Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Inflamm Bowel Dis. 2013 Jan;19(1):141-50. doi: 10.1002/ibd.22971.
Escherichia coli is increasingly implicated in the pathogenesis of ileal Crohn's disease (ICD), offering a potential therapeutic target for disease management. Empirical antimicrobial targeting of ileal E. coli has advantages of economy and speed of implementation, but relies on uniform susceptibility of E. coli to routinely selected antimicrobials to avoid apparent treatment failure. Therefore, we examined the susceptibility of ileal E. coli to such antimicrobials.
E. coli from 32 patients with ICD and 28 with normal ileum (NI) were characterized by phylogroup, pathotype, antimicrobial susceptibility, and presence of antimicrobial resistance genes.
In all, 17/32 ICD and 12/28 NI patients harbored ≥ 1 E. coli strain; 10/24 E. coli strains from ICD and 2/14 from NI were nonsuscepti-ble to ≥ 1 antimicrobial in ≥ 3 categories (multidrug-resistant). Resistance to amoxicillin/clavulanic-acid, cefoxitin, chloramphenicol, ciprofloxa-cin, gentamicin, and rifaximin was restricted to ICD, with 10/24 strains from 8/17 patients resistant to ciprofloxacin or rifaximin (P < 0.01). Adherent-invasive E. coli (AIEC) were isolated from 8/32 ICD and 5/28 NI, and accounted for 54% and 43% of E. coli strains in these groups. In all, 8/13 AIEC strains from ICD (6/8 patients) versus 2/6 NI (2/5 patients) showed resistance to the macrophage-penetrating antimicrobials ciprofloxacin, clarithromycin, rifampicin, tetracycline, and trimethoprim/sulfamethoxazole. Resistance was associated with tetA, tetB, tetC, bla-(TEM), bla(oxa)-1, sulI, sulII, dhfrI, dhfrVII, ant(3″)-Ia, and catI genes and prior use of rifaximin (P < 0.01).
ICD-associated E. coli frequently manifest resistance to commonly used antimicrobials. Clinical trials of antimicrobials against E. coli in ICD that are informed by susceptibility testing, rather than empirical selection, are more likely to demonstrate valid outcomes of such therapy.
大肠杆菌越来越多地参与到回肠克罗恩病(ICD)的发病机制中,为疾病管理提供了一个潜在的治疗靶点。针对回肠大肠杆菌的经验性抗菌治疗具有经济和实施速度快的优势,但依赖于大肠杆菌对常规选择的抗菌药物的一致敏感性,以避免明显的治疗失败。因此,我们研究了回肠大肠杆菌对这些抗菌药物的敏感性。
我们对 32 例 ICD 患者和 28 例正常回肠(NI)患者的大肠杆菌进行了 phylogroup、pathotype、抗菌药物敏感性和抗菌药物耐药基因的特征分析。
共有 17/32 例 ICD 和 12/28 例 NI 患者携带了≥1 株大肠杆菌;24 株 ICD 大肠杆菌和 14 株 NI 大肠杆菌中有 10 株对≥3 种类别的抗菌药物(多重耐药)不敏感。对阿莫西林/克拉维酸、头孢西丁、氯霉素、环丙沙星、庆大霉素和利福昔明的耐药性仅限于 ICD,17 例患者中有 8 例的 24 株菌株对环丙沙星或利福昔明耐药(P<0.01)。黏附侵袭性大肠杆菌(AIEC)从 32 例 ICD 患者和 28 例 NI 患者中分离出来,分别占这两组大肠杆菌菌株的 54%和 43%。共有 8/13 株 ICD 的 AIEC 菌株(8/8 例患者)与 6/6 株 NI(6/5 例患者)对抗巨噬细胞穿透性抗菌药物环丙沙星、克拉霉素、利福平、四环素和甲氧苄啶/磺胺甲恶唑有耐药性。耐药性与 tetA、tetB、tetC、bla-(TEM)、bla(oxa)-1、sulI、sulII、dhfrI、dhfrVII、ant(3″)-Ia 和 catI 基因以及利福昔明的使用有关(P<0.01)。
与 ICD 相关的大肠杆菌经常表现出对常用抗菌药物的耐药性。基于药敏试验而不是经验性选择的针对 ICD 中大肠杆菌的抗菌药物临床试验更有可能证明这种治疗的有效结果。