The causative PCR ribotypes of Clostridium difficile vary markedly across hospitals throughout Europe, with many types other than the well-known PCR ribotype 027 making headway there, according to a study published online Nov. 16 in Lancet.

In addition, both the overall mortality among patients infected with C. difficile and the mortality specifically related to those infections are “strikingly high,” said Dr. Martijn P. Bauer of the Centre for Infectious Disease Control Netherlands at the National Institute for Public Health and the Environment, Bilthoven, and his associates (Lancet 2010 [doi:10.1016/S0140-6736(10)61266-4]).

Dr. Bauer and his colleagues in 34 European countries performed an international hospital-based survey “to obtain a more complete overview of [C. difficile infection] in Europe and build capacity for diagnosis and surveillance ... both nationally and Europe-wide.” The survey was necessary, the researchers said, because “the attention given to this infection, diagnostic procedures in hospitals, presence and methodology of national surveillance, and availability of typing vary widely across Europe, which hampers comparisons between countries.”

A total of 97 hospitals participated in the survey; 62 (67%) of the participating centers were academic hospitals.

Each hospital submitted detailed data via a Web-based questionnaire on the first 10 cases of C. difficile infection that developed after the study’s start date among patients aged 2 years and older, including data from 3-month follow-up of every patient. Hospitals had been instructed to test for C. difficile both in inpatients and outpatients whose treating physicians suspected the infection and in all inpatients who developed diarrhea 3 days or more after admission.

A total of 509 cases were included in the analysis. The incidence of C. difficile infection varied widely among hospitals, as did the incidence of health-care–associated C. difficile in particular – from a low of 0/10,000 patient-days in Luxembourg to a high of 19/10,000 patient-days in Finland.

Having a high incidence of C. difficile infections (more than 10/10,000 patient-days) was significantly associated with a hospital’s use of first-generation cephalosporins (odds ratio, 7.0), aminopenicillins (OR, 2.7), and second-generation cephalosporins (OR, 2.4).

Surprisingly, many hospitals with high rates of C. difficile infection were in northern and central Europe, areas thought to have low antibiotic use, even during flu season. It might be that there was a heightened awareness of C. difficile in those hospitals, the investigators noted and that more testing for the organism was done in them. The rate of routine testing for C. difficile varied by a factor of 47 in the hospitals that participated in the survey.

A total of 65 different PCR ribotypes were identified in stool samples, including 6 new ones, now labeled types 228 through 232, and 234, Dr. Bauer and his associates wrote.

The most common PCR ribotypes were 014 and 020, which were both found in 19 countries; 001, found in 13 countries, and 078, found in 18 countries. PCR ribotype 027 – the one responsible for a recent epidemic that brought widespread attention to C. difficile – ranked sixth, found in six countries.

“Most patients fitted the previously established risk profile, with almost two-thirds aged 65 years or more, about two-fifths having severe comorbidity, and almost all having received antibiotics during the 3 months before their infection, most commonly cephalosporins, quinolones, and aminopenicillin/beta-lactamase-inhibitor combinations,” the researchers noted.

A total of 101 patients died, including 40 whose deaths were judged to be related to C. difficile infection. Seven patients died directly from C. difficile infection as the primary cause; six of those were aged 75 years or older and had severe comorbidity.

Infection by PCR ribotypes 018 and 056 were significantly associated with complications such as colectomy, ICU admission, or death. Such an association with those PCR ribotypes has not been reported previously, the investigators explained.

In an editorial accompanying Dr. Bauer’s report, Dr. Cirle A. Warren and Dr. Richard I. Guerrant wrote that Dr. Bauer et al. should be commended for their survey of the C. difficile landscape across Europe, where striking increases in infection rates, the need for colectomy and ICU care, and mortality have occurred in the past decade (Lancet 2010 [doi:10.1016/501440-6736(10)61885-5]).

Previously, increases in the number and severity of cases have been attributed to the PCR-ribotype 027, but this study shows a diversity of PCR ribotypes in play, including two types, 018 and 056, that are newly associated with severe complications and death, they said.

