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Peter Dittrich

Publications and source records attributed to Peter Dittrich.

10 recordsLinked to original sources
PubMed2006

Single-dose pharmacokinetics of fosfomycin during continuous venovenous haemofiltration.

OBJECTIVES: Dosage recommendations for fosfomycin are available for haemodialysed patients but there are no data for patients undergoing continuous renal replacement therapy. Therefore, the present study was designed to determine the concentration-versus-time profile of fosfomycin in continuous venovenous haemofiltration (CVVH). PATIENTS AND METHODS: A total of 12 anuric intensive care patients (10 males and 2 females) with suspected or proven infection requiring parenteral antibiotic therapy were included in the study. All patients underwent CVVH. Blood samples were drawn from the arterial (input) and venous (output) line of the extracorporeal circuit after application of a single dose of 8 g of fosfomycin. Ultrafiltration samples were collected from the outlet of the ultrafiltrate compartment of the haemofilter. Fosfomycin in the samples was quantified by gas chromatography. RESULTS: The peak serum concentration was 442.7+/-124 mg/L at the arterial port. The trough serum level was 103.1+/-36.6 mg/L at the arterial port after 720 min. The mean value of the area under the concentration-versus-time curve from 0 to 12 h (AUC0-12) was 2159.4+/-609.8 mg.h/L. Mean total removal of the drug was 76.7+/-6.2%. The mean calculated clearance was 1.1+/-0.2 L/h for CLHF. Mean CLtot was 6.4+/-7.7 L/h. CONCLUSIONS: A regimen of 8.0 g of fosfomycin every 12 h, which is usually used in patients with intact renal function, should be an appropriate antimicrobial treatment for patients undergoing CVVH.

Aged↗
PubMed2006

Analyzing molecular reaction networks: from pathways to chemical organizations.

Pathways are typically the central concept in the analysis of biochemical reaction networks. A pathway can be interpreted as a chain of enzymatical reactions performing a specific biological function. A common way to study metabolic networks are minimal pathways that can operate at steady state called elementary modes. The theory of chemical organizations has recently been used to decompose biochemical networks into algebraically closed and self-maintaining subnetworks termed organizations. The aim of this paper is to elucidate the relation between these two concepts. Whereas elementary modes represent the boundaries of the potential behavior of the network, organizations define metabolite compositions that are likely to be present in biological feasible situations. Hence, steady state organizations consist of combinations of elementary modes. On the other hand, it is possible to assign a unique (and possibly empty) set of organizations to each elementary mode, indicating the metabolites accompanying the active pathway in a feasible steady state.

Cell Physiological Phenomena↗
PubMed2005

Determinants of simulated RNA evolution.

Models of RNA secondary structure folding are widely used to study evolution in theory and simulation. However, systematic studies of the parameters involved are rare. In this paper, we study by simulation how RNA evolution is influenced by three different factors, namely the mutation rate, scaling of the fitness function, and distance measure. We found that for low mutation rates the qualitative evolutionary behavior is robust with respect to the scaling of the fitness function. For efficient mutation rates, which are close to the error threshold, scaling and distance measure have a strong influence on the evolutionary behavior. A global distance measure that takes sequence information additively into account lowers the error threshold. When using a local sequence-structure alignment for the distance, we observed a smoother evolution of the fitness over time. Finally, in addition to the well known error threshold, we identify another threshold of the mutation rate, called divergence threshold, where the qualitative transient behavior changes from a localized to an exploratory search.

Animals↗
PubMed2004

Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis.

OBJECTIVE: The present study was performed to test the ability of fosfomycin to penetrate into the CSF of neurointensive care patients with ventriculostomy-associated ventriculitis. PATIENTS AND METHODS: Six patients requiring neurointensive care monitoring, including extraventricular drainage due to secondary obstructive hydrocephalus, were enrolled into the study. All patients received 8 g of fosfomycin intravenously three times a day over a period of at least 5 days. Concentrations of fosfomycin in the CSF and plasma were measured after single-dose administration and at steady state. RESULTS: Mean values of the fosfomycin area under the time-concentration curves for the dosing interval of 8 h (AUC(8)) were 929 +/- 280 and 225 +/- 131 mg.h/L for plasma and CSF after single-dose administration, respectively (P < 0.03). The ratios of the AUC(8) for CSF to the AUC(8) for plasma were 0.23 +/- 0.07 after a single dose and 0.27 +/- 0.08 following multiple doses (P > 0.05, not significant). Additional in vitro experiments have shown that fosfomycin exerts non-concentration-dependent microbial growth inhibition. At steady state, the time above MIC (t > MIC) values were 98%, 92% and 61% for pathogens with MIC values of 8, 16 and 32 mg/L, respectively. CONCLUSION: The present pharmacokinetic study indicates that 8 g of fosfomycin three times per day should provide sufficient antimicrobial concentrations in the CSF for the overall treatment period. Thus, the co-administration of fosfomycin could be useful for the treatment of ventriculitis caused by susceptible pathogens.

Adult↗
PubMed2004

Prevalence of pathological glucose metabolism in patients undergoing elective coronary angiography.

Abnormal glucose metabolism is frequently observed in patients with acute myocardial infarction but less evidence exists for subjects with suspected coronary artery disease. Thus, the prevalence of abnormal glucose metabolism was investigated in 160 consecutive subjects undergoing elective coronary angiography. We observed 15% with normal glucose tolerance, 30% with impaired glucose tolerance and 55% with diabetes (32% previously known) but only 41% with elevated fasting glycemia. In conclusion, our data highlight the high frequency of disturbed glucose metabolism in patients with suspected coronary artery disease and the importance of the oral glucose tolerance test.

