Intracavitary Bacillus Calmette-Guerin in the Treatment of Superficial Bladder Tumors.

Patients with recurrent superficial bladder tumors have been treated by vesical and intradermal administration of Bacillus Calmette-Guerin. The pattern of recurrence in 9 patients has been altered favorably. Although the findings are still preliminary they appear to hold promise of a new therapeutic approach to the treatment of a group of neoplasms for which effective therapy is still lacking.

Urogenital infections in women: can probiotics help?

Urogenital infections not caused by sexual transmission, namely yeast vaginitis, bacterial vaginosis, and urinary tract infection remain a major medical problem in terms of the number of women afflicted each year. Although antimicrobial therapy is generally effective at eradicating these infections, there is still a high incidence of recurrence. The patient's quality of life is affected and many women become frustrated by the cycle of repeated antimicrobial agents whose effectiveness is diminishing due to increasing development of microbial resistance. There is good clinical evidence to show that the intestinal and urogenital microbial flora have a central role in maintaining both the health and wellbeing of humans. Furthermore, the use of "good bacteria" to replace or augment bacterial populations is gradually achieving scientific acceptance. This application is termed probiotics: "live micro-organisms which when administered in adequate amounts confer a health benefit on the host". The role of the intestinal, vaginal, and urethral flora and probiotics in urogenital health will be the focus of this review.

Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora.

Forty-two healthy women were randomized to receive one of three encapsulated Lactobacillus rhamnosus GR-1 plus Lactobacillus fermentum RC-14 probiotic dosage regimens or L. rhamnosus GG by mouth each day for 28 days. However, the vaginal flora, assessed by Nugent scoring, was only normal in 40% of the cases, and 14 patients had asymptomatic bacterial vaginosis. Treatment with L. rhamnosus GR-1/L. fermentum RC-14 once and twice daily correlated with a healthy vaginal flora in up to 90% of patients, and 7/11 patients with bacterial vaginosis converted to normal or intermediate scores within 1 month. Ingestion of L. rhamnosus GG failed to have an effect. This study confirms the potential efficacy of orally administered lactobacilli as a non-chemotherapeutic means to restore and maintain a normal urogenital flora, and shows that over 10(8) viable organisms per day is the required dose.

Could probiotics be an option for treating and preventing urogenital infections?

Considering the enormity of the problem in terms of women infected per year, urogenital infections receive far too little attention from scientists, government funding agencies, and the pharmaceutical industry. A recent resurgence in interest among clinicians is a result of consumer demands for better therapies, problems resulting from drug resistance, and the prospect of new diagnostics and treatments on the horizon. It is now recognized that the intestinal and urogenital microflora are critical for the health and well-being of humans. The concept of replenishing these flora with probiotic organisms seems to be an option that has a growing scientific basis. Although few strains have been selected and targeted for urogenital applications, and none are currently available on the market, evidence shows that probiotic therapy has the potential to make an impact on women's health.

Oral probiotics can resolve urogenital infections.

We report the first clinical evidence that probiotic lactobacilli can be delivered to the vagina following oral intake. In 10 women with a history of recurrent yeast vaginitis, bacterial vaginosis (BV) and urinary tract infections, strains Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 suspended in skim milk and given twice daily for 14 days, were recovered from the vagina and identified by morphology and molecular typing within 1 week of commencement of therapy. In six cases of asymptomatic BV or intermediate BV (based upon Nugent scoring) was resolved within 1 week of therapy.

Antibiotic hydrogel coated Foley catheters for prevention of urinary tract infection in a rabbit model.

