Resistance determinants for beta-lactam antibiotics in laboratory mutants of Streptococcus pneumoniae that are involved in genetic competence.

Laboratory mutants of Streptococcus pneumoniae resistant to either cefotaxime or piperacillin reveal defects in competence development independent of the selective beta-lactam. A resistance determinant ciaH encoding a putative histidine kinase of a two-component signal-transducing system that is also involved in competence regulation was recently identified in cefotaxime-resistant mutants. We show now that the CiaH protein can be phosphorylated by ATP in vitro, and that it also phosphorylates the cognate response regulator CiaR. The mutant C306 containing the CiaH mutation Thr-230-Pro is completely noncompetent. It does not release competence-inducing activity (competence factor) into the medium nor can such an activity be released from the cells. Competence in C306 cannot be induced upon addition of external competence factor, in contrast to the competence-defective piperacillin-resistant mutants P506 and P408. A novel resistance determinant cpoA specific for piperacillin was identified in piperacillin-resistant mutants. CpoA is responsible for the competence defect in P506 but not in P408. The results document a tight link between the action of beta-lactams and competence development in the pneumococcus and confirm that the two beta-lactams piperacillin and cefotaxime act via different primary targets.

The efficacy of pyrantel pamoate against ascarids and hookworms in cats.

The purposes of this study were to evaluate pyrantel pamoate administered orally at 20 mg/kg body weight for the removal of induced or natural infections of Ancylostoma tubaeformae and Toxocara cati in cats and to compare the efficacy of paste (40 mg base/g) and granule (80 mg base/g) formulations. Thirty cats of mixed breeding and various ages with natural and/or induced infections of A. tubaeformae and T. cati were assigned to one of three treatment groups: (1) non-medicated controls; (2) paste formulation at 20 mg base/kg; or (3) granule formulation at 20 mg base/kg. Infections were induced by feeding the cats on carcasses of infected mice. The study was conducted in replicates of at least one animal per treatment per replicate. The study parameters included clinical observations, physical examinations, faecal egg counts and the numbers, species and stages of worms recovered at necropsy. The paste formulation was 99.3% and 99.7% effective in reducing egg counts of Ancylostoma sp. and Toxocara sp. respectively. The granule formulation was 97.7% and 99.9% effective in reducing faecal egg counts of Ancylostoma sp. and Toxocara sp. respectively. When administered in paste form, pyrantel pamoate was 99.5% effective in removing adult Ancylostoma and 100.0% effective against adult Toxocara. The granule formulation was 97.9% effective against Ancylostoma and 100% effective against Toxocara. No toxic effects of either formulation of the drug were noted.