at the ICU of the LMU hospital until 31 July 2020 were collected. Data were processed using descriptive statistics. RESULTS: In total 70 critically ill patients were included in the data evaluation. The median SAPS II on admission to the ICU was 62 points. The median age was 66 years and 81% of the patients were male. More than 90% were diagnosed with ARDS and received invasive ventilation. Treatment with extracorporeal membrane oxygenation (ECMO) was necessary in 10% of the patients. The median duration of ventilation was 16 days, whereby 34.3% of patients required a tracheostomy. Of the patients 27.1% were transferred to the LMU hospital from external hospitals with reference to our ARDS/ECMO program. Patients from external hospitals had ARDS of higher severity than the total study population. In total, nine different substances were used for virus-specific treatment of COVID-19. The most frequently used substances were hydroxychloroquine and azithromycin. Immunomodulatory treatment, such as Cytosorb® (18.6%) and methylprednisolone (25.7%) were also frequently used. The overall in-hospital mortality rate of ICU patients requiring ventilation was 28.6%. The mortality rates of patients from external hospitals, patients with renal replacement therapy and patients with ECMO therapy were 47.4%, 56.7% and 85.7%, respectively. CONCLUSION: The mortality rate in the ventilated COVID-19 intensive care patients was considerably different from the general rate in Germany. The data showed that treatment in an ARDS referral center could result in a lower mortality rate. Low-dose administration of steroids may be another factor to improve patient outcome in a preselected patient population. In the authors' opinion, critically ill COVID-19 patients should be treated in an ARDS center provided that sufficient resources are available.


Subject(s)
COVID-19/therapy , Respiration, Artificial/statistics & numerical data , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/mortality , Critical Illness/therapy , Extracorporeal Membrane Oxygenation , Female , Germany , Hospital Mortality , Hospitals, University , Humans , Immunologic Factors/therapeutic use , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Patient Transfer , Renal Replacement Therapy/statistics & numerical data , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Treatment Outcome
13.
J Intensive Care ; 8(1): 86, 2020 Nov 23.
Article in English | MEDLINE | ID: mdl-33292582

ABSTRACT

OBJECTIVES: Beta-lactam antibiotics are often subject to therapeutic drug monitoring, but breakpoints of target attainment are mostly based on expert opinions. Studies that show a correlation between target attainment and infection resolution are missing. This analysis investigated whether there is a difference in infection resolution based on two breakpoints of target attainment. METHODS: An outcome group out of 1392 critically ill patients treated with meropenem or piperacillin-tazobactam was formed due to different selection criteria. Afterwards, three groups were created: group 1=free drug concentration (f) was < 100% of the time (T) above the minimal inhibitory concentration (MIC) (< 100% fT > MIC), group 2=100% fT > MIC < 4xMIC, and group 3=100% fT > 4xMIC. Parameters for infection control, renal and liver function, and estimated and observed in-hospital mortality were compared between those groups. Statistical analysis was performed with one-way analysis of variance, Tukey post hoc test, U test, and bivariate logistic regression. RESULTS: The outcome group consisted of 55 patients (groups 1-3, 17, 24, and 14 patients, respectively). Patients allocated to group 2 or 3 had a significantly faster reduction of the C-reactive protein in contrast to patients allocated to group 1 (p = 0.033 and p = 0.026). Patients allocated to group 3 had a worse renal function, a higher Acute Physiology and Chronic Health Evaluation (APACHE II) score, were older, and had a significantly higher in-hospital mortality compared to group 1 (p = 0.017) and group 2 (p = 0.001). The higher mortality was significantly influenced by worse liver function, higher APACHE II, and higher Sequential Organ Failure Assessment (SOFA) score and norepinephrine therapy. CONCLUSION: Achieving the target 100% fT > MIC leads to faster infection resolution in the critically ill. However, there was no benefit for patients who reached the highest target of 100% fT > 4xMIC, although the mortality rate was higher possibly due to confounding effects. In conclusion, we recommend the target 100% fT > MIC < 4xMIC for critically ill patients. TRIAL REGISTRATION: NCT03985605.

14.
Infection ; 49(2): 241-248, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32880845

ABSTRACT

BACKGROUND: Galactomannan antigen (GM) testing is widely used in the diagnosis of invasive aspergillosis (IA). Digestive enzymes play an important role in enzyme substitution therapy in exocrine pancreatic insufficiency. As digestive enzymes of fungal origin like Nortase contain enzymes from Aspergillus, a false-positive result of the test might be possible because of cross-reacting antigens of the cell wall of the producing fungi. We, therefore, asked whether the administration of fungal enzymes is a relevant cause of false-positive GM antigen test results. METHODS: Patients with a positive GM antigen test between January 2016 and April 2020 were included in the evaluation and divided into two groups: group 1-Nortase-therapy, group 2-no Nortase-therapy. In addition, dissolved Nortase samples were analyzed in vitro for GM and ß-1,3-D-glucan. For statistical analysis, the chi-squared and Mann‒Whitney U tests were used. RESULTS: Sixty-five patients were included in this evaluation (30 patients receiving Nortase and 35 patients not receiving Nortase). The overall false positivity rate of GM testing was 43.1%. Notably, false-positive results were detected significantly more often in the Nortase group (73.3%) than in the control group (17.1%, p < 0.001). While the positive predictive value of GM testing was 0.83 in the control group, there was a dramatic decline to 0.27 in the Nortase group. In vitro analysis proved that the Nortase enzyme preparation was highly positive for the fungal antigens GM and ß-1,3-D-glucan. CONCLUSIONS: Our data demonstrate that the administration of digestive enzymes of fungal origin like Nortase leads to a significantly higher rate of false-positive GM test results compared to that in patients without digestive enzyme treatment.

