MICA: Accelerating Development of Infection Diagnostics for Patient Management and Reduction of Antibiotic Misuse

20世纪早期抗生素的发现彻底改变了医疗保健服务，抗生素和其他抗菌剂已成为现代医疗保健不可或缺的一部分。然而，近几十年来，抗生素的使用大幅增加，不仅在医疗保健方面，而且在兽医和农业（牲畜）应用方面。这导致了抗菌素耐药性（AMR）的大幅上升，这在现代医疗保健中形成了一个日益严重的问题，对社会构成了严重威胁。对普通抗生素具有耐药性的感染病例数量正在迅速增加，对几乎所有已知抗生素都具有耐药性的菌株（例如耐甲氧西林金黄色葡萄球菌，MRSA）的细菌感染已造成大量死亡（2012年近300人，资料来源：国家统计局），并给受影响的患者和医疗保健提供者造成严重问题。解决办法似乎很简单：大幅减少抗菌剂的处方。然而，在医疗需要抗微生物药物的情况下，不开处方对病人来说是危险的，也是不道德的，并且可能通过增加传播率进一步对公众产生负面影响。有两种主要类型的感染：病毒和细菌。只有细菌感染可以用抗生素治疗，但两种感染的某些症状是共同的。一个典型的例子是喉咙痛，这可能是由细菌感染（如肺炎链球菌）或病毒感染（如流感）引起的，或者实际上可能是由非感染原因引起的，如心力衰竭。更严重的例子包括脑膜炎，当由细菌感染（脑膜炎球菌病）引起时，需要立即就医，而病毒性脑膜炎往往采取较温和的过程，需要休息和观察脑炎。我们认为，如果有更好的感染诊断，抗菌药物处方可以安全和合乎道德地减少。许多感染是由病毒引起的（因此不能从抗生素中受益），但通常抗生素是作为预防措施而开的，因为没有适当的诊断，医生无法确定感染的来源。虽然目前有一些基于实验室的检测，但这些检测可能需要几天时间才能给出明确的答案，因此在检测结果出来之前就开始了预防性抗生素治疗。在这一研究方案中，我们将开发可由医生本人（即初级保健诊所的全科医生或医院的会诊医生）执行的快速诊断测试，这些测试将在不到15分钟内给出答案，足以在开处方之前通知治疗。因此，该规划将开发的第一个诊断测试将是区分病毒感染和细菌感染。一旦诊断出细菌感染，或者出现表明细菌感染的症状，确定引起感染的细菌菌株是很重要的，因为不同的菌株需要不同的抗生素治疗。因此，本项目旨在开发的第二个诊断测试是测试导致感染的病原体，我们选择了艰难梭菌感染的例子，这是一种导致严重腹泻的常见感染。最后，许多细菌现在对普通抗生素有耐药性，如果已知耐药性的类型，就可以量身定制抗生素治疗以使其有效。因此，将开发的第三种诊断测试是诊断碳青霉烯耐药肠杆菌科（CRE）的一种常见亚型，这是一种常见的抗生素耐药性感染类型。这些快速和准确的检测将减少错误抗生素的处方，这不仅将减少抗生素的使用总量（从而减少抗菌素耐药性），而且还将导致更有效的患者管理。

The discovery of antibiotics early in the 20th century revolutionised healthcare provision and antibiotics and other antimicrobials have become an integral part of modern healthcare. However, in recent decades, the use of antibiotics has increased massively, not only in healthcare provision but also in veterinary and agricultural (live stock) applications. This has led to an enormous rise in antimicrobial resistance (AMR), which is forming an ever-growing problem in modern healthcare, proving a serious threat to society. The number of instances where infections are resistant against common antibiotics is increasing rapidly, and bacterial infections with strains that are resistant to almost all known antibiotics (e.g. meticillin-resistant staphylococcus aureusis, MRSA) have contributed to a significant number of death (almost 300 in 2012, source: Office for National Statistics) and caused significant problems for affected patients and healthcare providers.The solution seems simple: drastically reduce the prescriptions of antimicrobials. However, where antimicrobials are required for medical treatment, withholding prescription is dangerous for the patient and unethical, and could furthermore negatively impact on the general public through increased spreading rates.There are two major types of infections: viral and bacterial. Only bacterial infections can be treated with antibiotics, but certain symptoms are common to both types of infections. A typical example is throat pain, which could be caused by a bacterial infection (e.g. Streptococcus pneumonia) or viral (e.g. influenza), or in fact could be caused by non-infection causes such as heart failure. More critical examples include meningitis, which, when caused by a bacterial infection (meningococcal disease) needs immediate medical attention, while viral meningitis tends to take a milder course requiring rest and observation for encephalitis.We argue that antimicrobial prescriptions can be reduced safely and ethically if better infection diagnosis is available. Many infections are viral in origin (and hence do not benefit from antibiotics), but often antibiotics are prescribed as a precaution as without suitable diagnostics the doctor cannot be sure what the origin of the infection is. Although some laboratory-based tests are currently available, these can take several days to give a clear answer, and hence precautionary antibiotic treatments are started before the test results are available.In this research programme we will develop rapid diagnostic tests that can be performed by the doctor her/himself, i.e. a GP in a primary care clinic or a consultant in a hospital, which will give an answer in less than 15 minutes, quick enough to inform treatment before it is prescribed.The first diagnostic test that this programme will develop will thus be to distinguish between viral and bacterial infections. Once a bacterial infection is diagnosed, or if symptoms are encountered which indicate bacterial infections, it is important to identify the bacterial strain that causes the infection, as different strains require different antibiotic treatments. The second diagnostic test that this project aims to develop is thus to test for pathogen that causes the infections and we have chosen the example of C. difficile infections, a common infection that causes severe diarrhoea. Finally, many bacteria are now resistant to common antibiotics and if the type of resistance is known, the antibiotic treatment can be tailored to be effective. The third diagnostic test that will be developed is thus to diagnose a common subtype of Carbapenem Resistant Enterobacteriaceae (CRE), which is common type of infection with antibiotic resistance. These quick and accurate tests will reduce the prescription of the wrong antibiotics, which will not only reduce to the total amount of antibiotics used (thus reducing AMR), but will also lead to a more effective patient management.