Stapleton P, Wu P J, King A, Shannon K, French G, Phillips I
Department of Microbiology, UMDS, London, United Kingdom.
Antimicrob Agents Chemother. 1995 Nov;39(11):2478-83. doi: 10.1128/AAC.39.11.2478.
Among Escherichia coli organisms isolated at St. Thomas's Hospital during the years 1990 to 1994, the frequency of resistance to amoxicillin-clavulanic acid (tested by disk diffusion in a ratio of 2:1) remained constant at about 5% of patient isolates (10 to 15% of the 41 to 45% that were amoxicillin resistant). Mechanisms of increased resistance were determined for 72 consecutively collected such amoxicillin-clavulanic acid-resistant isolates. MICs of the combination were 16-8 micrograms/ml for 51 (71%) of these and > or = 32-16 micrograms/ml for the remainder. The predominant mechanism was hyperproduction of enzymes isoelectrically cofocusing with TEM-1 (beta-lactamase activities, > 200 nmol of nitrocefin hydrolyzed per min per mg of protein) which was found in 44 isolates (61%); two isolates produced smaller amounts (approximately 150 nmol/min/mg) of such enzymes, and two isolates hyperproduced enzymes cofocusing with TEM-2. Eleven isolates produced enzymes cofocusing with OXA-1 beta-lactamase, which has previously been associated with resistance to amoxicillin-clavulanic acid. Ten isolates produced increased amounts of chromosomal beta-lactamase, and four of these additionally produced TEM-1 or TEM-2. Three isolates produced inhibitor-resistant TEM-group enzymes. In one of the enzymes (pI, 5.4), the amino acid sequence change was Met-67-->Val, and thus the enzyme is identical to TEM-34. Another (pI, 5.4) had the substitution Met-67-->Ile and is identical to IRT-I67, which we propose now be given the designation TEM-40. The third (pI, 5.2) had the substitution Arg-241-->Thr; this enzyme has not been reported previously and should be called TEM-41. The rarity and diversity of inhibitor-resistant TEM-group enzymes suggest that they are the result of spontaneous mutations that have not yet spread.
在1990年至1994年期间于圣托马斯医院分离出的大肠杆菌菌株中,对阿莫西林 - 克拉维酸(以2:1的比例通过纸片扩散法检测)的耐药频率在患者分离株中保持恒定,约为5%(在对阿莫西林耐药的41%至45%的菌株中占10%至15%)。对连续收集的72株此类耐阿莫西林 - 克拉维酸的分离株进行了耐药性增加机制的研究。其中51株(71%)该组合的最低抑菌浓度(MIC)为16 - 8微克/毫升,其余菌株的MIC≥32 - 16微克/毫升。主要机制是与TEM - 1等电聚焦的酶过度产生(β - 内酰胺酶活性,每毫克蛋白质每分钟水解硝基头孢菌素>200纳摩尔),在其中44株(61%)中发现;2株产生较少量(约150纳摩尔/分钟/毫克)的此类酶,2株过度产生与TEM - 2等电聚焦的酶。11株产生与OXA - 1β - 内酰胺酶等电聚焦的酶,该酶先前已与对阿莫西林 - 克拉维酸的耐药性相关。10株产生的染色体β - 内酰胺酶量增加,其中4株还额外产生TEM - 1或TEM - 2。3株产生对抑制剂耐药的TEM组酶。在其中一种酶(pI为5.4)中,氨基酸序列变化为Met - 67→Val,因此该酶与TEM - 34相同。另一种(pI为5.4)有Met - 67→Ile的替换,与IRT - I67相同,我们现提议将其命名为TEM - 40。第三种(pI为5.2)有Arg - 241→Thr的替换;该酶此前未见报道,应称为TEM - 41。对抑制剂耐药的TEM组酶的罕见性和多样性表明它们是尚未传播的自发突变的结果。