Artemisinin—the next generation: Efficacies of artemisone against the malaria parasite are substantially greater than those of the current artemisinin “gold standard”, artesunate. Also, in contrast to most current artemisinins it displays low lipophilicity and negligible neuro‐ and cytotoxicity in in vitro and in vivo assays. Thus, the drug offers promise for use in artemisinin‐based combination therapy.

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Finafloxacin is a new fluoroquinolone antibiotic with the unique property of increasing antibacterial activity at pH values lower than neutral. Whereas its antibacterial activity at neutral pH matches that of other quinolones in clinical use, it is expected to surpass this activity in tissues and body fluids acidified by the infection or inflammation processes. Pharmacokinetic parameters of oral single and multiple doses of up to 800 mg of finafloxacin and safety/tolerability observations were assessed in a phase I study including 95 healthy volunteers. Finafloxacin is well absorbed after oral administration, generating maximum concentrations (C max s) in plasma at least comparable to those of other fluoroquinolones, with a half-life of around 10 h. About one-third of the dose is excreted unchanged in the urine. Renal elimination appears to be a saturable process leading to slight increases of the area under the concentration-time curve extrapolated to infinity and dose normalized (AUC ؕ,norm ) at dosages of 400 mg and above. Safety and tolerability data characterize finafloxacin as a drug with a favorable safety profile. In particular, adverse reactions regarded as class-typical of fluoroquinolones, such as, e.g., electrocardiogram (ECG) changes, neurotoxic effects, or hypoglycemia, were not observed in the study population.

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The peptidoglycan from cell walls of Pseudomonm aeruginosa consists of a macromolecular bag-shaped network of covalently linked repeating units. Metal ions obviously do not participate in conserving its structure, nor could any other component besides glutamic acid, 2,5-diaminopimelic acid, alanine, glucosamine and muramic acid (the latter two possibly being acetylated) be shown to be a constituent of the peptidoglycan sacculus.Approximately one out of four diaminopimelate residues of the repeating units of the peptidoglycan is cross-linked to another unit.The protein covalently bound to the peptidoglycan can be removed from the latter by proteolytic digestion. Lysis experiments proved that Tris buffer and EDTA attack the outer layers of the cell wall which protect the peptidoglycan against being hydrolyzed by lysozyme.The cell wall of gram-negative bacteria represents a very rigid structure, the form of which is maintained by a bag-shaped peptidoglycan macromolecule, the so-called sacculus The work presented here is to show that: a) no other components but those mentioned above could be shown to constitute the peptidoglycan of Ps. aeruginosa ; b) the entire peptidoglycan of one single cell wall is to be regarded as one covalently bound structure ; c) the lipopolysaccharide is not covalently linked to the peptidoglycan and can be resolved from the peptidoglycan merely by the action of detergents ; d) the covalently bound protein moieties are bound to a fraction of the subunits of the peptidoglycan by a trypsinlchymotrypsin-sensitive linkage. MATERIALS AND METHODSThe Pseudoinonus aeruginosa strain OSU 64 was provided by Dr Eagon (Athens, Ga.). Amino acid analyses were performed on a BioCal BC 200 amino acid analyzer. Atomic absorption analyses were carried out with a model 403 Perkin Elmer atomic absorption spectrophotometer. Cells were disrupted by a Biihler cell fractionator using glass beads. Electrophoreses were run on an electropherograph model "Frankfurt" (Hormuth & Vetter, Wiesloch). Cell suspensions in dodecylsulfate were homogenized by means of an Ultra-Turrax (Jahnke & Kunkel, Staufen). All reagents used were analytical grade. Preparation of the PeptidoglycanThe cells were harvested after having reached the stationary phase. Following centrifugation cells were resuspended in ten times their weight of a 40/, solution of sodium dodecylsulfate in water with the homogenizer. After standing for 10min, the homogenation was repeated three times with intermediate standing. The suspension was then centrifuged (20 min, 8000 xg). The sediment was resuspended in 4O/, sodium dodecyIsulfate and the suspension heated for 30 min on a boiling water bath and centrifuged. The sediment was suspended in 0.02 M NaHCO, and dialyzed against 2~ 10 1 of the same buffer, then twice with deionized water. The sediment collected by centrifugation of the dialyzed suspension will be called "cell walls'' hereafter. To remove the covalently bound protein, the cell walls were incubated overnight with trypsin/chymotrypsin (100 pg/ml each...

Twenty patients undergoing orthopaedic surgery for total hip replacement received a single prophylactic intravenous dose of 2.2 g Augmentin (2 g amoxycillin + 200 mg clavulanate). Bone samples removed during the operation were saved for amoxycillin and clavulanate assay. The proportion of inorganic matter in the bone samples was determined to calculate the concentrations of the drugs in their distribution volume. The cortical and cancellous bone were penetrated to a comparable extent by both compounds yielding maximum concentrations at one hour after the end of the infusion. The mean concentrations of amoxycillin in the cortex and spongy layer were 26.0 and 18.2 mg/kg within 1 h, 23.8 and 19.8 mg/kg in the interval from 1 to 2 h after infusion, and 9.2 and 5.9 mg/kg between 2 and 5 h. The corresponding values for clavulanate were 2.3 and 1.6 mg/kg, 2.5 and 1.6 mg/kg, and 1.0 and 0.7 mg/kg, respectively. No postoperative wound infections occurred in these patients.

The combination of amoxicillin and flucloxacillin not only widens the spectrum of pathogenic organisms covered by either of the substances alone; synergy has also been observed, particularly against beta-lactamase-producing organisms. For this reason, the possible interaction of these two penicillins regarding their pharmacokinetics was investigated with respect to therapeutic application. The parameters were calculated on the basis of an open two-compartment model. The highest serum levels of amoxicillin from 551 to 1074 mg/l when 4 g were administered alone, and from 403 to 1133 mg/l when administered together with 1 g flucloxacillin. Flucloxacillin concentrations ranged from 118 to 357 mg/l when administered alone, and from 151 to 226 mg/l in the presence of amoxicillin. Thus, there is no significant difference in the peak levels of either substance when given alone or in combination. The pharmacokinetic parameters of both substances basically do not depend on the presence of the other. A slight decrease was observed in the distribution rate of amoxicillin from the central to the peripheral compartment in the presence of flucloxacillin. Its relevance is questionable, however, since the effect was only minor.