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Prevention of urinary tract infection in spinal cord-injured patients: safety and efficacy of a weekly oral cyclic antibiotic (WOCA) programme with a 2 year follow-up--an observational prospective study.

POPULATION: Spinal cord injury (SCI) patients with neurogenic bladder have an increased risk for symptomatic urinary tract infection (UTI). Recurrent UTI requires multiple courses of antibiotic therapy, markedly increasing the incidence of multidrug-resistant (MDR) bacteria. METHODS: During an observational prospective study, we determined the safety and efficacy of a weekly oral cyclic antibiotic (WOCA) regimen to prevent UTI in SCI adult patients with neurogenic bladder undergoing clean intermittent catheterization. The WOCA regimen consisted of the alternate administration of an antibiotic once per week over a period of at least 2 years. The antibiotics chosen were efficient for UTI, well tolerated and with low selection pressure. RESULTS: There was a significant decrease in antimicrobial consumption linked to the dramatic decrease in the incidence of UTI. Before intervention, there were 9.4 symptomatic UTIs per patient-year, including 197 episodes of febrile UTI responsible for 45 hospitalizations. Under the WOCA regimen there were 1.8 symptomatic UTIs per patient-year, including 19 episodes of febrile UTI. No severe adverse events and no new cases of colonization with MDR bacteria were reported. CONCLUSIONS: In this prospective, observational pilot study a novel approach to the prevention and treatment of UTI in SCI was investigated. Our study shows the benefit of WOCA in preventing UTI in SCI patients.

Adult↗

Urologic diseases in America project: trends in resource use for urinary tract infections in women.

PURPOSE: Urinary tract infection (UTI) is one of the most common clinical diagnoses in women. In this study we examined epidemiological, economic and health care use trends for UTI in women in the United States. MATERIALS AND METHODS: The analytical methods used to generate these results have been described previously. RESULTS: The lifetime risk for UTI in women is high (greater than 50%). Between 1988 and 1994 the overall lifetime prevalence of UTI was estimated to be 53,067/100,000 women. Prescribing patterns demonstrated an increase in the trend toward using fluoroquinolones as first line therapy for UTI, which was associated with increased costs. Composite data revealed that overall expenditures for the treatment of UTIs in women in the United States, excluding spending on outpatient prescriptions, were approximately 2.47 billion dollars in 2000. Diagnosis and treatment of UTI in women is performed in various clinical settings. Inpatient hospitalization for UTI care has generally decreased in younger women but increased in elderly women. There has been a sharp increase in emergency room use by younger women, which may reflect disparities in access to health insurance or primary care providers. Most outpatient care of women with UTIs is performed in physician offices. CONCLUSIONS: Analysis of health care use and economic data on UTIs in women revealed various interesting trends. These findings will help shape understanding of UTI treatment in relation to other urological disorders in women. The results raise various important future research questions.

Adolescent↗

Molecular signatures of urinary cells distinguish acute rejection of renal allografts from urinary tract infection.

Acute rejection (AR) and urinary tract infection (UTI) continue to plague renal transplantation. We tested the hypotheses that UTI does not increase granzyme B mRNA levels in urinary cells, and that the levels distinguish AR from UTI. We measured the levels of granzyme B mRNA in 15 urine specimens from renal allograft recipients with UTI, 29 specimens from patients with AR but without UTI, and 14 specimens from patients without AR and without UTI. We also measured transcript levels in urine specimens from 41 nontransplant individuals, 11 with UTI and 30 without UTI. UTI did not increase granzyme B mRNA levels. Granzyme B mRNA levels were lower in renal allograft recipients with UTI compared with those with AR (P<0.0001). We conclude that bacterial UTI is unlikely to confound AR diagnosis made by measurement of granzyme B mRNA levels in urinary cells.

Acute Disease↗

Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers.

