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Patient-initiated treatment of uncomplicated recurrent urinary tract infections in young women.

BACKGROUND: Recurrent urinary tract infections (UTIs) are a common outpatient problem, resulting in frequent office visits and often requiring the use of prophylactic antimicrobial agents. Patient-initiated treatment of recurrent UTIs may decrease antimicrobial use and improve patient convenience. OBJECTIVE: To determine the safety and feasibility of patient-initiated treatment of recurrent UTIs. DESIGN: Uncontrolled, prospective clinical trial. SETTING: University-based primary health care clinic. PARTICIPANTS: Women at least 18 years of age with a history of recurrent UTIs and no recent pregnancy, hypertension, diabetes, or renal disease. INTERVENTION: After self-diagnosing UTI on the basis of symptoms, participating women initiated therapy with ofloxacin or levofloxacin. MEASUREMENTS: Accuracy of self-diagnosis determined by evidence of a definite (culture-positive) or probable (sterile pyuria and no alternative diagnosis) UTI on pretherapy urinalysis and culture. Women with a self-diagnosis of UTI that was not microbiologically confirmed were evaluated for alternative diagnoses. Post-therapy interviews and urine cultures were used to assess clinical and microbiological cure rates, adverse events, and patient satisfaction. RESULTS: 88 of 172 women self-diagnosed a total of 172 UTIs. Laboratory evaluation showed a uropathogen in 144 cases (84%), sterile pyuria in 19 cases (11%), and no pyuria or bacteriuria in 9 cases (5%). Clinical and microbiological cures occurred in 92% and 96%, respectively, of culture-confirmed episodes. No serious adverse events occurred. CONCLUSION: Adherent women can accurately self-diagnose and self-treat recurrent UTIs.

Adult↗

Adolescent urinary tract infections.

Urinary symptoms in adolescents are common, particularly in females. Urinary tract infections (UTIs) cause many of these symptoms. For uncomplicated UTIs, both lower and upper tract, therapy is straightforward. Commonly used antibiotics are trimethoprim/sulfamethoxazole (TMP/SMX), cefixime, and ciprofloxacin (off-label use) for 3 days for lower tract infections and 10ñ14 days for upper tract infections. Adolescent UTIs are markers for sexual activity, just as UTIs in younger children are often markers for anatomic defects, e.g., congenital abnormalities. Adolescents with upper and lower UTIs often have concurrent sexual activity or a complication of that activity. Issues among adolescents with UTIs are more similar to those of young adults than to those of younger children. It is as important to counsel adolescents about sexual activity and its consequences as it is to treat the UTIs. All adolescents with UTIs should be queried for sexual activity; evidence of sexually transmitted diseases (STDs) should be sought; and counseling for STDs and responsible sexual activity is recommended. Complicated UTIs include those in patients who have grown into adolescence after a childhood of infections or who have anatomic abnormalities, recurrent infections, reflux and reflux nephropathy, spina bifida and neurogenic bladder, transplanted kidneys, diabetes, and urolithiasis. These patients require individualized medical programs, unique for their condition, history, and microbiology.

Adolescent↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). III. Secular changes in susceptibility].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1998 to May 1999, and the results were compared with those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and complicated UTIs. Among E. faecalis strains, those with low susceptibilities to almost drugs have increased in the latest period. All 5 S. aureus strains isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM). Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to GM, and on the contrary the resistant strains have increased with the MIC90 of 256 micrograms/ml or above. Among S. aureus strains isolated from complicated UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the latest period compared to those during period of 1996-1997, and the MIC90s of them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4 micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from uncomplicated and complicated UTIs have been lower 2-3 classes in the latest period than those in 1997. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems had increased in 1997, but few of them were detected in the latest study. The sensitive strains of P. aeruginosa to almost drugs have increased during the latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa were the best in our history. The sensitive strains of P. aeruginosa to ceftazidime (CAZ) have increased and its percentage was 30%. Piperacilline (PIPC), cefoperazone (CPZ), GM and OFLX resistant P. aeruginosa strains have increased in the latest period.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). III. Secular changes in susceptibility].

