Search

Byline: A. Dalhoff (1), S. Schubert (1), U. Ullmann (1) Abstract: Abstract Antibiotic activity against common respiratory pathogens can be affected by the pH of the medium (in vitro) or the bodily fluid (in vivo) in which bacteria are present. The ionized fraction of an antibiotic is not able to efficiently penetrate bacterial or mammalian membranes, reducing the quantity of molecules able to exert their antibacterial effect resulting in elevated MIC values This study shows that the activity of macrolide antibiotics is particularly sensitive to acidic conditions, whereas a ketolide and fluoroquinolones are much less affected. Furthermore, induction of spontaneous and multistep macrolide resistance is greatly increased in acidic medium. In contrast, telithromycin and moxifloxacin did not induce resistance at any pH. Antibiotics which are less likely to induce resistance in vitro may also be less likely to induce the development of resistance in patients with respiratory tract infections. Author Affiliation: (1) Institute for Infection Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Str. 4, 24105, Kiel, Germany Article History: Registration Date: 01/01/2005

Byline: S. Schubert (1), A. Dalhoff (1), H. Stass (2), U. Ullmann (1) Abstract: Abstract Fluoroquinolones are known to penetrate well into the infectious foci such as lung mucosa, epithelial lining fluid and alveolar macrophages achieving higher target site concentrations than the corresponding serum levels. In order to intergrate the in vitro antibacterial activity and pharmacokinetics of moxifloxacin and levofloxacin, their bactericidal efficacy was assessed by simulating human serum and lung tissue concentrations using Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae as indicator organisms. The bacteria were exposed to fluctuating moxifloxacin and levofloxacin concentrations simulating the drug levels in serum, lung mucosa, epithelial lining fluid and alveolar macrophages. The following parameters were deduced from the kill curves: area under the bactericidal kill curve normalized to the initial inoculum (AUBKC norm), the time needed to reduce the inoculum by 3 log.sub.10 titers, and the initial bactericidal activity. In general, all these three parameters were for all the bacterial isolates having been exposed to moxifloxacin concentration dependent. In contrast, beyond a levofloxacin concentration of optimal bactericidal effect, higher drug concentrations did not further augment the bactericidal activity of levofloxacin. These data demonstrate that not all fluoroquinolones share the same pharmacodynamic targets needed to maximize their antibacterial effect. Author Affiliation: (1) Institute for Infection Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Str. 4, 24105, Kiel, Germany (2) Bayer Healthcare AG, Pharma Research Center, Dept. for Clinical Pharmacology, Wuppertal, Germany Article History: Registration Date: 01/01/2005 Article note: * This study was presented in part at the 22nd International Congress of Chemotherapy, Amsterdam, Netherlands, 2001 and the 13th European Congress of Clinical Microbiology and Infectious Diseases, Glasgow, UK, 2003.

Byline: K.-J. Schaper (1), S. Schubert (2), A. Dalhoff (2) Abstract: Abstract Traditionally, the in vitro activity of antibacterial agents is characterized by their minimal inhibitory concentrations. However, these endpoints are, by nature, discrete and do not provide information on time-dependent killing of the bacteria during the incubation period. Nevertheless, the pharmacodynamic characteristics of antibacterial agents are almost always defined by correlating a static endpoint describing the antibacterial activity of an agent with the pharmacokinetics, describing the time-dependent fluctuation of drug concentrations. This approach is basically a contradiction in itself. Therefore, it would be more logical to correlate pharmacokinetics to in vitro parameters describing the time- and concentration-dependent antibacterial action of an agent. Thus, experimental methods and mathematical models quantifying the decrease in growth rate of a bacterial population due to the action of an antibacterial agent as a function of time and drug concentration have been applied to quantitate their pharmacodynamics. The effect of nine antibacterial agents representing drug classes of penicillins, cephalosporins, penems, macrolides, and fluoroquinolones were mathematically analyzed by using three different but related models. The kill rate, maximal kill, the 50%-effective concentration (EC.sub.50), the Hill coefficient, and concentrations and times needed to obtain a 1,000-fold decrease of the initial number of viable counts were calculated. Both the phenotypic description of the time-kill curves and these five parameters mirror the bacteriostatic or bactericidal activity of all nine agents studied as a function of time and concentration. Therefore, it would be more logical to correlate a parameter quantifying the kinetics of antibacterial in vitro activity with the pharmacokinetics of the drug, thus, replacing static endpoints like minimal inhibitory concentrations. Author Affiliation: (1) Structural Biochemistry, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany (2) Institute for Infection Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Str. 4, 24105, Kiel, Germany Article History: Registration Date: 01/01/2005

The article presents a case study of a 32-year-old African woman who was brought to an emergency department due to abdominal pain. It states that three years earlier, the patient was diagnosed with HIV infection. She also undergone surgery for suspected appendicitis. An antihelminthic treatment with praziquantel and albendazole was given to the patient after three species of intestinal worms, including Schistosoma mansoni and Strongyloides stercoralis, were detected in a stool sample.

Presents a letter to the editor concerning the isolation of a Pantoea dispersa-like strain from a 71 year old woman with acute myeloid leukemia and multiple myeloma.

Purpose: To analyse the therapeutic efficacy of various phytotherapeutics and their antimicrobial compounds with regard to strain specificity and dose dependence., Methods: A representative strain collection of 40 uropathogenic bacteria isolated from complicated and uncomplicated urinary tract infection was subjected to various virulence assays (bacterial growth, mannose-sensitive agglutination, and motility) to determine the therapeutic impact of various compounds with antimicrobial activity. We tested proanthocyanidins (PAC), D-mannose, rosemary extract (Canephron ® ), and isothiocyanates (Angocin ® )., Results: D-mannose efficiently blocked the adhesive properties of all type 1 fimbriae-positive isolates in low concentration (0.2%), but showed no bacteriostatic effect. PAC also actively blocked agglutination, but the concentration varied considerably among isolates. Escherichia coli required the highest concentration (10%), while Enterobacter cloacae responded to low concentrations (0.1%). Allyl isothiocyanates not only impaired agglutination in all tested isolates, but also had a dramatic impact on flagella-mediated motility in Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (p < 0.001). The administration of rosemary extracts revealed a strong bacteriostatic effect in growth assays. All tested strains were strongly inhibited by the addition of 10 μg/ml or 1 μg/ml of purified rosemary extractions with the exception of Serratia marcescens. Morganella morganii responded only to 10 μg/ml., Conclusion: Phytotherapeutics and small-molecular compounds like mannosides have the potential to become an integral part in a multi-modal treatment concept for the treatment and prevention of urinary tract infections. Their efficiency can be optimised when strain specificities and therapeutic concentrations are taken into account.

The influence of Ly146032, a new acidic lipopeptide, on chemotaxis, luminol-dependent chemiluminescence of human polymorphonuclear leukocytes (PMN) and phythemagglutinin induced lymphocyte transformation of murine cells was investigated. At therapeutic range there was no remarkable effect on the parameters tested. Incubation with more than 20 mg/l Ly146032 was followed by depression of chemiluminescence, whilst transformation of maximally PHA stimulated lymphocytes was suppressed by more than 32 mg/l Ly146032.