Urinary tract infections (UTIs) are the most common infectious complication following renal transplantation. Previous studies uniformly report that renal transplant recipients develop UTIs more often than the general population, but widely differ on how frequently UTIs occur after transplantation. These studies also disagree on the risk factors associated with developing post-transplant UTIs, as well as the effect that UTIs may have on graft outcomes and patient mortality. We performed a retrospective cohort study including all the adult patients who received a renal transplant at two US transplant centers from January 1996 to December 2002 (500 patients). Two hundred and thirteen (43%) patients developed one or more post-transplant UTIs over a mean follow-up period of 42 months. Significant risk factors for post-transplant UTIs were advanced age, female gender, reflux kidney disease, use of azathioprine and cadaveric donor. UTIs did not increase risk for renal graft loss, but were associated with increased mortality (3.5 odds ratio, 95% confidence interval 1.68-7.23). We conclude UTIs may be associated with an increased mortality risk in renal transplant recipients. Prevention of UTIs in high-risk renal transplant patients or those with recurrent UTIs may possibly decrease post-transplant mortality.

Adolescent↗

Unexplained extra visits to general practitioners before the diagnosis of first urinary tract infection: a case-control study.

AIMS: To determine: (1) whether children diagnosed with a urinary tract infection (UTI) visited their general practitioner (GP) more frequently before the diagnosis of UTI was established compared to children never diagnosed with a UTI; and (2) whether those children with evidence of renal scarring at their first diagnosed UTI visited their GPs more frequently before diagnosis compared to children who did not have evidence of renal scarring when their first UTI was investigated. METHODS: Case-control study of 77 children with a UTI identified from a hospital radiology database (37 with and 40 without renal scarring), and 77 age, sex, and general practice matched controls. Main outcome measures were entries in general practice clinical records for types of illness, antibiotic prescriptions, and urine samples requested prior to the diagnosis of first UTI (cases) or equivalent time periods for controls. RESULTS: Cases had a mean 2.94 additional visits or 21% more visits (95% CI 1% to 41%) in the period (mean 2.4 years) prior to the visit at which their first UTI was diagnosed, including a mean 2.5 additional visits or 23% more visits for infectious illness (95% CI 1% to 45%). The cases had 114% (95% CI 41% to 184%) more visits for symptoms relating to the genitourinary tract, though the actual number of these visits was small. They were febrile at 49% more visits (95% CI 1% to 99%) and received significantly more courses of antibiotics than controls (5.2 v 4.1). They had more urine samples requested (37 v 3). Both the cases with and without renal scarring had similar excess GP visits. CONCLUSION: Compared to controls, children diagnosed with a first UTI had more visits at which symptoms of infection were recorded and more antibiotics prescribed prior to the visit at which the first UTI was diagnosed. These excess visits may have included undiagnosed UTIs. Both those with and without renal scarring had a similar degree of excess visits; additional aetiological factors must have played a role in scar formation.

Anti-Bacterial Agents↗

Urinary tract infections and lupus erythematosus.

BACKGROUND: Infections are one of the main causes of morbidity and mortality in patients with systemic lupus erythematosus. OBJECTIVE: To analyse urinary tract infection (UTI) risk factors in lupus patients; the influence of these factors on disease activity, organ damage, and disease development; the type and prevalence of UTI; and the micro-organisms involved. METHOD: 86 control subjects and 81 lupus patients were studied prospectively over a 12 month period and examined on five occasions. Epidemiological data and information on urinary symptoms, disease activity (SLEDAI), and organ damage (SLICC/ACR) data were collected. Autoantibodies, complement levels, urine culture, and antibiogram were determined; urological studies were also carried out. SPPS 10.0 and STATA 6.0. were used for statistical analysis. RESULTS: The prevalence of UTI in lupus patients was 36%. Lupus influences the onset of UTI (p = 0.001), regardless of other variables. UTI risk factors in lupus patients were age (p = 0.002), previous cases of UTI (p = 0.0001), antinuclear antibodies (ANA) >1/80 IU/ml (p = 0.022), thrombocytopenia (p = 0.02), and admission to hospital due to UTI (p = 0.002). Leucopenia (p = 0.09) and the weekly administration of methotrexate (p = 0.06) had a bearing on the onset of UTI; disease development (p = 0.99), lupus activity (p = 0.32), and organ damage (p = 0.36) do not. The uropathogen most frequently isolated was E coli (60%). CONCLUSIONS: Lupus patients are likely to have UTI, usually manifesting in the lower tract. They are community acquired, basically caused by E coli, and favoured by age, previous UTI, admissions to hospital due to UTI, thrombopenia, ANA, leucopenia, and methotrexate treatments.

