Kuck N A, Jacobus N V, Petersen P J, Weiss W J, Testa R T
Medical Research Division, American Cyanamid Co., Lederle Laboratories, Pearl River, New York 10965.
Antimicrob Agents Chemother. 1989 Nov;33(11):1964-9. doi: 10.1128/AAC.33.11.1964.
Tazobactam (YTR-830H), a novel beta-lactamase inhibitor, was compared with clavulanic acid and sulbactam for enhancement of the activity of piperacillin against beta-lactamase-producing, piperacillin-resistant clinical isolates. Piperacillin MICs were determined in media containing a fixed concentration of 2 or 4 micrograms of the inhibitors per ml. The higher concentration was generally more effective. Tazobactam was superior to sulbactam in enhancing the spectrum and potency of piperacillin. Although the calvulanic acid combination was more potent, tazobactam was effective for a similar spectrum of resistant gram-negative clinical isolates containing beta-lactamase. MICs were reduced to the susceptible range for Escherichia coli, Klebsiella pneumoniae, Proteus spp., Salmonella spp., and Shigella spp. Combinations with tazobactam and sulbactam, but not clavulanic acid, were effective against Morganella spp. Some antagonism of the activity of piperacillin was observed with clavulanic acid but not with tazobactam or sulbactam. The inhibitors were similarly effective with piperacillin against beta-lactamase-positive Staphylococcus spp. and the Bacteroides fragilis group. Piperacillin-tazobactam was more effective against a broader spectrum of gram-negative enteric bacteria than ticarcillin plus clavulanic acid was. Combinations with tazobactam or clavulanic acid had a broader spectrum of activity than combinations with sulbactam against bacteria that produce characterized plasmid-mediated enzymes of clinical significance. In particular, piperacillin with tazobactam or clavulanic acid, but not with sulbactam, inhibited TEM-1, TEM-2, and SHV-1 enzymes. In vitro activity was reflected in vivo. Tazobactam and clavulanic acid were superior to sulbactam in enhancing the therapeutic efficacy of piperacillin in mice infected with beta-lactamase-positive E. coli, K. pneumoniae, Proteus mirabilis, and Staphylococcus aureus. Only combinations with tazobactam and sulbactam were effective against the Morganella infection. Tazobactam has a good potential for enhancing the clinical efficacy of piperacillin.
新型β-内酰胺酶抑制剂他唑巴坦（YTR-830H）与克拉维酸和舒巴坦进行了比较，以评估其增强哌拉西林对产β-内酰胺酶且对哌拉西林耐药的临床分离菌株活性的能力。在每毫升含有固定浓度2微克或4微克抑制剂的培养基中测定哌拉西林的最低抑菌浓度（MIC）。较高浓度通常更有效。在增强哌拉西林的抗菌谱和效力方面，他唑巴坦优于舒巴坦。虽然克拉维酸联合用药的效力更强，但他唑巴坦对含有β-内酰胺酶的类似谱的耐药革兰氏阴性临床分离菌株有效。对于大肠埃希菌、肺炎克雷伯菌、变形杆菌属、沙门菌属和志贺菌属，MIC降至敏感范围。他唑巴坦和舒巴坦的联合用药对摩根菌属有效，但克拉维酸联合用药无效。观察到克拉维酸对哌拉西林的活性有一定拮抗作用，但他唑巴坦和舒巴坦没有。这些抑制剂与哌拉西林对β-内酰胺酶阳性葡萄球菌属和脆弱拟杆菌群同样有效。哌拉西林-他唑巴坦对革兰氏阴性肠道细菌的抗菌谱比替卡西林加克拉维酸更广。与舒巴坦相比，他唑巴坦或克拉维酸联合用药对产生具有临床意义的特征性质粒介导酶的细菌具有更广泛的活性谱。特别是，哌拉西林与他唑巴坦或克拉维酸联合用药可抑制TEM-1、TEM-2和SHV-1酶，但与舒巴坦联合用药则无效。体外活性在体内也有体现。在感染β-内酰胺酶阳性大肠埃希菌、肺炎克雷伯菌、奇异变形杆菌和金黄色葡萄球菌的小鼠中，他唑巴坦和克拉维酸在增强哌拉西林的治疗效果方面优于舒巴坦。只有他唑巴坦和舒巴坦的联合用药对摩根菌感染有效。他唑巴坦在增强哌拉西林临床疗效方面具有良好潜力。