15.
Antibiotics (Basel) ; 9(3)2020 Mar 21.
Article in English | MEDLINE | ID: mdl-32245195

ABSTRACT

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The extent to which therapeutic drug monitoring (TDM) in clinical practice can reduce insufficient antibiotic concentrations is an ongoing matter of investigation. We retrospectively evaluated routine meropenem and piperacillin measurements in critically ill patients who received antibiotics as short infusions in the first year after initiating a beta-lactam TDM program. Total trough concentrations above 8.0 mg/L for meropenem and above 22.5 mg/L for piperacillin were defined as the breakpoints for target attainment. We included 1832 meropenem samples and 636 piperacillin samples. We found that 39.3% of meropenem and 33.6% of piperacillin samples did not reach the target concentrations. We observed a clear correlation between renal function and antibiotic concentration (meropenem, r = 0.53; piperacillin, r = 0.63). Patients with renal replacement therapy or creatinine clearance (CrCl) of <70 mL/min had high rates of target attainment with the standard dosing regimens. There was a low number of patients with a CrCl >100 mL/min that achieved the target concentrations with the maximum recommended dosage. Patients with impaired renal function only required TDM if toxic side effects were noted. In contrast, patients with normal renal function required different dosage regimens and TDM-guided therapy to reach the breakpoints of target attainment.

18.
Int J Artif Organs ; 40(7): 358-360, 2017 Jul 05.
Article in English | MEDLINE | ID: mdl-28574114

ABSTRACT

We describe a young patient who ingested 18 g (240 times the daily therapeutic dose) of venlafaxine in a suicide attempt. She developed severe cardiomyopathy in a takotsubo distribution causing cardiogenic shock and multi-organ dysfunction syndrome (MODS). She was successfully treated with intravenous lipid emulsion (ILE), extracorporeal life support (ECLS) and CytoSorb®. This is remarkable as, to the best of the authors' knowledge, this is the highest amount of venlafaxine intake seen in the literature with a nonfatal outcome.


Subject(s)
Extracorporeal Membrane Oxygenation , Fat Emulsions, Intravenous/therapeutic use , Hemofiltration/methods , Serotonin and Noradrenaline Reuptake Inhibitors/poisoning , Takotsubo Cardiomyopathy/therapy , Venlafaxine Hydrochloride/poisoning , Female , Humans , Multiple Organ Failure/etiology , Multiple Organ Failure/therapy , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , Suicide, Attempted , Takotsubo Cardiomyopathy/etiology , Young Adult
19.
BMC Cardiovasc Disord ; 8: 27, 2008 Oct 10.
Article in English | MEDLINE | ID: mdl-18847481

ABSTRACT

BACKGROUND: To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus. METHODS: We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2+/-15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1+/-1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined. RESULTS: During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475+/-208) was significantly higher compared to those without cardiac events (236+/-199, p<0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p<0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p<0.01. CONCLUSION: By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.


Subject(s)
Calcinosis/diagnostic imaging , Cardiomyopathies/diagnostic imaging , Diabetes Mellitus, Type 2/diagnostic imaging , Myocardial Infarction/etiology , Tomography, X-Ray Computed , Adult , Aged , Calcinosis/complications , Calcinosis/mortality , Cardiomyopathies/complications , Cardiomyopathies/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Female , Health Status Indicators , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/mortality , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , ROC Curve , Risk Assessment , Risk Factors , Time Factors
20.
J Control Release ; 118(2): 196-203, 2007 Apr 02.
Article in English | MEDLINE | ID: mdl-17289207

ABSTRACT

Film forming polymeric solutions may present an alternative to the common transdermal dosage forms such as patches or gels. To evaluate the potential of these systems for transdermal drug delivery the permeation of ethinylestradiol from four formulations with different polymers was tested across heat separated human epidermis. The formulation with the best results was then modified by incorporating chemical enhancers to further increase the efficiency of the delivery system. Finally, drug delivery from the developed film forming systems was compared to a commercially available transdermal patch in vitro as well as in vivo in pigs. Among the tested preparations the formulation with polyurethane-14-AMP-acrylates copolymer (DynamX) showed the highest ethinylestradiol permeation. The drug transport was further increased with the incorporation of oleic acid as penetration enhancer, especially when used in combination with propylene glycol. The enhancing effect of oleic acid/propylene glycol was concentration-dependent and increased disproportionately with rising enhancer content. The film forming solution showed a higher ethinylestradiol permeation through heat separated human epidermis than the commercial EVRA patch in vitro and achieved measurable plasma concentrations of ethinylestradiol in vivo in pigs. These promising results encourage the further development of film forming polymeric solutions as novel transdermal dosage form.


Subject(s)
Contraceptive Agents/pharmacokinetics , Drug Carriers , Epidermis/metabolism , Ethinyl Estradiol/pharmacokinetics , Polymers/chemistry , Skin Absorption , Acrylates/chemistry , Administration, Cutaneous , Animals , Chemistry, Pharmaceutical , Contraceptive Agents/administration & dosage , Contraceptive Agents/blood , Contraceptive Agents/chemistry , Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Combined/metabolism , Diffusion Chambers, Culture , Dosage Forms , Drug Combinations , Drug Compounding , Epidermis/drug effects , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/blood , Ethinyl Estradiol/chemistry , Ethinyl Estradiol/metabolism , Female , Humans , Hypromellose Derivatives , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Norgestrel/administration & dosage , Norgestrel/analogs & derivatives , Norgestrel/metabolism , Oleic Acid/pharmacology , Organ Culture Techniques , Permeability , Polyurethanes/chemistry , Propylene Glycol/pharmacology , Silicones/chemistry , Skin Absorption/drug effects , Swine , Time Factors
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