Efficacy of organo-selenium-incorporated urinary catheter tubing for in vitro growth inhibition of E. coli, K. pneumoniae, P. aeruginosa, and H. influenzae.

PURPOSE: Catheter-associated urinary tract infections are of significant medical burden in cost, morbidity, and mortality. Experimental selenium-coated medical devices have demonstrated non-toxic in vitro and in vivo antimicrobial activity. While antimicrobial-coated catheters have shown efficacy in preventing CAUTIs, selenium has not been tested in this context. The purpose of this in vitro study is to evaluate selenium-incorporated urinary catheters for inhibition of uropathogenic bacterial growth and biofilm formation. METHODS: Urinary catheters incorporated with 1% organo-selenium and standard (uncoated) catheters were incubated in vitro with E. coli, K. pneumoniae, P. aeruginosa, H. influenzae, and combinations of these bacteria. Growth was evaluated by colony-forming unit count and visualized with confocal laser and scanning electron microscopy. Organo-selenium catheter material integrity was also tested by soaking the tubing in phosphate-buffered saline for 12 weeks at 37 °C. RESULTS: Organo-selenium-incorporated catheters demonstrated total reduction (100%) of in vitro bacterial growth and biofilm formation for E. coli, K. pneumoniae, H. influenzae, and a combination of these species when compared to control. P. aeruginosa growth was inhibited by approximately 4 logs (99.99%). Complete inhibition of E. coli growth was maintained after long-term phosphate-buffered saline soaking. CONCLUSION: The results demonstrate that organo-selenium was stably incorporated into catheter tubing and inhibited bacterial attachment, growth, and biofilm formation for multiple uropathogenic organisms. Furthermore, long-term soaking of organo-selenium tubing in phosphate-buffered saline did not show any decline in bacterial growth inhibition or biofilm formation. These findings suggest that organo-selenium-incorporated catheters may be advantageous in preventing catheter-associated urinary tract infections and warrant further in vivo and clinical evaluation.

Bioengineered phytomolecules-capped silver nanoparticles using Carissa carandas leaf extract to embed on to urinary catheter to combat UTI pathogens.

Rising incidents of urinary tract infections (UTIs) among catheterized patients is a noteworthy problem in clinic due to their colonization of uropathogens on abiotic surfaces. Herein, we have examined the surface modification of urinary catheter by embedding with eco-friendly synthesized phytomolecules-capped silver nanoparticles (AgNPs) to prevent the invasion and colonization of uropathogens. The preliminary confirmation of AgNPs production in the reaction mixture was witnessed by the colour change and surface resonance plasmon (SRP) band at 410nm by UV-visible spectroscopy. The morphology, size, crystalline nature, and elemental composition of attained AgNPs were further confirmed by the transmission electron microscopy (TEM), selected area electron diffraction (SAED), X-ray diffraction (XRD) technique, Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The functional groups of AgNPs with stabilization/capped phytochemicals were detected by Fourier-transform infrared spectroscopy (FTIR). Further, antibiofilm activity of synthesized AgNPs against biofilm producers such as Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were determined by viability assays and micrographically. AgNPs coated and coating-free catheters performed to treat with bacterial pathogen to analyze the mat formation and disruption of biofilm formation. Synergistic effect of AgNPs with antibiotic reveals that it can enhance the activity of antibiotics, AgNPs coated catheter revealed that, it has potential antimicrobial activity and antibiofilm activity. In summary, C. carandas leaf extract mediated synthesized AgNPs will open a new avenue and a promising template to embed on urinary catheter to control clinical pathogens.

