Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

[Analysis and options for optimization of preoperative assessment for anesthesia at a university hospital]. / Analyse und Möglichkeiten der Optimierung von Prämedikationsgesprächen an einem Universitätsklinikum.

BACKGROUND: Risk assessment prior to elective surgery is an important tool in the context of perioperative patient care; however, only a few studies have been carried out to address the processes and problems during preoperative assessment for anesthesia. AIM: Over a period of several weeks all preoperative anesthesia evaluations prior to elective surgery were prospectively recorded in order to generate a data pool with a view to identifying options for process optimization. MATERIAL AND METHODS: All preoperative evaluations over a period of 38 working days at the University Medical Center Regensburg were recorded and analyzed with respect to waiting time for the patient and the duration of the preoperative consultation on medication. Also documented were the patient age, ASA score, the faculty carrying out the operation, type and risk of surgery, planned time of surgery, professional experience of the anesthesiologist and the approval status for surgery. In addition, all problems which occurred during the preoperative anesthesia evaluation were documented using a questionnaire. RESULTS: Overall 2233 preoperative assessments for anesthesia were recorded and analyzed. The number of patients attending the preoperative assessment clinic differed markedly in the course of a day and was lower at the end of the week. Approval for surgery with no reservations was given more frequently by anesthesiologists with more than 5 years professional experience and consultants compared to younger colleagues. The main reason for approval with reservations or no approval was the lack of patient records and test results, which should have been presented according to the in-house standard for preoperative assessment for anesthesia. The mean waiting time was 58.6 ± 30.3 min, the mean duration of the patient documentation review and physician-patient consultation together was 33.6 ± 16.3 min. Anesthesiologists with 2-5 years professional experience needed significantly less time for patient documentation reviews and physician-patient consultations than younger and more experienced colleagues. The duration of the preoperative assessment for anesthesia correlated with the ASA score and risks of surgery. CONCLUSION: The analysis of processes and problems in the context of preoperative assessment for anesthesia revealed several options for optimization. Major efforts should be the implementation of an appointment system for the preoperative assessment clinic in order to generate a homogeneous distribution of patients during the course of a day. Furthermore, surgeons and case managers should be requested to refer patients to the preoperative assessment clinic only with complete records and test results according to the in-house standard.

[Optimization of blood gas analysis in intensive care units : Reduction of preanalytical errors and improvement of workflow]. / Optimierung von Blutgasanalysen auf der Intensivstation : Reduzierung präanalytischer Fehler und Verbesserung der zeitlichen Abläufe.

BACKGROUND: Point of care testing with blood gas analysis (BGA) is an important factor for intensive care medicine. Continuous efforts to optimize workflow, improve safety for the staff and avoid preanalytical mistakes are important and should reflect quality management standards. AIM: In a prospective observational study it was investigated whether the implementation of a new system for BGA using labeled syringes and automated processing of the specimens leads to improvements compared to the previously used procedure. MATERIAL AND METHODS: In a 4-week test period the time until receiving the final results of the BGA with the standard method used in the clinical routine (control group) was compared to the results in a second 4-week test period using the new labeled syringes and automated processing of the specimens (intervention group). In addition, preanalytical mistakes with both systems were checked during routine daily use. Finally, it was investigated whether a delay of 10 min between taking and analyzing the blood samples alters the results of the BGA. RESULTS: Preanalytical errors were frequently observed in the control group where non-deaerated samples were recorded in 87.3 % but in the intervention group almost all samples (98.9 %) were correctly deaerated. Insufficient homogenization due to omission of manual pivoting was seen in 83.2 % in the control group and in 89.9 % in the intervention group; however, in the intervention group the samples were homogenized automatically during the further analytical process. Although a survey among the staff revealed a high acceptance of the new system and a subjective improvement of workflow, a measurable gain in time after conversion to the new procedure could not be seen. The mean time needed for a complete analysis process until receiving the final results was 244 s in the intervention group and 201 s in the control group. A 10-min delay between taking and analyzing the blood samples led to a significant and clinically relevant elevation of the values for partial pressure of oxygen (pO2) in both groups compared to the results when analyzing the samples immediately (118.4 vs. 148.6 mmHg in the control group and 115.3 vs. 123.7 mmHg in the intervention group). When using standard syringes the partial pressure of carbon dioxide (pCO2) was significantly lower (40.5 vs. 38.3 mmHg) whereas no alterations were seen when using the labeled syringes. CONCLUSION: The implementation of a new BGA system with labeled syringes and automated processing of the specimens was possible without any difficulties under daily clinical routine conditions in this 10-bed intensive care unit (ICU). A gain of time could not be measured but a reduction in preanalytical errors using the labeled syringes with automated processing was found. Delayed analysis of blood samples can lead to significant changes in pO2 and pCO2 depending on the type of syringe used.

