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Combination assay of urinary free L-fucose and trypsin inhibitor may be useful indicators of disease activity in patients with hematologic malignancies.

L-Fucose is a monosaccharide located at the non-reducing ends of sugar chains of glycoconjugates. Urinary L-fucose (U-FC) is excreted as free L-fucose, and clinically useful as a tumor marker of digestive organ cancers. We evaluated the clinical usefulness of U-FC levels in patients with various hematologic malignancies because U-FC for hematologic malignancies has only rarely been described. The mean U-FC levels in the acute nonlymphocytic leukemia (ANLL), myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) groups were significantly higher than in the control group (P < 0.05). Recently, we reported that urinary trypsin inhibitor (UTI) levels in patients with ANLL, MDS, non-Hodgkin's lymphoma and multiple myeloma were significantly elevated, compared with those in healthy adult volunteers. Noninvasive combination assays of UTI and U-FC may have a higher accuracy in diagnosis of ANLL and MDS than those of UTI or U-FC alone. UTI and U-FC combination assays, noninvasive for patients, could be expanded as useful indicators in hematologic malignancies.

Biomarkers↗

Systematic review of risk factors for urinary tract infection in adults with spinal cord dysfunction.

Recurrent urinary tract infections (UTIs) occur frequently in persons with neurogenic bladders due to spinal cord dysfunction, resulting in increased morbidity and cost. The authors conducted a systematic review to identify risk factors for UTI using controlled clinical trials, cohort, and cross-sectional studies that assessed risk factors for UTI and included bacteriuria or UTI as an outcome. Twenty-two studies met the inclusion criteria. Quality assessment revealed important methodological deficiencies. Two studies provide evidence supporting increased bladder residual volume as a risk factor. Most of the retrieved studies investigated method of drainage with the consistent finding that persons using intermittent catheterization had fewer infections than those with indwelling catheters. There is conflicting evidence over the value of sterile or "no touch" catheter techniques compared with clean intermittent catheterization. There is insufficient evidence to assess risk due to psychosocial, behavioral, and hygiene factors; sex; level of function; and time since injury.

Adult↗

Evaluation of cranberry supplement for reduction of urinary tract infections in individuals with neurogenic bladders secondary to spinal cord injury. A prospective, double-blinded, placebo-controlled, crossover study.

OBJECTIVE: To determine the effectiveness of cranberry supplement at preventing urinary tract infections (UTIs) in persons with spinal cord injury (SCI). DESIGN: A prospective, double-blinded, placebo-controlled, crossover study. PARTICIPANTS: 21 individuals with neurogenic bladders secondary to SCI. MAIN OUTCOME MEASURES: Favorable or unfavorable response of cranberry supplement vs placebo on urinary bacterial counts and white blood cell (WBC) counts and the combination of bacterial and WBC counts. METHODS: Individuals with neurogenic bladders due to SCI were recruited and randomly assigned to standardized 400-mg cranberry tablets or placebo 3 times a day for 4 weeks. After 4 weeks and an additional 1-week "washout period," participants were crossed over to the other group. Participants were seen weekly, during which a urine analysis was obtained. UTI was defined as significant bacterial or yeast colony counts in the urine and elevated WBC counts (WBC count > or = 10 per high power field) in centrifuged urine. Participants with symptomatic infections were treated with appropriate antibiotics for 7 days and restarted on the cranberry tablet/ placebo after a 7-day washout period. Urinary pH between the cranberry and placebo groups was compared weekly. Data were analyzed using the Ezzet and Whitehead's random effect approach. RESULTS: There was no statistically significant treatment (favorable) effect for cranberry supplement beyond placebo when evaluating the 2 treatment groups for bacterial count, WBC count, or WBC and bacterial counts in combination. Urinary pH did not differ between the placebo and cranberry groups. CONCLUSION: Cranberry tablets were not found to be effective at changing urinary pH or reducing bacterial counts, urinary WBC counts, or UTIs in individuals with neurogenic bladders. Further long-term studies evaluating specific types of bladder management and UTIs will help to determine whether there is any role for the use of cranberries in individuals with neurogenic bladders.

Colony Count, Microbial↗

Nitrite and leukocyte dipstick testing for urinary tract infection in individuals with spinal cord injury.

