Evaluation in an animal model and in vitro of the combination clavulanic acid and cephalosporins against beta-lactamase producing and nonproducing Staphylococcus aureus strains.

Beta-lactamase enzymes are the most common cause of bacterial resistance to Beta-lactam antibiotics. They hydrolyze the amide bound in the Beta-lactam ring and produce acidic derivatives that have no antibacterial properties. The aim of this study was to evaluate a combination of clavulanic acid with cephalosporins against Beta-lactamase-producing and nonproducing strains of Staphylococcus aureus using in vitro tests and a rat animal model. In vitro tests (MIC) of the drug combination were done using standard methods. In an animal model, rats were submitted to surgical implantation of polyurethane sponges in their backs to induce granulomatous tissue. After seven days, the animals received cephalexin, cephalexin with clavulanic acid, ceftriaxone, ceftriaxone with clavulanic acid or clavulanic acid alone. One hour after the drug administration, granulomatous tissue was removed and placed in Petri dishes previously inoculated with 10(8) cfu of producing or non-producing Beta-lactamase Staphylococcus aureus. After 24h at 37 degrees C, the inhibition zones formed by granulomatous tissue was measured and scored for statistical analysis. Both tests (ex vivo ¿animal model¿ and in vitro) showed that the cephalexin was more active than ceftriaxone against non-producing Beta-lactamase S.aureus (p<0.01). Against Beta-lactamase producing S.aureus, ceftriaxone was more active than cephalexin, which was inactive. Combinations of clavulanic acid with cephalexin or ceftriaxone had similar antimicrobial activity against non-producing Beta-lactamase S.aureus compared to the cephalosporins used alone. When tested using Beta-lactamase producing strains, the combination of clavulanic acid with cephalosporins showed synergism. We conclude that the combination of cephalosporins with clavulanic acid could be useful in staphylococcal infections caused by Beta-lactamase producing strains.