The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined and the results were compared with those obtained between 1991 and 1998. Comparison was made by classifying strains isolated from patients into those with uncomplicated UTIs and those with complicated UTIs (including with or without indwelling catheter). About E. faecalis, increase of low sensitive strains noted in the former year showed a decreasing tendency, however, one strain each with MIC of 4 micrograms/ml to vancomycin (VCM) was detected in patients with both uncomplicated and complicated UTIs. As for S. aureus, many sensitive strains to cephems, imipenem (IPM) and VCM were noted, and each MIC50 was better than that in the former years. S. aureus strains showing low susceptibility to arbekacin (ABK) were detected in patients with complicated UTIs in this year as well as in the former year, and one strain each with MIC of 16 micrograms/ml and 32 micrograms/ml was detected. Susceptibilities of E. coli were effective to all drugs except for penicillins and minocycline (MINO). Decrease of low sensitive strains was also noted in all drugs except for quinolones. Each MIC90 of ciprofloxacin (CPFX) and sparfloxacin (SPFX) in patients with complicated UTIs against E. coli was 3 degrees classes lower than that in patients with uncomplicated UTIs. As for Klebsiella pneumoniae, decrease of low sensitive strains to cephems was noted in patients with uncomplicated UTIs in 1998. In 1999, low sensitive strains decreased also in patients with complicated UTIs, and few were detected. Susceptibilities of K. pneumoniae to quinolones were effective as compared with those in the former years with the MIC80s of 0.125 microgram/ml or below without detection of low sensitive strains. One low sensitive strain of K. pneumoniae with MIC of 8 micrograms/ml was detected for gentamicin (GM). Susceptibilities of P. aeruginosa to carbapenems were notable. The MIC90 of meropenem (MEPM) and IPM was 4 micrograms/ml each which was 2 degrees better than that in 1998. Resistant P. aeruginosa strains to other drugs except for monobactams decreased in 1999.

Anti-Bacterial Agents↗

Randomised controlled trial of nitrofurantoin versus placebo in the treatment of uncomplicated urinary tract infection in adult women.

BACKGROUND: Urinary tract infections (UTIs) are very common and have been treated with apparent success with antimicrobials for many years. However, there is a paucity of placebo-controlled clinical trials. AIM: To measure the symptomatic and bacteriological short-term effect of nitrofurantoin treatment versus placebo, in the treatment of uncomplicated UTI in adult non-pregnant women. DESIGN OF STUDY: Randomised placebo-controlled trial in general practice. SETTING: Non-pregnant women, aged between 15 and 54 years old, consulting a general practitioner for symtoms suggestive of uncomplicated lower UTI and with pyuria (positive for leucocyte esterase test). METHOD: A dipslide was inoculated in first-void midstream urine and sent for examinion. The patients were randomised to receive nitrofurantoin 100 mg or placebo four times daily for three days. After three, seven, and 14 days a new dipslide was inoculated and symptoms of UTI were checked or improvement of symptoms and bacteriuria. RESULTS: Of 166 women consulting with symptoms suggestive for UTI, 78 had pyuia and agreed to participate in the study (the clinically suspected UTI group); of these, 40 received nitrofurantoin and 38 received placebo. The result for combined symptomatic improvement and cure after three days was 27/35 in the nitrofurantoin group and 19/35 in the placebo group (c2 with Yates' correction P = 0.008; number needed to treat [NNT] = 4.4, 95% confidence interval [CI] = 2.3 to 79). After seven days, combined improvement and cure was observed in 30/34 and 17/33 respectively (P = 0.003, NNT = 2.7, 95% CI = 1.8 to 6.0). At inclusion, 56 women had bacteriuria of > or = 10(5) CFU/ml (the bacteriologically proven UTI group). Of these, 29 received nitrofurantoin and 27 received placebo. After three days the bacteriological cure was 21/26 in the treatment group, compared with 5/25 in the placebo group (P < 0.001; NNT = 1.6, 95% CI= 1.2 to 2.6). After seven days the bacteriological cure rate was 17/23 in the intervention group and 9/22 in the placebo group (P = 0.05, NNT = 3, 95% CI = 1.7 to 17). CONCLUSION: In women with bacteriologically proven UTI, nitrofurantoin was significantly more effective than placebo in achieving bacteriological cure and symptomatic relief in just three days; this was still present after seven days. In patients with clinically suspected UTI the symptomatic effect was statistically significant after

Adolescent↗

[A prospective, descriptive study on the practice of management of urinary tract infections by general practitioners in Italy: clinical pathways (Part II)].

