在第54届欧洲肝脏研究学会年会（EASL2019）的继续教育课程中，前AASLD主席、美国耶鲁大学Guadalupe Garcia-Tsao教授详细剖析了抗生素在肝硬化患者中的应用，包括在哪些情况下应该使用抗生素、使用哪种抗生素以及剂量等。演讲结束后，Garcia-Tsao教授接受了《国际肝病》的采访，就“预防性抗生素治疗”发表了她的见解。

 

《国际肝病》：演讲中您讲到“医生应当是优秀的抗生素管理员”，这句话很有意义，您可以解释一下吗？

 

Garcia-Tsao教授：我们现在面临的问题是对常用抗生素耐药的微生物的出现，这并不只见于肝病领域，而是广泛存在。作为医生，我们都必须进行抗生素管理，我们要熟知在使用抗生素治疗时可能导致耐药细菌出现的危险因素。任何人在使用抗生素时都可能产生多重耐药菌，这可以发生在每一个人身上。因此，重点之一是确保在开始抗生素治疗之前患者的确发生了感染。然后需要选择正确的抗生素，并在适当的时间应用，短疗程应用，这样做是有效的。这就是抗生素管理的一部分。

 

<Hepatology Digest>: You used a very quotable phrase in your talk today at EASL 2109 in Vienna. You said that, “doctors should be good stewards of antibiotics”. Can you define that for us?

 

Dr Garcia-Tsao: The problem we are now having, not only in hepatology, but in general, is the emergence of micro-organisms that are resistant to our most common antibiotics. As physicians, we all have to practice antibiotic stewardship where we are very cognizant of the risk factors of creating these organisms when treating them with antibiotics. Administering antibiotics to anybody and everybody can generate multi-drug resistant organisms, so one of the main issues is being sure that the patient is infected before commencing antibiotic therapy. Then the correct antibiotic needs to be selected, and provided at the proper time, of a short course duration, and that it is effective. This is part of what antibiotic stewardship is about.

 

《国际肝病》：讨论中有学者提出了“预防性应用抗生素”，您表示您并不是这种方法的拥趸，这是为什么？

 

Garcia-Tsao教授：这是我个人的观点。很多指南都强调“预防”，但预防可以导致产生多重耐药菌，因此我支持开发非抗生素方法来预防感染，例如通过改变肠道菌群。我的研究就在向这个方向努力，尝试避免使用抗生素。现在已经存在多重耐药微生物，预防性治疗对这些病原体不会起作用，因此我对于使用抗生素预防性治疗持谨慎态度。

 

当然在某些特定情况下，例如胃肠道出血时，在出血期间短期使用抗生素预防感染是可行的。但是对于感染的一级预防（即患者没有出现感染而要预防感染时），我表示极大的怀疑，因为在我看来，这些患者真的不需要抗生素预防。也没有证据显示这样做可改善患者的生存，而这是我们最终想要看到的——改善生存期。二级预防也未显示能改善生存期，尽管如此，如果患者既往有感染，那么使用抗生素来预防二次感染是说得通的。

 

在我看来，应该接受预防性抗生素治疗的患者是在移植名单上处于前几名、即将接受移植的患者，一些因素使这些患者容易发生感染。他们应该接受短期抗生素治疗。

 

<Hepatology Digest>: In the discussion today, there was talk about prophylactic antibiotics, and you stated you were not a fan of that.

 

Dr Garcia-Tsao: Correct. This is my own opinion. Many guidelines outline prophylaxis. Firstly, prophylaxis can generate multi-drug resistant organisms, so I am a proponent of finding non-antibiotic ways of preventing infections, such as by changing the gut microbiome. My research is directed towards this and the avoidance of antibiotic usage. Now that we do have multi-drug resistant organisms, prophylaxis will not work on those pathogens, so I am wary of using antibiotic prophylaxis. There are certain settings, GI hemorrhage, for example, where short-course antibiotics while the patient is bleeding is justified to prevent infections. But for primary prophylaxis of infections (where there is no prior infection and you want to prevent infection), that is where I have my greatest qualms, because in my mind, these patients really don’t require antibiotic prophylaxis. Use has not been demonstrated to improve survival of patients, and at the end of the day, this is what we need to show – an improvement in survival. Secondary prophylaxis has also not been shown to improve survival, but nevertheless, it makes sense that if a patient has been previously infected, a second infection can be prevented. In my mind, the people who should receive prophylactic antibiotics are those at the top of the transplant list and are about to be transplanted who have criteria that make them prone to infections. They should receive short-term antibiotics.

 

《国际肝病》：您刚才提到肠道微生物组是一种非抗菌治疗，可以展开来谈一谈吗？

 

Garcia-Tsao教授：这方面的尝试有多种方法，例如使用胆汁酸来改变微生物组，粪菌移植，或使用益生菌和益生元来调节肠道菌群和预防细菌转位。这方面目前还不太成功，但我认为研究应该向这个方向努力。

 

<Hepatology Digest>: You mentioned the gut microbiome as a non-antibiotic treatment. Can you expand on that?

 

Dr Garcia-Tsao: Different approaches have been tried for this, using bile acids to change the microbiome, or fecal transplants, or using probiotics and prebiotics to modify the gut flora and prevent translocation. We have not been very successful so far, but I think research efforts should head in that direction.

 

《国际肝病》：针对肝硬化患者，需要应用抗生素时，您会选择哪些抗生素？

 

Garcia-Tsao教授：这取决于患者来自哪里。如果是一例来自社区医院或从家里来的自发性细菌性腹膜炎患者，之前从未使用抗生素，我可能会以三代头孢作为起始治疗。相反，如果患者是在住院期间感染或者不久前刚出院，或者使用过抗生素，那么开始就需要使用更广谱的药物，如哌拉西林-他唑巴坦。

 

<Hepatology Digest>: Specifically in cirrhosis patients where antibiotics need to be used, which antibiotics are your choice?

 

Dr Garcia-Tsao: As I said in my lecture, that depends on where the patient has come from. If a patient is coming with a spontaneous bacterial peritonitis (SBP) from the community or their home and have never seen an antibiotic, then I would probably start a third-generation cephalosporin. If the patient, on the other hand, has acquired the infection while in hospital or has recently been discharged or received previous antibiotics, then you need to start with something much broader like a piperacillin-tazobactam.