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.
View: Text | PDF
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

×

Figure 2

Innate immune cells robustly migrate into the bladder rapidly after catheterization.

Options: View larger image (or click on image) Download as PowerPoint
Innate immune cells robustly migrate into the bladder rapidly after cath...
Naive C57BL/6 female mice were implanted with catheters. At the indicated hour after catheterization (hpc), bladders were recovered and processed into a single-cell suspension, labeled with antibodies listed in Supplemental Table 6, and acquired on a Sony SP6800 Spectral Analyzer. (A) The total number of cells per bladder at the indicated hpc. (B) Representative dot plots from a mouse 24 or 48 hpc illustrate the gating strategy used to identify immune cell subsets graphed in C and D. (C and D) The total number of the specified cell populations per bladder at indicated hpc. (E) The dot plot (48 hpc) illustrates the gating strategy used to identify NK cells and eosinophils, and the graphs depict the total number of NK cells and eosinophils per bladder at the indicated hpc. (F) The spider plot depicts absolute values in pg/ml of the indicated cytokines at 0 (naive), 1, 3, 6, and 24 hpc. In A and C–E, each dot represents 1 mouse, and the experiment was performed 2 times (n = 6–7 mice per experimental group). In F, the experiment was performed 2 times (n = 5 mice per experimental group). In A and C–F, experiments are pooled. The presence of a catheter was verified at the time of sacrifice, and mice without a catheter were excluded from the analysis. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 for experimental groups compared with the control naive group, Kruskal-Wallis test with Dunn’s post-test to correct for multiple comparisons.