PURPOSE: We developed an antibiotic liposome (ciprofloxacin liposome) containing hydrogel for external coating of silicone Foley catheters and evaluated its efficacy in a rabbit model. Our goal was to create a catheter that would hinder the development of catheter associated nosocomial urinary tract infections. MATERIALS AND METHODS: We inserted either an untreated, liposomal hydrogel coated or a liposome hydrogel with ciprofloxacin coated 10F silicone Foley catheter into New Zealand White rabbits. We challenged the system with 5x10(6) virulent Escherichia coli at the urethral meatus twice daily for 3 days. Urine cultures were evaluated twice daily for 7 days. When urine cultures became positive, the rabbits were sacrificed and urine, urethral catheter and urethral tissue were cultured. RESULTS: The time to bacteriuria detection in 50% of the specimens was double for hydrogel with ciprofloxacin coated catheters versus untreated and hydrogel coated catheters. A significant (p = 0.04) improvement in average time to positive urine culture from 3.5 to 5.3 days and a 30% decrease in the bacteriuria rate for hydrogel with ciprofloxacin coated catheters were noted compared to untreated catheters. CONCLUSIONS: A significant benefit was realized by coating the extraluminal catheter surface with a ciprofloxacin liposome impregnated hydrogel. We believe this procedure will provide a significant clinical advantage, while reducing health care costs substantially.

A liposomal hydrogel for the prevention of bacterial adhesion to catheters.

The adhesion of bacteria to medical implants and the subsequent development of a biofilm frequently results in the infection of surrounding tissue and may require removal of the device. We have developed a liposomal hydrogel system that significantly reduces bacterial adhesion to silicone catheter material. The system consists of a poly (ethylene glycol)-gelatin hydrogel in which liposomes containing the antibiotic ciprofloxacin are sequestered. A poly (ethylene glycol)-gelatin-liposome mixture was applied to a silicone surface that had been pre-treated with phenylazido-modified gelatin. Hydrogel cross-linking and attachment to surface-immobilized gelatin was accomplished through the formation of urethane bonds between gelatin and nitrophenyl carbonate-activated poly (ethylene glycol). Liposomal hydrogel-coated catheters were shown to have an initial ciprofloxacin content of 185+/-16 microg cm(-2). Ciprofloxacin was released over seven days with an average release rate of 1.9+/-0.2 microg cm(-2) h(-1) for the first 94 h. In vitro assays using a clinical isolate of Pseudomonas aeruginosa established the antimicrobial efficacy of the liposomal hydrogel. A modified Kirby-Bauer assay produced growth-inhibition zone diameters of 39+/-1 mm, while bacterial adhesion was completely inhibited on catheter surfaces throughout a seven-day in vitro adhesion assay. This new antimicrobial coating shows promise as a prophylactic and/or treatment for catheter-related infection.

Effect of nutrient composition on the in vitro growth of urogenital lactobacilli and uropathogens.

Previous clinical studies have shown that nutrients and probiotic agents can alter the composition of the vaginal flora. The present in vitro study has shown that uropathogens have a growth advantage over lactobacilli, but potentially there are natural substances that could be applied vaginally to stimulate lactobacilli growth to the detriment of the pathogens. When chemically defined medium representative of vaginal fluid at pH 5.5 was supplemented with skim milk, it acted as a better substrate for Lactobacillus rhamnosus GR-1 than for uropathogenic bacteria and Candida albicans. Lactobacillus MRS medium, even at pH 4.5, supports the growth of pathogens, but when supplemented with ascorbic acid or EDTA, Lactobacillus growth was significantly higher. When L. rhamnosus GR-1 was coincubated in a combined nutrient composition of vitamins and lactose, it survived better than Escherichia coli and Enterococcus faecalis. These in vitro results provide a basis for testing nutritional supplements to alter the urogenital flora in an attempt to enhance restoration and maintenance of a normal disease-free state.

A new paradigm for clinical laboratory science education: a case study for survival and growth.

Clinical laboratory science (CLS) education programs are faced with declining numbers of qualified students and resources. A solution is to move toward a new education paradigm. The new paradigm emphasizes cooperation between institutions, asynchronized learning and advising, the use of technology for teaching and advising and the decentralization of the teaching process. This article presents a case study describing how 1 CLS program was able to go from a scarcity mentality to an abundance mentality by implementing the new paradigm.

Pseudomonas aeruginosa biofilms are more susceptible to ciprofloxacin than to tobramycin.

