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Fleroxacin in complicated urinary tract infections.

The clinical evaluation of antimicrobial agents for the treatment of urinary tract infections (UTIs) requires clinically useful categorization of patients plus concurrent laboratory diagnosis. Appropriate diagnostics include (1) proper collection techniques, (2) quantitative urine culture, (3) urinalysis to determine pyuria, and (4) radiological, urological and gynecological evaluation. Categorization of patients suffering from UTIs should take into consideration (1) the site of infection, (2) the clinical presentation, (3) the frequency of infections, and (4) the coexistence of complicating factors. UTIs in men and older women are mostly complicated. The characterization of a UTI as complicated or uncomplicated is important since in the former condition, multiresistant nosocomial microorganisms are frequently encountered. Experience with fleroxacin 200 or 400 mg once daily (o.d.) in > 1,000 patients with complicated UTIs in noncomparative and comparative trials with other quinolones and cephalosporins has been very promising, with overall clinical and bacteriological cure rates of 86-95 and 89-95%, respectively. As with other quinolones, relapses and superinfections were mostly attributed to Enterococcus, Staphylococcus and Pseudomonas spp. The reported results make oral o.d. fleroxacin appropriate as an alternative to parenteral antimicrobials or for intravenous-to-oral switch therapy in complicated UTIs.

Anti-Bacterial Agents↗

Urinary trypsin inhibitor has a protective effect on the amnion.

Urinary trypsin inhibitor-related substance (UTI-R) was measured in the amniotic fluid (n = 30), first neonatal urine (n = 10), meconium (n = 10), and adult urine (n = 10). The concentration of UTI-R excreted in the neonatal urine was significantly higher than in adult urine and meconium. Positive immunostaining for UTI was observed in amnion, umbilical cord and placenta. The effect of UTI was studied on the amnion using fura-2-acetoxymethyl ester. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-beta (TNF-beta) led to a significant increase in relative fluorescence release (RFR) of fura-2 (p < 0.05 and p < 0.02, respectively) while endotoxin did not show significant changes of RFR of fura-2. The effect of IL-1 beta and TNF-beta was almost abolished after incubation of UTI with the amnion cells (p < 0.03). This suggests that UTI may have a protective effect on the amnion especially against IL-1 beta and TNF-beta.

Amnion↗

Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo.

Tissue factor (TF) plays a critical role in the pathogenesis of disseminated intravascular coagulation (DIC) observed in patients with septic shock. Urinary trypsin inhibitor (UTI), a multivalent protease inhibitor, is currently used for treatment of patients with septic shock. This study was undertaken to determine whether UTI reduces LPS-induced coagulation abnormalities by inhibiting lipopolysaccharide (LPS)-induced expression of TF by monocytes. UTI inhibited LPS-induced increases in both TF activities and TF mRNA expression in monocytes without affecting the viability. Although activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and extracellular signal-regulated kinase (ERK)1/2 were shown to be critically involved in LPS-induced increases in TF activities in isolated monocytes, UTI inhibited phosphorylation of ERK1/2 and decreased expression of early growth response factor-1 (Egr-1) induced by LPS without affecting the activation of NF-kappaB and AP-1. UTI inhibited both the expression of TF mRNA in whole blood, increases in TF activities in mononuclear cells, and increases in serum levels of fibrin and fibrinogen degradation products (E) in rats given LPS without affecting the number of monocytes in the peripheral blood. Taken together these results strongly suggested that UTI might reduce LPS-induced coagulation abnormalities in rats by inhibiting TF expression in monocytes through inhibition of Egr-1 expression.

Animals↗

Prevalence of delirium and urinary tract infection in a psychogeriatric unit.

A retrospective study involving 407 patients discharged over a 2-year period from a psychogeriatric unit found that 83 (20.4%) had urinary tract infection (UTI) and 54 (13.3%) had delirium diagnoses at admission. Of the 54 with delirium, 14 (25.9%) had UTI. Of these 14 patients, delirium cleared in nine (64.3%) after appropriate treatment of UTI, two (14.3%) improved with treatment of concomitant medical disorders, and three (21.4%) did not improve. Only six of the 14 (42.8%) showed symptoms of UTI, with only one of the 14 (7.1%) showing fever and leukocytosis. Urine analyses were abnormal in all cases with 13/14 (92.8%) having positive cultures. Dementia was an associated risk factor in 71.4% of the 14 patients with UTI and delirium. Clinicians need to have a high index of suspicion relative to the presence of UTI in the elderly, especially with pre-existing cognitive impairment, since it can precipitate delirium. Early recognition and appropriate treatment decreases morbidity.