Aged↗
PubMed2004

Penetration of meropenem into pneumonic human lung tissue as measured by in vivo microdialysis.

Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited. We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication. Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values. Serum and microdialysis samples were collected at 20-min intervals for at least 8 h following a single intravenous dose of 1 g of meropenem. The maximum free interstitial concentration (mean and standard deviation) of meropenem in infected lung tissue was 11.4 +/- 10.9 mg/liter, and that in serum was 47.3 +/- 21.0 mg/liter. The areas under the curve for infected lung tissue (36.2 +/- 17.9 mg. h/liter) and serum (95.4 +/- 46.6 mg. h/liter) revealed a significant difference. This technique enabled quasi-continuous tissue pharmacokinetic measurements of free, unbound antibiotic in pneumonic lung tissue of patients with pneumonia. The present data corroborate the use of meropenem in the treatment of lung infections caused by extracellular bacteria, demonstrating the excellent distribution profile for meropenem in the interstitial space of human pneumonic lung tissue.

Adult↗
PubMed2004

Dynamic subset selection based on a fitness case topology.

A large training set of fitness cases can critically slow down genetic programming, if no appropriate subset selection method is applied. Such a method allows an individual to be evaluated on a smaller subset of fitness cases. In this paper we suggest a new subset selection method that takes the problem structure into account, while being problem independent at the same time. In order to achieve this, information about the problem structure is acquired during evolutionary search by creating a topology (relationship) on the set of fitness cases. The topology is induced by individuals of the evolving population. This is done by increasing the strength of the relation between two fitness cases, if an individual of the population is able to solve both of them. Our new topology-based subset selection method chooses a subset, such that fitness cases in this subset are as distantly related as is possible with respect to the induced topology. We compare topology-based selection of fitness cases with dynamic subset selection and stochastic subset sampling on four different problems. On average, runs with topology-based selection show faster progress than the others.

Algorithms↗
PubMed2003

Target site penetration of fosfomycin in critically ill patients.

OBJECTIVE: The present study was undertaken to investigate the target site penetration properties of fosfomycin, an antibiotic particularly suitable for treatment of soft tissue infections (STIs) in critically ill patients. METHODS AND RESULTS: The study population included nine patients with sepsis. Penetration of fosfomycin into the interstitial space fluid of skeletal muscle was measured using the microdialysis technique, following a single intravenous administration of 8.0 g of fosfomycin to patients. The median (range) fosfomycin area under the concentration versus time profile for plasma and skeletal muscle were 673 (459-1108) and 477 (226-860) mg x h/L (P < 0.011), respectively. Interstitial maximum concentrations were lower than plasma values (P < 0.029). Median fosfomycin concentrations in the interstitium and plasma exceeded 70 mg/L throughout the observation period of 4 h and covered MICs for Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa. Simulation of bacterial growth inhibition of S. pyogenes, based on tissue concentration data, confirmed the bactericidal properties of fosfomycin described in previous studies. CONCLUSION: Fosfomycin concentrations in muscle interstitium and plasma exceeded the MICs for a range of clinically relevant pathogens in critically ill patients. Thus, fosfomycin exhibits a tissue pharmacokinetic profile, which appears to offer an alternative to other broad-spectrum antibiotics in intensive care patients suffering from STI.

Aged↗
PubMed2003

Penetration of piperacillin and tazobactam into pneumonic human lung tissue measured by in vivo microdialysis.

OBJECTIVES: The pharmacokinetic profile of antibiotics at the site of anti-infective action is one of the most important determinants of drug response, since it correlates with antimicrobial effect. Up to now, only limited information on the lung tissue pharmacokinetics of antibiotic agents has been available. The aim of this study was to measure, using a new microdialysis-based approach, antibiotic penetration into the extracellular space fluid of pneumonic human lung parenchyma. PATIENTS AND METHODS: The lung penetration of a combination of piperacillin and tazobactam, substances with low protein binding, was determined in five patients suffering from pneumonia and metapneumonic pleural empyema. The condition was treated by decortication after lateral thoracotomy. Intra-, or post-operatively, respectively, two microdialysis probes were inserted into pneumonic lung tissue, and into healthy skeletal muscle to obtain reference values. Serum and microdialysis samples were collected at 20-min intervals for at last 8 h following i.v. administration of a single dose of 4 g piperacillin and 500 mg tazobactam. RESULTS: The mean free interstitial concentration profiles of piperacillin in infected lung tissue and serum showed a maximal tissue concentration (Cmax) of 176.0 +/- 105.0 mg l-1 and 326.0 +/- 60.6 mg l-1, respectively. The mean AUC (area under the curve) for infected lung tissue was 288.0 +/- 167.0 mg.h l-1 and for serum 470.0 +/- 142.0 mg.h l-1. There was a statistically significant difference between AUC (lung) and AUC (serum) (P = 0.018) as well as between AUC (lung) and AUC (muscle) (P = 0.043). The intrapulmonary concentrations of piperacillin and tazobactam exceeded the minimum inhibitory concentrations (MIC) for most relevant bacteria for 4-6 h. The procedure was well tolerated by all patients and no adverse events or microdialysis-associated side-effects were observed. CONCLUSION: This microdialysis technique enabled continuous tissue pharmacokinetic measurement of free, unbound anti-infective agents in the lung tissue of patients with pneumonia. The present data corroborate the use of piperacillin and tazobactam in the treatment of lung infections caused by extracellular bacteria and demonstrate the distribution of piperacillin and tazobactam in the interstitial space of pneumonic lung tissue.

Adult↗