Modifiable risk factors for multidrug-resistant Gram-negative infection in critically ill burn patients: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to identify potentially modifiable risk factors for multidrug-resistant Gram-negative colonization or infection in critically ill burn patients. METHODS: A systematic search was conducted of PubMed, Embase, CINAHL, Web of Science and Central (Cochrane). Risk factors including antibiotic use and hospital interventions were summarized in a random-effects meta-analysis. Risk of publication bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation method and funnel plots. RESULTS: A total of 11 studies met the inclusion criteria. We identified several potentially modifiable risk factors and were able to grade their importance based on effect size. Related to prior antibiotic exposure, extended-spectrum cephalosporins (pooled odds ratio (OR) 7.00, 95% confidence interval (CI) 2.77-17.67), carbapenems (pooled OR 6.65, 95% CI 3.49-12.69), anti-pseudomonal penicillins (pooled OR 4.23, 95% CI 1.23-14.61) and aminoglycosides (pooled OR 4.20, 95% CI 2.10-8.39) were most significant. Related to hospital intervention, urinary catheters (pooled OR 11.76, 95% CI 5.03-27.51), arterial catheters (pooled OR 8.99, 95% CI 3.84-21.04), mechanical ventilation (pooled OR 5.49, 95% CI 2.59-11.63), central venous catheters (pooled OR 4.26, 95% CI 1.03-17.59), transfusion or blood product administration (pooled OR 4.19, 95% CI 1.48-11.89) and hydrotherapy (pooled OR 3.29, 95% CI 1.64-6.63) were most significant. CONCLUSION: Prior exposure to extended-spectrum cephalosporins and carbapenems, as well as the use of urinary catheters and arterial catheters pose the greatest threat for infection or colonization with multidrug-resistant Gram-negative organisms in the critically ill burn patient population.

Prevention of urinary catheter-associated infections by coating antimicrobial peptides from crowberry endophytes.

Urinary catheters are extensively used in hospitals, being responsible for about 75% of hospital-acquired infections. In this work, a de novo designed antimicrobial peptide (AMP) Chain201D was studied in the context of urinary catheter-associated infections. Chain201D showed excellent antimicrobial activity against relevant ATCC strains and clinical isolates of bacteria and yeast and demonstrated high stability in a wide range of temperatures, pH and salt concentrations. Moreover, the bactericidal activity of Chain201D immobilized on a model surface was studied against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), some of the most prevalent strains found in urinary catheter-associated infections. Chain201D was successfully tethered to ((1-mercapto-11-undecyl)-(tetra(ethylene glycol) (EG4)) terminated self-assembled monolayers (SAMs), (EG4-SAMs), activated by 1,1'-Carbonyldiimidazole (CDI) at different concentrations. Chain201D surfaces can bind and kill by contact a high percentage of adherent bacteria. These achievements are obtained without any peptide modification (for chemoselective conjugation) and without the use of a spacer. Moreover, increased amounts of immobilized AMP lead to higher numbers of adhered/dead bacteria, revealing a concentration-dependent behaviour and demonstrating that Chain201D has excellent potential for developing antimicrobial urinary catheters.

Evaluation of the potential of colicins to prevent extraluminal contamination of urinary catheters by Escherichia coli.

The feasibility of using colicins to create an antimicrobial lubricant to prevent extraluminal catheter contamination during urinary catheter insertion was assessed. Levels of resistance of uropathogenic Escherichia coli to antibiotics and colicins were compared. The results showed that antibiotics and colicins possess similar frequencies of resistance to a single drug, whereas colicins exhibit significantly lower levels of multidrug resistance (22%) than antibiotics (42%). Colicins and antibiotics showed complementary inhibitory activity, with each targeting different subsets of pathogenic isolates. The collateral impact of these two antimicrobials on genera that are members of the fecal/vaginal/urinary microbiome was assessed, with colicins showing significantly less collateral damage than antibiotics. Using a novel colicin, SR4, minimum inhibitory concentrations (MICs) for a panel of 30 uropathogenic isolates were determined and showed that SR4 achieved the same antimicrobial efficacy as gentamicin using 20-30% less drug. An SR4-impregnated catheter lubricant was created and its ability to prevent extraluminal urinary catheter contamination in vitro was demonstrated. These data indicate that a colicin-impregnated lubricant may provide a viable prophylactic option for preventing catheter-associated urinary tract infections.

Phenazine-1-carboxamide functionalized mesoporous silica nanoparticles as antimicrobial coatings on silicone urethral catheters.