OBJECTIVES: The aim of this prospective, descriptive study was to draw the picture of the diagnostic and therapeutic pathways of general practitioners (GPs) in the practice of management of urinary tract infections (UTIs) in Italy. The study results are published in two separate papers. We report here the clinical pathways followed by GPs to diagnose and treat UTIs. MATERIALS AND METHODS: A total of 2.696 GPs were requested to fulfill a questionnaire on their perception of the prevalence of UTIs and their habits in the management of patients either before (IVU1 study, 1.111 GPs) or after (IVU2 study, 1.585 GPs) a specific training course. The clinical management pathway was analysed. RESULTS: GPs turned out to share an appropriate management of UTIs, even though some discrepancies between the clinical habits and UTIs guidelines were focused. After the training course the discrepancies were partly amended (IVU2 study). Urinalysis and urine culture are nearly always requested by GPs, frequently including blood examinations. Older and newer fluoroquinolones are mostly prescribed for UTIs, followed by fosfomycin tromoetamol. Lifestyle recommendations for UTIs containment and prevention are released to patients by GPs. CONCLUSION: The clinical results of this study contribute to assess the habits of Italian GPs in diagnosing and treating UTIs. These data may be helpful for urologists in the management of community-acquired UTIs.

Adult↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). III. Secular changes in susceptibility].

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of these bacteria to various antimicrobial agents were measured. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1995 and 2003. The drug sensitivity of S. aureus in this year was similar to those in up to the previous year and S. aureus showed the best susceptibility to vancomycin (VCM) and arbekacin (ABK). The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous year. The susceptibility of E. coli to cephems in this year was generally good and was similar to those in up to the previous year. MIC90 of cefozopran (CZOP) was the most stable and 0.125 microg/mL or less since 1995. The susceptibility of E. coli to cefpirome (CPR) and cefotiam (CTM) also was good but to cefaclor (CCL), cefixime (CFIX), and cefpodoxime (CPDX) was largely decreased in complicated UTI groups. The sensitivity of E. coli to carbapenems also was good but to carumonam (CRMN) tended to decrease. The susceptibility of E. coli to quinolones, however, has largely changed and has decreased since 2003 in uncomplicated UTIs and 2000 in complicated UTIs. That was suggested the development of the resistance to the drug. The susceptibility of Klebsiella spp. to cefazolin (CEZ), CTM, CCL, CPDX, and cefditoren (CDTR) decreased in the previous year and recovered to the year before the previous year in this year. The susceptibility of Klebsiella spp. to other cephems was stable since 1995, especially against CZOP, the highest sensitivity (MIC90: < or = 0.125 microg/mL) was maintained. The susceptibility of Klebsiella spp. to carbapenems and CRMN also was good. The susceptibility of Klebsiella spp. to aminoglycosides was lower than to CZOP but was stable since 1995. The susceptibility of P. aeruginosa was generally low and has largely changed against the majority of the agents since 1995. The susceptibility of P. aeruginosa isolated from uncomplicated UTIs has largely changed against ceftazidime (CAZ), cefsulodin (CFS), CZOP, imipenem (IPM), meropenem (MEPM), aztreonam (AZT), CRMN, gentamicin (GM), and tobramycin (TOB). The susceptibility of P. aeruginosa isolated from complicated UTIs has largely changed against CSF, CZOP, MEPM, GM, and ciprofloxacin (CPFX). The susceptibility of P. aeruginosa isolated from complicated UTIs has been stable against amikacin (AMK). For annual changes in MIC50, TOB and IPM had a relatively stable and high activity (MIC50: 0.5-2 microg/mL).

Anti-Bacterial Agents↗

[Clinical efficacy of T-3262, a new quinolone compound, on urinary tract infection in 1988].

