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Biomedical subjects

F Thalhammer

Publications and source records attributed to F Thalhammer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Continuous infusion versus intermittent administration of meropenem in critically ill patients.

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.

Adolescent↗
PubMed1999

The assessment of four different methods to verify tracheal tube placement in the critical care setting.

UNLABELLED: One of the most serious complications of conventional endotracheal intubation is unidentified placement of the tube in the esophagus. The aim of our study was to evaluate four different methods for immediate detection of the tube position: auscultation, capnographic determination of ETCO2, esophageal detection method (EDM) using a self-inflating bulb, and the transillumination method using a lighted stylet (Trachlight; Laerdal, Armonk, NY). Thirty-eight endotracheally intubated patients admitted to our medical intensive care unit were enrolled in the study. A second identical tube was inserted into the esophagus under laryngoscopic control. The endotracheal tube was then disconnected from the ventilator. Two blinded examiners, one experienced, the other inexperienced, determined the tube position within 30 s using one of the four methods. The order of the tubes tested and the methods used were randomized. In 130 of 152 examinations, both examiners correctly diagnosed the position of the tube. The wrong result was obtained by both examiners 4 times; only the experienced examiner was wrong 4 times, and only the inexperienced examiner was wrong 14 times. Using ETCO2, both examiners were correct in all cases. Auscultation showed an obvious relation to the examiner's experience: the experienced examiner was correct in all cases, the inexperienced examiner was correct in only 68% of cases. Using the self-inflating bulb, there were two wrong results of the experienced examiner and one wrong result of the inexperienced examiner. The transillumination technique was associated with a high error rate by both examiners (16% and 13%, respectively). Comparing all four methods showed that capnography is superior to auscultation (P = 0.0005) and to the Trachlight detection method (P = 0.0078). EDM was not statistically superior to auscultation and transillumination. Capnography was the most reliable method for rapid evaluation of tube position, followed by EDM, whereas auscultation and Trachlight did not seem to be of comparable value. Experience was a determining factor for auscultation. IMPLICATIONS: To prevent unidentified esophageal intubation, a serious complication in the critical care setting, four methods for detecting tube position were tested by two examiners (one experienced, the other inexperienced) in endotracheally intubated patients after insertion of a second tube into the esophagus.

Adult↗
PubMed1999

Novel C5-dependent mechanism of neutrophil stimulation by bioincompatible dialyzer membranes.

The objective of the study was to evaluate the contribution of reactive oxygen intermediate formation for receptor modulation on neutrophils by the cellulosic dialyzer membrane cuprophan (CU). In patients dialyzed with CU, CD11b and CD66b upregulation on neutrophils (by 104.3 +/- 37.9% and 85.7 +/- 31.1%, respectively), and a downregulation of L-selectin (by 44.9 +/- 26.9%) was seen, whereas expression of CD11a remained unaltered. Hemodialysis with polysulfone did not bring about major changes in surface receptor expression. In vitro incubation of isolated neutrophils in the presence of serum with hollow fibers of CU or polysulfone showed similar results: Only CU resulted in upregulation of CD11b and CD66b expression (by 65.5 +/- 18.7% and 60.1 +/- 24%) and a decrease in CD62L expression (by 60.6 +/- 18.2%). In contrast to receptor alterations, generation of reactive oxygen intermediate by CU occurred in the absence of serum. Inhibition experiments with soluble complement receptor 1, which produced only partial inhibition of receptor up-/down-regulation, indicated the existence of also other than alternate complement-dependent mechanisms for neutrophil activation. By using C5-depleted serum instead of normal human serum, up-/down-regulation of CD11b, CD62L, and CD66b by CU was dramatically reduced, whereas C3-depleted serum did not produce that effect. C5-deficient serum repleted with purified C5, as well as purified C5 alone, was able to induce receptor modulation by CU comparable to normal human serum. L-Methionine, a specific inhibitor for the oxidative activation of C5, blocked the modulatory effect of CU in assays with purified C5 as well as with serum. As a result, in addition to the alternative pathway of complement, a C5-dependent mechanism probably activated by neutrophil-derived reactive oxygen intermediate leads to receptor modulation and subsequent generation of the well known side effects of bioincompatible dialyzer membranes.