Microbial infections due to biofilms on medical implants can be prevented by antimicrobial coatings on biomaterial surfaces. Mesoporous silica nanoparticles (MSNPs) were synthesized via base-catalyzed sol-gel process at room temperature, functionalized with phenazine-1-carboxamide (PCN) and characterized by UV-visible, FT-IR, DLS, XRD spectroscopic techniques, SEM, TEM, TGA and BET analysis. Native MSNPs, PCN and PCN-MSNPs were evaluated for anti-Candida minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), Candida albicans (C. albicans) biofilms and C. albicans-Staphylococcus aureus (S. aureus) polymicrobial biofilm inhibition. PCN-MSNPs were four-fold effective (MIC 3.9 µg mL-1; 17.47 µM) and MFC (7.8 µg mL-1; 34.94 µM) as compared to pure PCN (MIC 15.6 µg mL-1; 69.88 µM) and MFC (31.2 µg mL-1; 139.76 µM). PCN-MSNPs inhibited in vitro C. albicans MTCC 227-S. aureus MTCC 96 biofilms at very low concentration (10 µg mL-1; 44.79 µM) as compared to pure PCN (40 µg mL-1; 179.18 µM). Mechanistic studies revealed that PCN induced intracellular ROS accumulation in C. albicans MTCC 227, S. aureus MTCC 96 and S. aureus MLS-16 MTCC 2940, reduction in total ergosterol content, membrane permeability, disruption of ionic homeostasis followed by Na+, K+ and Ca2+ leakage leading to cell death in C. albicans MTCC 227 as confirmed by confocal laser scanning micrographs. The silicone urethral catheters coated with PCN-MSNPs (500 µg mL-1; 2.23 mM) exhibited no formation of C. albicans MTCC 227 - S. aureus MTCC 96 and C. albicans MTCC 227 - S. aureus MLS -16 MTCC 2940 biofilms. This is the first report on PCN-MSNPs for use as antimicrobial coatings against microbial adhesion and biofilm formation on silicone urethral catheters.

Spray coating of foley urinary catheter by chlorhexidine-loadedpoly(ε-caprolactone) nanospheres: effect of lyoprotectants, characteristics, and antibacterial activity evaluation.

In this study, chlorhexidine-loaded poly(ε-caprolactone) nanospheres (CHX-NS) were prepared and successfully coated on the urinary catheters. Properties of CHX-NS were evaluated including drug loading content and the nanosphere size. Effects of different lyoprotectants for long-term storage of CHX-NS were also investigated. In vitro release study and antibacterial activity were also conducted using 20 cycles coated-urinary catheters. Results showed that the high-pressure emulsification-solvent evaporation technique provided the drug loading content at 1.14 ± 0.16% and the size of nanospheres was 152 ± 37 nm. The suitable lyoprotectant for long-term storage of CHX-NS was sucrose which provided noticeably no aggregation at the degree of reconstitution at 89.95%. The amount of CHX loading on coated catheters was at 4.55 ± 0.31 mg. Drug release from the coated catheters in artificial urine could be prolonged up to 2 weeks and bacteria proliferation was inhibited up to 14 days. These results suggest that the antimicrobial activity of CHX-NS reduces the adherence of the uropathogens to the catheter surface. Chlorhexidine-loaded polymeric nanospheres were fabricated which can be successfully coated on urinary catheters. These systems have potential use for prolonged antimicrobial applications.

Catheter-associated bacterial flora in patients with benign prostatic hyperplasia: shift in antimicrobial susceptibility pattern.

BACKGROUND: Men with urinary retention secondary to benign prostatic hyperplasia (BPH) are prone to genitourinary infections. Physicians should be aware of the current antimicrobial susceptibility pattern in this population if empirical treatment is needed. The goal of this study was to evaluate variations in prevalence, composition and antimicrobial susceptibility of bacterial flora in men with indwelling catheters subjected to surgery for BPH in chosen time periods since 1994. Necessary changes in empirical therapy were also assessed. METHODS: All patients with indwelling catheters admitted to a single urological center for BPH surgery in the years 1994-1996, 2004-2006, and 2011-2015 were considered. Catheterization times and results of urine cultures from samples collected at admission were evaluated. Susceptibility for selected antimicrobials was compared separately for Gram negative and Gram positive species. For each agent and for their combinations effectiveness of empirical therapy was calculated dividing the number of patients with bacteriuria susceptible to the agents by the total number of patients with bacteriuria. RESULTS: Bacteriuria was present in 70% of 169, 72% of 132, and 69% of 156 men in the respective time periods. The incidence of Gram-positive strains increased from 10 to 37% (P < 0.001). Their susceptibility to amoxicillin/clavulanate was fluctuating (81, 61, 77%; P=NS). No vancomycin-resistant strain was present. Gram-negative flora composition was stable. Their susceptibility decreased to ciprofloxacin (70 to 53%; P = 0.01) and amoxicillin/clavulanate (56 to 37%; P < 0.01) while it increased to gentamycin (64 to 88%; P < 0.001) and co-trimoxazole (14 to 62%; P < 0.001); susceptibility to amikacin remained high (> 85%). Only two cases of resistance to carbapenems in 2004-2006 were found. In vitro effectiveness of amikacin + amoxicillin/clavulanate in empirical therapy was slowly decreasing (87 to 77%; P=NS). Imipenem was found the most effective single agent (90-95%) and its efficacy was even improved by adding vancomycin (97-98%). CONCLUSIONS: Substantial rise in the incidence of Gram-positive species and fluctuations in antimicrobial susceptibility patterns were found. Empirical therapy of genitourinary infection in catheterized men with BPH should now involve antimicrobial agents effective both to Enterococci and Enterobacteriaceae. Periodic monitoring and publishing data on antimicrobial susceptibility for this population is necessary.

