Knudsen Per Kristian, Brandtzaeg Petter, Høiby E Arne, Bohlin Jon, Samuelsen Ørjan, Steinbakk Martin, Abrahamsen Tore G, Müller Fredrik, Gammelsrud Karianne Wiger
Department of Paediatric Medicine, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
PLoS One. 2017 Nov 7;12(11):e0187618. doi: 10.1371/journal.pone.0187618. eCollection 2017.
We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the observed phenotypic resistance in all 28 multidrug-resistant E. coli isolates examined.
我们前瞻性地研究了与未接触或低剂量接触抗生素的健康儿童相比，广泛使用抗生素治疗对囊性纤维化（CF）儿童队列和癌症儿童队列中耐抗生素肠杆菌科细菌粪便携带情况的影响。该研究在挪威耐药率较低的环境中进行。对32名CF儿童纵向采集的60份粪便样本、45名癌症儿童的88份样本以及70名健康儿童的127份样本进行了检测。采用直接MIC梯度条法，将Etest条直接应用于接种粪便样本的琼脂平板上，以检测耐药肠杆菌科细菌。对28株多重耐药大肠杆菌分离株的全基因组测序（WGS）数据进行分析，以确定耐药机制。所有研究组对第三代头孢菌素、庆大霉素和环丙沙星的耐药率均较低。纳入研究时，CF组中氨苄西林耐药大肠杆菌和甲氧苄啶-磺胺甲恶唑耐药大肠杆菌的患病率与健康对照组相比分别为58.6%对28.4%（p = 0.005）和48.3%对14.9%（p = 0.001），研究结束时患病率相似。与健康儿童相比，癌症儿童中耐药肠杆菌科细菌的患病率没有显著差异，即使在癌症儿童接受了多疗程广谱抗生素治疗后的研究结束时也是如此。癌症儿童主要接受静脉抗生素治疗，而CF组主要接受口服治疗。我们的观察结果表明，抗生素的给药方式和社区中的总体抗菌耐药水平可能会对抗生素治疗期间肠道肠杆菌科细菌耐药性的出现产生影响。WGS分析检测到了获得性耐药基因和/或染色体突变，这些可以解释所检测的所有28株多重耐药大肠杆菌分离株中观察到的表型耐药性。
