Robert Sauermann
Medical University of Vienna
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Featured researches published by Robert Sauermann.
Pharmacology | 2008
Robert Sauermann; Markus Rothenburger; Wolfgang Graninger; Christian Joukhadar
Daptomycin is the first approved member of a new class of antibiotics, namely the cyclic lipopeptides. Daptomycin has rapid bactericidal activity against Gram-positive pathogens. It acts by penetrating into the bacterial cell wall with consecutive formation of pores, loss of electrical membrane potential and inhibition of peptidoglycan synthesis. As the mode of action of daptomycin is ‘concentration-dependent’, the pharmacokinetic/pharmacodynamic indices that correlate best with its activity are the ratios of the peak concentration (Cmax) to minimum inhibitory concentration (MIC) or the area under the curve (24-hour AUC) to MIC. Daptomycin should be administered intravenously once daily, because adverse effects on skeletal muscle associated with an increase in plasma levels of creatine phosphokinase and myopathy were observed more frequently at shorter dosing intervals. Overall, the rate of adverse events during daptomycin therapy is comparable to that of other standard regimens. Daptomycin was shown to be not inferior to antimicrobial standard therapy and therefore was approved for complicated skin and skin structure infections at a dose of 4 mg/kg, for Staphylococcus aureus bacteremia and right-sided endocarditis at a dose of 6 mg/kg. Dosage regimens remain a matter of discussion, and an increase in the currently approved doses from 4–6 to 6–8 mg/kg per day for severe infections seems promising. Though not approved up to now, daptomycin appears to be a treatment alternative for Gram-positive bone and joint infections based on clinical observations. Large international studies showed high susceptibility of relevant Gram-positive pathogens to daptomycin, even in multidrug-resistant strains. Thus, treatment of infections caused by Gram-positive cocci resistant to other antimicrobial drugs is a potential indication of daptomycin. Since glycopeptides and daptomycin have the same target site, there appears to be a risk of reduced susceptibility to both drugs after consecutive use. Therefore, daptomycin should be used with caution for treatment of vancomycin-resistant isolates or after prior vancomycin (glycopeptide) therapy. This review describes the history, mechanism of action, susceptibility, recent discoveries and clinical experience regarding daptomycin, discussing its current role in the field of infectious diseases.
Neuropsychopharmacology | 2008
Julia Sacher; Nilufar Mossaheb; Christoph Spindelegger; Nikolas Klein; T. Geiss-Granadia; Robert Sauermann; Edith Lackner; Christian Joukhadar; Markus Müller; Siegfried Kasper
Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n=14) or ziprasidone 80 mg/day (n=15) for 10 days. A significant decrease (p<0.001) in whole body insulin sensitivity from 5.7 ml/h/kg (=mean, SM=0.4 ml/h/kg) at baseline to 4.7 ml/h/kg (=mean, SM=0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2±0.3 ml/h/kg baseline vs 5.1±0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.
Antimicrobial Agents and Chemotherapy | 2005
Robert Sauermann; Georg Delle-Karth; Claudia Marsik; Ilka Steiner; Markus Zeitlinger; Bernhard X. Mayer-Helm; Apostolos Georgopoulos; Markus Müller; Christian Joukhadar
ABSTRACT The objective of the present study was to evaluate whether cefpirome, a member of the latest class of broad-spectrum cephalosporins, sufficiently penetrates subcutaneous adipose tissue in septic patients. After the administration of the drug at 2 g, tissue cefpirome concentrations in septic patients (n = 11) and healthy controls (n = 7) were determined over a period of 4 h by means of microdialysis. To assess the antibacterial effect of cefpirome at the target site, the measured pharmacokinetic profiles were simulated in vitro with select strains of Staphylococcus aureus and Pseudomonas aeruginosa. The tissue penetration of cefpirome was significantly impaired in septic patients compared with that in healthy subjects. For subcutaneous adipose tissue, the area under the concentration-versus-time curve values from 0 to 240 min were 13.11 ± 5.20 g · min/liter in healthy subjects and 6.90 ± 2.56 g · min/liter in septic patients (P < 0.05). Effective bacterial growth inhibition was observed in all in vitro simulations. This was attributed to the significantly prolonged half-life in tissue (P < 0.05), which kept the tissue cefpirome levels above the MICs for relevant pathogens for extended periods in the septic group. By consideration of a dosing interval of 8 h, the values for the time above MIC (T > MIC) in tissue were greater than 60% for pathogens for which the MIC was ≤4 mg/liter in all septic patients. The present data indicate that cefpirome is an appropriate agent for the treatment of soft tissue infections in septic patients. However, due to the high interindividual variability of the pharmacokinetics of cefpirome in tissue, dosing intervals of not more than 8 h should be preferred to ensure that susceptible bacterial strains are killed in each patient.