OBJECTIVE: To determine sensitivity, specificity, and positive and negative predictive values of nitrite (NIT) and leukocyte esterase (LE) testing in relation to laboratory evidence of significant bacteriuria and urinary tract infection (UTI) in persons with spinal cord injury (SCI). DESIGN: Monthly urine cultures were compared with results of dipstick testing. SETTING: Community based. METHODS: Fifty-six people with SCI were evaluated on a monthly basis with dipstick testing for NIT and LE as well as urine cultures. Participants reported whether they believed that they had a UTI and, if so, whether they were treated for the UTI and what symptoms they had experienced. RESULTS: The sensitivity rate for the most comprehensive criteria--defined as positive NIT test, a positive LE positive, or both a positive NIT test and positive LE test--was 0.64 and the specificity rate was only 0.52. No single type of bacteria was found to occur in more than 30% of the urine samples. CONCLUSION: Reliance on dipstick testing for NIT and LE in individuals with SCI can lead to high rates of overtreatment for UTI, given the fact that regular catheterization is associated with significant bacteriuria. Individuals with SCI should be evaluated with urine culture to ensure proper treatment.

Adult↗

A single dose of aztreonam in the prevention of urinary tract infections in elderly catheterized patients.

We have compared the effects of aztreonam and placebo in the prevention of urinary tract infections (UTI) in elderly hospitalized patients who needed urethral catheterization. 162 patients (96 males, 66 females; age range 60-91 years) were randomly allocated to receive double-blind a single dose of aztreonam (2 g i.m. 80 patients) or placebo (4 ml lidocaine 2%, 82 patients) three hours before catheterization. All patients were followed-up for 7 days. Urine culture was performed before, at the first, third and seventh day of catheterization. At the end of follow-up 71/80 patients (88.7%) who received a single preventing dose of aztreonam had negative urine culture without clinical signs of UTI. On the contrary, in the group treated with placebo at the end of follow-up only 38/82 patients (46.3%) had negative urine without clinical signs of UTI. In conclusion, our data suggest that a single 2g i.m. dose of aztreonam is effective in preventing UTI in elderly patients needing indwelling urethral catheterization.

Aged↗

Development of an ELISA test for determination of the urinary trypsin inhibitor: analytical performance and applications.

Increased urinary excretion of urinary trypsin inhibitor (UTI) has been reported in various inflammatory conditions and in Alzheimer's subjects, but its diagnostic potential remains to be elucidated. A reliable and specific enzyme-linked immunosorbent assay (ELISA) test for the determination of the UTI in human urine was developed. This assay was performed using 96-well microtiter plates. The plate surface is coated with an anti-UTI polyclonal antibody, the urine sample was added in a dilution range, and the detection was achieved using the enzyme-conjugated antibody. The assay was quantified by the build-up of colored product upon the addition of the substrate. Recoveries were 93%, and the intra- and inter-assay CVs were 4.25% and 21%, respectively. The ELISA showed parallelism of standard and urine samples and no significant interference by the biological matrix. The usefulness of the assay has been demonstrated by applying it to urine samples from Alzheimer's disease patients, and comparing with negative controls. UTI urinary levels are significantly increased in Alzheimer's subjects.

Aged↗

Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart.

Neutrophils migrate to infected mucosal sites that they protect against invading pathogens. Their interaction with the epithelial barrier is controlled by CXC chemokines and by their receptors. This study examined the change in susceptibility to urinary tract infection (UTI) after deletion of the murine interleukin 8 receptor homologue (mIL-8Rh). Experimental UTIs in control mice stimulated an epithelial chemokine response and increased chemokine receptor expression. Neutrophils migrated through the tissues to the epithelial barrier that they crossed into the lumen, and the mice developed pyuria. In mIL-8Rh knockout (KO) mice, the chemokine response was intact, but the epithelial cells failed to express IL-8R, and neutrophils accumulated in the tissues. The KO mice were unable to clear bacteria from kidneys and bladders and developed bacteremia and symptoms of systemic disease, but control mice were fully resistant to infection. The experimental UTI model demonstrated that IL-8R-dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells. Patients prone to acute pyelonephritis also showed low CXC chemokine receptor 1 expression compared with age-matched controls, suggesting that chemokine receptor expression may also influence the susceptibility to UTIs in humans. The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.

Animals↗

Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens.

