Jones R N, Barry A L, Thornsberry C, Gerlach E H, Fuchs P C, Gavan T L, Sommers H M
Department of Pathology, Kaiser Foundation Laboratory (Oregon Region), Clackamas, Oregon 97015, USA.
J Antimicrob Chemother. 1981 Sep;8 Suppl B:187-211. doi: 10.1093/jac/8.suppl_b.187.
The in-vitro qualities of ceftazidime, as compared to other beta-lactams and three other antimicrobials (amikacin, gentamicin and chloramphenicol), were evaluated in a multilaboratory, multiphasic study in the United States. A total of 12,986 recent clinical isolates were tested by reference dilution methods in six medical centres over 45-60 days. Ceftazidime was superior to the comparison cephalosporin (cefamandole) and comparable in spectrum and activity to gentamicin against Enterobacteriaceae. Of 8038 enteric bacilli tested, over 98% had CTAZ MICs < or = 8 mg/l with a mode of < or = 0.12 mg/l. Only Citrobacter freundii and Enterobacter aerogenes had ceftazidime MIC(90S) in the resistant range ( > or =32 mg/l). Staphylococcus aureus strains were less susceptible to ceftazidime (mode MIC 8 mg/l) compared to cefamandole or gentamicin. Ceftazidime was more effective than cefamandole or gentamicin against the beta-haemolytic streptococci and the pneumococcus. More than 90% of Pseudomonas aeruginosa, most other Pseudomonas spp. and Acinetobacter spp. were inhibited by ceftazidime at concentrations of 8 mg/l. In other comparative studies ceftazidime was found remarkably similar in spectrum to cefotaxime, cefoperazone and moxalactam against the Enterobacteriaceae, staphylococci and Streptococcus spp. Enterobacter cloacae was the only enteric species having ceftazidime MIC90 >8 mg/l. Only cefsulodin (mode MIC 2 mg/l) and cefoperazone (mode MIC 4 mg/l) shared the ceftazidime activity against Ps. aeruginosa. Ceftazidime MIC(50S) for Neisseria gonorrhoeae and Haemophilus influenzae (including beta-lactamase producers) were 0.03-0.06 and 0.015 mg/l, respectively. Ceftazidime was found to be bactericidal against most strains at or one doubling dilution above the MIC, and was relatively unaffected by increasing inoculum concentration (some strain variations). It perfused readily into bacterial cells and was effective against the majority of strains resistant to currently available cephalosporins and aminoglycosides. beta-lactamases of Types I-V and Bacillus cereus failed to significantly hydrolyse ceftazidime. Ceftazidime inhibited only Type I Ent. cloacae beta-lactamase hydrolysis. Disc diffusion tests favour the use of a 30 microg ceftazidime disc for the methods described by the National Committee Clinical Laboratory Standards (NCCLS). Quality control data are presented. Tentative 30 microg disc interpretive criteria, based on susceptible MICs of < or =8 mg/l(> 17 mm) and resistant > or =32 mg/l ( < or =13 mm), resulted in < 1% (false resistance or false susceptible) interpretive error rates. Staph. aureus was the species most commonly found to have strains with indeterminate ceftazidime zones or MICs. We found ceftazidime to possess one of the widest clinically usable antimicrobial spectrum by in-vitro testing of any beta-lactam tested and to be most comparable to broad-spectrum aminoglycosides such as amikacin, gentamicin and tobramycin.
在美国进行的一项多实验室、多阶段研究中,对头孢他啶与其他β-内酰胺类药物以及其他三种抗菌药物(阿米卡星、庆大霉素和氯霉素)的体外特性进行了评估。在45至60天的时间里,六个医疗中心通过参考稀释法对总共12986株近期临床分离株进行了检测。头孢他啶优于对照头孢菌素(头孢孟多),在针对肠杆菌科细菌的谱和活性方面与庆大霉素相当。在8038株肠道杆菌的检测中,超过98%的菌株头孢他啶的最低抑菌浓度(MIC)≤8mg/L,众数≤0.12mg/L。只有弗氏柠檬酸杆菌和产气肠杆菌的头孢他啶MIC90处于耐药范围(≥32mg/L)。与头孢孟多或庆大霉素相比,金黄色葡萄球菌菌株对头孢他啶的敏感性较低(MIC众数为8mg/L)。头孢他啶对β溶血性链球菌和肺炎球菌的效果比头孢孟多或庆大霉素更好。超过90%的铜绿假单胞菌、大多数其他假单胞菌属和不动杆菌属在8mg/L的浓度下被头孢他啶抑制。在其他比较研究中发现,头孢他啶在针对肠杆菌科细菌、葡萄球菌和链球菌属的谱方面与头孢噻肟、头孢哌酮和莫西沙星非常相似。阴沟肠杆菌是唯一一种头孢他啶MIC90>8mg/L的肠道菌。只有磺苄西林(MIC众数为2mg/L)和头孢哌酮(MIC众数为4mg/L)与头孢他啶对铜绿假单胞菌具有相同的活性。头孢他啶对淋病奈瑟菌和流感嗜血杆菌(包括产β-内酰胺酶菌株)的MIC50分别为0.03 - 0.06mg/L和0.015mg/L。发现头孢他啶对大多数菌株在MIC或高于MIC一倍稀释度时具有杀菌作用,并且相对不受接种物浓度增加的影响(存在一些菌株差异)。它很容易渗透到细菌细胞中,并且对大多数对现有头孢菌素和氨基糖苷类耐药的菌株有效。I - V型β-内酰胺酶和蜡样芽孢杆菌不能显著水解头孢他啶。头孢他啶仅抑制I型阴沟肠杆菌β-内酰胺酶的水解。纸片扩散试验支持使用30μg头孢他啶纸片用于美国国家临床实验室标准委员会(NCCLS)描述的方法。给出了质量控制数据。基于≤8mg/L(>17mm)为敏感MIC和≥32mg/L(≤13mm)为耐药的初步30μg纸片解释标准,导致的解释错误率<1%(假耐药或假敏感)。金黄色葡萄球菌是最常发现有头孢他啶抑菌圈或MIC不确定菌株的菌种。通过体外测试,我们发现头孢他啶拥有任何测试过的β-内酰胺类药物中最宽的临床可用抗菌谱之一,并且与广谱氨基糖苷类如阿米卡星、庆大霉素和妥布霉素最为相似。