Livermore D M
London Hospital Medical College, Department of Medical Microbiology, England.
Intensive Care Med. 1994 Jul;20 Suppl 3:S10-3. doi: 10.1007/BF01745245.
beta-Lactamases present the greatest single challenge to beta-lactam antibiotics, including piperacillin. beta-Lactamase-mediated resistance to supposedly beta-lactamase stable agents such as second- and third-generation cephalosporins is now emerging and inhibitor combinations provide an alternative strategy to overcome this problem. The success of this strategy depends on 1) how efficiently the inhibitor inhibits important beta-lactamases, 2) on how much beta-lactamase the bacteria produce, 3) on the drug that is to be protected, 4) on the permeability and intrinsic susceptibility of the organisms and 5) on the conditions, notably the pH. Tazobactam inhibits most of the clinically important beta-lactamases that give piperacillin resistance, except for the Class I types. Piperacillin itself is a relatively easy drug to protect, particularly against the TEM-type enzymes. The result is that tazobactam greatly extends the activity of piperacillin, notably against enterobacteria, but also against staphylococci and anaerobes. The survey confirmed the very broad spectrum of activity of piperacillin/tazobactam. Resistance occurred in about 17% of the Enterobacter, Citrobacter, Serratia group, where we believe it to have been caused by derepressed Class I enzymes since these strains were cross-resistant to third-generation cephalosporins. Otherwise, resistance was largely confined to such organisms as E. faecium and methicillin-resistant staphylococci, which have piperacillin insensitive penicillin-binding proteins. Finally, some question remains on the antistaphylococcal activity of piperacillin/tazobactam, where MIC tests gave a more favorable impression than disc tests. Nevertheless, early clinical results against staphylococcal infection appear good, with a response rate of nearly 90% [15].
β-内酰胺酶是β-内酰胺类抗生素（包括哌拉西林）面临的最大单一挑战。β-内酰胺酶介导的对第二代和第三代头孢菌素等本应稳定的β-内酰胺酶的耐药性正在出现，抑制剂联合用药提供了一种克服这一问题的替代策略。该策略的成功取决于：1）抑制剂抑制重要β-内酰胺酶的效率；2）细菌产生β-内酰胺酶的量；3）要被保护的药物；4）生物体的通透性和固有敏感性；5）条件，尤其是pH值。他唑巴坦可抑制大多数导致哌拉西林耐药的临床重要β-内酰胺酶，但I类酶除外。哌拉西林本身是一种相对容易保护的药物，尤其是针对TEM型酶。结果是他唑巴坦大大扩展了哌拉西林的活性，特别是对肠杆菌科细菌，也包括葡萄球菌和厌氧菌。该调查证实了哌拉西林/他唑巴坦具有非常广泛的活性谱。在肠杆菌属、柠檬酸杆菌属、沙雷菌属中约17%的菌株出现耐药，我们认为这是由I类酶去阻遏引起的，因为这些菌株对第三代头孢菌素交叉耐药。否则，耐药性主要局限于粪肠球菌和耐甲氧西林葡萄球菌等具有对哌拉西林不敏感青霉素结合蛋白的生物体。最后，关于哌拉西林/他唑巴坦的抗葡萄球菌活性仍存在一些疑问，MIC试验比纸片试验给出的结果更有利。尽管如此，针对葡萄球菌感染的早期临床结果似乎良好，有效率近90%[15]。
