Deguchi K, Yokota N, Koguchi M, Fukayama S, Nishimura Y, Nakane Y, Oda S, Tanaka S, Kato M, Sato K
Section of Studies, Tokyo Clinical Research Center.
Jpn J Antibiot. 1987 Oct;40(10):1752-61.
Antimicrobial activities of sulbactam/cefoperazone (SBT/CPZ) against 50 fresh clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were compared to those of CPZ, Cefotiam (CTM), Cefotaxime (CTX) and Latamoxef (LMOX). Minimal inhibitory concentrations (MIC's) of SBT and CPZ mixed in a ratio of 1:1 were determined by the dilution method using Mueller-Hinton agar and expressed by absolute concentrations of CPZ. Antimicrobial activities of SBT/CPZ against principally penicillinase (PCase) producing bacteria, i.e., S. aureus, E. coli, K. pneumoniae, P. mirabilis, were superior to those of CPZ alone. The presence of SBT in concentrations around 0.39 approximately 1.56 micrograms/ml clearly enhanced CPZ's antimicrobial activities against these PCase producing strains. The synergistic antimicrobial effects of SBT in combination with CPZ were less pronounced against principally cephalosporinase (CEPase) producing bacteria, i.e., C. freundii, Enterobacter spp., S. marcescens, P. vulgaris, and P. aeruginosa, and exerted with SBT at concentrations around 3.13 approximately 12.5 micrograms/ml. Comparative antimicrobial activities indicated by MIC80's of tested agents showed that SBT/CPZ had more stable activities against bacteria ranging from Gram-positive to Gram-negative bacteria than CTM, CTX and LMOX. MIC's of SBT/CPZ were higher than 25 micrograms/ml against 8% of S. aureus, 18% of C. freundii, 10% of Enterobacter spp., 26% of S. marcescens, 2% of P. vulgaris, and 18% of P. aeruginosa. These resistant strains against which the addition of SBT showed no synergism, may possess other mechanism of resistance than beta-lactamase production. It is concluded that the presence of CPZ resistant strains is an actual current problem and not an imaginary future problem, and that the number of resistant strains against other new cephems which have different chemical structure from CPZ is increasing. When these present bacteriological environments are considered, the appearance of SBT/CPZ in the clinical practice is timely and meaningful.
将舒巴坦/头孢哌酮(SBT/CPZ)对50株新鲜临床分离的金黄色葡萄球菌、大肠埃希菌、肺炎克雷伯菌、弗氏柠檬酸杆菌、肠杆菌属、黏质沙雷菌、奇异变形杆菌、普通变形杆菌和铜绿假单胞菌的抗菌活性,与头孢哌酮(CPZ)、头孢替安(CTM)、头孢噻肟(CTX)和拉氧头孢(LMOX)进行了比较。采用稀释法,使用Mueller-Hinton琼脂,以1:1的比例混合SBT和CPZ,测定其最低抑菌浓度(MIC),并以CPZ的绝对浓度表示。SBT/CPZ对主要产生青霉素酶(PCase)的细菌,即金黄色葡萄球菌、大肠埃希菌、肺炎克雷伯菌、奇异变形杆菌的抗菌活性优于单独使用CPZ。浓度约为0.39至1.56微克/毫升的SBT的存在明显增强了CPZ对这些产生PCase菌株的抗菌活性。SBT与CPZ联合的协同抗菌作用对主要产生头孢菌素酶(CEPase)的细菌,即弗氏柠檬酸杆菌、肠杆菌属黏质沙雷菌、普通变形杆菌和铜绿假单胞菌不太明显,且在SBT浓度约为3.13至12.5微克/毫升时发挥作用。受试药物的MIC80所显示的比较抗菌活性表明,SBT/CPZ对革兰氏阳性菌到革兰氏阴性菌的抗菌活性比CTM、CTX和LMOX更稳定。SBT/CPZ对8%的金黄色葡萄球菌、18%的弗氏柠檬酸杆菌、10%的肠杆菌属、26%的黏质沙雷菌、2%的普通变形杆菌和18%的铜绿假单胞菌的MIC高于25微克/毫升。这些添加SBT后无协同作用的耐药菌株,可能具有除产生β-内酰胺酶以外的其他耐药机制。得出结论,CPZ耐药菌株的存在是当前实际存在的问题,而非想象中的未来问题,且与CPZ化学结构不同的其他新型头孢菌素的耐药菌株数量正在增加。考虑到当前这些细菌学环境,SBT/CPZ在临床实践中的出现是及时且有意义的。