TY - JOUR
TI - Effect of ceftriaxone on the outcome of murine pyelonephritis caused by extended-spectrum-β-lactamase-producing Escherichia coli
AU - Tratselas, A.
AU - Simitsopoulou, M.
AU - Giannakopoulou, A.
AU - Dori, I.
AU - Saoulidis, S.
AU - Kollios, K.
AU - Papaioannidou, P.
AU - Pournaras, S.
AU - Roilides, E.
JO - Antimicrobial Agents and Chemotherapy
PY - 2014
VL - 58
TODO - 12
SP - 7102-7111
PB - American Society for Microbiology
SN - 0066-4804, 1098-6596
TODO - 10.1128/AAC.03974-14
TODO - 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
TODO - 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.
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