Adult↗
PubMed1998

A case of visceral leishmaniasis in Austria.

We report a patient aged 41 years with fever of unknown origin. Notable aspects of his travel history were a trip to the Philippines and a sailing trip around Sicily. The patient presented with fever up to 40 degrees C since 4 weeks, weakness, headache, hepatosplenomegaly and night sweat. No specific cause could be found. Based on clinical findings tuberculosis was suspected and empirical tuberculostatic treatment was started. However, during the following 6 weeks the patient's condition deteriorated. A bone marrow biopsy performed to exclude a haematological malignancy revealed Leishmania sp. in macrophages. This histological diagnosis was confirmed retrospectively by re-examination of a previously performed liver biopsy and by an increased anti-leishmania serum antibody titer of 1:1280. The patient was treated with sodium stibogluconate (pentostam, 850 mg) for 30 days and recovered slowly.

Adult↗
PubMed1998

Measurement of serum nitrite/nitrate concentrations using high-performance liquid chromatography.

Previous studies have reported increased serum concentrations of nitrite/nitrate - the degradation products of nitric oxide - in Plasmodium vivax malaria and uncomplicated Plasmodium falciparum malaria. In all these studies, however, nitrite/nitrate has been measured spectrometrically using Griess reagent which carries major disadvantages in the determination of serum nitrite/nitrate. The method does not allow an exact differentiation of nitrite and biogenic amines that are physiologically present in plasma. In the present study we introduce high-performance liquid chromatography as a new, accurate and cost effective method for determination of serum nitrite/nitrate levels. Significantly increased nitrate concentrations were found in malaria patients and serum values remained above normal levels for at least 21 days. It could be shown that our HPLC method is a sensitive and cost-effective method for direct determination of nitrite/nitrate in serum samples, which is not influenced by the presence of biogenic amines.

Adolescent↗
PubMed1998

Prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis.

The aim of the present study was to evaluate the potential prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis. Twenty-eight patients with gram-positive sepsis were compared to 11 patients with gram-negative sepsis and 15 healthy volunteers. Sepsis was defined by the criteria of Bone et al. (Crit. Care Med. 21, 5447-5463, 1993) and by isolation of at least two positive blood cultures with gram-positive/gram-negative bacteria. Plasma samples for determination of the immunological parameters were collected daily. Analysis of cytokines and adhesion molecules was performed on days 0 (day of sepsis criteria fulfillment), 4, and 7 (or 1 day before death). In the gram-positive group 10 of 28 patients died; in the gram-negative group 4 of 11 died. Only sELAM-1 plasma concentrations were found to be a useful early parameter in predicting patients' outcome in gram-positive sepsis. sELAM-1 concentrations at the onset of the study (day 0) were significantly higher in the nonsurviving patients than those in the survivors. MIP-1 alpha levels were significantly higher only on days 4 and 7. With regard to the measured plasma concentrations we believe that MIP-1 alpha is not a useful parameter for predicting patients' prognosis. The increase of sVCAM-1 might play a role in the pathogenesis of gram-positive sepsis; however, it could not be relied upon as an early prognostic parameter. The potential role of TGF-beta 2 in the development of gram-positive sepsis could not evaluated in the present study, whereas routine measurements of TGF-beta 2 offered no additional prognostic information.

Adult↗
PubMed1998

Teicoplanin in the prevention of infection in total hip replacement.