A newly developed quinolone compound, T-3262, was administered in the treatment of 36 cases of urinary tract infection (UTI) between June and August in 1988. Thirteen cases of acute uncomplicated cystitis (AUC) were evaluated with the Japanese UTI criteria at a dose of 300 mg a day for 3 days after the administration of the drug. The clinical efficacy was obtained as 92.3%. Twenty two cases of chronic complicated UTI (CC-UTI) were evaluated with the criteria, the clinical efficacy rate was 86.4% at a dose of 300-450 mg a day for 5 days administration. The clinical efficacy judged by doctor in charge was evaluated as effective for 100% on AUC and for 90.9% on CC-UTI. Minimum inhibitory concentration (MIC) of new quinolones for clinical strains isolated in the clinical study was compared with that of the strains isolated from CC-UTI at our and other institutes in the last two years. There were no significant differences in in vitro activity found among the three groups. Comparing the efficacy rate on CC-UTI with that of the open trial in Japan in 1987, despite a general tendency for increase of resistant strains to new quinolones, a high effectiveness such as 82.3% in CC-UTI that was almost similar to the open trial was achieved. Neither side reactions except for mild and transient gastric discomfort in 2 patients nor significant clinical abnormal values were encountered. In conclusion, T-3262 is an effective and useful antimicrobial drug in the treatment of UTI, and its effectiveness is still almost comparable to the result of clinical studies that have been carried out in the last two years.

4-Quinolones↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1989). II. Background of patients].

Clinical background was investigated on 1,197 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period from June, 1989 to May, 1990. 1. Distribution of sex and age A majority of female patients with UTIs accounted for a twenties and thirties. The proportion of male patients with UTI has increased with age, accounting for majority in patients 70 years or older. 2. Distribution of infection types and age Most cases among twenties or thirties were uncomplicated UTIs. Fifties and older cases were most frequent in complicated UTIs. 3. Distribution of isolated bacteria and age Escherichia coli was most frequent on the whole, followed by Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus spp. and Klebsiella spp.. E. coli had declined with age, and on the other hand, E. faecalis and P. aeruginosa had increased with age. 4. Administration of antibiotics and pathogens isolated from UTIs. In uncomplicated UTIs, pathogens, after administration of antibiotics, isolated from patients have obviously decreased from 439 to 4. Before an administration of antibiotics, E. coli was mainly detected, but after an administration of antibiotics, E. coli has decreased into two strains. After administration of antibiotics, pathogens of complicated UTIs, without indwelling catheter, have decreased from 324 to 19: E. coli has decreased from 86 to 2, but E. faecalis, Staphylococcus spp., Enterobacter spp. and P. aeruginosa have increased. Pathogens of complicated UTIs with indwelling catheter, have decreased from 156 to 14 after administration of antibiotics, and mainly isolated pathogens were E. faecalis and P. aeruginosa.

Adolescent↗

Inhibition of the soluble and the tumor cell receptor-bound plasmin by urinary trypsin inhibitor and subsequent effects on tumor cell invasion and metastasis.

The present study was undertaken to determine whether highly purified human urinary trypsin inhibitor (UTI) efficiently inhibits the soluble and the tumor cell receptor-bound plasmin. The ability of plasmin inhibitors to regulate invasion by tumor cells which express membrane-associated plasmin was also examined. UTI and two other plasmin inhibitors [alpha 2-anti-plasmin (alpha 2AP) and alpha 2-macroglobulin (alpha 2M)] were used. alpha 2AP and alpha 2M, as well as UTI, rapidly inactivate the soluble plasmin that is not bound to cells. Experiments were performed in vitro using cultures of ovarian cancer HOC-I cells and gestational choriocarcinoma SMT-ccl cells. HOC-I and SMT-ccl cells had plasmin(ogen) on their cell surface, and the plasmin activity was detected on their cell surface enzymologically and immunologically. Receptor-bound plasmin reacted effectively with UTI and was directly inactivated by UTI. In contrast, receptor-bound plasmin was not inhibited by alpha 2AP and alpha 2M. Using a modified Boyden chamber and an artificial basement membrane, Matrigel, it was found that UTI, but not alpha 2AP or alpha 2M, can inhibit HOC-I and SMT-ccl cells invasion in vitro. Furthermore, in the experimental lung metastasis model, UTI inhibited the formation of lung metastasis by Lewis lung carcinoma cells. The inhibition of tumor cell invasion was not due to direct antitumor effects of UTI. These results suggest that inhibition of receptor-bound plasmin by UTI is associated with significantly reduced tumor cell invasiveness in vitro and with a decreased number of metastasis in vivo.

Animals↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1990). II. Background of patients].

