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Biomedical subjects

B A Nies

Publications and source records attributed to B A Nies.

8 recordsLinked to original sources

Comparative activity of cefixime and cefaclor in an in vitro model simulating human pharmacokinetics.

The dependence of the antibacterial activity of the two oral cephalosporins cefixime and cefaclor on pharmacokinetic properties was investigated in an in vitro model using strains of enterobacteria and a streptococcal strain. In the cultures the course of serum concentrations of the respective antibiotic was simulated. The more rapidly attained (1 h) high peak levels (17.5 micrograms/ml) of cefaclor (500 mg dose) in no case showed an advantage over the more slowly reached (3 h) low peak levels (2.5 micrograms/ml) of cefixime (200 mg dose). Cefixime was comparable to cefaclor with respect to its initial killing velocity, whereas it was generally superior with respect to maximum values for reduction of bacterial counts. Due to its long elimination half-life (2.5 h) cefixime prevented regrowth for at least twice as long as cefaclor, which has a short half-life (0.7 h). As a result of its antibacterial activity and pharmacokinetic properties cefixime can be administered less frequently than cefaclor.

Cefaclor

Role of transposition and homologous recombination in the rearrangement of plasmid DNA.

The multi-resistance plasmid pBP16 was used to analyse the variability of R-factors from clinical isolates and the molecular structures and processes involved. The observed rearrangement in pBP16 and its derivatives included inversion, deletion, replicon fusion and dissociation, and transposition. All these events could be traced to the presence and activity of multiple copies of the IS-element IS160 within pBP16. Since IS-elements are common in R-factors, it is likely that they are one of the main reasons for plasmid instability and that they are involved in a major way in plasmid evolution.

DNA Transposable Elements

R1767, an example of the evolution of resistance plasmids.

The Salmonella R-factor system R1767 undergoes frequent rearrangement of its plasmid components. The flux of genetic material within this plasmid system depends on a combination of illegitimate and homologous recombination. The presence of several copies of IS160 and two multiresistance transposons, Tn2410 and Tn2411, are substantial reasons for the observed variations.

Biological Evolution

Evolution of Tn21-related transposons: isolation of Tn2425, which harbours IS161.

The isolation of two multi-resistance transposons, Tn2425 and Tn1831, and their relation to Tn21 and Tn2424, is described. A 1.7 kb segment present in Tn2424 and Tn2425 was identified as an IS element by rec-independent transposition, resulting in a cointegrate structure that carries two direct repeated copies of the IS element. By the isolation of this IS element we demonstrated that transposition is one mechanism leading to sequence variations in Tn21-like structures, especially in the region between the mer operon and the sul gene.

Ampicillin

Evolution of plasmid-coded resistance to broad-spectrum cephalosporins.

A clinical isolate of Klebsiella ozaenae with transferable resistance to broad-spectrum cephalosporins produces a beta-lactamase determined by plasmid pBP60. The beta-lactamase had the same isoelectric point as SHV-1 (7.6). From heteroduplex analysis, an extensive homology between the two bla genes could be deduced; therefore, the new beta-lactamase was designated SHV-2. Enzymatic studies revealed that SHV-2 was able to hydrolyze broad-spectrum cephalosporins due to an increased affinity of these compounds for the enzyme. The assumption that SHV-2 is a natural mutant of SHV-1 was strongly supported by the isolation of a laboratory mutant of SHV-1 that showed activities similar to those of SHV-2.

Cephalosporins