Perioperative antibiotic prophylaxis has been shown to be effective in reducing postoperative wound infections. The rising incidence of infections secondary to methicillin-resistant strains of Staphylococcus aureus. S. epidermidis and S. enterococcal prompted us to administer Teicoplanin to infection in elective total joint arthroplasty. In 111 patients Teicoplanin was given in a single intravenous dose of 10 mg/kg prior to surgery. In the postoperative period no deep infection of the prosthetic device was found in a 14-month follow-up. In two patients the following organisms were isolated from superficial infections of the wound: S. epidermidis (methicillin-sensitive), Pseudomonas aeruginosa, and Enterobacter sp. In no patient was revision surgery necessary. The serum concentration of Teicoplanin was within the therapeutic range during surgery, and tissue levels of Teicoplanin in cancellous (6.2 mg/kg, range 3.8-10.9 mg/kg) and cortical (7.1 mg/kg, range 2.6-12.1 mg/kg) bone during surgery in 16 patients exceeded the minimum inhibitory concentration of 90% (MIC90) of methicillin-resistant strains reported for methicillin-resistant strains. In our experience a single dose regimen of Teicoplanin is a safe and effective method of antibiotic prophylaxis in hip joint replacement, particularly when methicillin-resistant bacteria are present.

Acetabulum↗
PubMed1998

Ofloxacin clearance during hemodialysis: a comparison of polysulfone and cellulose acetate hemodialyzers.

The pharmacokinetics of ofloxacin were studied in 13 patients with end-stage renal disease during hemodialysis using two different dialyzers: a polysulfone membrane (Fresenius F6) and a cellulose acetate dialyzer (Nissho Nipro FB-150T). All patients received 100 mg ofloxacin orally per day before dialysis. The hemodialysis clearance per square meter surface area was significantly different, with 5.0+/-0.7 L/h and 3.7+/-1.6 L/h, respectively. The serum concentration was reduced by a 3-hour hemodialysis by 49.6%+/-5.8% per square meter surface area and 45.5%+/-4.8% per square meter surface area. The half-life was 4.2+/-1.8 hours and 4.8+/-1.6 hours during the hemodialysis period and 22.8+/-2.2 hours and 23.3+/-1.7 hours between the dialysis sessions, respectively. Comparing polysulfone and cellulose acetate dialyzers, the material of the membrane influences the half-life, the dialysis clearance, and the percentage of drug extracted during hemodialysis. We conclude that the type of dialyzer used has to be taken into account in dosage recommendations for antimicrobial therapy in hemodialysis patients.

Adult↗
PubMed1998

Time course of immunological markers in patients with the systemic inflammatory response syndrome: evaluation of sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and TGF-beta 2.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) is viewed as a system-wide inflammatory response. Up until now, no parameter has been available for predicting the development of septic shock. In the present study, we evaluated the usefulness of serum levels of CD14, vascular cells adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), macrophage inflammatory protein (MIP) 1 alpha and transforming growth factor beta 2 (TGF-beta 2) as early markers of outcome in patients with SIRS. METHODS: A group of 28 SIRS patients (13 survivors/15 non-survivors) was compared with a healthy control group and with patients with local inflammation. Blood samples were analysed on days 0, 4 and 7. Proinflammatory parameters such as sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and anti-inflammatory parameters such as TGF-beta 2 were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: At the beginning, all evaluated proinflammatory immunological parameters with the exception of sVCAM-1 were significantly increased in patients with SIRS compared with the healthy control group. However, no significant difference could be observed for all immunological parameters comparing survivors and non-survivors, with the exception of interleukin (IL) 6 at day 7. CONCLUSION: All evaluated proinflammatory parameters were increased in patients with SIRS during the course of the disease. However, the parameters have no correlation with outcome and prognosis of SIRS patients.

Adult↗
PubMed1998

Single-dose pharmacokinetics of meropenem during continuous venovenous hemofiltration.

The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 +/- 18.6 ml/min and 2.46 +/- 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 +/- 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 +/- 2.7 microgram/ml, and trough levels after 6 h of CVVH were 6.6 +/- 1.5 microgram/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 +/- 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

Aged↗
PubMed1998

Serum procalcitonin levels in severe Plasmodium falciparum malaria.