Adult↗

Current issues in the management of urinary tract infections: extended-release ciprofloxacin as a novel treatment option.

Symptomatic urinary tract infections (UTIs) are a major public health concern in the developed world, accounting for almost 8 million annual outpatient and emergency department visits in the US alone, while also representing one of the most common hospital-acquired infections. The vast majority of uncomplicated UTIs are caused by the Gram-negative bacillus Escherichia coli, with other pathogens including enterococci, Staphylococcus saprophyticus, Klebsiella spp. and Proteus mirabilis. Effective management of UTIs in both the inpatient and outpatient settings has been complicated by the fact that many uropathogenic strains have developed resistance to antimicrobials, including cotrimoxazole (trimethoprim/sulfamethoxazole), the current first-line treatment for uncomplicated UTIs in the US and many other countries. In some countries, other antimicrobial therapies, such as trimethoprim and nitrofurantoin, are also used for treatment of uncomplicated UTIs. Antimicrobial resistance has been associated with an increased rate of clinical failure, and reports from Canada and the US indicate that the prevalence of cotrimoxazole resistance exceeds 15% and can be as high as 25%.The emergence and dissemination of antimicrobial resistance can be reduced with the use of agents that have favourable pharmacokinetic/pharmacodynamic profiles and convenient dose administration regimens that facilitate patient adherence and, therefore, pathogen eradication. Fluoroquinolones have been used successfully to treat a wide range of community- and hospital-acquired infections, and the rates of fluoroquinolone resistance have remained low. Use of fluoroquinolones is recommended for uncomplicated UTIs in areas where the incidence of cotrimoxazole resistance exceeds 10%, as well as for the treatment of complicated UTIs and acute pyelonephritis. Ciprofloxacin is a widely used fluoroquinolone with high bactericidal activity against uropathogens and well established clinical efficacy in the treatment of UTIs. A new, extended-release formulation of ciprofloxacin (Cipro XR) provides systemic drug exposure comparable with that achieved with twice-daily administration of conventional, immediate-release ciprofloxacin, while also attaining higher maximum plasma concentrations with less interpatient variability. Therapeutic drug concentrations with extended-release ciprofloxacin are established immediately after dose administration and maintained throughout the 24-hour dosage interval, permitting convenient, once-daily treatment. Clinical trial results confirm that extended-release ciprofloxacin is as safely used and effective as the conventional, immediate-release formulation of ciprofloxacin in patients with uncomplicated UTIs, complicated UTIs or acute uncomplicated pyelonephritis. These findings support the use of extended-release ciprofloxacin as a well tolerated, effective and convenient therapy for UTIs, which may improve patients' adherence to therapy and, thereby, reduce the risk of infection recurrence and emergence of antimicrobial resistance.

Anti-Infective Agents↗

[Role of levofloxacin in the treatment of urinary tract infections].

The treatment of urinary tract infections (UTIs) and prostatitis has to be tailored on the clinical features of patients. UTIs should be differentiated in uncomplicated UTIs, acute pyelonephritis, complicated UTIs and UTIs in men, and asymptomatic UTIs. Prostatic inflammatory disease can be divided in 5 categories. Uncomplicated UTIs should be treated with a 3-day course of oral antibiotics, pyelonephritis and complicated UTIs with a 14-day course of oral antibiotics. In the case of high fever with chills intensive treatment with an appropriate antibiotic administered intravenously is needed until subsidence of the acute symptoms. This should be followed by oral antibiotic for two weeks. The treatment of asymptomatic UTIs should be considered for children and pregnant women. Antibiotics should be administered for 14-42 days in category I to IIIA of inflammatory prostatic disease. In the last decade acquired resistance of uropathogens to aminopenicillins and trimethoprim-sulfamethoxazole appears to have been increasing in the United States and Europe, while the susceptibility to systemic fluoroquinolones has remained unchanged at 98-99%. Particularly levofloxacin showed activity against Gram-positive bacteria without loss of Gram-negative spectrum. In normal adults levofloxacin reached urinary, bladder and prostate concentrations after a 250 mg oral dose above the MIC90 for all typical uropathogens. Multicenter clinical studies on clinical and microbiological efficacy of levofloxacin were carried out in the treatment of genitourinary tract infections. Levofloxacin 250 mg once daily for three days was highly effective in the treatment of uncomplicated UTIs. Levofloxacin 250 mg once daily for 7-10 days was clinically and microbiologically effective also for the treatment of acute pyelonephritis and complicated UTIs. In patients with nonchlamydial chronic prostatitis the bacteriological response was 85.4%. Finally levofloxacin showed a superior tolerability profile than other fluoroquinolones.

