[What’s New in Intensive Care]: 解决抗生素耐药问题的10个建议

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[What’s New in Intensive Care]: 解决抗生素耐药问题的10个建议
2015年05月13日 ⁄ 时讯速递,


Antibiotic resistance has increased dramatically in the past few years and nowadays represents a serious threat to public health [1–3]. Reasons are multiple, the excess in antibiotic consumption being the most important one. Therefore, antibiotic prescription must be carefully discussed for each patient. Unfortunately, antibiotic prescription is still considered as a trivial act in both humans and animals, in both the hospitals and community. Antibiotic resistance is a worldwide issue. The prevalence of Enterobacteriaceae resistant to third generation cephalosporins reaches 70–80 % in several countries, the prevalence of carbapenemases in Klebsiella pneumoniae being more than 50 % in many countries [4, 5] (Fig. 1). In the ESAC network in Europe [6], antibiotic consumption in the community ranges from 11 to 32 DDDs per 1,000 inhabitants per day. Similar differences are seen in other continents. Between 2000 and 2010, consumption of antibiotics increased in 71 countries by 36 %, Brazil, Russia, India, China and South Africa accounting for 76 % of this increase [7]. Animal consumption represents 80 % of total antibiotic consumption. Large differences are seen in the consumption in animals [8]. In Europe, France and The Netherlands were the highest consumers. The Netherlands has been able to reduce its consumption by more than 60 % and France by 35% in the last 5 years.



抗生素耐药问题在过去数年间日趋严重，目前已经成为对公共健康的严重威胁[1-3]。引起抗生素耐药的原因众多，其中最重要的因素是抗生素的过度使用。因此，必须根据每位患者的具体情况决定抗生素的应用。遗憾的是，无论在医院抑或社区，给人或动物开具抗生素处方仍被视为微不足道的小事。抗生素耐药是世界性的难题。一些国家中肠杆菌科细菌对三代头孢菌素耐药比例已达70 – 80%，而很多国家肺炎克雷伯菌产碳青霉烯酶的比例也超过了50% [4,5](图1)。根据欧洲抗生素使用调查(ESAC)网络数据，各国社区的抗生素使用量为每日每1000人11 – 32 DDD。其它大洲也观察到类似差异。2000 – 2010年间，71个国家抗生素总使用量增加36%，其中巴西、俄罗斯、印度、中国和南非占总增加量的76%[7]。动物的抗生素使用量占抗生素总使用量的80%。不同地区动物的抗生素使用量差异极大[8]。在欧洲，法国和荷兰是动物抗生素使用最多的国家。在过去5年间，荷兰的抗生素用量减少了60%以上，法国则减少了35%。



The World Alliance Against Antibiotic Resistance (WAAAR)

世界反抗生素耐药联盟

The WAAAR is an alliance created 2 years ago in order to raise awareness of politicians, policy makers, health care professionals and citizens. It comprises 720 people from 55 different countries, coming from various horizons, including medical doctors from many specialties, veterinarians, pharmacists, nurses, ecologists, environmental specialists, advocacy groups of patients and citizens. It is supported by 145 medical specialties and various groups. The WAAAR proposes the ten following actions.



世界反抗生素耐药联盟在2年前成立。其宗旨是提高政治家、政策制定者、医务工作者及普通民众对抗生素耐药问题的认识。该组织由55个国家的720人组成，其成员来自不同领域，包括不同专科的医生、兽医、药剂师、护士、生态学家、环保学者、患者权益组织及普通民众。目前WAAAR得到了145个医学专科组织和其他组织的支持。WAAAR建议采取以下10项举措：



Awareness of all the stakeholders, including the general public, of the threat represented by antibiotic resistance. Strong cooperation among the WHO, OIE and FAO, which must take the lead in the world program against antibiotic resistance.
所有利益相关方（包括普通公众）充分了解抗生素耐药问题所带来的危害。世界卫生组织(WHO)、世界动物卫生组织(OIE)和联合国粮农组织(FAO)需加强合作，以引领全球反抗生素耐药计划的实施。



Organization, in each country of a financed national plan for the containment of antibiotic resistance, with the involvement of all the actors, including consumers.
在每个已经制定了财政计划遏制抗生素耐药问题的国家中，组织所有相关方面包括用药者的积极参与。



Permanent access to antibiotics of assured quality, in particular in middle- and low-income countries.
保证获得质量可靠的抗生素的固定渠道，尤其在中低收入国家。



Cautious, controlled and monitored approaches to the use of antibiotics (antibiotic stewardship).
对抗生素使用进行谨慎的控制和监测（抗生素管理工作）



A list of ‘‘protected’’ antibiotics must be available in each hospital. These antibiotics can only be prescribed by referents or infectious diseases specialists. Each antibiotic prescription must be carefully balanced according to advantages and risks of the product. The risks include side effects of the drug (early events) and the risk of resistance (late events). Antibiotic therapy must be reserved for bacterial infections. In practice, many viral infections, including those of the upper respiratory tract, are treated with antibiotics. Rapid diagnostic tests would help greatly to differentiate viral and bacterial infections. In the ICU, all these measures are of paramount importance, since 60 to 70 % of the patients are treated with antibiotics. A systematic re-evaluation must be performed and a de-escalation must be systematically discussed [9]. The antibiotic dose must be increased because of particularities of PK/PD parameters in ICU patients. Combination therapy must be applied rarely and limited to therapy of ventilator-associated pneumonia, severe sepsis and septic shock. The duration of antibiotic therapy must be reduced as much as possible [10].

每家医院均应设立“保护性使用”抗生素名单。只有特殊人群或感染科专家才能开具这些抗生素。开具抗生素时均需仔细权衡获益和风险。抗生素的风险包括药物副作用（早期事件）和耐药风险（晚期事件）。抗生素必须限于细菌性感染的治疗。但在实践中，包括上呼吸道感染在内的很多病毒感染均应用了抗生素。快速诊断性检验有助于鉴别细菌和病毒感染。在ICU中，约60 – 70%的患者接受抗生素治疗，这些措施就显得尤为重要。必须对抗生素的疗效进行系统的再评价，并讨论降阶梯治疗的可行性[9]。对于ICU患者，由于药代动力学和药效学的特殊性，应用抗生素时需增加剂量。应当严格控制抗生素的联合使用，仅限于呼吸机相关肺炎、严重全身性感染和感染性休克的治疗。抗生素治疗的疗程应尽量缩短[10]。



Antibiotherapy in animals is also an important issue. Antibiotic usage as a growth factor, which is implemented in many countries, including the USA, must be abandoned (this has been the case in Europe since 2006). Similarly, the prophylactic prescription of antibiotics must be a very rare event. Antibiotics must be prescribed for a precise duration, with an appropriate dosage. Performing a reevaluation at day 2 or 3 is very important. In most cases, the initial antibiotic therapy, which is often empiric, can be altered for drugs with less antibiotic pressure or can be stopped.

动物的抗生素使用也是一个重要问题。包括美国在内的很多国家将抗生素作为生长因子，这种做法必须停止（欧洲在2006年后已经停止了类似做法）。与此相似，预防性抗生素也必须得到限制。抗生素处方必须包括准确的疗程以及合理的剂量。在应用抗生素2 – 3天后进行重新评价至关重要。对于多数病例而言，初始的经验性抗生素治疗可更换为抗生素压力较小的药物或者直接停用。



In developing countries, antibiotics are often available over the counter, without any prescription. This must be combatted.

在发展中国家，抗生素往往可