Berndt Sjöberg

Clinical Pharmacological Studies with Bacampicillin

Ampicillin is a widely used semisynthetic penicillin with a high activity in vitro against Gram-positive and Gram-negative bacteria. A disadvantage, however, is its incomplete oral absorption, 30–50% of the drug being excreted unchanged in the urine (Rolinson et Sutherland 1973). In attempts to improve absorption, derivatives which are hydrolysed to ampicillin in vivo have been made. Metampicillin and hetacillin, condensation products of ampicillin with formaldehyde and acetone respectively, were reported to give superior blood levels of ampicillin (Franchi et Perraro 1967; Bunn et al. 1966) but this has later been questioned (Sutherland et al. 1972; Sutherland et Robinson 1967). Certain ampicillin esters, such as pivampicillin and talampicillin, are orally well absorbed giving serum levels of ampicillin higher than those obtained with ampicillin itself (Daehne et al. 1970; Clayton et al. 1974; Shiobara et al. 1974). In comparative trials between ampicillin and pivampicillin upper gastrointestinal discomfort appears to be more troublesome while the frequency of diarrhoea seems to be less pronounced with pivampicillin (Wilcox et al. 1973). Preliminary reports from Japan on talampicillin indicate a higher frequency of upper gastrointestinal side effects than normally seen with ampicillin (Gomi et al. 1975).

Pyridines Affecting FFA Mobilization In Vivo

In man an intimate correlation exists between clinical manifestations of atherosclerosis and raised levels of lipids in blood plasma. An increased mobilization of FFA into plasma, which may be caused, e.g. by emotional stress (1, 2, 3), could be one of several factors causing high plasma lipid levels (3, 4). One approach to the prevention and treatment of atherosclerotic disease would be to lower plasma lipid levels by means of drugs able to inhibit FFA mobilization. Nicotinic acid is such an agent (5, 6). Long term administration of this drug lowers elevated levels of triglycerides and cholesterol in plasma (7). However, nicotinic acid has such disadvantages as short duration of action (8) and certain side effects such as flush and gastro-intestinal irritation.

Synergy of mecillinam and clavulanic acid with other beta-lactam antibiotics

SummaryMecillinam was combined with ampicillin, carbenicillin, cloxacillin, and cefalexin and tested in vitro against clinical isolates of gram-negative bacteria. Synergy was frequently found, but test medium and inoculum size affected the extent of synergy. No synergy was obtained for combinations between mecillinam and penicillins against β-lactamase-producingHaemophilus influenzae orNeisseria gonorrhoeae, while combinations of clavulanic acid and penicillins showed strong synergism. Strains resistant to mecillinam were cultured in vitro, but the development of resistance was slower for the combinations than for mecillinam itself.ZusammenfassungKombinationen von Mecillinam mit Ampicillin, Carbenicillin, Cloxacillin und Cephalexin wurden auf ihre Aktivität in vitro gegen in der Klinik isolierte, gramnegative Keime geprüft. Eine synergistische Wirkung zwischen den Komponenten wurde oft gefunden, ihr Ausmaß wurde aber von Nährmedium und Größe der Einsaat beeinflußt. Kombinationen von Mecillinam und Penizillinen zeigten keinen synergistischen Effekt gegen β-Laktamase-produzierendeHaemophilus influenzae undNeisseria gonorrhoeae. Dagegen wurde bei diesen Keimen ein starker Synergismus zwischen Klavulansäure und Penizillinen gefunden. Stämme, die resistent gegenüber Mecillinam sind, konnten in vitro gezüchtet werden, aber ihre Resistenzentwicklung erwies sich für die Mecillinam-Kombinationen langsamer als für Mecillinam selbst.