E. Böhni

Total synthesis of the antibiotic polymyxin B1

Es wird über die Synthese des cyclo-Decapeptides 7α, in welchem alle Dab-Reste diel-Konfiguration aufweisen, berichtet. Dieses erwies sich als identisch mit natürlichem Polymyxin B1 (Figur 2).

Total synthesis of two cyclodecapeptides exerting polymyxin-like activity.

Von den vier Cyclodekapeptiden, die als mögliche Strukturen für Polymyxin B1 vorgeschlagen wurden, konnten nun auch die Ringstrukturen mit 7 Aminosäuren, nämlich 7γ und 7α (vgl. Fig.), synthetisiert werden. Diese erwiesen sich im Gegensatz zu 8γ und 8α als hochaktive antimikrobielle Wirkstoffe mit Wirkungsqualitäten der Polymyxine. Ob 7γ oder 7α mit natürlichem Polymyxin B1 identisch ist, wird durch weitere Versuche abgeklärt.

Clinical and Bacteriological Results in Urinary Tract Infections with Single-Dose Ro 13–9904 (Rocephin®)

In two studies, the therapeutic effect of a single intramuscular dose of Ro 13-9904 (Rocephin) of 500 or 250 mg, respectively, was compared with a single intramuscular dose of 80 mg tobramycin in chronic urinary tract infections. 7 days after 500 mg Ro 13-9904, the infections were eradicated in 10 of the 11 patients; 7 days after 250 mg Ro 13-9904, 4 of 11 patients were reinfected with selected resistant Streptococcus faecalis. After tobramycin, 9 of 23 patients were cured. Considering enterococci as dangerous organisms in several respects we recommend a single dose of 500 mg Ro 13-9904 with a satisfactory local tolerance. Tobramycin is unsuitable for single-dose treatment.

Bacteriostatic and Bactericidal Activity of Two Trimethoprim-Sulfonamide Combinations

Sulfamoxole (SDMO) has the same half-life of elimination from human plasma as sulfamethoxazole. Its antibacterial properties, however, are often inferior to those of co-trimoxazole. Its less pronounced antibacterial effect, especially against gram-negative pathogens, also becomes evident in the combination with trimethoprim (TM). The inhibition zones are often smaller around discs containing the same amount of the components SDMO/TM as those with co-trimoxazole and the inhibitory concentrations needed are frequently 2-4 times higher, especially against gram-negative bacteria, such as Escherichia coli and Proteus vulgaris. Accordingly, the curative doses 50% of the new combination are 2-3 times higher than those of co-trimoxazole in experimental infections with E. coli and P. vulgaris in mice. The bactericidal action in human urine, collected after a course of treatment with the combination SDMO/TM in the planned lower dosage, is not only often retarded, but also frequently incomplete in comparison with that in urine after co-trimoxazole in standard dosage. Clinically, this might lead to increased development of resistance or to an increase of recurrent infections.

Synthesen in der Depsipeptid-Reihe, 4. Mitt.: Struktur und mikrobiologische Aktivität in der Enniatin-Reihe

Es wird der Einflus der Ringstruktur, der Ringgrose und der Anzahl der N-Methylgruppen auf die mikrobiologische Aktivitat der Enniatine untersucht. Alle diese Faktoren scheinen fur die Aktivitat wichtig zu sein.