Anti-Infective Agents, Urinary↗

[Mechanism of tumor cell-induced extracellular matrix degradation--inhibition of cell-surface proteolytic activity might have a therapeutic effect on tumor cell invasion and metastasis].

Tumor cells produce urokinase-type plasminogen activator (uPA) in an enzymatically inactive proenzyme form (pro-uPA). Secreted pro-uPA can immediately bind to the specific uPA receptors (uPAR) on tumor cell surface with high affinity. The uPAR specifically recognizes enzymatically inactive pro-uPA and active high molecular weight-uPA (HMW-uPA) by their growth factor-like terminal domain. uPAR is a glycoprotein of approximately 55 kDa; the affinity for uPA is high (0.2 nM) and the rate of dissociation is low. Receptor-bound uPA catalizes the formation of plasmin on the cell surface to generate the proteolytic cascade that contributes to the breakdown of basement membrane and extracellular matrix. The plasma membrane uPAR has attracted considerable attention because of its role in migration and tissue invasion by mononuclear phagocytes and malignant cells. In some cell types uPAR localizes uPA to cell-cell and cell-substratum contact sites, providing the possibility of a directional proteolysis that may be involved in cell migration and invasion. Recently it has been reported that competitive displacement of uPA from uPAR resulted in decreased proteolysis, suggesting that the cell surface is the preferred site for uPA-mediated protein degradation. Various very different approaches to interfere with the expression or reactivity of uPA or uPAR at the gene or protein level were successfully tested including antisense oligonucleotides, antibodies, inhibitors and recombinant or synthetic uPA and uPAR analogues. Recently we have reported that a highly purified urinary trypsin inhibitor (UTI) efficiently inhibits soluble and tumor cell-surface receptor-bound plasmin. UTI inhibits not only tumor cell invasion in an in vitro assay but also production of experimental and spontaneous lung metastasis in an in vivo mouse model. The anti-invasive effect is dependent on the anti-plasmin activity of UTI. UTI peptide, which inhibits plasmin activity, synthesized by an automated peptide synthesizer showed mouse 3LL cell invasion inhibitory activity. UTI and the effective peptide inhibited tumor cell invasion through Matrigel. UTI did not inhibit tumor cell proliferation or the binding of the cells to Matrigel. Also, UTI did not inhibit chemotactic migration of tumor cells to fibronectin. It is likely that UTI acts as a protease inhibitor. We attempted to synthesize conjugates between ATF and UTI. Thus, conjugating a physiological plasmin inhibitor to ATF might target it to reduce cell-associated proteolytic activity to the close environment of the uPAR-expressing tumor cell surface and subsequently may effectively inhibit tumor cell invasion and metastasis, because the cell surface uPAR might be a critical component of the metastatic machinery. A method of conjugation of the UTI domain II (HI-8), to the receptor-binding amino-terminal fragment (ATF) of uPA has been developed utilizing the heterobifunctional cross-linking reagent, N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP). The conjugate retained its protease inhibiting activity and showed a binding reactivity to uPAR on the surface of tumor cells. We have shown that the conjugate exhibits plasmin inhibition to the close environment of the cell surface and subsequently inhibits the tumor cell invasion through Matrigel in an in vitro invasion assay. In order to extend our idea, we attempt to produce a novel hybrid molecule consisting of the ATF of uPA placed at the N-terminus of UTI domain II (HI-8) by protein engineering techniques. Exogenously applied ATFHI hybrid protein can immediately bind to the specific uPAR on cell surfaces with high affinity. The receptor-bound hybrid protein focuses the protease-inhibiting activity to the tumor cell surface. This is effectively a bifunctional molecule which, in addition to inhibiting trypsin and plasmin activities directly, is able toblock unoccupied uPAR, thereby preventing localization of uPA activity.

