Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
Int J Antimicrob Agents. 2012 Apr;39(4):283-94. doi: 10.1016/j.ijantimicag.2011.12.012. Epub 2012 Mar 3.
Resistance trends have changed greatly over the 14 years (1997-2011) whilst I was Director of the UK Antibiotic Resistance Monitoring and Reference Laboratory (ARMRL). Meticillin-resistant Staphylococcus aureus (MRSA) first rose, then fell with improved infection control, although with the decline of one major clone beginning before these improvements. Resistant pneumococci too have declined following conjugate vaccine deployment. If the situation against Gram-positive pathogens has improved, that against Gram-negatives has worsened, with the spread of (i) quinolone- and cephalosporin-resistant Enterobacteriaceae, (ii) Acinetobacter with OXA carbapenemases, (iii) Enterobacteriaceae with biochemically diverse carbapenemases and (iv) gonococci resistant to fluoroquinolones and, latterly, cefixime. Laboratory, clinical and commercial aspects have also changed. Susceptibility testing is more standardised, with pharmacodynamic breakpoints. Treatments regimens are more driven by guidelines. The industry has fewer big profitable companies and more small companies without sales income. There is good and bad here. The quality of routine susceptibility testing has improved, but its speed has not. Pharmacodynamics adds science, but over-optimism has led to poor dose selection in several trials. Guidelines discourage poor therapy but concentrate selection onto a diminishing range of antibiotics, threatening their utility. Small companies are more nimble, but less resilient. Last, more than anything, the world has changed, with the rise of India and China, which account for 33% of the world's population and increasingly provide sophisticated health care, but also have huge resistance problems. These shifts present huge challenges for the future of chemotherapy and for the edifice of modern medicine that depends upon it.
在我担任英国抗生素耐药性监测和参考实验室（ARMRL）主任的 14 年期间（1997-2011 年），耐药趋势发生了巨大变化。耐甲氧西林金黄色葡萄球菌（MRSA）在感染控制得到改善后先上升后下降，尽管在这些改进之前，一种主要的克隆开始下降。随着结合疫苗的部署，耐药性肺炎球菌的数量也有所下降。如果革兰氏阳性病原体的情况有所改善，那么革兰氏阴性病原体的情况则恶化，（i）耐喹诺酮类和头孢菌素类的肠杆菌科细菌、（ii）产 OXA 碳青霉烯酶的不动杆菌、（iii）具有不同生物化学特性的碳青霉烯酶的肠杆菌科细菌和（iv）对氟喹诺酮类和最近对头孢克肟耐药的淋病奈瑟菌的传播。实验室、临床和商业方面也发生了变化。药敏试验更加标准化，具有药效学折点。治疗方案更多地受到指南的驱动。该行业的大盈利公司减少，小公司没有销售收入增加。这里有好有坏。常规药敏试验的质量有所提高，但速度没有提高。药效学增加了科学，但过度乐观导致了几项试验中剂量选择不当。指南劝阻不良治疗，但将选择集中在越来越少的抗生素上，威胁到它们的效用。小公司更灵活，但适应性较差。最后，最重要的是，世界发生了变化，印度和中国崛起，它们占世界人口的 33%，提供越来越复杂的医疗保健，但也存在巨大的耐药问题。这些变化对未来的化疗和依赖于它的现代医学大厦构成了巨大的挑战。
