Τίτλος:
Effect of ceftriaxone on the outcome of murine pyelonephritis caused by extended-spectrum-β-lactamase-producing Escherichia coli
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. Copyright © 2014 American Society for Microbiology. All Rights Reserved.
Συγγραφείς:
Tratselas, A.
Simitsopoulou, M.
Giannakopoulou, A.
Dori, I.
Saoulidis, S.
Kollios, K.
Papaioannidou, P.
Pournaras, S.
Roilides, E.
Περιοδικό:
Antimicrobial Agents and Chemotherapy
Εκδότης:
American Society for Microbiology
Λέξεις-κλειδιά:
ceftriaxone; interleukin 6; antiinfective agent; beta lactamase; ceftriaxone; interleukin 6, animal cell; animal experiment; animal model; animal tissue; antibiotic therapy; Article; bacterial load; colony forming unit; controlled study; Escherichia coli infection; extended spectrum beta lactamase producing Escherichia coli; female; fibroblast; histopathology; immunohistochemistry; kidney medulla; lymphocyte; macrophage; monocyte; mouse; neutrophil; nonhuman; outcome assessment; pyelonephritis; treatment response; animal; antagonists and inhibitors; Bagg albino mouse; biosynthesis; disease model; drug effects; enzymology; Escherichia coli; Escherichia coli Infections; gene expression; genetics; kidney; metabolism; microbiology; pathology; pyelonephritis; treatment outcome, Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactamases; Ceftriaxone; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Female; Gene Expression; Interleukin-6; Kidney; Mice; Mice, Inbred BALB C; Pyelonephritis; Treatment Outcome
DOI:
10.1128/AAC.03974-14