Animals↗

Use of spermicide-coated condoms and other risk factors for urinary tract infection caused by Staphylococcus saprophyticus.

BACKGROUND: Staphylococcus saprophyticus is the second most common cause of urinary tract infection (UTI) in young women. Relatively little is known about risk factors for this infection including exposure to vaginal spermicides, which increases the risk of UTI caused by Escherichia coli. PATIENTS AND METHODS: We conducted a case-control study in a large health maintenance organization Case patients were sexually active young women with acute UTIs caused by S saprophyticus identified from computerized laboratory files during 1990 to 1993. Population-based control patients were randomly selected from the organization's enrollment files. Exposures such as sexual activity and contraceptive practice were determined by interview. RESULTS: Of 1299 eligible women, 66% (96 case patients and 629 control patients) were interviewed. Case patients were more often unmarried and were more sexually active. Ninety-nine percent of case patients and 57% of control patients reported previous UTIs. Exposure to any type of condom during the previous year was reported by 53% of case patients and 31% of control patients. Exposure to spermicide-coated condoms during the previous month was associated with a higher risk of UTI (odds ratio [OR], 3.8; 95% confidence interval, 1.4-10.3). The OR for exposure during the previous year ranged from 2.2 (95% confidence interval, 1.0-4.8) for less than once weekly to 6.05 (95% confidence interval, 2.2-16.6) for more than twice weekly. In multivariate analyses, younger age (OR, 0.97 per year), intercourse frequency (OR, 1.2 per weekly episode), prior UTI (OR, 3.3), and frequency of exposure to spermicide-coated condoms (OR, 8.4 for more than once weekly and 10.9 for more than twice weekly) were independent predictors of UTI. Among women exposed to spermicide-coated condoms, 74% of UTIs caused by S saprophyticus were attributable to this exposure. CONCLUSIONS: Spermicide-coated condoms were associated with an increase risk of UTI caused by S saprophyticus. Because sexual activity and spermicide exposure are important risk factors for UTI caused by both S saprophyticus and E coli, it is likely that they share a similar pathogenesis.

Case-Control Studies↗

Role of O-linked carbohydrate of human urinary trypsin inhibitor on its lysosomal membrane-stabilizing property.

Human urinary trypsin inhibitor (UTI) was digested with various enzymes to obtain O-glycoside linked N-terminal glycopeptide (UTIm1), N-glycoside linked C-terminal tandem Kunitz-domains (domain I and II, UTIm2), UTI lacking O-glycoside (UTIc), asialo UTI (UTIa) and UTI lacking N-glycoside (UTIn). We investigated the membrane stabilizing effect of these UTI derivatives on rat renal lysosome by measurement of lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG) release after hypotonic treatment. Intact UTI suppressed NAG release, but aprotinin, gabexate mesilate (FOY), nafamostat mesilate (FUT) and recombinant domain II of UTI (R-020) had no effect, indicating that inhibition of serine proteases was not involved and the carbohydrate moiety of UTI might be necessary for this property. Among UTI derivatives, UTIm1, UTIm2, UTIm1+ UTIm2, and UTIc had no effect. In contrast, UTIa or UTIn suppressed NAG release. From these results, we conclude that O-glycoside linked core protein without N-glycoside is essential to the lysosomal membrane-stabilizing property of UTI.

Acetylglucosaminidase↗

Risk factors for recurrent urinary tract infection in 4,332 Belgian schoolchildren aged between 10 and 14 years.