Aged↗

Comparison of trimethoprim-sulfamethoxazole, cephadroxil and cefprozil as prophylaxis for recurrent urinary tract infections in children.

The aim of this study was to compare the efficacy of prophylactic trimethoprim-sulfamethoxazole (TMP/SMZ), cefprozil and cephadroxil treatments in children who have recurrent urinary tract infection, but no urinary tract pathology. After acute urinary tract infections (UTIs) were treated, the patients were divided into 3 groups randomly and TMP/SMZ was given to 21 patients, cephadroxil was given to 25 patients and cefprozil was given to 34 patients for 3 months--one dose at night. All patients were followed for 6 months following prophylaxis. The frequency of symptomatic UTIs among groups during prophylaxis was not statistically different, however the number of symptomatic UTIs in the cephadroxil group was lower than the other groups. Asymptomatic bacteriuria episodes were detected in TMP/SMZ and cefprozil groups, whereas no asymptomatic bacteriuria episodes were seen in the cephadroxil group. The number of patients with symptomatic UTI during the follow-up period was not different between groups, however all the asymptomatic bacteriuria episodes were encountered in the cefprozil group. In conclusion, in this study cephadroxil was found to be slightly superior to TMP/SMZ and cefprozil in preventing asymptomatic bacteriuria episodes and symptomatic UTIs in children with recurrent UTI and normal urinary tract system.

Administration, Oral↗

The prevalence of urinary tract infections and sexually transmitted disease in women with symptoms of a simple urinary tract infection stratified by low colony count criteria.

OBJECTIVES: Urinary tract infections (UTIs) and early pelvic infections due to sexually transmitted disease (STD) may cause similar symptoms. Therefore, a simple history and urine dip to establish a diagnosis of UTI may result in overtreatment of UTIs and undertreatment of STDs. The objective of this study was to determine the proportion of women with symptoms suggestive of a UTI who are urine culture positive versus urine culture negative, the prevalence of STDs between groups, and if elements of the history or examination may predict those requiring STD screening. METHODS: This was a prospective cohort study in an urban emergency department. Women 18-55 years of age with urinary frequency, urgency, dysuria, and no new vaginal discharge or change in discharge were enrolled. The following were performed: detailed history; bladder catheterization for urinalysis, urine dip, and urine culture; pelvic examination and cervical samples for gonorrhea and Chlamydia trachomatis DNA ligase; and wet mount examinations. Main outcome measurements were the percentage of women who were urine culture positive (using low count criteria of 10(2) colony-forming units [CFU]/mL), the proportion of STDs between urine culture groups, and univariate analysis and logistic regression of historical and examination elements. RESULTS: Ninety-two patients were enrolled; the mean age was 26 years (range, 18-51 years). All had samples for DNA ligase (one quantity not sufficient) and urinalysis or urine dip, while 75 of 92 had urine cultures performed. A total of 57.3% (43/75) were urine culture positive at 10(2) CFU/mL, while the STD rate for those with urine cultures was 17.3% (13/75). There was no statistically significant difference in the number of STDs between urine culture positive and urine culture negative groups. The only variable on logistic regression predictive of an STD (based on all 91 patients) was more than one sex partner in the past year (p = 0.013). No other element of the history or pelvic examination helped differentiate those who tested positive for an STD. CONCLUSIONS: A total of 17.3% of women with symptoms of a UTI in this study had an STD, while only 57.3% were urine culture positive by catheterization using low count criteria. The proportion of STDs between those with and without a UTI was not significantly different.

Adolescent↗

Ultrasound of the pelvis and renal tract combined with a plain film of abdomen in young women with urinary tract infection: can it replace intravenous urography? A prospective study.