The objective of this study was to determine and compare the biofilm elimination concentrations (BEC: the concentration which reduced the viability of biofilm organisms by at least 99.9%) of ciprofloxacin and tobramycin for Pseudomonas aeruginosa, a common cause of nosocomial biomaterial-related infections. Bacterial biofilms were produced in the modified. Robbins device using continuous culture flow at 60 ml/h for 40-44 h, and the sessile organisms were then exposed to either ciprofloxacin or tobramycin at a range of concentrations for 12 or 36h. The BEC of ciprofloxacin was 5 mug/ml for the 12 and 36 h treatments, a value 10 x greater than the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). In contrast, the BEC of tobramycin was > 100 mu/ml after 12h and 75 ug/ml following 36 h of drug exposure, that is 75-100 x the MIC and MBC. The results demonstrated that the BEC is a more suitable indicator of the antibiotic susceptibility of P. aeruginosa biofilms than the MIC and MBC. Ciprofloxacin was significantly more effective than tobramycin in the treatment of P. aeruginosa adherent to biomaterials. With respect to clinical application, if the intention of antibiotic use is to eradicate bacteria adherent to devices, only biofilm-active agents should be used.

Identification and plasmid profiles of Lactobacillus species from the vagina of 100 healthy women.

It was hypothesized that Lactobacillus acidophilus might not be the dominant aerobic or microaerophilic Lactobacillus species in the human vagina, and that the dominant isolates are likely to express a variety of properties associated with colonization. To examine the question, vaginal swabs were collected from 100 healthy premenopausal women and cultured to detect the dominant aerobic or microaerophilic isolates of Lactobacillus. Only eight species were detected, with Lactobacillus jensenii being the dominant colonizers in the highest number (35) of women. Twelve different plasmid profiles were found amongst the isolates, but there was no association between plasmids and vaginal colonization or hydrogen peroxide production. Of the strains tested, few were resistant to the spermicidal agent nonoxynol-9. The data identify species within which strains may possess properties associated with maintenance of a healthy vaginal ecology.

Impact of pathologic extraprostatic disease on local and systemic progression following radical prostatectomy.

Fifty patients underwent radical prostatectomy for localized prostate cancer (Stages A2, B) between 1977 and 1982. Surgical specimens were examined for tumor grade and extraprostatic extension of the disease. Forty-one of the 50 patients had capsular involvement (82%), 26 (52%) positive margins and 14 (28%) seminal vesicular involvement. Six patients progressed locally, six systematically and three both. Eight patients progressed at five years and an additional seven at ten years. In all 15 progressors tumor involved the capsule yet four patients with capsular involvement alone progressed. Eleven of the 26 patients (42%) with positive margins progressed. Five of the 14 patients (37%) with seminal vesicle involvement progressed, all five had positive margins as well. None of the patients with disease confined within the capsule progressed. Gleason score for non-progressors ranged between three and nine with a median of six while for progressors it ranged between five and nine with a median of seven. Long rank test and Cox Proportional Hazard Model statistical analysis were employed among all the factors: capsular involvement, positive margins, positive seminal vesicles and grade of tumor. Positive margins was the only statistically significant factor affecting local progression of the disease in both univariate and multivariate analysis at a 95% confidence (p=0.04). All factors were statistically insignificant in affecting systemic progression (p>0.5).

Effects of ciprofloxacin and vancomycin on physicochemical surface properties of Staphylococcus epidermidis, Escherichia coli, Lactobacillus casei and Lactobacillus acidophilus.

Under clinical conditions, during antibiotic treatment, micro-organisms often grow at sub-inhibitory concentrations. This may lead to altered adhesive cell surface properties and to a disruption of the indigenous microflora, in addition to the creation of a more pathogenic biofilm. The effects of growing Staphylococcus epidermidis, Escherichia coli and lactobacilli in the presence of sub-inhibitory concentrations of ciprofloxacin and vancomycin were determined. Growing the cells under antibiotic burden sometimes led to altered cell surface hydrophobicity (by adhesion to hexadecane), changes in the pH-dependence of zeta potentials, and elemental surface compositions or in different SDS-PAGE protein profiles. For several isolates only one of the surface properties was altered by the presence of an antibiotic in the growth medium and no systematic effects were observed for all isolates representing a certain species or even strain. The important conclusion to be drawn from the results of this study is that the effects of growing cells under antibiotic burden on their adhesive cell surface properties can only be established when using a variety of techniques.

The influence of nonoxynol-9-containing spermicides on urogenital infection.

