Sir Arnold Theiler's research in 1908/09 led to the discovery of the first rickettsial pathogen, Anaplasma marginale, and set the stage for his development and implementation of an effective live vaccine based on a less virulent strain, A. marginale ss. centrale. His 1910 report, describing A. marginale, is among the classic monographs in infectious disease research, presenting not only observations in exacting detail but also highlighting the deductive reasoning leading to association of a new pathogen with a specific disease. With a centennial perspective and both conceptual frameworks and molecular tools unimaginable in Theiler's time, the significance of several observations in the original report - cyclic bacteremia, strain superinfection, and taxonomic position - is now clear and highlight the broad applicability of key principles of pathogen biology.
Clavulanic acid is an inhibitor of beta-lactamase (penicillinase) and when used with amoxycillin the resulting combination becomes active against most bacteria resistant to amoxycillin through production of beta-lactamase. A total of 551 bacterial isolates from dogs and cats were examined by disc sensitivity testing, which showed that there was amoxycillin resistance particularly among staphylococci (50 per cent), Klebsiella species (97 per cent) and Escherichia coli (28 per cent). A combination of potassium clavulanate and amoxycillin reduced the incidence of resistance to 0.3, 3 and 7 per cent, respectively. Minimum inhibitory concentrations were determined for a number of the isolates and showed marked reductions in the presence of potassium clavulanate. A formulation containing amoxycillin trihydrate and potassium clavulanate (4:1) was dosed to beagles at 12.5 mg/kg. Concentrations of the drugs in blood, tissue fluid and skin showed that both drugs were sufficiently well absorbed and distributed to allow a prediction of efficacy against infections caused by beta-lactamase producing bacteria.
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