Urinary tract infection (UTI) is common in women and intravenous urography (IVU) is a frequently requested radiological investigation for recurrent UTI. The aim of this study was to assess whether pelvic and renal ultrasound combined with a plain film of the abdomen (KUB) could replace IVU as the initial radiological investigation in young women with recurrent UTI. Ninety-four young women with recurrent UTI who were referred for IVU were studied. Ultrasound of the pelvis and renal tract was performed, and information obtained from ultrasound and KUB was compared with that obtained from the IVU examination. Patient management was altered as a result of radiological investigation in eight cases. A case of staghorn calculus and a case of pelviureteric junction obstruction were diagnosed by both IVU and ultrasound with KUB. An intrarenal abscess was diagnosed by ultrasound in a patient with a normal IVU. In addition ultrasound demonstrated significant findings in the pelvis, including ovarian and uterine abnormalities and an ectopic and an intrauterine pregnancy. In all cases the patient had symptoms referable to the urinary tract and a history of documented UTI. The KUB did not yield any unsuspected finding not diagnosed by ultrasound, but did serve to delineate more clearly the extent of calculus disease in two patients. We suggest that ultrasound of the pelvis and renal tract combined with a KUB should be the radiological investigation of choice in young women with UTI.

Adolescent↗

Distribution of uropathogenic virulence factors among Escherichia coli strains isolated from dogs and cats.

A variety of virulence factors (VFs) such as type 1 fimbriae, pilus associated with pyelonephritis, S fimbriae, afimbrial adhesin, alpha-hemolysin, aerobactin and cytotoxic necrotizing factor 1 are associated with uropathogenic Escherichia coli. In this study, 80 uropathogenic E. coli strains in 50 dogs and 30 cats suffering from UTI. In addition, 60 E. coli strains were isolated from fecal samples from 30 each of healthy dogs and cats. The distribution of VFs of uropathogenic E. coli strains isolated from dogs and cats suffering from urinary tract infections (UTI) were examined by the colony hybridization test with seven DNA probes specific for VFs, and the results were compared with those obtained in the studies on strains from humans with UTI. In uropathogenic E. coli strains isolated from dogs and cats suffering from UTI, VFs were detected as frequently as in the strains isolated from humans with UTI. Although less frequently, genes encoding these VFs especially pap, sfa, hly, and cnf 1 genes were also associated with E. coli strains isolated from feces of healthy cats, in contrast to the distribution pattern of uropathogenic E. coli observed in humans. Furthermore, all VFs except pil were significantly more frequently detected in strains isolated from urine of animals with cystitis than in those isolated from feces of healthy humans. These results indicate that VFs of E. coli contribute to the pathogenesis of UTI in dogs and cats.

Adhesins, Bacterial↗

Minimum incidence and diagnostic rate of first urinary tract infection.

OBJECTIVE: To study awareness of urinary tract infections (UTIs) by determining the diagnostic rate of first UTI in children <2 years of age and to estimate the minimum incidence. METHODS: Twenty-six of a total of 43 pediatric centers participated in the study. Sixty-four percent of the total childhood population <2 years of age was covered. The number of all children included in the study was used to calculate the diagnostic rate. Only UTI confirmed by either suprapubic aspiration (any growth) or midstream or bag samples with >/=100 000 bacteria/mL, together with a positive nitrite reaction, was used to estimate the minimum incidence. RESULTS: The mean diagnostic rate was 1.5% for boys (range, 0.7%-3.0%) and 1.7% for girls (range, 0.7%-2.9%). The diagnostic rate was significantly higher in June than in December. The mean incidence was 1.0% for both boys and girls (range, 0.3%-3.0% and 0.4%-2.9%, respectively). The minimum cumulative incidence at 2 years of age was estimated to be 2.2% for boys and 2.1% for girls. CONCLUSION: This study suggests a high UTI awareness in Sweden as indicated by a higher diagnostic rate and, despite stricter diagnostic criteria, a higher incidence of UTI in children <2 years of age than previously reported. It is suggested that a high UTI awareness may reduce chronic renal failure because of pyelonephritic renal scarring.

Female↗

Antibiotic sensitivity profiles do not reliably distinguish relapsing or persisting infections from reinfections in cats with chronic renal failure and multiple diagnoses of Escherichia coli urinary tract infection.