Clinical background was investigated on 861 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period from June, 1990 to May, 1991. 1. Distribution of sex, age and infections: Among over fifties males, the complicated urinary tract infections was most frequent. Among females, the uncomplicated urinary tract infections was most frequent without a relation of age. 2. Distribution of sex, age and pathogens isolated from UTIs: In uncomplicated UTIs, Escherichia coli was most frequently isolated without a relation of age. In complicated UTIs without indwelling catheter, E. coli and Enterococcus faecalis were isolated with a frequency of 20-30%, respectively. In complicated UTIs with indwelling catheter, Pseudomonas aeruginosa were most frequently isolated, and next E. faecalis. 3. Administration of antibiotics and pathogens isolated from UTIs: In uncomplicated UTIs and complicated UTIs without indwelling catheter, pathogens, after administration of antibiotics, isolated from patients have obviously decreased. In complicated UTIs with indwelling catheter, pathogens, before and after administration of antibiotics, isolated from patients were not decreased. And the distribution of pathogens after administration of antibiotics was similar.

Adolescent↗

Transurethral laser therapy and urinary tract infections.

To date transurethral laser ablation of the prostate (TULAP) in benign prostatic hyperplasia (BPH) is the commonest form of transurethral laser surgery. The invention of the so-called "sidefire" laser fibre was the prerequisite condition for effective transurethral laser ablation of the prostate. Since the first transurethral laser ablation in human BPH was performed by Costello in September 1990, a multitude of urologists have adopted this technique. In the meantime, a great many studies have been carried out and a lot of data have been published. The initial, to some extent euphoric, enthusiasm of some urologists as well as some patients, especially in the USA and Europe, has turned into a more critical reflection. There is no doubt at all that TULAP is a feasible alternative treatment method with reasonable results. Especially in the high-risk patient, there is neither severe blood loss nor an uptake of irrigation fluid. It is also beneficial to allow unlimited treatment in patients on anticoagulant medication. Nevertheless, the value of TULAP in comparison to transurethral electroresection of the prostate (TURP), generally accepted as the "gold-standard" in the surgical therapy of BPH, remains unclear. A final assessment will only be possible when further data on mortality, short and long term morbidity and outcome with this method have been presented. Strong evidence exists that the operation can be performed without blood loss and uptake of irrigation fluid. A further advantage seems to be preservation of sexual function, especially anterograde ejaculation in the majority of patients, in comparison to the "gold-standard" TURP. In most studies, the value of TULAP is further compared with regard to the elimination of obstruction by means of pressure-flow-studies. The aspect most frequently neglected by all investigators to date is the frequency and severity of urinary tract infections (UTI) in patients in whom TULAP is performed. Basically, UTI in the form of cystitis, ascending infections such as male adnexitis or pyelonephritis, prostatitis of the remaining parts of the prostate and catheter-induced urethritis are associated with transurethral surgery in general. Certain data indicate an age-related frequency of UTI. From a rate of approximately 1% of UTI in infants, the frequency rises to 30% in the 8th decade of life. According to these data, one can expect that in a study of TULAP in high risk patients, most of whom are elderly, a large number present for surgery with a preexisting UTI. Other data demonstrate that after 4.5 days 50% and more of patients with an indwelling catheter develop an ascending UTI, although a closed urinary drainage system has been used. In most cases enterobacteriaceae, in 80% Escherichia coli, are detected. Especially in TULAP, a period of prolonged catheterisation has to be expected in the majority of patients. The risk of UTI in the perioperative phase is therefore expected to be higher. There are several higher risks and possibilities of complications in transurethral surgery in patients with UTI. Taking this into account, all our patients routinely undergo low dose antibiotic prophylactic treatment. The frequency of infections of the remaining parts of the prostate after prostatic surgery is strongly correlated to the flow characteristics in the prostatic urethra and to the amount of destruction of the prostatic tissue. Here are further reasons for a higher risk of infection after TULAP. Due to the fact that the prostatic tissue is not removed by a clear cut, but coagulated by laser beam, a rough surface due to tissue necrosis results. This is an ideal culture medium for bacteria aggravated by the disturbed laminar flow in the prostatic urethra, which favours an intraprostatic reflux of infected urine. There is evidence that UTI are the most important factor of morbidity during the first weeks after TULAP because of their bothersome symptoms.(ABSTRACT TRUNCATED)

Aged↗

Urinary tract infection following ritual Jewish circumcision.

