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

Abstract

International audienceCatheter-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

Enterococcus faecalispromotes innate immune suppression and polymicrobial catheter-associated urinary tract infection

“…The enrichment of GO terms associated with immune function within down-regulated genes during co-infection in the presence E. faecalis suggested that we might also observe differential gene expression specifically in genes associated with the cell populations responding to CAUTI [19]. To test this, we examined the Immunological Genome Project (ImmGen) database, which comprises publicly available data from a collection of immune cell types in C57BL/6J mice [13, 26].…”

“…After 24 hours, whole bladders were removed and incubated overnight in RNAlater (Qiagen) to allow complete tissue penetration by the protectant prior to storage at −80°C. RNA was extracted as described [60]. For each sample condition, a total of three sequencing libraries were constructed from 50-200 ng of rRNA-depleted RNA.…”

“…PRJ-NA335539). RNA sequencing results were analyzed as described in [19]. Briefly, reads were quality checked and adapters trimmed with cutadapt-1.4.1 using default parameters.…”

“…In a mouse urinary tract infection (UTI) model, the cellular response to E. faecalis infection is primarily monocytic and is independent of Toll-like receptor (TLR) 2 [16]. In a CAUTI model, the presence of a urinary catheter alone elicits a strong pro-inflammatory response in the bladder composed of neutrophils and monocyte-derived cells [17-19]. Infection of catheterized bladders with E. faecalis results in the development of high titer catheter-associated biofilms and bladder infection, despite the presence of the strong inflammatory response induced by catheterization (19).…”

Nutritional Immunity and Antibiotic Drug Treatments Influence Microbial Composition but Fail to Eliminate Urethral Catheter Biofilms in Recurrently Catheterized Patients

“…Bladder catheterization itself was reported to cause sterile inflammation in a murine model, with CD 45+ neutrophils as the main infiltrating immune cells. Using this model, E. coli and E. faecalis infections were shown to cause urothelial barrier disruption and further immune cell infiltration (27). Pyuria is known to occur in patients with indwelling catheters independent of the symptomology (7).…”