UNLABELLED: To analyse the risk factors for recurrent urinary tract infection (UTI) and the possible influence of potty-training, a questionnaire with 41 questions was completed by 4,332 parents of children completing the last 2 years of normal primary school. Statistical analysis was done with the Chi-squared test and Yates correction. Three groups of children emerged: one without any history of UTI ( n=3818), a group with one actual or former UTI ( n=382) and a group with recurrent UTI ( n=132). Mean age was 11.5+/-0.56 years. A strong correlation between daytime and/or night-time wetting, voiding frequency of more than 10 times a day and nocturia and recurrent UTI was found. No correlation between these factors and a single UTI could be demonstrated. In the 343 bed-wetting children, equal infections for boys and girls were found. Potty-training started significantly earlier in children without UTI. Parents of children with recurrent UTIs insisted more when the first attempt to void was unsuccessful: in the group without UTI, most parents just postponed and had the child try later again. In the group with recurrent UTI, more parents asked the child to strain, made special noises or turned on a tap. CONCLUSION: Daytime with/without night-time wetting, more than 10 voidings a day and nocturia are indicators of recurrent urinary tract infections. If they are simultaneously present, the relative risk for recurrent urinary tract infections is 60%. Consequently, paediatricians should take urinary symptoms very seriously into account, and as incontinence is still a hidden condition, question the child on this topic.

Adolescent↗

Resistive index in febrile urinary tract infections: predictive value of renal outcome.

In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis is a challenge, particularly during infancy. In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured intrarenal resistive index (RI). We evaluated its ability to predict renal involvement as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. In total 157 patients admitted to the pediatric department of the Sişli Etfal Hospital with clinical signs of febrile UTI were included in the study. The children were divided into groups according to their age at the time of ultrasonography (US). RI was measured from the renal arteries with Doppler US in the first 72 h in all 157 children. Renal involvement was assessed by (99m)Tc-DMSA scintigraphy in the first 7 days after admission. The examination was repeated at least 6 months later if the first result was abnormal. All available patients with an abnormal scintigraphy underwent voiding cystourethrography 4-6 weeks after the acute infection. All patients with vesicoureteral reflux and scarred kidneys were excluded from the study. DMSA scintigraphy demonstrated abnormal changes in 114 of 157 children and was normal in the remaining 43 children. Of these 114 children, 104 underwent repeat scintigraphy, of whom 77 showed partially or totally reversible lesion(s). Of these 77 children, 17 children (22%) with vesicoureteral reflux were excluded. Thus, we compared the 43 children with lower UTI with the 60 children with definite acute pyelonephritis at admission. Kidneys with changes of acute pyelonephritis had a mean RI of 0.744+/-0.06 in infants, 0.745+/-0.03 in preschool children, and 0.733+/-0.09 in patients of school age with upper UTI. However, the mean RI was 0.703+/-0.06 in infants, 0.696+/-0.1 in preschool children, and 0.671+/-0.09 in school-aged patients with lower UTI. The mean RI values were significantly higher in patients with upper UTI ( P<0.001). There was a highly significant correlation between RI values and the severity of the renal lesion as ranked by DMSA scintigraphy ( P<0.001). When the cut-off RI value was 0.715, there was an 80% sensitivity and a 89% specificity for diagnosing upper UTI. Refluxing kidneys and scarred kidneys also had higher RI values. In conclusion, RI values were increased significantly in children with febrile UTI when renal parenchymal involvement (assessed by DMSA scintigraphy) was present. Our results also support the view that the children with high RI values are at a high risk of reflux, scarring, or both, which was frequently observed in febrile UTI. This might allow identification of patients at risk for severe renal lesions that require more aggressive therapy, investigation, and follow-up than those with lower UTI.

Child↗

Comparative evaluation of five chromogenic media for detection, enumeration and identification of urinary tract pathogens.