Circumcision seems to reduce the overall incidence of urinary tract infections (UTI), although a few studies have suggested that ritual circumcision may be a predisposing factor for UTI within the first 2 weeks following the procedure. The aim of this study was to investigate a possible causal relationship between ritual circumcision and UTI. The study comprised 82 infants with UTI, 55 females and 27 males under the age of 1 year. All males were circumcised on the eighth day of life. The median age of infection was 0.75 and 7.0 months for males and females, respectively. Fifty-two percent (14/27) of UTI episodes were diagnosed within the 2 weeks following circumcision. A significantly lower incidence in Escherichia coli-induced UTI was observed in males compared to females, 67% and 93%, respectively. Similarly, the incidence of E. coli-induced UTI was also significantly lower in males presenting within 2 weeks following circumcision (57%) compared to infants presenting prior or more than 2 weeks following the procedure (92%). Positive blood cultures of an identical microorganism were observed in 6/27 males compared to 2/55 females. The incidence of urinary tract malformations and their severity were similar in both sexes. We conclude that the high incidence of UTI following a ritual Jewish circumcision, as well as the relatively high preponderance of bacteria other than E. coli, may suggest a causal relationship between circumcision and UTI.

Age Distribution↗

[Urinary infection and reflux nephropathy in children].

Urinary tract infection (UTI) is relatively frequent in children. The symptoms are often atypical; the more so, the younger the child. UTI is often associated with functional or malformative uropathy, such as vesico-ureteral reflux or obstruction. Radiological investigation should be carried out in every child presenting with his first UTI. The prognosis of uncomplicated UTI is good, but is less favorable when UTI is associated with urological abnormalities. Development of pyelonephritic lesions can lead to kidney scarring for which the occurrence of intrarenal reflux, associated with a specific type of papilla, is probably responsible. Short-term treatment is recommended for uncomplicated UTI. Uncomplicated UTI with frequent relapses, or UTI associated with vesio-ureteral reflux, requires prophylactic chemotherapy. Worsening of reflux and/or the development of pyelonephritic lesions while on prophylactic treatment are an indication for surgical intervention. Surgery is always indicated in the presence of a major urological malformation. Be it medical or surgical, treatment of UTI should always be followed by regular urine cultures for several years.

Child↗

How general practitioners manage children with urinary tract infection: an audit in the former Northern Region.

BACKGROUND: Urinary tract infections (UTIs) in childhood are common and may be difficult to diagnose because of non-specific symptoms and technical problems with urine collection. Active management is important because UTIs may cause permanent renal scarring in young children. AIM: To determine how general practitioners (GPs) manage children with suspected UTIs. METHOD: A postal questionnaire to 494 GPs in the former Northern Region (a random selection of 26.2%) asking how they manage children with suspected UTI and their perception of their training needs. RESULTS: A total of 333 (67.4%) GPs replied. On weekdays, up to 22.9% of GPs treated children who had symptoms suggestive of UTI without collecting a diagnostic urine sample, and up to 64.8% did so at weekends. Urine collection was satisfactory in 73.2% of boys and girls aged under one year, but in only 50.4% of older boys and 48.0% of older girls, caused in part by the use of unreliably 'cleaned' potties in the older group. On weekdays, up to 87.2% of GPs culture the urine, but up to 4.8% use dipsticks as the sole diagnostic test; at weekends, only up to 58.6% culture urines, and up to 19.1% rely on dipsticks alone. Up to 11.0% of GPs examine urine under a microscope for bacteria to test for UTI on weekdays and at weekends. Up to 23.8% of GPs who collect urines on weekdays wait for a positive culture result before starting antibiotics. At weekends, only 3.9% of GPs build in this delay to treatment, mainly because far fewer take urine samples at all. GPs refer younger children for diagnostic imaging more readily than older ones, and boys more readily than girls at all ages. Although virtually all GPs refer all children under five years, some still do so only after recurrent infections. Over half the GPs wanted more training in managing UTI in children. CONCLUSION: There is a wide variation in clinical practice by GPs. Some always appropriately collect and test urine samples, treat without delay and refer for imaging after one proven UTI. Some never collect urines, treat blindly and refer only young infants with recurrent UTIs. Many vary their standards of practice from weekdays to weekends. The provision for GPs of clear, local, practical guidelines, drawn up between paediatricians and GPs and backed up with study days, might produce a consistent improvement in standards.