Antimicrobial Agents and Chemotherapy | 2005
Robert Sauermann; Rudolf Karch; Herbert Langenberger; Joachim Kettenbach; Bernhard X. Mayer-Helm; Martina Petsch; Claudia Wagner; Thomas Sautner; Rainer Gattringer; Georgios Karanikas; Christian Joukhadar
ABSTRACT The present study was performed to evaluate the ability of fosfomycin, a broad-spectrum antibiotic, to penetrate into abscess fluid. Twelve patients scheduled for surgical or computer tomography-guided abscess drainage received a single intravenous dose of 8 g of fosfomycin. The fosfomycin concentrations in plasma over time and in pus upon drainage were determined. A pharmacokinetic model was developed to estimate the concentration-time profile of fosfomycin in pus. Individual fosfomycin concentrations in abscess fluid at drainage varied substantially, ranging from below the limit of detection up to 168 mg/liter. The fosfomycin concentrations in pus of the study population correlated neither with plasma levels nor with the individual ratios of abscess surface area to volume. This finding was attributed to highly variable abscess permeability. The average concentration in pus was calculated to be 182 ± 64 mg/liter at steady state, exceeding the MIC50/90s of several bacterial species which are commonly involved in abscess formation, such as streptococci, staphylococci, and Escherichia coli. Hereby, the exceptionally long mean half-life of fosfomycin of 32 ± 39 h in abscess fluid may favor its antimicrobial effect because fosfomycin exerts time-dependent killing. After an initial loading dose of 10 to 12 g, fosfomycin should be administered at doses of 8 g three times per day to reach sufficient concentrations in abscess fluid and plasma. Applying this dosing regimen, fosfomycin levels in abscess fluid are expected to be effective after multiple doses in most patients.
Pharmacology | 2006
Claudia Wagner; Robert Sauermann; Christian Joukhadar
Although drainage is considered the gold standard in abscess treatment, abscesses of different sizes and locations have been successfully cured by means of antibiotic treatment alone. The penetration of an antibiotic into an encapsulated purulent lesion is limited and highly dependent on the degree of abscess maturation. In fact, in vivo pharmacokinetic data demonstrate that substantial antibiotic concentrations can be reached within abscesses in humans and animals, provided the choice of an appropriate agent and an optimal dosing regimen. However, the efficacy of antibiotics in pus may be hampered by various factors like low pH, protein binding and degradation by bacterial enzymes. This article provides a comprehensive review on conservative abscess treatment, presenting clinical data on success rates of antibiotic therapy. Antibiotic concentrations measured in abscesses of humans and animals are outlined, and theoretical considerations on the understanding of pharmacokinetics and efficacy of antibiotics in abscesses are discussed.
Journal of Antimicrobial Chemotherapy | 2008
Markus Zeitlinger; Robert Sauermann; Manfred Fille; Johann Hausdorfer; Irmgard Leitner; Markus Müller
OBJECTIVES In contrast to most antimicrobial classes, there is a doubt about the impact of protein binding (PB) on the antimicrobial activity of fluoroquinolones. We set out to evaluate the suitability of previously used models for investigating the influence of PB on bacterial killing by fluoroquinolones. METHODS PB of moxifloxacin and trovafloxacin was determined in Mueller-Hinton broth (MHB) containing different concentrations of human serum or albumin. Bacterial growth curves of Staphylococcus aureus and Pseudomonas aeruginosa were determined in pure serum, pure MHB and MHB containing different amounts of serum or albumin. Killing of both strains at concentrations equal to the MIC was investigated for moxifloxacin and trovafloxacin in MHB and also in medium that showed PB values identical to those of pure serum. RESULTS Frequently used media for investigating the impact of PB, i.e. MHB containing 20% to 70% serum or 4% albumin, did not reach the level of PB achieved in pure serum or significantly hampered bacterial growth compared with pure MHB. PB in MHB containing 12% albumin was identical to that in pure serum but did not impair bacterial growth. Addition of 12% albumin significantly reduced bacterial killing by both fluoroquinolones compared with that found in pure MHB. CONCLUSIONS For fluoroquinolones, standard media might be insufficient to investigate the impact of PB on bacterial killing. MHB containing 12% albumin seems to be a promising medium in this context. For moxifloxacin and trovafloxacin, PB leads to significant reduction of antimicrobial activity.