This study evaluated whether trimethoprim-sulfamethoxazole (TMP-SMX) is effective for treatment of uncomplicated urinary tract infections (UTIs) due to TMP-SMX-resistant (TMP-SMX-R) pathogens. Healthy nonpregnant premenopausal women with symptomatic lower UTI were assessed for the presence of pyuria and bacteriuria; if either was present, a urine sample was cultured and TMP-SMX was prescribed. Clinical and microbiologic cure was assessed at days 5-9 and 28-42 after cessation of therapy. For 71%, of patients, cultures grew TMP-SMX-susceptible (TMP-SMX-S) microorganisms, and for 29%, cultures grew TMP-SMX-R organisms. Escherichia coli remained the predominant bacteria in both groups of cultures. At visit 2, microbiological cure had been achieved in 86% of the patients in the TMP-SMX-S group and 42% of those in the TMP-SMX-R group. Similar differences were found at visit 3 by clinical evaluation. Treatment with TMP-SMX of uncomplicated UTI caused by TMP-SMX-R microorganisms results in microbiologic and clinical failure. In high-resistance areas, TMP-SMX should not be the empiric drug of choice for uncomplicated UTI.

Adult↗

The role of bacterial virulence and host factors in patients with Escherichia coli bacteremia who have acute cholangitis or upper urinary tract infection.

We studied the pathogenic role of host and Escherichia coli virulence factors in the development of E. coli bacteremia in patients with acute cholangitis (AC) or upper urinary tract infection (UTI). Isolates recovered from 75 adult patients consecutively admitted to the hospital with E. coli bacteremia caused by AC (n=24) or upper UTI (n=51) were evaluated, as were 30 fecal strains isolated from healthy control individuals. Virulence genes of E. coli were detected by polymerase chain reaction analysis, including papG genes (classes I-III), sfa/foc, fimH, afa, hlyA, cnf1, and iutA. Our results show that biliary tract obstruction and urinary tract obstruction are important host factors for the development of E. coli bacteremia in patients with AC and upper UTI, respectively. With regard to E. coli virulence factors, the papG class II gene might play a more important role in the development of E. coli bacteremia in patients with upper UTI than in those with AC.

Acute Disease↗

A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury.

BACKGROUND: Urinary tract infection (UTI) is common among patients with spinal cord injury. The optimal duration of treatment for symptomatic UTI has not been determined. METHODS: A randomized, double-blind, placebo-controlled trial compared 3-day and 14-day regimens of ciprofloxacin, 250 mg twice daily, for the treatment of acute UTI in patients with spinal cord injury. Patients with pyelonephritis, struvite stones, hydronephrosis, or long-term indwelling catheters were excluded from the trial. RESULTS: Sixty patients with spinal cord injury were enrolled in the trial, with 30 patients assigned to each study arm. The most common infecting organisms were Klebsiella species (30%), Enterococcus species (22%), and Escherichia coli (22%); 33% of the infections were polymicrobial. Microbiological cure at long-term follow-up was significantly better among patients who received therapy for 14 days than among patients who received therapy for 3 days. By 6 weeks of follow-up, microbiological relapse (in 11 [37%] of 30 patients vs. 2 [7%] of 30 patients; 95% confidence interval [CI], 1.38-3.18; P=.01) and symptomatic relapse (in 7 [23%] 30 patients vs. 0 of 30 patients; 95% CI, 1.69-3.13; P=.01) both occurred more frequently in patients treated for 3 days. Reinfection occurred with similar frequency in patients in the 2 study arms. Six of 7 evaluable patients with treatment failure had a fluoroquinolone-resistant organism isolated at enrollment. CONCLUSIONS: For patients with spinal cord injury, treatment of acute symptomatic UTI for 14 days leads to improved clinical and microbiological outcomes, compared with short-course therapy.

Acute Disease↗

Nosocomial infections in combined medical-surgical intensive care units in the United States.

OBJECTIVE: To describe the epidemiology of nosocomial infections in combined medical-surgical (MS) intensive care units (ICUs) participating in the National Nosocomial Infection Surveillance (NNIS) System. DESIGN: Analysis of surveillance data on 498,998 patients with 1,554,070 patient-days, collected between 1992 and 1998 from 205 MS ICUs following the NNIS Intensive Care Unit protocol, representing 152 participating NNIS hospitals in the United States. RESULTS: Infections at three major sites represented 68% of all reported infections (nosocomial pneumonia, 31%; urinary tract infections (UTIs), 23%; and primary bloodstream infections (BSIs), 14%: 83% of episodes of nosocomial pneumonia were associated with mechanical ventilation, 97% of UTIs occurred in catheterized patients, and 87% of primary BSIs in patients with a central line. In patients with primary BSIs, coagulase-negative staphylococci (39%) were the most common pathogens reported; Staphylococcus aureus (12%) was as frequently reported as enterococci (11%). Coagulase-negative staphylococcal BSIs were increasingly reported over the 6 years, but no increase was seen in candidemia or enterococcal bacteremia. In patients with pneumonia, S. aureus (17%) was the most frequently reported isolate. Of reported isolates, 59% were gram-negative bacilli. In patients with UTIs, Escherichia coli (19%) was the most frequently reported isolate. Of reported isolates, 31% were fungi. In patients with surgical-site infections, Enterococcus (17%) was the single most frequently reported pathogen. Device-associated nosocomial infection rates for BSIs, pneumonia, and UTIs did not correlate with length of ICU stay, hospital bed size, number of beds in the ICU, or season. Combined MS ICUs in major teaching hospitals had higher device-associated infection rates compared to all other hospitals with combined medical-surgical units. CONCLUSIONS: Nosocomial infections in MS ICUs at the most frequent infection sites (bloodstream, urinary, and respiratory tract) almost always were associated with use of an invasive device. Device-associated infection rates were the best available comparative rates between combined MS ICUs, but the distribution of device-associated rates should be stratified by a hospital's major teaching affiliation status.

