No abstract

Prevention of nosocomial urinary tract infections by iontophoresis is addressed. An iontophoretic generator was used to provide microamperage (10 to 400 ILA) to vials containing either synthetic urine or supplemented synthetic urine. Bacteria were added to vials, and parameters of growth, bacterial killing, and multiple electrode materials were examined. Escherichia coli and Proteus species were both inhibited and killed at various microamperages and with several electrode types, the most efficient being gold-gold as the anodecathode combination. KlebsieUapneumoniae in supplemented synthetic urine was least inhibited in growth, and higher microamperage (200 to 400 pA) was most effective in killing the bacteria. Bacterial growth reduction and killing were directly related to increasing microamperage and were inversely related to bacterial concentration.Prevention of nosocomial urinary tract infections (UTI) has long been a goal of clinicians. Urinary catheters are the leading cause of nosocomial UTI, and UTI is the most common predisposing factor for cases of fatal gram-negative sepsis that originate in hospitals (5, 7). Consequently, prevention of UTI related to urinary catheters could lead to a substantial reduction in morbidity and mortality from nosocomial gram-negative sepsis. Such prevention could also decrease morbidity and mortality in geriatric patients, because those who require catheterization can have a high incidence of bacteriuria (9,15).

lontophoresis with gold, carbon, and platinum electrodes was shown to effectively reduce or eliminate gram-positive, gram-negative, and Candida albicans inocula in synthetic urine. Platinum and gold electrodes were more effective than carbon electrodes, but platinum showed the best longevity and may reduce or eliminate microbial colonization of catheters.For decades, catherters have been associated with nosocomial infections and are thought to be the most common cause of sepsis in hospitals (6,8). We and other investigators have evaluated the effect of iontophoresis on organisms, and we have suggested that iontophoretic technology may be used in urinary and, potentially, other types of catheters (1-5).Long electrode life span and effectiveness in killing microbes are two major criteria for incorporation of electrodes into catheters, although other considerations are important (e.g., cost and effects on tissue or urine composition). The best electrodes developed to date for use in fluids have been gold electrodes (4, 5). The present study was done to evaluate gold, carbon, and platinum electrodes in terms of effectiveness of killing microbes and, for gold and platinum, electrode longevity.A 10-channel microampere generator (synthesized at University of Texas Medical Branch; wiring diagram available on request) was used to provide constant amperage with variable current (4). Vented stoppered vials were connected to the generator by metal connectors. A diagram of our system has been published elsewhere (4). Wires (gold or platinum, 0.2-mm diameter) or carbon rods (approximately 3-mm diameter) were attached to the bases of metal connectors so that approximately 2 cm of each wire or rod was covered by synthetic urine (4, 5). Synthetic urine was used to avoid variations in constituents normally found in human urine (7).The following microorganisms were used: Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Proteus mirabilis, and Klebsiella pneumoniae. The bacteria were chosen because gram-negative bacteria are responsible for more than 80% of all urinary tract infections, with E. coli being responsible for more infections than all other genera combined (6,8 Gold and platinum were examined for their longevity after multiple challenges with bacteria to stimulate the proposed frequent seeding of bacteria by the ascending route in clinical systitis (8). Vials were inoculated with E. coli CFU (108) every other day. Immediately before inoculation, the same inoculum volume (0.1 ml) was removed and the number of CFU per unit volume were determined. After 90 days, this procedure was changed to inoculation with 108 E. coli CFU once per week. In addition to 0.2-mm gold wire electrodes, braided gold wire (three strands of 0.2-mm wire) and 0.6-mm solid gold wire were also used.In general, gold and platinum electrodes were better than carbon electrodes in reducing or eliminating an inoculum of microbes ( Fig. 1 through 3). Gold electrodes were particularly effective at killing gram-negative organisms ( Fig. 1 through 3)...

The effects of carbohydrates (mannose and dextrose), Escherichia coli 07KL, and Klebsiella pneumoniae on Candida albicans attachment to epithelial cells was studied. Dextrose had no effect on yeast attachment to epithelial cells. Conversely, mannose significantly decreased both yeast and piliated bacterial attachment (E. coli 07KL, heavily piliated K. pneumoniae) whereas having no effect on nonpiliated K. pneumoniae attachment to epithelial cells. The number of yeasts attaching to epithelial cells was enhanced by preincubation of epithelial cells with piliated strains of bacteria, whereas preincubation with nonpiliated strains of bacteria had no effect on yeast attachment. Scanning electron microscopy showed that piliated bacteria and yeasts were juxtaposed on the epithelial cell surface. These data suggest that certain piliated strains of bacteria can enhance C. albicans attachment to epithelial cells and that type 1 pili of bacteria can be a factor in the enhanced attachment of C. albicans to epithelial cells.

The dependence of microbial killing on chloride ions present in solutions undergoing iontophoresis is addressed. A 400-,uA current was applied to vials containing synthetic urine or saline, and the production of chlorine-based substances (CBSs) was detected by the N,N-diethyl-p-phenylene diamine colorimetric method.It was found that as the time of current application increased, the'total concentration of CBSs also increased.The iontophoretic current converted (through oxidation) chloride ions present in the solutions into CBSs such as free chlorine, chlorine dioxide, chlorite, monochloramine, and dichloramine (the last two were produced by iontophoresis only when nitrogenous substances were present in the solution). Two of the CBSs (free Cl and C102), when they were separately added back to microbial suspensions (approximately 3 x 105 CFU/ml) at the same concentrations at which they were detected in either 0.46% (wt/vol) NaCl solution or synthetic urine iontophoresed for 4 h at 400 ,LA, reduced or eliminated bacterial genera and a fungus. However, when free Cl and C102 were jointly added back to microbial suspensions, bacterial and fungal killing was synergistic and more rapid and complete than when these chlorine-based biocides were added separately. Therefore, iontophoresis of solutions containing chloride ions produces chlorine-based biocides that are responsible for the antimicrobial effect of iontophoresis.For many years urinary catheters have been identified as both the leading cause of nosocomial-induced urinary tract infections (UTIs) and the most common predisposing factor in fatal gram-negative sepsis in hospitals (13,24). Therefore, reducing the threat of nosocomial UTIs from catheter usage has been an important goal for our laboratory. We have designed a catheter-power supply system that delivers an iontophoretic current of 400 ,A to the urinary bladder through platinum electrodes (7). Previous research has demonstrated that this current will eliminate microbial populations only when it is passed through solutions containing chloride ions (11). We have also previously shown that platinum electrodes have the best durability and microbial killing efficiency and that iontophoresis for 4 h at 400 ,uA in synthetic urine generates a biocidal effect against selected fungi and gram-positive and gram-negative bacteria for more than 6 h after iontophoresis ceases (9, 10). Furthermore, bacterial killing efficiency was found to be directly related to increasing microamperage (up to 400 VA) and to chloride ion concentration, while it was found to be inversely related to the number of bacteria present in the solution undergoing iontophoresis (12). Preliminary work suggested that the reason for biocidal activity was the production of chlorine-containing oxidants. Therefore, the aim of the study described here was to both identify and quantify the various iontophoretically produced chlorine-based substances (CBSs) such as free chlorine (i.e., Cl2, OCI-, and HOCI), chlorine dioxide (CG02), chlorite (CdO2-), monochlo-...