Five chromogenic agar plates--CPS ID2 medium (bioMérieux, France), CHROMagar Orientation medium (Becton Dickinson, France), UriSelect3 medium (Sanofi Diagnostics Pasteur, France), Rainbow Agar UTI medium (Biolog, USA) and Chromogenic UTI medium (Oxoid, Germany)--for the detection, enumeration and direct identification of urinary tract pathogens were compared using 443 urine specimens at two hospital laboratories. The enumeration of microorganisms was consistent on the five media for 403 of the 477 (84.5%) microorganisms. Chromogenic UTI, CPS ID2, UriSelect3, CHROMagar Orientation and Rainbow UTI gave detection rates of 98.3%, 97.9%, 97.3%, 96.9% and 94.1%, respectively, with some problems in yeast growth occurring on Rainbow UTI agar and problems in Staphylococcus spp. growth occurring on UriSelect3. For the direct identification of Escherichia coli, sensitivities were 93.8%, 88.5%, 86.1% and 82.2% for CHROMagar Orientation, CPS ID2, UriSelect3 and Rainbow UTI, respectively. Chromogenic UTI medium did not allow the accurate identification of Escherichia coli, since the indole reaction cannot be applied to this medium. Depending on the media, Enterococcus spp. could be identified at the genus or the species level. Slight differences were detected in the presumptive identification of the Proteus-Morganella-Providencia group and the Klebsiella-Enterobacter-Serratia group. Additionally, on Rainbow UTI agar, 12 of 20 Klebsiella pneumoniae strains and two of nine Pseudomonas aeruginosa strains were correctly identified. In conclusion, CPS ID2 medium and CHROMagar Orientation medium showed similar performance overall, while the UriSelect3, Rainbow UTI and Chromogenic UTI media require some improvement.

Agar↗

Immunological evaluation of urinary trypsin inhibitors in blood and urine: role of N- & O-linked glycoproteins.

Urinary trypsin inhibitors (uTi) suppress serine proteases during inflammation. After liberation from proinhibitors (P-alpha-I and I-alpha-I) by the white blood cell (WBC) response, uTi readily pass through the kidneys into urine. A key uTi, bikunin, is attached to O-linked and N-linked glycoconjugates. Recently, uTi inhibitors, called uristatins, were found to lack the O-linked glycoconjugates. Monoclonal antibodies were produced using purified uristatin and screened for binding differences to uristatin, bikunin, P-alpha-I, and I-alpha-I. Antibody-binding patterns were characterized using immunoaffinity binding onto protein-chip surfaces and analysis by Surface Enhanced Laser Desorption/Ionization mass spectrometry (SELDI), using specimens from patients and from purified uTi standards. Antibodies were developed and used in an enzyme-linked immunosorbent assay (ELISA) method for uTi measurement in urine and plasma specimens. ELISA was performed on specimens from normal, presumed healthy, controls and from patients who had been screened for inflammation using a high sensitivity C-reactive protein (CRP) test and a complete blood count (CBC). Polyclonal antibody against uTi showed cross-reactivity with the Tamm-Horsfall protein (THP) and with proinhibitors. Screening of anti-uTi monoclonal antibodies (Mab) revealed antibodies that did not cross-react with either of the above, thus providing a tool to measure both uristatin and bikunin in urine with Mab 3G5 and in plasma with Mab 5D11. The monoclonal antibody 5D11 cross-reacts with specific N-linked glycoconjugates of uristatin present in plasma. In ca 96% of healthy adults, uTi were present at <12 mg/l in urine and <4 mg/l in plasma. We also found that patients with an inflammation and a CRP of >2.0 mg/l had higher urinary concentrations of uTi than the control population in every subject. Free uristatin and bikunin pass readily into urine and are primarily bound to heavy chains that constitute the proinhibitor form in plasma.

Animals↗

N-acetyl-beta-D-glucosaminidase (NAG) and NAG isoenzymes in children with upper and lower urinary tract infections.

