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Purpose: We determined if the deliberate establishment of asymptomatic bacteriuria with Escherichia coli 83972 in patients with incomplete bladder emptying and recurrent urinary tract infection protects against recurrence. Materials and Methods: In phase 1 of the study the patients were randomized to blinded inoculations with E. coli 83972 or saline. Crossover occurred after monitoring for 12 months or after a urinary tract infection. The outcome was the time to the first urinary tract infection in patients with and without E. coli 83972 bacteriuria. In phase 2 patients were subjected to additional blinded inoculations to extend periods with and without E. coli 83972 bacteriuria. The outcome was the number of urinary tract infections during 12 months with and 12 months without E. coli 83972 bacteriuria. Results: A total of 20 patients completed the study. In phase 1 the time to the first urinary tract infection was longer with than without E. coli 83972 bacteriuria (median 11.3 vs 5.7 months, sign test p = 0.0129). Phase 2 was analyzed after patients had spent a total of 202 months with and 168 months without E. coli 83972 bacteriuria. There were fewer reported urinary tract infection episodes with vs without E. coli 83972 bacteriuria (13 vs 35 episodes, paired t test p = 0.009, CI 0.31-1.89). There was no febrile urinary tract infection episode in either of the study arms and no significant side effects of intravesical bacterial inoculation were reported. Conclusions: Deliberately induced E. coli 83972 bacteriuria protected patients with incomplete bladder emptying who are prone to urinary tract infection from recurrent urinary tract infection as demonstrated by the delay in time to urinary tract infection and the decrease in number of urinary tract infection episodes.

We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers.

The increasing microbial antibiotic resistance motivates research for non-antibiotic treatment alternatives. In recurrent urinary tract infections (UTIs), 'bacterial interference' has attracted interest as a possible alternative treatment option. The observation that asymptomatic bacteriuria (ABU) protects against recurrent UTI has prompted clinical trials with deliberate colonization of the human urinary tract as an alternative approach in patients with recurrent UTI. The strain used for colonization, the ABU isolate Escherichia coli 83972, has been shown to cause symptom-free colonizations for long periods of time. Patients on long-term colonization report a subjective benefit, and UTI treatments are rare in colonized patients. This report presents an update on open long-term E. coli 83972 colonization trials and describes the design of an ongoing randomized trial.

Objectives To assess the level of infectious complications and the impact of timing of a single, prophylactic, oral dose of ciprofloxacin 750mg given either 2hours before or in conjunction with ultrasound-guided core biopsy of the prostate in men without recognised risk factors and to analyse potential risk factors. Methods All men undergoing prostate biopsy for elevated prostate specific antigen or clinical suspected prostate cancer were enrolled in an open, comparative prospective study. Excluded were men with recognised risk factors for infective complications. Two end points were chosen: febrile genitourinary infection and the results of postbiopsy urine culture. Results A total of 1322 prostate biopsy occasions were made in 1157 men. Twelve (0.9%) cases of febrile genitourinary infections were recorded, two of which had proven sepsis. Administrating the drug 2hours before or at the time of biopsy ( p >0.5) showed no statistical difference. Eight of 12 patients were shown to have prebiopsy undisclosed risk factors. Four percent developed postbiopsy, asymptomatic, significant bacteriuria. In addition, three (27%) men with prebiopsy unrecognised bacteriuria, who were accidentally enrolled, developed febrile genitourinary infection; one had proven sepsis. Conclusions A single high-dose of oral ciprofloxacin 750mg can be administered in direct conjunction with prostate biopsy to men without recognised risk factors, keeping the infection rate at approximately 1%. Bacteriuria before biopsy is a major risk factor for infective complications. Attention given to recognising individual risk factors would reduce the risk of infection further.