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: A Tratselas, M Simitsopoulou, A Giannakopoulou, I Dori, S Saoulidis, K Kollios, P Papaioannidou, S Pournaras, E Roilides
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 58 Issue 12 Pg. 7102-11 (Dec 2014) ISSN: 1098-6596 [Electronic] United States
• PMID: 25224003 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Interleukin-6
• Ceftriaxone
• beta-Lactamases

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Bacterial Load (drug effects)
• Ceftriaxone (pharmacology)
• Disease Models, Animal
• Escherichia coli (drug effects, enzymology, genetics)
• Escherichia coli Infections (drug therapy, microbiology, pathology)
• Female
• Gene Expression
• Interleukin-6 (antagonists & inhibitors, biosynthesis)
• Kidney (drug effects, microbiology, pathology)
• Mice
• Mice, Inbred BALB C
• Pyelonephritis (drug therapy, microbiology, pathology)
• Treatment Outcome
• beta-Lactamases (genetics, metabolism)