Levels of procalcitonin (ProCT) have been found to be elevated in individuals with severe bacterial infections such as sepsis and peritonitis, and this correlates well with the severity of the disease. Recently, increased levels have been described in melioidosis and Plasmodium falciparum malaria. In this study ProCT levels were measured in 27 Thai patients with complicated malaria before and during/after treatment with artesunate and mefloquine. Initial parasite counts averaged 290,680/microl (range = 533-1,147,040). On admission, ProCT levels were elevated in all but one patient (median = 40 ng/ml, range = 0.04-662, normal values < 0.5 ng/ml). With treatment, levels decreased to 1.3 ng/ml (range = 0.01-6.5). Nitrite/nitrate levels in patients were higher than in controls throughout the study. The ProCT levels correlated with initial parasite density (P < 0.05), which is a marker of disease severity, and with nitrite/nitrate levels (P < 0.05). Based on the changes of ProCT levels over the course of the disease a possible role in the acute-phase reaction seems likely.

Adolescent↗
PubMed1997

[Aminoglycoside-induced nephrotoxicity].

In severe gram-negative infections aminoglycosides generally remain the first-line antibiotic. Their use is limited by the high risk of side effects and, especially, nephrotoxicity. High peak levels are crucial for antibacterial activity, whereas toxic side effects are determined by the more prolonged trough levels. Thus, aminoglycosides should not be given by intramuscular injection because the peak levels achieved are inadequate, whilst long-lasting elevated plasma trough levels result. On administration of a daily single dose intravenously high antibacterial efficacy can be combined with low nephrotoxicity. Besides the dose-dependent bactericidal effect, the post-antibiotic effect of aminoglycosides is of importance. The main site of nephrotoxicity are the proximal tubule epithelial cells. Renal toxicity is usually reversible after discontinuation of drug therapy. Toxic acute renal failure is not uncommon (5-35%) and usually dependent on the underlying disease, preexisting renal function, hydration state, age, cumulative dose, additional medication, previous therapy with aminoglycosides and the choice of the specific aminoglycoside. By implementing a single daily dose regimen in conjunction with adequate hydration, alkalization therapy with bicarbonate, monitoring of plasma trough levels and minimization of the duration of therapy (5 days), development of renal impairment can be prevented in the large majority of patients. Hence, acute renal failure has become an avoidable, and much less frequently observed complication of aminoglycoside therapy due to these measures.

Acute Kidney Injury↗
PubMed1997

Single-dose pharmacokinetics of teicoplanin during hemodialysis therapy using high-flux polysulfone membranes.

Teicoplanin is a new glycopeptide antibiotic with potent activity against Gram-positive bacteria. It has been considered to be non-dialyzable due to its high molecular weight (1875-1891 d) and high protein binding (89%). Therefore, a reduced dose was recommended for patients on hemodialysis therapy, with the loading dose being followed by a considerably lower maintenance dose and/or extension of the interval between doses. The present study was performed to evaluate the pharmacokinetics of teicoplanin during hemodialysis therapy using high flux membranes. The pharmacokinetic parameters of teicoplanin were studied in 15 patients with chronic renal failure on hemodialysis. A high flux polysulfone membrane (ultrafiltration coefficient of 40 ml/h/mmHg) was used. Teicoplanin was administered at a dosage of 10 mg.kg-1 body weight in 100 ml isotonic saline solution during the first 10 minutes of hemodialysis therapy. Pharmacokinetic analysis was performed using a three compartment analysis. After a single dose of teicoplanin plasma peak levels were 26.4 +/- 12.0 micrograms/mL (mean +/- SD) after 30 minutes. Teicoplanin concentrations rapidly declined to a nadir of 6.1 +/- 2.5 micrograms/mL at the end of the 3.5-hour session dialysis. Extracorporeal clearance was 39.7 +/- 24.5 mL/min. Removal of 19.3 +/- 7.7% of the drug was estimated if infused during hemodialysis. T 1/2 alpha were 0.37 +/- 0.25 hrs, t 1/2 beta 20.1 +/- 7.1 hrs, and t 1/2 gamma 549.7 +/- 210.5 hrs. We conclude that teicoplanin levels are reduced to a subtherapeutic range during one single high-flux dialysis session if the drug is administered during hemodialysis. Thus, in contrast to previous suggestions relevant amounts of teicoplanin are removed during hemodialysis and thus teicoplanin cannot be viewed as non-dialyzable drug. We recommend obligatory drug monitoring to achieve therapeutic plasma concentrations.

Adult↗