title: Effect of ceftriaxone on the outcome of murine pyelonephritis caused by extended-spectrum-β-lactamase-producing Escherichia coli.
abstract: 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.
authors.affiliation: Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Tratselas
authors.affiliation: Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Simitsopoulou
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Aristotle University School of Health Sciences, Thessaloniki, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Giannakopoulou
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Aristotle University School of Health Sciences, Thessaloniki, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Dori
authors.affiliation: Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Saoulidis
authors.affiliation: Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Kollios
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Aristotle University School of Health Sciences, Thessaloniki, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Papaioannidou
authors.affiliation: Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Pournaras
authors.affiliation: Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece roilides@med.auth.gr.
authors.forename: E
authors.initials: E
authors.lastname: Roilides
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D058491:Bacterial Load / Q000187:drug effects; D002443:Ceftriaxone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015850:Interleukin-6 / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011704:Pyelonephritis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D015850:Interleukin-6; D001618:beta-Lactamases; D000093242:Interleukin-6 Inhibitors