Tratselas A, Simitsopoulou M, Giannakopoulou A, Dori I, Saoulidis S, Kollios K, Papaioannidou P, Pournaras S, Roilides E
Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece.
Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Aristotle University School of Health Sciences, Thessaloniki, Greece.
Antimicrob Agents Chemother. 2014 Dec;58(12):7102-11. doi: 10.1128/AAC.03974-14. Epub 2014 Sep 15.
Urinary tract infections (UTIs) due to extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae in children are becoming more frequent, and they are commonly treated initially with a second- or third-generation cephalosporin. We developed a murine model of ascending UTI caused by ESBL-producing Escherichia coli. Using this model, we investigated the renal bacterial burden, interleukin-6 (IL-6) expression, and histopathological alterations caused by ESBL- and non-ESBL-producing bacteria after 1, 2, or 6 days with or without ceftriaxone therapy. The renal bacterial burden, IL-6 concentration, and histological inflammatory lesions were not significantly different between mice infected with ESBL- and non-ESBL-producing bacteria without treatment at any of the time points examined. Following ceftriaxone administration, the bacterial burden was eliminated in the kidneys of mice infected with ESBL- and non-ESBL-producing bacteria on the 6th postinfection day. The histological analysis demonstrated that among mice treated with ceftriaxone, those infected with ESBL-producing bacteria had more profound renal alterations than those infected with non-ESBL-producing bacteria on the 6th day (P < 0.001). In comparison, microbiological outcomes did not differ significantly between mice infected with ESBL- and non-ESBL-producing bacteria at any of the time points examined. The effectiveness of ceftriaxone in mice with UTIs due to ESBL-producing E. coli may have therapeutic implications; it is, however, hampered by limited activity on the histopathological lesions, a finding that needs further investigation.
儿童中由产超广谱β-内酰胺酶（ESBL）的肠杆菌科细菌引起的尿路感染（UTIs）越来越常见，通常最初用第二代或第三代头孢菌素进行治疗。我们建立了由产ESBL的大肠杆菌引起的上行性UTI小鼠模型。利用该模型，我们研究了在有或没有头孢曲松治疗的情况下，1天、2天或6天后由产ESBL和不产ESBL的细菌引起的肾脏细菌负荷、白细胞介素-6（IL-6）表达和组织病理学改变。在任何检查时间点，未治疗的感染产ESBL和不产ESBL细菌的小鼠之间，肾脏细菌负荷、IL-6浓度和组织学炎症病变均无显著差异。给予头孢曲松后，感染产ESBL和不产ESBL细菌的小鼠在感染后第6天肾脏中的细菌负荷被消除。组织学分析表明，在接受头孢曲松治疗的小鼠中，感染产ESBL细菌的小鼠在第6天的肾脏改变比感染不产ESBL细菌的小鼠更严重（P < 0.001）。相比之下，在任何检查时间点，感染产ESBL和不产ESBL细菌的小鼠之间微生物学结果没有显著差异。头孢曲松对产ESBL大肠杆菌引起的UTI小鼠的有效性可能具有治疗意义；然而，它对组织病理学病变的活性有限，这一发现需要进一步研究。