[Placement of a central venous catheter in cases of persistent left superior vena cava]. / Anlage eines zentralen Venenkatheters bei persistierender V. cava superior sinistra.

This article presents a case report on the placement of a central venous catheter (CVC) in a patient with an unknown persistent left superior vena cava (PLSVC). Normally, PLSVCs remain asymptomatic but can be associated with disastrous consequences for the patient during placement of a CVC particularly due to vascular perforation and pulmonary injury. A PLSCV is particularly common in association with congenital heart defects; however, otherwise healthy patients can also be affected. As the presence of a PLSCV is normally unknown special attention must be paid in every patient during placement of a CVC.

[Secondary sclerosing cholangitis after multiple trauma and long-term intensive care treatment: case report of a characteristic course]. / Sekundär-sklerosierende Cholangitis nach Polytrauma und Langzeitintensivtherapie : Fallbericht eines charakteristischen Verlaufs.

This article reports on a patient who needed intensive care treatment because of multiple trauma. The patient had no preexisting liver disease but developed secondary sclerosing cholangitis and finally died. The etiology, diagnosis and therapeutic options of this clinical picture are discussed and a review of the literature is presented.

Ceramic membrane ultrafiltration of natural surface water with ultrasound enhanced backwashing.

Ultrafiltration membrane cleaning with ultrasound enhanced backwashing was investigated with two ceramic membrane systems in parallel. One of them was subjected to ultrasound during backwashing, the other acted as a reference system. The feed water was directly taken from a creek with a sedimentation process as only pre-treatment. The cleaning performance was improved with ultrasound but after 3 weeks of operation damages occurred on the membranes. These effects were studied with online measurements of flux, trans-membrane-pressure and temperature, but also with integrity tests, turbidity measurements and visual examination.

Efficient primer design algorithms.

MOTIVATION: Primer design involves various parameters such as string-based alignment scores, melting temperature, primer length and GC content. This entails a design approach from multicriteria decision making. Values of some of the criteria are easy to compute while others require intense calculations. RESULTS: The reference point method was found to be tractable for trading-off between deviations from ideal values of all the criteria. Some criteria computations are based on dynamic programs with value iteration whose run time can be bounded by a low-degree polynomial. For designing standard PCR primers, the scheme offers in a relative gain in computing speed of up to 50: 1 over ad-hoc computational methods. Single PCR primer pairs have been used as model systems in order to simplify the quantization of the computational acceleration factors. The program has been structured so as to facilitate the analysis of large numbers of primer pairs with minor modifications. The scheme significantly increases primer design throughput which in turn facilitates the use of oligonucleotides in a wide range of applications including: multiplex PCR and other nucleic acid-based amplification systems, as well as in zip code targeting, oligonucleotide microarrays and nucleic acid-based nanoengineering.

T-type and L-type calcium channel blockers exert opposite effects on renin secretion and renin gene expression in conscious rats.

1. This study aimed to investigate and to compare the effects of pharmacological T-type calcium channel and of L-type calcium channel blockade on the renin system. To this end, male healthy Sprague-Dawley rats were treated with the T-channel blocker mibefradil or with the L-channel blocker amlodipine at doses of 5 mg kg(-1), 15 mg kg(-1) and 45 mg kg(-1) per day for four days and their effects on plasma renin activity (PRA) and kidney renin mRNA levels were determined. 2. Whilst amlodipine lowered basal systolic blood pressure at 5 mg kg(-1), mibefradil had no effect on basal blood pressure in the whole dose range examined. Amlodipine dose-dependently induced up to 7 fold elevation of PRA and renin mRNA levels. Mibefradil significantly lowered PRA and renin mRNA levels at 5 mg kg(-1) and moderately increased both parameters at a dose of 45 mg kg(-1), when PRA and renin mRNA levels were increased by 100% and 30%, respectively. In primary cultures of renal juxtaglomerular cells neither amlodipine nor mibefradil (0.1-10 microM) changed renin secretion. 3. In rats unilateral renal artery clips (2K-1C) mibefradil and amlodipine at doses of 15 mg kg(-1) day(-1) were equally effective in lowering blood pressure. In contrast mibefradil (5 mg kg(-1) and 15 mg kg(-1) day(-1)) significantly attenuated the rise of PRA and renin mRNA levels, whilst amlodipine (15 mg kg(-1)) additionally elevated the rise of PRA and renin mRNA levels in response to renal artery clipping. 4. These findings suggest that T-type calcium channel blockers can inhibit renin secretion and renin gene expression in vivo, whilst L-type calcium channel blockers act as stimulators of the renin system. Since the inhibitory effect of T-type antagonists is apparent in vivo but not in vitro, one may infer that the effect on the renin system is indirect rather than directly mediated at the level of renal juxtaglomerular cells.