Cross Infection↗

Urinary tract infections in long-term-care facilities.

Urinary tract infection (UTI) is the most common bacterial infection occurring in residents of long-term-care facilities. It is a frequent reason for antimicrobial administration, but antimicrobial use for treating UTIs is often inappropriate. Achieving optimal management of UTI in this population is problematic because of the very high prevalence of bacteriuria, evidence that the treatment of asymptomatic bacteriuria is not beneficial, and the clinical and microbiological imprecision in diagnosing symptomatic UTI. This position paper has been developed, using available evidence, to assist facilities and healthcare professionals in managing this common problem.

Age Distribution↗

Surveillance of nosocomial infections in a neurologic intensive care unit.

OBJECTIVE: To assess data on the epidemiology of nosocomial infection (NI) among neurologic intensive care patients. DESIGN: Prospective periodic surveillance study. SETTING: An 8-bed neurologic intensive care unit (ICU). PATIENTS: All those admitted for more than 24 hours during five 3-month periods between January 1999 and March 2003. METHODS: Standardized surveillance within the German infection surveillance system. RESULTS: Three hundred thirty-eight patients with a total of 2,867 patient-days and a mean length of stay of 8.5 days were enrolled during the 15-month study period. A total of 71 NIs were identified among 52 patients. Urinary tract infections (UTIs) were the most frequent NI (36.6%), followed by pneumonia (29.6%) and bloodstream infections (BSIs) (15.5%). The overall incidence and incidence density of NIs were 21.0 per 100 patients and 24.8 per 1,000 patient-days, respectively. Incidence densities were 9.8 UTIs per 1,000 urinary catheter-days (CI95, 6.4-14.4), 5.6 BSIs per 1,000 central venous catheter-days (CI9s, 2.8-10.0), and 12.8 cases of pneumonia per 1,000 ventilation-days (Cl95, 8.0-19.7). Device-associated UTI and pneumonia rates were in the upper range of national and international reference data for medical ICUs, despite the intensive infection control and prevention program in operation in the hospital. CONCLUSION: Neurologic intensive care patients have relatively high rates of device-associated nosocomial pneumonia and UTI. For a valid comparison of surveillance data and implementation of targeted prevention strategies, we would strongly recommend provision of national benchmarks for the neurologic ICU setting.

Cross Infection↗

Sharing of virulent Escherichia coli clones among household members of a woman with acute cystitis.

BACKGROUND: Within-household transmission of extraintestinal pathogenic Escherichia coli (ExPEC) may contribute to the pathogenesis of urinary tract infection (UTI), but this is poorly understood. METHODS: A woman with acute UTI, 4 human household members who cohabited with her, and the family's pet dog underwent prospective longitudinal surveillance for colonizing E. coli for 7-9 weeks after the woman's UTI episode. Unique clones were resolved by random amplified polymorphic DNA and pulsed-field gel electrophoresis analysis. Virulence genes, phylogenetic group, and O types were defined by PCR. Comparisons with reference strains were made using random amplified polymorphic DNA profiling. RESULTS: Serial fecal and urine samples from the 6 household members yielded 7 unique E. coli clones (4 of which were ExPEC and 3 of which were non-ExPEC). For 3 clones, extensive among-host sharing was evident in patterns suggesting host-to-host transmission. The mother's UTI clone, which represented E. coli O1:K1:H7, was the clone that was most extensively shared (in 5 hosts, including the dog) and most frequently recovered (in 45% of samples and at all 3 time points). The other 3 ExPEC clones corresponded with E. coli O6:K2:H1, O1:K1:H7, and O2:F10,F48. CONCLUSIONS: E. coli clones, including ExPEC, can be extensively shared among human and animal household members in the absence of sexual contact and in patterns suggesting host-to-host transmission.