Older cats with chronic renal failure (CRF) commonly develop urinary tract infections (UTI). Uropathogenic Escherichia coli (UPEC) is identified as the causal agent of UTI in most affected cats. Infections are often complicated, and UPEC infections may persist or recur in these cats. Antibiotic sensitivity profiles have been used to distinguish relapsing or persisting UTI from reinfection by different clones of the same species. However, the accuracy with which antibiograms discriminate different urinary E coli clones in cats is uncertain. We studied 17 cystocentesis-derived UPEC isolates collected from 5 cats with stable CRF and multiple diagnoses of UTI. UTIs were classified as relapses versus persistent infections or reinfections using antibiograms determined by Kirby-Bauer discs and Etests. Subsequently, clonality of UPEC isolates was determined by pulsed-field gel electrophoresis (PFGE). A comparison of PFGE results with antibiograms indicated that antibiotic resistance patterns varied considerably within several individual E coli clones. Both antibiotic susceptibility tests differentiated between relapsing or persistent infections and reinfections with only 58% overall efficiency. Thus, antibiotic sensitivity profiles cannot be relied upon to distinguish between persisting or relapsing infections as compared to reinfections in cats with CRF and multiple diagnoses of E coli UTI.

Animals↗

Optimal treatment of urinary tract infections in elderly patients.

Elderly patients are at high risk for urinary tract infection (UTI). Infections of the urinary tract may be classified as asymptomatic bacteriuria, uncomplicated cystitis, uncomplicated pyelonephritis or complicated UTI. The micro-organisms responsible for causing UTI are largely predictable and dictate therapy when indicated. UTIs may be diagnosed by both nonculture and culture techniques. Asymptomatic bacteriuria, though quite common in the elderly, should rarely be treated. Treatment of symptomatic uncomplicated and complicated UTIs is largely dictated by the known or expected pathogen(s) and classification of the infection. Additional features affecting the treatment of UTI in the elderly include allergies, adverse reactions to therapy, drug interactions and modification for renal insufficiency.

Aged↗

Catheter-related urinary tract infection.

Indwelling urinary catheters are used frequently in older populations. For either short- or long-term catheters, the infection rate is about 5% per day. Escherichia coli remains the most common infecting organism, but a wide variety of other organisms may be isolated, including yeast species. Bacteria tend to show increased resistance because of the repeated antimicrobial courses. Urinary tract infection (UTI) usually follows formation of biofilm on both the internal and external catheter surface. The biofilm protects organisms from both antimicrobials and the host immune response. Morbidity from UTI with short-term catheter use is limited if appropriate catheter care is practised. In patients with long-term catheters, fever from a urinary source is common with a frequency varying from 1 per 100 to 1 per 1000 catheter days. Long-term care facility residents with chronic indwelling catheters have a much greater risk for bacteraemia and other urinary complications than residents without catheters. Asymptomatic catheter-acquired UTI should not be treated with antimicrobials. Antimicrobial treatment does not decrease symptomatic episodes but will lead to emergence of more resistant organisms. For treatment of symptomatic infection, many antimicrobials are effective. Wherever possible, antimicrobial selection should be delayed until culture results are available. Whether to administer initial treatment by an oral or parenteral route is determined by clinical presentation. If empirical therapy is required, antimicrobial selection is based on variables such as route of administration, anticipated infecting organism and susceptibility, and patient tolerance. Renal function, concomitant medications, local formulary and cost may also be considered in selection of the antimicrobial agent. The duration of therapy is usually 10-14 days, but patients who respond promptly and in whom the catheter must remain in situ may be treated with a shorter 7-day course to reduce antimicrobial pressure. Relevant clinical trials are necessary to define optimal antimicrobial regimens for the management of catheter-acquired UTI. Prevention of catheter-acquired UTI and its complications is a major goal. With short-term catheters, avoiding their use or limiting the duration of use to as short a time as possible are the most effective prevention strategies. Maintaining a closed drainage system and adhering to appropriate catheter care techniques will also limit infection and complications. As the duration of catheterisation is the principal determinant of infection with long-term indwelling catheters, it is not clear that any interventions can decrease the prevalence of bacteriuria in this setting. Catheter flushing or daily perineal care do not prevent infection and may, in fact, increase the risk of infection. Complications of infection may be prevented by giving antibacterials for bacteriuria immediately prior to any invasive urological procedure, and by avoiding catheter blockage, twisting or trauma. The major focus of future advances in prevention of catheter-acquired UTI is the development of biomaterials resistant to biofilm formation. There is substantial current research addressing this issue, but current catheter materials all remain susceptible to biofilm formation.

