Import and spread of extended-spectrum β-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study
Import and spread of extended-spectrum β-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study
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DOI：
10.1016/s1473-3099(16)30319-x
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发表时间：
2017-01-01
影响因子：
56.3
通讯作者：
Penders, John
中科院分区：
文献类型：
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作者：
Arcilla, Maris S.;van Hattem, Jame M.;Penders, John
背景 国际旅行有助于抗菌素耐药性的传播。我们调查了国际旅行期间产生超广谱 β-内酰胺酶的肠杆菌 (ESBL-E) 的感染情况，重点关注感染的预测因素、定植持续时间和继续传播的可能性。 方法 在前瞻性多中心 COMBAT 研究中，招募了 2001 名荷兰旅行者和 215 名非旅行家庭成员。在旅行前以及返回后立即和 1、3、6 和 12 个月收集粪便样本和有关人口统计、疾病和行为的调查问卷。筛选样品中是否存在 ESBL-E。对旅行后样本中的 ESBL 基因进行测序，并使用质粒编码的 β-内酰胺酶 TEM、SHV 和 CTX-M 第 1、2、8、9 和 25 组的特异性引物进行 PCR，以确认后续样本中是否存在 ESBL 基因。使用多变量回归分析和数学模型来确定感染和持续携带的预测因素，并确定家庭传播率。这项研究已在 ClinicalTrials.gov 注册，编号为 NCT01676974。结果显示，在 1847 名旅行前 ESBL 阴性且回国后有可用样本的旅行者中，有 633 名 (34.3%) 在国际旅行期间感染了 ESBL-E (95% CI 32.1-36.5)，其中感染数量最多的是前往南亚旅行的旅行者，其中 181 名旅行者中有 136 名 (75.1%， 95% CI 68.4-80.9）。获得 ESBL-E 的重要预测因素是旅行期间抗生素的使用（调整后比值比 2.69，95% CI 1.79-4.05）、返回后持续的旅行者腹泻（2.31，1.42-3.76）以及先前存在的慢性肠道疾病（2.10，1.13-3.90）。旅行后定植的中位持续时间为 30 天 (95% CI 29-33)。 577 只中有 65 只（11.3%）在 12 个月后仍被定植。 CTX-M 酶组 9 ESBL 与持续携带风险显着增加相关（中位持续时间 75 天，95% CI 48-102，p=0.0001）。 168 名家庭成员中有 13 人（7.7%）发现了进一步传播。将 ESBL-E 传播给其他家庭成员的概率为 12% (95% CI 5-18)。 解释 在国际旅行期间和之后，ESBL-E 的获得和传播是大量且令人担忧的。前往 ESBL-E 感染高风险地区的旅行者在返回后 12 个月内应被视为潜在的 ESBL-E 携带者。
Background International travel contributes to the dissemination of antimicrobial resistance. We investigated the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) during international travel, with a focus on predictive factors for acquisition, duration of colonisation, and probability of onward transmission.Methods Within the prospective, multicentre COMBAT study, 2001 Dutch travellers and 215 non-travelling household members were enrolled. Faecal samples and questionnaires on demographics, illnesses, and behaviour were collected before travel and immediately and 1, 3, 6, and 12 months after return. Samples were screened for the presence of ESBL-E. In post-travel samples, ESBL genes were sequenced and PCR with specific primers for plasmid-encoded beta-lactamase enzymes TEM, SHV, and CTX-M group 1, 2, 8, 9, and 25 was used to confirm the presence of ESBL genes in follow-up samples. Multivariable regression analyses and mathematical modelling were used to identify predictors for acquisition and sustained carriage, and to determine household transmission rates. This study is registered with ClinicalTrials.gov, number NCT01676974.Findings 633 (34.3%) of 1847 travellers who were ESBL negative before travel and had available samples after return had acquired ESBL-E during international travel (95% CI 32.1-36.5), with the highest number of acquisitions being among those who travelled to southern Asia in 136 of 181 (75.1%, 95% CI 68.4-80.9). Important predictors for acquisition of ESBL-E were antibiotic use during travel (adjusted odds ratio 2.69, 95% CI 1.79-4.05), traveller's diarrhoea that persisted after return (2.31, 1.42-3.76), and pre-existing chronic bowel disease (2.10, 1.13-3.90). The median duration of colonisation after travel was 30 days (95% CI 29-33). 65 (11.3%) of 577 remained colonised at 12 months. CTX-M enzyme group 9 ESBLs were associated with a significantly increased risk of sustained carriage (median duration 75 days, 95% CI 48-102, p=0.0001). Onward transmission was found in 13 (7.7%) of 168 household members. The probability of transmitting ESBL-E to another household member was 12% (95% CI 5-18).Interpretation Acquisition and spread of ESBL-E during and after international travel was substantial and worrisome. Travellers to areas with a high risk of ESBL-E acquisition should be viewed as potential carriers of ESBL-E for up to 12 months after return.