The use of N-acetyl-beta-D-glucosaminidase (NAG) to diagnose the site of urinary tract infection was studied in pediatric patients. Differentiation between upper and lower tract infections (UTI) was based on clinical grounds and on elevated erythrocyte sedimentation rate, C-reactive protein and fever. NAG excretion expressed as nmol X h-1 X mg-1 of urinary creatinine was higher in children with upper UTI (mean +/- SE 906 +/- 236) than in those with lower UTI (145 +/- 23) or healthy children (151.6 +/- 10) (p less than 0.01 by Duncan's test). In children with upper UTI, NAG excretion fell in parallel with the remission due to antibiotic treatment. This however was not seen in children treated with aminoglycosides. A specific and significant elevation (p less than 0.01) of the B isoenzyme of NAG was documented in children with upper UTI but not in those with lower UTI (B form in upper UTI 49.2% +/- 3.9 versus 21.9 +/- 3.3 in lower UTI; healthy children 18.9 +/- 3.4). The percentage of B isoenzyme excreted was high in two children with upper UTI but was low total NAG urinary excretion, suggesting that the quantification of isoenzymes offers further specificity in diagnosis. We conclude that the measurement of NAG and its isoenzymes in children with UTI provides useful information in the diagnosis of the site of infection.

Acetylglucosaminidase↗

The etiology of urinary tract infection: traditional and emerging pathogens.

The microbial etiology of urinary infections has been regarded as well established and reasonably consistent. Escherichia coli remains the predominant uropathogen (80%) isolated in acute community-acquired uncomplicated infections, followed by Staphylococcus saprophyticus (10% to 15%). Klebsiella, Enterobacter, and Proteus species, and enterococci infrequently cause uncomplicated cystitis and pyelonephritis. The pathogens traditionally associated with UTI are changing many of their features, particularly because of antimicrobial resistance. The etiology of UTI is also affected by underlying host factors that complicate UTI, such as age, diabetes, spinal cord injury, or catheterization. Consequently, complicated UTI has a more diverse etiology than uncomplicated UTI, and organisms that rarely cause disease in healthy patients can cause significant disease in hosts with anatomic, metabolic, or immunologic underlying disease. The majority of community-acquired symptomatic UTIs in elderly women are caused by E coli. However, gram-positive organisms are common, and polymicrobial infections account for up to 1 in 3 infections in the elderly. In comparison, the most common organisms isolated in children with uncomplicated UTI are Enterobacteriaceae. Etiologic pathogens associated with UTI among patients with diabetes include Klebsiella spp., Group B streptococci, and Enterococcus spp., as well as E coli. Patients with spinal cord injuries commonly have E coli infections. Other common uropathogens include Pseudomonas and Proteus mirabilis.Recent advances in molecular biology may facilitate the identification of new etiologic agents for UTI. The need for accurate and updated population surveillance data is apparent, particularly in light of concerns regarding antimicrobial resistance. This information will directly affect selection of empiric therapy for UTI.

Enterobacteriaceae↗

Urinary trypsin inhibitor reduces the release of histamine from rat peritoneal mast cells.

We determined the ability of urinary trypsin inhibitor (UTI), which is a Kunitz-type protease inhibitor present in serum and in urine, to inhibit rat peritoneal mast cell (RPMC) mediator release induced by several stimuli. UTI attenuated the immunoglobulin E-mediated release of both preformed (histamine) and newly formed (leukotriene C4) mediators from RPMCs. Inhibition (21%+/-5%) of the anti-IgE-triggered release of histamine was observed after a 30-minute incubation of RPMCs with UTI (5 micromol/L). To investigate the specificity of the UTI effect, we studied the stimulatory activity of phorbol ester (phorbol 12-myristate 13-acetate (PMA)) or calcium ionophore A23187 in control and UTI-treated mast cells. The efficacy of UTI as an inhibitor was dependent on the nature of the stimulus, because histamine release induced by PMA-mediated or calcium ionophore A23187-mediated processes was not inhibited by UTI. A series of structurally distinct protease inhibitors did not inhibit IgE-induced release of mediators from RPMCs. The Kunitz-type protease inhibitors are important in the regulation of RPMC function. In parallel with the UTI-related decrease in anti-IgE stimulatory activity on mediator release, increased microviscosity of membrane lipids could be observed by two independent experiments on fluorescence polarization with diphenylhexatriene (DPH) and on the fluorescence probe fluorescein isothiocyanate-concanavalin A. UTI reduces mediator release by a mechanism-possibly an interruption of the coupling of receptor and effector systems-because UTI acts as an agent to decrease biologic lipid membrane fluidity.

Animals↗