Humans↗

Risk factors for symptomatic urinary tract infection in women with diabetes.

OBJECTIVE: Women with diabetes have urinary tract infections (UTIs) more often than women without diabetes. The aim of the present multicenter study was to evaluate which clinical characteristics are associated with the development of a symptomatic UTI during an 18-month follow-up period. RESEARCH DESIGN AND METHODS: Patients with either type 1 or type 2 diabetes who were between 18 and 75 years of age were included. Follow-up results were available for 589 of the 636 women included in this study. All patients were interviewed, their medical history was noted, and at least one uncontaminated urine culture was collected at the moment of study entry. RESULTS: Of the 589 women, 115 (20%) developed a symptomatic UTI, 96 (83%) of whom were prescribed antimicrobial therapy A total of 34 women (14%) with type 1 diabetes developed a UTI. The most important risk factor for these women was sexual intercourse during the week before entry into the study (44% without vs. 53% with sexual intercourse, relative risk [RR] = 3.0, P = 0.01). A total of 81 (23%) women with type 2 diabetes developed a UTI. The most important risk factor for these women was the presence of asymptomatic bacteriuria (ASB) at baseline (25% without vs. 42% with ASB, RR = 1.65, P = 0.04). CONCLUSIONS: Risk factors for developing a UTI are the presence of ASB for women with type 2 diabetes and sexual intercourse during the week before entry into the study for women with type 1 diabetes.

Adolescent↗

Episioplasty for the treatment of perivulvar dermatitis or recurrent urinary tract infections in dogs with excessive perivulvar skin folds: 31 cases (1983-2000).

OBJECTIVE: To evaluate the effectiveness of episioplasty for the treatment of perivulvar dermatitis or chronic or recurrent urinary tract infections (UTI) believed to be secondary to excessive perivulvar skin folds in dogs and to document whether a causal relationship exists between the presence of chronic or recurrent UTI and excessive perivulvar skin folds in female dogs. DESIGN: Retrospective study. ANIMALS: 31 female dogs. PROCEDURE: Medical records of dogs with vulvar dermatitis (group 1; n = 15) or UTI (group 2; 16) were reviewed for history, signalment, physical examination findings, hematologic findings, results of urine or vaginal bacteriologic culture, and results of additional diagnostic procedures. RESULTS: 14 of 15 dogs in group 1 had complete resolution of perivulvar dermatitis and associated clinical signs following episioplasty. One dog had a relapse of clinical signs and vulvar dermatitis 2 years after surgery in association with a 9-kg (1 9.8-1b) weight gain. Sixteen of 16 dogs in group 2 had complete resolution of clinical signs of UTI following episioplasty. Urine samples were obtained via cystocentesis no earlier than 1 month after surgery to confirm resolution of UTI in 13 of 16 of dogs in group 2. Mild-to-moderate incisional swelling was the only surgical complication reported for either group, with the exception of 1 dog in group 2 that had wound dehiscence. All owners were satisfied with surgical outcomes. CONCLUSIONS AND CLINICAL RELEVANCE: All owners reported complete resolution of clinical signs for both groups of dogs. Episioplasty is an effective low morbidity treatment for perivulvar dermatitis and chronic UTI associated with excessive perivulvar skin folds.

Animals↗

Frequency of urinary tract infection among dogs with pruritic disorders receiving long-term glucocorticoid treatment.