Clinical Pharmacokinectics | 2009
Andreas Peyrl; Robert Sauermann; Friederike Traunmueller; Amedeo A. Azizi; Mariella Gruber-Olipitz; Astrid Gupper; Irene Slavc
AbstractBackground and objective: Liposomal cytarabine (DepoCyte®) is a slow-release formulation for intrathecal application, ensuring prolonged drug exposure. Although there is an urgent need for new treatment options for infants with leptomeningeal dissemination of a malignant brain tumour, there are no clinical and pharmacokinetic data available on this drug for children aged <3 years. The objective of this pilot study was to determine the feasibility, safety and pharmacokinetics of cytarabine after intrathecal administration of liposomal cytarabine 25 mg in patients aged <3 years. Patients and methods: Six male patients with a mean age of 21 months and CNS primitive neuroectodermal tumours (n = 3) or atypical teratoid/rhabdoid tumours (n = 3) were included. Liposomal cytarabine (25 mg) was administered intraventricularly. One patient also received the drug by lumbar puncture. Dexamethasone was used concomitantly for 3–5 days to prevent arachnoiditis. Cerebrospinal fluid (CSF) and plasma samples were collected before administration of liposomal cytarabine and 1 hour, 12 hours, 24 hours, 1 week and 2 weeks post-dosing. Noncompartmental pharmacokinetic analysis of CSF and plasma was performed. Results: Liposomal cytarabine was generally well tolerated; only grade 2 headache occurred in one patient. After intraventricular administration of cytarabine 25 mg, free and encapsulated drug concentrations above the cytotoxic drug level of 0.1 μg/mL were detectable in the CSF for at least 7 days and up to 14 days post-dosing. The average elimination half-lives were 56.7 hours for encapsulated cytarabine and 59.3 hours for free cytarabine. After intralumbar administration, the elimination half-life of free cytarabine, measured in the ventricular CSF during two courses in one patient, was significantly shorter (32.7 hours). Conclusion: Application of liposomal cytarabine with concomitant dexamethasone appears to be safe and well tolerated in children aged <3 years. Drug exposure in infants aged <3 years after an intraventricular dose of 25 mg is comparable to that after administration of 50 mg in adult patients and 35 mg in older children.
Antimicrobial Agents and Chemotherapy | 2005
Christian Joukhadar; Pejman Dehghanyar; Friederike Traunmüller; Robert Sauermann; Bernhard X. Mayer-Helm; Apostolos Georgopoulos; Markus Müller
ABSTRACT The present study addressed the effect of microcirculatory blood flow on the ability of ciprofloxacin to penetrate soft tissues. Twelve healthy male volunteers were enrolled in an analyst-blinded, clinical pharmacokinetic study. A single intravenous dose of 200 mg of ciprofloxacin was administered over a period of approximately 20 min. The concentrations of ciprofloxacin were measured in plasma and in the warmed and contralateral nonwarmed lower extremities. The microdialysis technique was used for the assessment of unbound ciprofloxacin concentrations in subcutaneous adipose tissue. Microcirculatory blood flow was measured by use of laser Doppler flowmetry. Warming of the extremity resulted in an increase of microcirculatory blood flow by approximately three- to fourfold compared to that at the baseline (P < 0.05) in subcutaneous adipose tissue. The ratio of the maximum concentration (Cmax) of ciprofloxacin for the warmed thigh to the Cmax for the nonwarmed thigh was 2.10 ± 0.90 (mean ± standard deviation; P < 0.05). A combined in vivo pharmacokinetic (PK)-in vitro pharmacodynamic (PD) simulation based on tissue concentration data indicated that killing of Pseudomonas aeruginosa (ATCC 27853 and two clinical isolates) was more effective by about 2 log10 CFU/ml under the warmed conditions than under the nonwarmed conditions (P < 0.05). The improvement of microcirculatory blood flow due to the warming of the extremity was paralleled by an increased ability of ciprofloxacin to penetrate soft tissue. Subsequent PK-PD simulations based on tissue PK data indicated that this increase in tissue penetration was linked to an improved antimicrobial effect at the target site.
Antimicrobial Agents and Chemotherapy | 2013
Richard Schwameis; Z. Erdogan-Yildirim; Mohammad Manafi; Markus Zeitlinger; Sabine Strommer; Robert Sauermann
ABSTRACT Time-kill curve experiments were performed with linezolid, doripenem, tigecycline, moxifloxacin, and daptomycin against Staphylococcus aureus and with colistin, moxifloxacin, and doripenem against Pseudomonas aeruginosa to evaluate the effect of porcine pulmonary surfactant on antimicrobial activity. Pulmonary surfactant significantly impaired the activities of moxifloxacin and colistin. When antibiotics are being developed for respiratory tract infections, the method described here might be used to preliminarily quantify the effect of pulmonary surfactant on antimicrobial activity.
Antimicrobial Agents and Chemotherapy | 2007
Robert Sauermann; Claudia Marsik; Ilka Steiner; Katja Seir; Tuende Cvitko; Markus Zeitlinger; Oswald Wagner; Christian Joukhadar
ABSTRACT To evaluate the effect of fosfomycin on proinflammatory cytokines, a bolus of 2 ng of bacterial lipopolysaccharide/kg of body weight was injected intravenously into healthy volunteers. After 2 h, subjects received 8 g of fosfomycin or placebo in a randomized crossover study design. The resulting concentrations of tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-6 expressed as protein and mRNA levels were almost identical with and without fosfomycin.