An important follow-through to the snapshot of clinically relevant C. difficile provided by this study would be to assess the genotypic and phenotypic resistance patterns of the isolates. “These are the isolates that will probably spill over into the community, the food supply, and animal husbandry – which can also be another source of antibiotic pressure and potential reservoirs for C. difficile – and cause C. difficile infection in those who otherwise have no risk factors,” they noted.

To stay ahead of “costly and deadly outbreaks” such as the 027 epidemic that recently placed C. difficile “back in the limelight,” researchers and clinicians “need to know what is out there and to identify and ameliorate what is driving their increasing frequency and severity,” Dr. Warren and Dr. Guerrant, both of the University of Virginia, Charlottesville, wrote.

The European Centre for Disease Prevention and Control funded the study. The investigators declared no conflicts of interest. Dr. Guerrant reported being on a scientific advisory board for Probiotics and is a cofounder of AIGlutamine.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

《柳叶刀》11月16日在线发表的一项研究显示，欧洲各国医院发现的艰难梭菌PCR核糖型存在显著差别，除了众所周知的PCR核糖型027之外，其他多种PCR核糖型也呈上升势头。此外，艰难梭菌感染患者的总病死率和艰难梭菌感染相关发病率非常高(Lancet 2010 [doi:10.1016/S0140-6736(10)61266-4])。

 

本研究对欧洲34个国家的医院进行了调查，旨在全面了解欧洲的艰难梭菌感染情况，并在这些国家和整个欧洲建立针对性的诊断和监测机制。共97家医院参与调查，其中62家(67%)为学术型医院。调查对象为2岁以上的患者，所有医院通过网络问卷的方式提交研究开始后发生艰难梭菌感染的前10例病例的详细数据以及所有患者3个月的随访数据。要求医院对诊治医生怀疑患有艰难梭菌感染的住院患者和门诊患者以及入院后≥3天发生腹泻的所有住院患者进行艰难梭菌检查。

 

共509例病例被纳入分析。各国医院之间的艰难梭菌感染发生率存在显著差异，医源性艰难梭菌感染发生率的差异尤其显著，在卢森堡最低，为0/10,000患者•日，而在芬兰则高达19/10,000患者•日。艰难梭菌感染高发生率 (＞10/10,000患者•日)与医院应用第一代头孢菌素类[比值比(OR) 7.0]、氨基青霉素类(OR 2.7)和第二代头孢菌素类(OR 2.4)显著相关。欧洲北部和中部被认为是抗生素应用率低的地区(甚至是在流感季节期间)，但这些地区的许多医院却存在较高的艰难梭菌感染发生率。这可能是因为这些地区的医院高度重视艰难梭菌感染，且更常进行这方面的检查。艰难梭菌常规检查率在不同医院间相差47倍。

 

在粪便样本中共检出65种不同的PCR核糖型，其中6种为新型，目前标记为228型~232型及234型。最常见的PCR核糖型为同时在19个国家发现的014和020、在13个国家发现的001以及在18个国家发现的078。第6位为在6个国家发现的PCR核糖型027，该型近期引起的感染疫情使艰难梭菌受到广泛关注。

 

大部分患者具有感染风险，其中近2/3为65岁以上，约2/5存在严重合并症，并且几乎所有患者在感染前3个月内应用抗生素，最常用的抗生素为头孢菌素类、喹诺酮类和氨基青霉素/β-内酰胺酶抑制剂。共101例患者死亡，其中40例死亡被认为与艰难梭菌感染相关。7例死亡由原发性艰难梭菌感染直接引起，其中6例为75岁以上且存在严重合并症。本研究首次发现，PCR核糖型018和056引起的感染与结肠切除术、入住ICU和死亡等并发症显著相关。

 

此前研究显示，PCR核糖型027是导致艰难梭菌感染病例数量增加及感染程度加重的原因，但本研究显示，018和056等多种PCR核糖型也参与其中。

 

本研究由欧洲疾病预防控制中心资助。研究者声明无经济利益冲突。

 

爱思唯尔  版权所有