First cases and risk factors of super yeast Candida auris infection or colonization from Shenyang, China.

For the first time, we identified 15 cases of Candida auris in Shenyang, China, and then performed a risk factor assessment for these patients compared with 30 control subjects who were hospitalized in the same ward during the same period of time as the infected patients. We found that diarrhea, gastrointestinal decompression, infection, or colonization with other Candida isolates (especially Candida albicans) and tetracycline antibiotics were all risk factors for C. auris infection or colonization. Diarrhea and tetracycline antibiotics were independent risk factors. We suggest clinicians pay special attention to the emergence of multidrug-resistant C. auris infections or colonization.

Antifungal activity of a ß-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.

UNLABELLED: Catheter-associated urinary tract infections (CAUTI) are the most common type of hospital-acquired infection, with more than 30 million catheters placed annually in the US and a 10-30% incidence of infection. Candida albicans forms fungal biofilms on the surfaces of urinary catheters and is the leading cause of fungal urinary tract infections. As a step toward new strategies that could prevent or reduce the occurrence of C. albicans-based CAUTI, we investigated the ability of antifungal ß-peptide-based mimetics of antimicrobial peptides (AMPs) to kill C. albicans and prevent biofilm formation in synthetic urine. Many α-peptide-based AMPs exhibit antifungal activities, but are unstable in high ionic strength media and are easily degraded by proteases-features that limit their use in urinary catheter applications. Here, we demonstrate that ß-peptides designed to mimic the amphiphilic helical structures of AMPs retain 100% of their structural stability and exhibit antifungal and anti-biofilm activity against C. albicans in a synthetic medium that mimics the composition of urine. We demonstrate further that these agents can be loaded into and released from polymer-based multilayer coatings applied to polyurethane, polyethylene, and silicone tubing commonly used as urinary catheters. Our results reveal catheters coated with ß-peptide-loaded multilayers to kill planktonic fungal cells for up to 21days of intermittent challenges with C. albicans and prevent biofilm formation on catheter walls for at least 48h. These new materials and approaches could lead to advances that reduce the occurrence of fungal CAUTI. STATEMENT OF SIGNIFICANCE: Catheter-associated urinary tract infections are the most common type of hospital-acquired infection. The human pathogen Candida albicans is the leading cause of fungal urinary tract infections, and forms difficult to remove 'biofilms' on the surfaces of urinary catheters. We investigated synthetic ß-peptide mimics of natural antimicrobial peptides as an approach to kill C. albicans and prevent biofilm formation in media that mimics the composition of urine. Our results reveal these mimics to retain structural stability and activity against C. albicans in synthetic urine. We also report polymer-based approaches to the local release of these agents within urinary catheter tubes. With further development, these materials-based approaches could lead to advances that reduce the occurrence of fungal urinary tract infections.

Prevention of Bacterial Biofilms Formation on Urinary Catheter by Selected Plant Extracts.