OBJECTIVE: To determine frequency of urinary tract infection (UTI) among dogs with pruritic disorders that were or were not receiving long-term glucocorticoid treatment. DESIGN: Observational study. ANIMALS: 127 dogs receiving glucocorticoids for > 6 months and 94 dogs not receiving glucocorticoids. PROCEDURE: Bacterial culture of urine samples was performed in dogs receiving long-term glucocorticoid treatment, and information was collected on drug administered, dosage, frequency of administration, duration of glucocorticoid treatment, and clinical signs of UTI. For dogs not receiving glucocorticoids, a single urine sample was submitted for bacterial culture. RESULTS: Multiple (2 to 6) urine samples were submitted for 70 of the 127 (55%) dogs receiving glucocorticoids; thus, 240 urine samples were analyzed. For 23 of the 127 (18.1%) dogs, results of bacterial culture were positive at least once, but none of the dogs had clinical signs of UTI. Pyuria and bacteriuria (present vs absent) were found to correctly predict results of bacterial culture for 89.9% and 95.8% of the samples, respectively. Type of glycocorticoid, dosage, frequency of administration, and duration of treatment were not associated with frequency of UTI. None of the urine samples from dogs not receiving glucocorticoids yielded bacterial growth. The frequency of UTI was significantly higher for dogs treated with glucocorticoids than for dogs that had not received glucocorticoids. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dogs receiving long-term glucocorticoid treatment have an increased risk of developing a UTI. On this basis, we recommend that urine samples be submitted for bacterial culture at least yearly for such dogs.

Animals↗

Urinary tract infection in primary health care in northern Sweden. I. Epidemiology.

During a 12-month study at the primary health care (PHC) centre in Vännäs (population 8,000) 632 encounters by 265 individuals because of suspected urinary tract infection (UTI) or control after treatment resulted in 279 episodes of bacteriuria in 185 patients. Nine per cent of the episodes concerned patients with indwelling catheter or incontinence requiring other aids. Symptoms of lower and higher UTI were recorded in 56 and 12%, respectively, whereas one third of the episodes were associated with vague or no symptoms and discovered mainly at planned treatment controls. The annual incidence of bacteriuria recorded increased from 0.5% in the first decade of life to more than 10% in the age group 90-100 years. Male UTI comprised 13% of the episodes, increased after middle age and contributed 40% at greater than or equal to 80 years of age. The risk of recurrence (on average 50% during the year studied) was relatively independent of sex and age. No seasonal variation of UTI was observed except for a peak in late summer due to Staphylococcus saprophyticus confined to females aged 15-64 years and causing 28% of the episodes in August. Although UTI in PHC appears to be similar globally it represents a far more complex patient group than indicated by the UTI drug trials frequently published.

Adolescent↗

Urinary tract infection in primary health care in northern Sweden. III. Bacteriology in relation to clinical and epidemiological factors.

The spectrum of bacteria causing urinary tract infection (UTI) and their patterns of drug resistance were found to be more associated with the process of selecting the patients and their sex and age than with the symptoms of the patient (lower, upper or asymptomatic UTI). UTI caused by Staphylococcus saprophyticus was seen mainly in female patients in primary health care (PHC), showed a peak in August and was rarely complicated by therapeutic failures or recurrences. The average risk of resistance of the infecting strain to the seven drugs tested increased from eight per cent for the uncomplicated and 17% for the average PHC patient to 36% among PHC patients with indwelling catheter or urinary incontinence, whereas recurrences of UTI were associated with a surprisingly small increase of drug resistance. In all UTI patient groups studied, the lowest incidences of bacterial resistance were recorded for trimethoprim and co-trimoxazole (0-17%). Thus, rational selection of UTI therapy in PHC requires knowledge of the influence of clinical factors on the expected bacteriology including the local pattern of drug resistance.

Bacteria↗

Urinary interleukin-2 inhibition in patients with cystitis.

An inhibitor of interleukin-2 activity (IL-2-IN) is present in the urine of most patients during the acute phase of untreated bacterial cystitis (UTI). We measured urinary IL-2-IN activity in 30 adults with uncomplicated UTIs and followed the patients for an additional 6 months. Urinary IL-2-IN activity ranged between 0 and 1.97 units/mg urine creatinine (U/mg u.c.). Relatively low levels of IL-2-IN (less than 0.5 U/mg u.c.) correlated with a prior history of recurrent UTIs (p less than 0.01), and also were predictive of a subsequent UTI during the 6 month follow-up, regardless of the prior medical history (p less than 0.01). Measurement of urinary IL-2-IN during the untreated phase of a UTI may prove helpful for directing antibiotic prophylaxis against subsequent UTIs.

Bacterial Infections↗