Bladder catheterization increases susceptibility to infection that can be prevented by prophylactic antibiotic treatment
Matthieu Rousseau, … , Molly A. Ingersoll, Kimberly A. Kline
Matthieu Rousseau, … , Molly A. Ingersoll, Kimberly A. Kline
Published September 22, 2016
Citation Information: JCI Insight. 2016;1(15):e88178. https://doi.org/10.1172/jci.insight.88178.
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Categories: Research Article Infectious disease Microbiology

Bladder catheterization increases susceptibility to infection that can be prevented by prophylactic antibiotic treatment

Abstract

Catheter-associated urinary tract infections (CAUTI) are the most common hospital-associated infections. Here, we report that bladder catheterization initiated a persistent sterile inflammatory reaction within minutes of catheter implantation. Catheterization resulted in increased expression of genes associated with defense responses and cellular migration, with ensuing rapid and sustained innate immune cell infiltration into the bladder. Catheterization also resulted in hypersensitivity to Enterococcus faecalis and uropathogenic Escherichia coli (UPEC) infection, in which colonization was achieved using an inoculum 100-fold lower than the ID90 for infection of an undamaged urothelium with the same uropathogens. As the time of catheterization increased, however, colonization by the Gram-positive uropathogen E. faecalis was reduced, whereas catheterization created a sustained window of vulnerability to infection for Gram-negative UPEC over time. As CAUTI contributes to poorer patient outcomes and increased health care expenditures, we tested whether a single prophylactic antibiotic treatment, concurrent with catheterization, would prevent infection. We observed that antibiotic treatment protected against UPEC and E. faecalis bladder and catheter colonization as late as 6 hours after implantation. Thus, our study has revealed a simple, safe, and immediately employable intervention, with the potential to decrease one of the most costly hospital-incurred infections, thereby improving patient and health care economic outcome.

Authors

Matthieu Rousseau, H.M. Sharon Goh, Sarah Holec, Matthew L. Albert, Rohan B.H. Williams, Molly A. Ingersoll, Kimberly A. Kline

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Figure 1

Catheterization induces substantial gene expression changes in the bladder.

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Catheterization induces substantial gene expression changes in the bladd...
Female C57BL/6 mice were implanted with a 5-mm silicon catheter, which naive control animals did not receive. After 24 hours, bladders were processed and RNA was recovered. Gene expression analysis was performed as described in the Methods. (A) Summary of gene ontology (GO) enrichment analysis in the top 200 most differentially expressed genes (Padj < 5 × 10-26) that showed increased mRNA levels in catheterized versus noncatheterized bladders. Each data point shows the log2 mean expression ratio between catheterized and noncatheterized animals (x axis). Genes are categorized by annotation to each enriched GO biological process term (y axis). Gray bars show the mean log fold change for genes annotated to each enriched term. See Supplemental Table 4 for further results. (B) To identify differentially expressed genes (d.e.) associated with specificity for a given cell type in the ImmGen data, we calculated the percentage of the top 200 genes that was contained in the top 1% of the distribution of the cell-type–specific enrichment score (51) (solid black line; compared with 100 sets of size- and abundance-matched random genes [summarized by gray lines]). SP, stem and progenitor cells; B, B cells; MF, macrophages; MO, monocytes; GN, granulocytes; T4, CD4+ cells; T8, CD8+ cells; GDT, γδ T cells; SC, stromal cells. See Supplemental Tables 1–5 and Supplemental Figures 1–3 for related analyses. The experiment was performed twice (n = 3 mice per group/experiment). Representative data are shown from one experiment.