With the extension of indwelling time, double J stent associated urinary tract infections would inevitably occur and become a common complication. As early as 1676, Antonie observed the existence of bacterial biofilm from dental plaque, which widely exists in the natural environment. It was not until 1978 that Costerton J and colleagues[9] first put forward the theories related to biofilms. Bacterial biofilms can be formed on the surface of various implants and internal mucosa and induce the aggravation of drug resistance through a variety of mechanisms. Catheter-related infections mainly play a role in clinical chronic infections.
This study confirmed that the detection rate of biofilm bacteria in double J stent was significantly higher than that in urine, which may due to the lack of normal protective mechanisms of body tissue on the surface of double J stent. In addition, Prior research indicated that salts and other substances in urine were deposited on the double J stent within minutes of double J stent implantation, creating favorable conditions for bacterial colonization. Common pathogens of urinary tract infections, such as Escherichia coli, Proteus, Staphylococcus and Enterococcus, can colonize the surface of ureteral stents within 24 hours[10], and fibrin membrane deposition appears on the catheter within 24 to 48 hours after catheter implantation, which become a scaffold for bacterial migration adhesion[11]. The process of biofilm formation includes several parts: bacterial adhesion to the surface of the implant; formation of microcolonies; maturation of biofilm and dissemination of biofilms.
In the double J-stent samples, there were no significant difference in the proportion of Gram-positive bacteria and Gram-negative bacteria separated from biofilm bacteria versus the urine-cultured pathogens. And our research demonstrated that the detection rate of Gram-negative bacteria was high, Escherichia coli were the most common(18.9% / 19.1%), followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus mirabilis. Moreover, Enterococcus and Staphylococcus accounted for a high proportion of Gram-positive bacteria, which was highly consistent with the common pathogenic bacteria species of urinary system and was basically in line with the previous research results[7, 12]. Escherichia coli was the most common pathogen, which may own to the adhesins distributed at the apex of E.coli cilia could combine with specific receptors on the surface of muco-associated cells and thus remained in the urinary tract for a long time[13]. Undoubtedly, this deserves our vigilance.
The analysis of drug resistance of pathogenic bacteria in our study confirmed that Gram-negative bacilli were extremely resistant to semi-synthetic penicillin and were slightly higher resistance for first, second, and third-generation cephalosporins, quinolones, tetracycline, cotrimoxazole and nitrofurantine. On the contrary, they were extremely sensitive to drugs with β-lactamase inhibitors, fosfomycin tromethamine and carbapenems, which was basically in line with the previous research results[7, 12]. Gram-positive cocci were highly resistant to penicillins, cephalosporins, quinolones, and erythromycin drugs, which own to their unique natural resistance mechanisms. It is noteworthy that higher drug resistance was observed in biofilm bacteria versus urine-cultured pathogens (P < 0.05). The exacerbation of drug resistance of biofilm bacteria may be related to the following factors:①Biofilm plays a barrier role and shows a cluster distribution structure on the whole with a certain gap between the two clusters[14], which can protects the bacteria inside from antibiotics and the body's immune system. ②Some components of the biofilm can alter the permeability of antimicrobial agents. ③The structure of biofilm is heterogeneity with concentration gradients of nutrients and signal molecules in the internal environment. RATH and his workers[15] found that there were always inactive biomolecules at the bottom of the biofilm, which could escape the killing effect of antimicrobial agents by changing into a spore-like state and reducing their metabolism and growth rate.④The quorum-sensing system, anti-immune clearance mechanism, special growth characteristics, and the opening of biofilm resistance genes[16] are also play major roles in the aggravation of drug resistance. Bacterial biofilm mainly consists of glycocalyx, extracellular DNA(eDNA), lipids, and proteins and imipenem can play an anti-biofilm role by reducing the eDNA component of the biofilm[17]. However, β-lactamase is also presented in ground substance of biofilm[18], which may lead to a lower susceptibility of imipenem or meropenem to carbapenem-resistant strains. Through these resistance pathways, biofilm bacteria can survive in antibiotics with concentrations of 1,000–1,500 times higher than that in which the floating bacteria can be eliminated, causing great difficulties in clinical treatment.
The more severe the infections of biofilm bacteria, the more attention is paid to the risk factors. Our analysis further showed that patients with advanced age, less water intake, long-term catheterization, or accompanied by underlying diseases had a higher incidence of biofilm bacteria associated infections. Scholars have found that the formation of bacterial biofilm is positively correlated with catheter implantation time, immune dysfunction, diabetes, etc., and serum creatinine greater than 176µmol/L and long operation time are risk factors[19], which is similar to our research results. Degeneration of organ function in the elderly, chronic malnutrition and decreased of the number and function of immune cells in person with hypoproteinemia, insufficient urine volume due to chronic inadequate water intake, and the indiscriminate use of antibiotics, these factors all provide conditions for bacterial propagation. Previous studies have confirmed that high glucose environment can promote the formation of staphylococcal biofilm[20]. In addition, hydronephrosis and acute kidney injury caused by upper urinary tract obstruction can also provide conditions for biofilm bacteria associated infections through the production of a large number of metabolites and lipid peroxidation. Relevant evidence also demonstrated that hydronephrosis and acute renal insufficiency can lead to urinary tract infection in patients with upper urinary calculi[21]. Hence, we believe that the prevention of biofilm bacteria associated infections should be carried out in various ways: ①Controlling risk factors of infection in susceptible persons, such as treating the underlying diseases, reducing the time of catheterization, increasing the amount of drinking water, and rationally using antibiotics.②Using antimicrobial materials(coating biomaterials with antibiotics or silver ions) in the hope that meeting the optimal local concentration to prevent bacterial adhesion, which has been shown to be feasible[22, 23].