Acute Disease↗

Inverse association of H2O2-producing lactobacilli and vaginal Escherichia coli colonization in women with recurrent urinary tract infections.

Women with recurrent urinary tract infection (UTI) often demonstrate persistent vaginal colonization with Escherichia coli. Since strains of lactobacilli that produce hydrogen peroxide inhibit the growth of E. coli, the absence of these strains may predispose to E. coli colonization and to UTI. To test this hypothesis, vaginal introital cultures were obtained from 140 women, 65 with recurrent UTI (case-patients) and 75 without (controls). Vaginal E. coli colonization was significantly more frequent in case-patients than controls (35% vs. 11%; P < .001) and in women without H2O2-positive lactobacilli than in women with (odds ratio [OR], 4.0; P = .01). Spermicide use was associated with greater risk of vaginal E. coli colonization (OR, 12.5; P < .001) and with absence of H2O2-positive lactobacilli (OR, 2.9; P = .04). The inverse association between H2O2-positive lactobacilli and vaginal E. coli colonization remained in case-patients after controlling for spermicide use (OR, 6.5; P = .02). Thus, absence of H2O2-positive lactobacilli may be important in the pathogenesis of recurrent UTI by facilitating E. coli introital colonization.

Adult↗

An approach to evaluating antibacterial agents in the treatment of urinary tract infection.

The evaluation of antibacterial therapy for urinary tract infection (UTI) is based on the results of randomized, controlled comparative studies (preferably double-blinded) in which sufficient numbers of patients are entered into both arms to ensure statistical validity. Since the term UTI encompasses a broad array of clinical syndromes (acute uncomplicated UTI; acute uncomplicated pyelonephritis; complicated UTI; and asymptomatic bacteriuria), the design of clinical studies should include a careful definition of the clinical syndromes being studied, the course of therapy prescribed, and the microbiological characterization necessary for evaluability. End points to be considered in the evaluation of new therapies include the effect of therapy on clinical symptoms; the ability of the therapy to eradicate the original infecting organism; the incidence of reinfection posttherapy; the number of instances of primary drug resistance of the infecting inoculum; and the incidence of adverse effects with a particular regimen.

Acute Disease↗

Virulence characteristics of Escherichia coli in relation to host response in men with symptomatic urinary tract infection.

To assess virulence properties in uropathogenic Escherichia coli isolates from men with symptomatic urinary tract infection (UTI), we analyzed 88 urinary isolates from men with acute pyelonephritis (n = 41), febrile UTI without clinical signs of renal infection (n = 33), or acute cystitis (n = 14) for O:K:H serotype, P fimbriae, and production of hemolysin and aerobactin. In the three diagnostic groups, 88%, 67%, and 79% of the strains, respectively, were represented by 10 O antigen groups commonly associated with acute pyelonephritis in women and children. Fifty-eight different O:K:H serotypes could be identified, of which O18ac:K5:H- predominated (n = 8). There was a higher frequency of hemolytic strains among patients with pyelonephritis (73%) and febrile UTI (76%) and a lower frequency of P-fimbriated strains (56% and 45%, respectively) and aerobactin-positive strains (51% and 39%, respectively) among these patients than was previously encountered in women and children with uncomplicated acute pyelonephritis. The distribution of bacterial properties was unrelated to patient age and underlying complicating factors. The findings suggest differences in host-parasite relationships between men and women with symptomatic UTI caused by E. coli.

Adult↗

Recurrent urinary tract infections in female patients: an overview of management and treatment.

Several major factors have contributed to the current availability of highly successful techniques for the management of recurrent urinary tract infection (UTI) in female patients. Since UTI cannot be diagnosed by symptoms alone, greater accuracy in diagnostic techniques that establish whether bacteria in the voided urine are present in the bladder urine is the most important factor. Second, the recognition that almost all recurrent UTIs are reinfections is crucial. Third, it has been observed that bacteriuria in female patients is preceded by colonization of the introital mucosa of the vagina and urethra with Enterobacteriaceae from the rectal flora; it is at these sites that oral antimicrobial agents can determine the character of subsequent reinfections of the urinary tract. A fourth factor is the development of highly effective prophylactic regimens, including trimethoprim-sulfamethoxazole, nitrofurantoin, cinoxacin, and cephalexin. In addition, the management of patients with UTI has improved because correctable causes of bacterial persistence are now well recognized and there is an improved understanding of the kinds of patients at increased risk. Finally, new antimicrobial agents with more favorable pharmacokinetic properties have become available.

Anti-Bacterial Agents↗