In this study, we investigated the feasibility of using Psidium guajava, Mangifera indica and Ocimum gratissimum leaf extracts in preventing Escherichia coli biofilm formation. The plants extractions were done with methanol under cold extraction. The various concentrations 5.0, 10.0 and 20.0 mg mL(-1) were used to coat 63 catheters under mild heat from water bath. Biofilm formation on the catheter was induced using cultures of E. coli. Biofilm formation was evaluated using aerobic plate count and turbidity at 600 nm. From the obtained results, Psidium guajava, Mangifera indica and Ocimum gratissimum delayed the onset of biofilm formation for a week. Ocimum gratissimum coated catheter had the highest inhibitory effect at 5.0, 10.0 and 20.0 mg mL(-1) with bacterial count ranging from 2.2 x 10(5)-7.0 x 10(4) and 5.7 x 10(5)-3.7 x10(5) for 120 and 128 h, respectively. The Psidium guajava coated catheter had the lowest inhibitory effect at 5.0, 10.0 and 20.0 mg mL(-1), with bacterial count ranging between 4.3 x 10(5)-1.9 x 10(3) and 7.7 x 10(5)-3.8 x 10(5) for 120 and 128 h, respectively. Despite the antimicrobial activities, the differences in the activity of these plant extracts were statistically not significant (p < 0.05).

Soft robotic concepts in catheter design: an on-demand fouling-release urinary catheter.

Infectious biofilms are problematic in many healthcare-related devices and are especially challenging and ubiquitous in urinary catheters. This report presents an on-demand fouling-release methodology to mechanically disrupt and remove biofilms, and proposes this method for the active removal of infectious biofilms from the previously inaccessible main drainage lumen of urinary catheters. Mature Proteus mirabilis crystalline biofilms detach from silicone elastomer substrates upon application of strain to the substrate, and increasing the strain rate increases biofilm detachment. The study presents a quantitative relationship between applied strain rate and biofilm debonding through an analysis of biofilm segment length and the driving force for debonding. Based on this mechanism, hydraulic and pneumatic elastomer actuation is used to achieve surface strain selectively within the lumen of prototypes of sections of a fouling-release urinary catheter. Proof-of-concept prototypes of sections of active, fouling-release catheters are constructed using techniques typical to soft robotics including 3D printing and replica molding, and those prototypes demonstrate release of mature P. mirabilis crystalline biofilms (e.g., ≈90%) from strained surfaces. These results provide a basis for the development of a new urinary catheter technology in which infectious biofilms are effectively managed through new methods that are entirely complementary to existing approaches.

Biocide activity against urinary catheter pathogens.

Antimicrobial effects of essential oils against bacteria associated with urinary catheter infection was assessed. Tests were performed on 14 different bacterial species cultured either planktonically or as biofilms. Biofilms were found to be up to 8-fold more tolerant of the test agents. Higher antimicrobial tolerance was also evident in tests conducted in artificial urine. Eugenol exhibited higher antimicrobial effects against both planktonic cells and biofilms than did terpinen, tea tree oil, and cineole.

Solidago, orthosiphon, birch and cranberry extracts can decrease microbial colonization and biofilm development in indwelling urinary catheter: a microbiologic and ultrastructural pilot study.

PURPOSE: Plants extracts are used in urology to manage urinary tract infections. We aimed to evaluate the efficacy of a preparation with solidago, orthosiphon, birch and cranberry extracts (CISTIMEV PLUS(®)) in reducing microbial colonization and biofilm development in patients with indwelling urinary catheters. METHODS: All consecutive outpatients attending our department between January and June 2010 for the substitution of indwelling catheters were considered for this single-blinded, randomized and controlled pilot study to test superiority of the preventative management (CISTIMEV PLUS(®), 1 tablet daily for 30 days) in respect to no treatment. A sample size of 10-40 participants per group was considered adequate. All patients underwent urine culture the same day of the catheter substitution and were then randomized into test group (n = 48) and control group (n = 35). Ultrastructural analysis was also performed. After 30 days, the catheter was replaced and the analysis repeated. The primary outcome was the rate of positive urinary culture at the end of the entire study period. RESULTS: Ten patients abandoned the study. At 30 days, according to per-protocol analysis, the groups statistically differed regarding the rate of positive urine cultures: test group 10/43 and control group 16/30 (p = 0.013) (-30.1 % [95 % CI -51.94 to -8.21]). The most common isolated bacteria were Escherichia coli and Enterococcus faecalis. CONCLUSIONS: The use of solidago, orthosiphon, birch and cranberry extracts resulted in a significant reduction of microbial colonization in patients with indwelling urinary catheters. Larger clinical trials are needed to demonstrate that the effects here reported are sufficient to reduce symptomatic catheter-associated urinary tract infections.