Child↗

Urinary tract infection in premature infants: the role of imaging studies and prophylactic therapy.

BACKGROUND: The prevalence of urinary tract infection (UTI) in premature infants ranges from 4% to 25%. It is surprising, however, that scant information exists regarding management of UTI in premature infants, particularly the need for radiologic evaluation of the urinary tract and the use of preventive antibiotic therapy after the first episode of UTI occurs. The aim of this study was to answer these questions. PATIENTS AND METHODS: Twenty-seven (8%) premature infants (< 1750 gm birth weight) born during the period from 1990 through 1993 had UTI. Eleven of them were of extreme low birth weight (ELBW) (birth weight < 1000 gm). Ultrasound examination of the urinary tract was performed in all premature infants 7 days after a diagnosis of UTI was made and was repeated 1 month later, if disease was detected. Voiding cystography was performed in 21 premature infants (8 with ELBW) 6 to 8 weeks after a diagnosis of UTI was made. RESULTS: The mean birth weight of premature infants with UTI was 1112 +/- 294 gm. The prevalence of UTI was significantly higher (p < 0.01) in infants with ELBW (13%) compared with that in premature infants with birth weight >1000 gm (6%). The male/female ratio in all premature infants was 2.9:1 and was significantly higher in infants with ELBW (10:1; p < 0.01). Organisms involved were Klebsiella (59%), Candida albicans (15%), Escherichia coli (15%), and Enterobacter (11%). Only premature infants with ELBW had Candida UTI. Five premature infants (four with ELBW) had mild transient hydronephronis, and one had persistent hydronephrosis and hydroureter. Voiding cystography showed that three premature infants had vesicoureteral reflux and that one had a bladder diverticulum. All premature infants with pathologic voiding cystography had birth weight >1000 gm and had normal ultrasound examination. CONCLUSIONS: Premature infants with birth weight 1000 to 1750 gm should be given preventive antibiotic therapy at least until imaging evaluation (ultrasonography and voiding cystography) is complete. Premature infants with ELBW are more susceptible to fungal infection and do not seem to have underlying urinary tract abnormalities. Prophylactic therapy and voiding cystography may be unwarranted in this population subset.

Anti-Bacterial Agents↗

Down-regulation of interleukin-8 gene expression in HL60 cell line by human Kunitz-type trypsin inhibitor.

Urinary trypsin inhibitor (UTI) is one of the Kunitz-type protease inhibitors in human. Little is known about its anti-inflammatory functions other than protease inhibition. We studied the effect of UTI on gene expression of interleukin-8 (IL-8), an inflammatory cytokine. UTI inhibited IL-8 gene expression induced by lipopolysaccharide (LPS) in HL60 cells. The IL-8 concentrations in the cells and medium after LPS stimulation increased time-dependently in the absence of UTI, but did not increase in the presence of UTI. On the other hand, UTI did not inhibit either the synthesis or the release of IL-8 induced by the calcium ionophore A23187. UTI inhibited increase of cytosolic Ca2+ stimulated by LPS but not by A23187. Our results suggest that the inhibition by UTI is due to its effect on the cell membrane involved in regulating Ca2+ influx.

Calcimycin↗

Kunitz-type trypsin inhibitor prevents LPS-induced increase of cytosolic free Ca2+ in human neutrophils and HUVEC cells.

The protease inhibitor part of inter-alpha trypsin inhibitor is identical to urinary trypsin inhibitor (UTI). Preincubation of neutrophils and HUVEC cells with UTI inhibited increase of cytosolic free Ca2+ induced by LPS. Increase of cytosolic free Ca2+ induced by LPS in the presence of EGTA was also inhibited by UTI. In contrast, UTI did not inhibit increase of cytosolic free Ca2+ in cells stimulated by Ca2+ ionophore with or without EGTA. The effects of nine synthetic peptides of UTI on the concentration of cytosolic free Ca2+ in the neutrophils induced by LPS were examined. Preincubation with a peptide of UTI domain 2, NLPIVRGPCRAFIQL (83-97), was completely inhibited by the increase of cytosolic free Ca2+ in neutrophils. This region is identical to the trypsin inhibitor site of UTI. We propose that a function of UTI other than as a protease inhibitor is in regulation of intracellular Ca2+ and that this is due to its trypsin inhibitor region.

Amino Acid Sequence↗