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[Lancet Infect Dis专家述评]: 产ESBL肠杆菌科细菌的简单控制措施?
2019年09月18日 研究点评, 进展交流 暂无评论

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Simplified control measures for ESBL-producing Enterobacteriacae?

Jean-Christophe Lucet, Jean-Ralph Zahar

Lancet Infect Dis Published:August 23, 2019 DOI:https://doi.org/10.1016/S1473-3099(19)30412-8

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriacae have disseminated worldwide, with very high prevalence in countries of low and middle income1 and a roughly 10% prevalence in the community and at hospital admission in high-income countries.23 Infections caused by ESBL-producing Enterobacteriacae are associated with higher mortality and morbidity than are infections caused by β-lactamase-susceptible Enterobacteriacae. When compared with other multidrug-resistant organisms, ESBL-producing Enterobacteriacae have the highest prevalence and are an ever-increasing burden in European hospitals.4

How to control the spread of ESBL-producing Entero-bacteriacae has been debated for years.5 Schematically, several experts have argued for a horizontal approach, based on high compliance with hand hygiene and improving environmental cleaning. However, most current recommendations still push for a vertical approach, based on active surveillance culture and contact precautions for colonised patients.6 Contact precautions include wearing gowns and gloves when in direct contact with the patient and are usually associated with placement in a single-bed room.

Placement of patients with ESBL-producing Entero-bacteriaceae in single-bed rooms is also a matter of debate, considering the risk for transmission from a wardmate or directly from a contaminated environment. In The Lancet Infectious Diseases, Marjolein Kluytmans-van den Bergh and colleagues report findings of a cluster-randomised non-inferiority study at 16 hospitals in the Netherlands.7 They showed that, for patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample, an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room: of 275 index patients assigned to a single-bed room strategy, there were 11 (4%) cases of ESBL-producing Enterobacteriaceae transmitted to at least one wardmate, compared with 14 (7%) cases among 188 index patients assigned to a multiple-bed room strategy (crude risk difference 3·4%, 90% CI −0·3 to 7·1). The study had high enrolment of eligible patients and the authors did genomic analysis to assess transmission. The results were robust to sensitivity analyses, including duration of standard precautions before implementing contact precautions and type of ESBL-producing Enterobacteriacae. This study is the first randomised trial to answer the question about single-bed versus multiple-bed rooms, which previously has not been tackled adequately.8

Despite a pragmatic and well-designed study, several limitations should be noted. First, Kluytmans-van den Bergh and colleagues did not assess compliance with hand hygiene and contact precautions. Since compliance is an intermediate process stage between planned measures and their actual effect, we miss the effect of single-bed rooms on compliance with hand hygiene. Second, screening of wardmates occurred within 7 days after known exposure, which could miss positive yet still undetectable rectal colonisation because of low rectal concentration of ESBL-producing Enterobacteriacae. Third, 37 (12%) of 312 patients allocated to the single-bed room strategy and 116 (38%) of 304 patients assigned to the multiple-bed room strategy could not be adequately placed in the planned room, and this non-adherence could have affected the results. The non-inferiority margin was set at 10%, which is large with respect to the 5% observed frequency of transmission in the single-bed room. Non-inferiority would have held true with margins of at least 8% and 5% in per-protocol and intention-to-treat analyses, respectively, but these margins are still large.

These results might be generalisable to health-care facilities with high hand hygiene compliance, a high quality of environmental cleaning, and a low prevalence of ESBL-producers that are not Escherichia coli, such as facilities in the Netherlands. Similar to findings by others,9 Kluytmans-van den Bergh and colleagues noted a higher risk of transmission from patients with ESBL-producing Enterobacteriaceae that were not E coli. Results could, therefore, be less pronounced in other species of ESBL-producing Enterobacteriacae, because environmental contamination is more frequently associated with non-E coli species and might have a role as a secondary reservoir for cross-transmission.10

The study findings accord with European guidelines,11 with a balanced recommendation for putting patients with ESBL-producing non-E coli infections or patients from an epidemic outbreak in single-bed rooms while also enforcing contact precautions. On the other hand, in an endemic situation, with most cases being ESBL-producing E coli infections, standard precautions might be enough, with no need for a single-bed room.11

The study by Kluytmans-van den Bergh and colleagues did not address the question of the role of standard precautions compared with contact precautions for controlling the spread of ESBL-producing Enterobacteriacae and whether the combination of contact precautions and placement in a single-bed room could be synergistic. Findings of a cluster-randomised study3 showed that contact precautions were not superior to standard precautions for control of the spread of ESBL-producing Enterobacteriacae, confirming results of several observational, cohort, and before-and-after studies.12 The fact that only 5% of ESBL-colonised wardmates later had a positive clinical culture in the study by Kluytmans-van den Bergh and colleagues further supports a horizontal approach, with high adherence to hand hygiene required for all patients, irrespective of ESBL-producing Enterobacteriacae status.

Among multidrug-resistant organisms, including meticillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp, and emerging Gram-negative bacilli resistant to carbapenems, ESBL-producing Enterobacteriacae have not received enough attention. This study comes at the perfect time in view of the massive and widespread burden of these microorganisms.

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