de Sá Del Fiol F, Rocha De Mattos Filho T, Groppo F C
Pharmacy School, University of Marilia; Piracicaba Dental School, Unicamp, SP/Brazil.
Braz J Infect Dis. 2000 Feb;4(1):36-42.
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.
β-内酰胺酶是细菌对β-内酰胺类抗生素耐药的最常见原因。它们水解β-内酰胺环中的酰胺键，产生没有抗菌特性的酸性衍生物。本研究的目的是通过体外试验和大鼠动物模型，评估克拉维酸与头孢菌素联合使用对产β-内酰胺酶和不产β-内酰胺酶的金黄色葡萄球菌菌株的效果。药物组合的体外试验（MIC）采用标准方法进行。在动物模型中，将大鼠背部进行手术植入聚氨酯海绵以诱导肉芽肿组织形成。7天后，动物接受头孢氨苄、头孢氨苄与克拉维酸、头孢曲松、头孢曲松与克拉维酸或单独的克拉维酸。给药1小时后，取出肉芽肿组织并置于预先接种了10⁸ cfu产或不产β-内酰胺酶金黄色葡萄球菌的培养皿中。在37℃下培养24小时后，测量肉芽肿组织形成的抑菌圈并进行评分以进行统计分析。两项试验（体外——动物模型——和体外试验）均表明，头孢氨苄对不产β-内酰胺酶的金黄色葡萄球菌比头孢曲松更具活性（p<0.01）。对于产β-内酰胺酶的金黄色葡萄球菌，头孢曲松比无活性的头孢氨苄更具活性。与单独使用的头孢菌素相比，克拉维酸与头孢氨苄或头孢曲松的组合对不产β-内酰胺酶的金黄色葡萄球菌具有相似的抗菌活性。当使用产β-内酰胺酶菌株进行测试时，克拉维酸与头孢菌素的组合显示出协同作用。我们得出结论，头孢菌素与克拉维酸的组合可能对由产β-内酰胺酶菌株引起的葡萄球菌感染有用。
