Background
Catheter-associated urinary tract infection (CAUTI) is a common nosocomial device-associated infection. Urinary tract infection (UTI) accounts for up to 40% of nosocomial infections and is one of the main types of healthcare-associated infections (HAI). About 80% of UTIs are catheter-associated [
1,
2]. In the United States, approximately 95% of UTIs were associated with the indwelling catheters [
3], and interestingly, 15-25% of patients in short-term hospital care need to be inserted with indwelling urinary catheters [
4]. Every year, there are more than 5 million patients necessitating catheterization therapy [
5] and approximately 1 million patients suffering from CAUTI [
6]. The findings of a European study indicated that 5.4% of patients aged 65 or above required the use of an indwelling urinary catheter [
7].
CAUTI is a highly common infection and comes with considerable risk. The duration of hospitalization owing to CAUTI increased from 2.4 to 5.4 days in the United States [
8]. On average, the costs of diagnosing and treating CAUTI is US$ 589, excluding extension of hospital costs [
9]. Taking into account the expenses of hospitalization, the average cost increases from US$ 2,836 to 3,803 [
10,
11]. The Centers for Disease Control and Prevention (CDC) pointed out that UTI leads to deaths of over 13,000 patients every year in the United States [
12], indicating a growing medical problem.
It is now recognized that the high infection rates were caused by the formation of biofilm on the surface of the catheters that decreases the susceptibility to antibiotics and results in anti-microbial resistance [
8,
13,
14]. The formation of biofilm as a result of extracellular polysaccharide matrix secretions from microorganisms has been demonstrated in clinical studies. Bacterial biofilm is a special honeycomb-shaped structure that forms a very complex ecosystem; magnification of biofilm will reveal microcolonies under the microscope [
15‐
18]. Organisms with biofilm can withstand shear force, pH changes, and antimicrobial agents, and prevent macrophage phagocytosis [
13,
19]. The proximity of cells allows more frequent genetic information exchange than other free cells [
20]. Therefore, antimicrobial resistance genes and strains can be spread easily. With respect to catheters, the formation of biofilm will protect the pathogenic bacteria residing at the urinary tract from antimicrobial medicine and host immune response [
15]. It will then facilitate the growth of bacteria which further complicates the problem of CAUTI [
13].
Recent research focused on the development of preventive methods for biofilm formation and changes, including furanone, furacilinum, silver-coated catheters, in addition to other techniques. [
21‐
24]. Johnson
et al. [
21,
2] discovered that catheters containing silver hydrogel and nitrofurazone coating have excellent effects of inhibiting biofilm formation, but no inhibitory effects for
Pseudomonas aeruginosa. According to the study conducted by CDC, the results of a comparison of patients inserted with silver-coated catheters and standard catheters for one week revealed no difference in bacteriuria prevention [
25]. Silver-bearing catheters can decrease the effect of bacteriuria in a week after indwelling. Burton
et al.[
8] discovered the new oPDM-plus-PS (N, N'-(1,2-phenylene) dimaleimide [oPDM]-plus-protamine sulfate [PS]) coating can inhibit
Pseudomonas aeruginosa and
Staphylococcus epidermidis adhering to the catheters, but now these coated catheters can only provide short-term CAUTI prevention upon urinary catheter insertion [
13]. Recently, Stickler
et al.[
26] revealed that bacteria on the biofilm of catheters produced quorum-sensing signal that can control the genetic expression of forming biofilm. If the signal is blocked, the formation of biofilm can be impeded. For example, the mutant
Pseudomonas aeruginosa in the absence of quorum-sensing signal was unable to produce a three-dimensional biofilm [
27]. An important finding was established regarding iron and the formation of biofilm. Clinical investigations have detected that elements such as iron are necessary nutrients for biofilm formation. The production of catheters without iron is a new development, but it has not been tested in clinical trials [
13]. The use of probiotics can also be considered. Trautner
et al.[
28,
29] observed that the rates of pathogenic bacterial infection and CAUTI were reduced if the catheters were inoculated with the non-pathogenic
Escherichia coli (
E. coli). Although these methods are considerable, there is no conclusive evidence and the cost-effectiveness remains unclear.
The traditional use of JUC applied to the wounds of post-surgery patients has proven to be effective in the hospital and out-patient setting: application of JUC did not result in drug resistance, nor stimulate serious adverse reactions and reduced the average wound healing time of patients [
30]. JUC is composed by nano-manufacture technology, with nano-cations on the nano-scale molecular structure produced and then prepared in water-soluble spray [
31]. JUC achieves antibacterial action on skin and wound surface by physical mechanisms and can therefore be regarded as a physical antimicrobial agent [
31]. Upon application, JUC prevents bacterial growth by forming an invisible, positively charged protective film on the sprayed surface, isolating and eradicating negatively charged pathogenic micro-organisms including bacteria, fungi and viruses [
31,
32].
There is no effective way to prohibit biofilm formation clinically; therefore, there is still an unmet need for the establishment of a new clinical application. In this study, we performed an in vitro test to explore the mechanism of biofilm formation and subsequently conducted a multicenter clinical trial to investigate the efficacy of CAUTI prevention with the application of JUC, a nanotechnology antimicrobial spray.
Acknowledgements
We express our heartfelt thanks for the strong support of Chinese Medical Association Society of Urology. We are also thankful for the close collaborations with Tongji Affiliated Hospital of Tongji Medical College of the Huazhong University of Science & Technology, the Second Hospital of Lanzhou University, Peking University People's Hospital, the Second Military Medical University (Shanghai Changhai Hospital), the First Affiliated Hospital of the Sun Yat-sen University, the Second Affiliated Hospital of the Sun Yat-sen University, the Third Affiliated Hospital of the Sun Yat-sen University, the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, the First Affiliated Hospital of Southern Medical University (Nanfang Hospital), the First Affiliated Hospital of Guangzhou Medical University, General Hospital of Guangzhou Military Command of PLA, Wuhan General Hospital of Guangzhou Military Region, Guangzhou First Municipal People's Hospital, Foshan Hospital of Traditional Chinese Medicine, West China Hospital of the Sichuan University, Daping Hospital of the Third Military Medical University, Xiangya Hospital of the Central-south University, the Second Hospital of Xi'an Jiaotong University, the First Affiliated Hospital of Nanjing Medical University, Nanjing Drum Tower Hospital Affiliated to the Nanjing University Medical School, the Second Affiliated Hospital of Kunming Medical College, Huai'an First Hospital Affiliated to Nanjing Medical University and the Affiliated Hospital of Nantong University.
This article has been published as part of
Journal of Translational Medicine Volume 10 Supplement 1, 2012: Selected articles from the Organisation for Oncology and Translational Research (OOTR) 7th Annual Conference. The full contents of the supplement are available online at
http://www.translational-medicine.com/supplements/10/S1.
Competing interests
The authors state they have no competing interests to declare.
Authors' contributions
QC, NC, JC, JPC, CG, WH, XJ, LL, ZL, SL, XL, PL, LL, XM, LM, WQ, LQ, ZR, XS, WS, YT, PW, XW, DW, ZW, BW, QY, ZY, ZY, YZ, HZ, YZ equally conducted clinical test planning and performance. LWCC, WTYL, MNBC, AYSY and ELYN participated in the writing of the manuscript.