PIP: The most common spermicidal compound in use in North America is nonoxynol-9. Barrier methods of contraception used in combination with a spermicidal product help prevent a variety of sexually transmitted diseases. In 1991 the Centers for Disease Control reported a total of 620,478 cases of gonorrhea, 128,569 of syphilis, and 43,672 of acquired immunodeficiency syndrome (AIDS). The evidence for antimicrobial activity of spermicides against sexually transmitted disease pathogens has been accumulated during the last 20 years from in vitro and in vivo studies on Neisseria gonorrhea, Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, Herpes simplex viruses 1 and 2, and the human immunodeficiency virus. Uropathogenic bacteria, including E. coli, Proteus mirabilis, Enterococcus faecalis and Staphylococcus species, have been found to grow in concentrations of 25% or greater of nonoxynol-9. Less well known is the effect of nonoxynol-9 on the growth of lactobacilli, the predominant organisms colonizing the vagina of most healthy postpubertal and premenopausal women, which according to in vitro studies could inhibit the colonization and ascending infection of the bladder by E. coli and as E. faecalis. The organisms associated with bacterial vaginosis have been found to be inhibited by low concentrations of nonoxynol-9 (0.0019-0.5%). However, spermicide use does not appear to have any effect on the development of bacterial vaginosis. Clinical studies to date, with one exception, have shown no significant differences in bacterial vaginosis infection rates among users of diaphragms, contraceptive sponges and condoms and other contraceptive methods that do not involve exposure to spermicides. A history of nonoxynol-9 use as well as the use of antimicrobial agents should be considered in recurrent urogenital infections, since both can potentially disrupt the urogenital microbial flora. The physician must weigh the risk of exposure to sexually transmitted diseases or an unwanted pregnancy against the prevention of urinary tract infection or vaginal candidiasis before advising the patient to discontinue the use of nonoxynol-9-containing spermicides.^ieng

Effects of ciprofloxacin, norfloxacin, and ofloxacin on in vitro adhesion and survival of Pseudomonas aeruginosa AK1 on urinary catheters.

Pretreatment of urinary silicone latex catheters in vitro with 0.1 and 0.5 microgram of ciprofloxacin per ml for 1, 24, and 48 h significantly reduced the adhesion and survival of the clinical isolate Pseudomonas aeruginosa AK1. UV spectroscopy and high-performance liquid chromatography confirmed the presence of ciprofloxacin adsorbed onto the catheters and showed that up to 56% of the drug leached into the surrounding fluid within 24 h. Scanning electron microscopy demonstrated that the adherent organisms were malformed and elongated after exposure to ciprofloxacin. Transmission electron microscopy showed the presence of fimbriae on the bacterial surfaces, but there was no conclusive evidence of changes in the fimbriae upon exposure to ciprofloxacin. It was found that a significant eradication of 24-h Pseudomonas biofilms could be achieved with ciprofloxacin as well as with ofloxacin and norfloxacin. Preincubation of catheters with 50- and 100-micrograms/ml concentrations of ciprofloxacin resulted in up to a 99% reduction in the number of adherent bacteria in comparison with the reduction on control catheters. In addition, adherent biofilms were eradicated by 24 h of challenge with 50 and 100 micrograms of ciprofloxacin per ml at pH 7.0 and 5.5. Results of these in vitro studies suggest that there could be a clinical role for fluoroquinolones in preventing and treating urinary tract infections associated with P. aeruginosa adherence to prosthetic devices.

Adhesion of lactobacilli to urinary catheters and diapers: effect of surface properties.

Thirteen strains of lactobacilli were tested for their ability to adhere to commercial devices used in the urinary tract. Although it appeared that the most hydrophilic organisms adhered in highest numbers, there was no significant correlation between water contact angle and adhesiveness to catheters. Five organisms tested were found to be highly adherent to Huggies commercial diapers. Loss in hydrophobicity upon serial culture of Lactobacillus fermentum B-54 was not due to a proteinaceous S layer, although protein involvement per se cannot be ruled out. It was evident that, not only can members of the normal female urogenital flora adhere to commonly used commercial prostheses, but their ability to attach is related to hydrophilic as well as hydrophobic surface components.