Stimulation of renin secretion by NO donors is related to the cAMP pathway.

This study aimed to characterize the cellular pathways along which nitric oxide (NO) influences the secretion of renin from the kidney. Using the isolated perfused rat kidney model, we found that the NO donor sodium nitroprusside (SNP) (1-30 mumol/l) induced a prompt, concentration-dependent fourfold increase of basal renin secretion. The membrane-permeable cGMP analogs 8-bromo-cGMP and 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP; each 5-50 mumol/l) inhibited basal renin secretion and attenuated the stimulation of renin secretion by SNP. Conversely, the renin stimulatory effect of SNP was enhanced in the presence of the G kinase inhibitor Rp-8-CPT-cGMPS (10 mumol/l). The renin stimulatory effect of SNP was amplified in nominally calcium-free perfusate and was abolished in the presence of angiotensin II (1 nmol/l). Renin secretion stimulated by SNP was clearly attenuated by the A kinase inhibitor Rp-8-CPT-cAMPS (25 mumol/l). These findings indicate that the renin stimulatory effect of NO donors in renal juxtaglomerular cells cannot be explained by activation of G kinase and is also less likely to be causally related to the regulation of renin secretion by calcium. Because A kinase activity is required for the stimulation of renin secretion by SNP, it appears as if the renin stimulatory effect is causally related to the cAMP pathway controlling renin secretion.

Density functional study of isomerization of fluoro- and chloroformaldehyde radical cations.

Ab initio and density functional (DFT) calculations were performed on radical cations with the formula HXCO(+˙) (X = H, F, and CI) and their isomers XCOH(+˙) . Hartree-Fock, Møller-Plesset at second order (MP2), and quadratic configuration interaction including singles and doubles (QCISD) methods were employed for geometry optimizations at the ab initio level. Becke's 1988 and three-parameter exchange potentials, together with Vosko-Wilk-Nusair (VWN) and Lee-Yang-Paar (LYP) correlation potentials (BVWN, BLYP, and B3LYP) were used for the DFT calculations. HF and MPn isomerization energies are severely in error, mostly due to a bad description of the XHCO(+˙) cation radicals at the Hartree-Fock level, leading to oscillatory behavior of the perturbation series. QCISD methods, at least, are needed to obtain accurate results at the conventional ab initio level, even using large extended basis sets. B3LYP results are most similar to QCISD results for the isomerization energies of the three cation radicals. Parent neutral species are also described to a high degree of accuracy. B3LYP methods are faster than QCISD (and as exact as them) for all the cases studied here. MP2 methods, although giving incorrect results, are faster than B3LYP up to about 80 basis functions. For larger problems, B3LYP methods are faster. The best theoretical results obtained indicate that fluoro- and chloroformaldehyde cation radicals are less stable than their hydroxyfluoro- and hydroxychloromethylene isomers, the reverse situation than for the formaldehyde cation radical. The best values found in this article for the isomerization energy of XHCO(+˙) are -26 ± 2 kJ/mol (X = H), +37 ± 2 kJ/mol (X = F), and +28 ± 2 kJ/mol (X = CI). Ionization energies of 10.9, 12.3, and 11.4 eV are predicted for the XHCO species (X = H, F, CI). © 1996 by John Wiley & Sons, Inc.

Computer simulation of antisense DNA containing enantio-deoxynucleotides in the double helix.

Computer modeling of DNA double helices containing L-oligodeoxynucleotides and their complementary D-beta-strands in different orientations and conformations was performed using empirical force-field and semiempirical methods. In particular, the parallel and antiparallel orientations of L-alpha and L-beta-configured strands have been extensively simulated. The parallel oriented double helix with L-alpha-2'-deoxynucleotides has been found to be the enantio-deoxynucleotides. The energy difference between this enantio-DNA and native DNA is approximately 6kcal/mol per base pair, favoring the latter. The theoretical results compared well with preliminary experimental data on the hybridization of recently synthesized 11-mer L-oligodeoxynucleotides, L-d-5' (TpCpGpCpTpGpCpTpTpCpT)3' and L-d-5' (TpCpTpTpCpGpTpCpGpCpT)3' containing the complementary D-beta-oligodeoxynucleotides. As predicted by the calculations, experimental results can be interpreted by assuming that hybridization occurs only in the parallel L-alpha-2'-oligodeoxynucleotides.