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

ABSTRACT

ß-lactamase enzymes are the most common case of bacterial reistance to ß-lactam antibiotics. They hydrolyse the amide bound in the ß-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 ß-lactamase-producing and nonproducing stains of Staphylococcus aureus using in vitro tests and a rat animal model. In vitro test (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 eight cfu of producing or non-producing ß-lactamase Staphylococcus aureus. After 24h at 37§C, the inhibition zones formad 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 ß-lactamase. S. aureus (p<0.01). Against ß-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 ß-lactamase S. aureus compared to the cephalosporins used alone. When tested using ß-lactamase produzing 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 cauded by ß-lactamase producing strains.