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Urinary tract infections, VUR, and autosomal dominant polycystic kidney disease.

This case series of 16 patients with autosomal dominant polycystic kidney disease (ADPKD) describes 4 girls who presented with a urinary tract infection (UTI). Radiological evaluation revealed that each of these patients had vesicoureteral reflux (VUR). The frequency of VUR was significantly higher in the patients with ADPKD compared with otherwise healthy age-matched children who underwent testing after a UTI (100% versus 15%, P<0.002). These findings suggest VUR is an associated somatic anomaly in children with ADPKD that may contribute to the occurrence of UTI in this patient population.

Child↗

Vesicoureteric reflux in Kuwaiti children with first febrile urinary tract infection.

The prevalence of vesicoureteric reflux (VUR) in children with urinary tract infection (UTI) varies among different racial groups. The purpose of this study was to determine the frequency of VUR and associated renal changes in a group of Arab Kuwaiti children with their first documented febrile UTI and to compare our findings with those reported from other racial groups. One hundred and seventy-four children (38 males and 136 females) fulfilled the study criteria and were divided into three age groups (<1 year, 1-5 years, and >5 years). Patients in each group had both micturating cystourethrography (MCUG) and 99m-Tc-dimercaptosuccinic acid (DMSA) renal scan after diagnosis. VUR was detected in 39 children (22%). Two-thirds of cases had mild reflux (grade I and II). Females ( n=32) had more reflux than males ( n=7) (24% vs. 18%). Sixty-three patients (36%) had abnormal (DMSA) renal scans (acute pyelonephritis [AP] or renal scars). Of these, 79% were children below 5 years. Abnormal DMSA scans were found in 4 of 38 males (11%) versus 59 of 136 females (43%). Abnormal scans in children with VUR were seen in 1 of 7 males (14%) versus 19 of 32 females (59%). In total, the combination of abnormal scan with VUR occurred in 1 of 38 males (3%) and in 19 of 136 females (14%), whereas abnormal scan without demonstrable VUR was seen in 3 of 38 males (8%) versus 40 of 136 females (29%). Our data showed that the frequency of VUR in Arab Kuwaiti children with febrile UTI is midway between Caucasian and other racial groups. In this study, males had a lower-risk profile than females, the latter having a higher rate of reflux as well as a higher rate of abnormal DMSA scans, irrespective of demonstrable VUR.

Age Distribution↗

Antibiotic resistance of urinary tract pathogens and rationale for empirical intravenous therapy.

Empirical antibiotic treatment in urinary tract infection (UTI) in children must rely on surveillance data on the epidemiology and resistance patterns of common uropathogens. A retrospective analysis of bacteria isolated from children with UTI irrespective of underlying disease or pre-treatment was performed at the University Hospital of Freiburg, Germany, in 1997, and from 1999 to 2001. In the first study period, 261 positive urine samples and in the second period 684 positive samples were analyzed. Escherichia coli (57.2%) was the leading uropathogen followed by Enterococcus spp. (13.7%), Pseudomonas aeruginosa (7.0%), Proteus spp. (5.9%), Klebsiella spp. (4.7%), and Enterobacter/Citrobacter spp. (4.3%). Almost 50% of the E. coli isolates were resistant to ampicillin, but effectively no resistance against cephalosporins, aminogylcosides, ciprofloxacin, nitrofurantoin, and imipenem was observed. In Enterococcus spp. the resistance to ampicillin was about 15% and 40% to netilmicin, while none of the latter showed high-level aminoglycoside resistance. In P. aeruginosa, there was no resistance to aminoglycosides. No difference in resistance patterns between the two study periods was observed. We conclude that an empirical combination treatment of ampicillin and gentamicin, netilmicin, or tobramycin is appropriate in children with UTI independent of pre-treatment or underlying disease. This therapy should be clinically efficacious, well tolerated, and cost effective, and should prevent unnecessary development of antimicrobial resistance.

Bacteria↗

Power Doppler ultrasonography in the diagnosis of acute childhood pyelonephritis.

In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis (APN) is a challenge, particularly during infancy. In an attempt to differentiate APN from lower urinary tract infection (UTI), we evaluated the ability of power Doppler ultrasonography (PDU) to predict renal parenchymal involvement, as assessed by dimercaptosuccinic acid ((99m )Tc-DMSA) scintigraphy. The study comprised 62 patients, 46 girls and 16 boys, aged 2 weeks to 5 years, admitted to the pediatric department with febrile UTI. All children were examined by PDU and DMSA scintigraphy within the first 3 days of admission. In the group of 31 patients with one or more DMSA scan abnormalities, the PDU showed a matching perfusion defect in 27 (87%). Of 26 children with normal DMSA scintigraphy, the PDU evaluation was also normal in 24. The sensitivity and specificity of PDU for the detection of affected kidneys were 87% and 92.3%, and the positive predictive value and negative predictive value were 93.1% and 85.7%, respectively. These data indicate the PDU has a high sensitivity and specificity for differentiating APN from lower UTI and may be a useful and practical tool for the diagnosis of APN in infants and children.

Acute Disease↗

Transforming growth factor-beta1 in the urine of young children with urinary tract infection.

Urinary tract infection (UTI) is a frequent cause of morbidity during the first years of life and may lead to renal insufficiency. Transforming growth factor-beta1 (TGF-beta) is both immunoregulatory and an important mediator of interstitial fibrosis. TGF-beta was detected in the urine of 52% of 48 children aged 1-24 months with a first episode of UTI (94% due to Escherichia coli) and no obstructive nephropathy compared with 0 of 20 healthy young children (P<0.001). TGF-beta was detected in the urine only during the early stage (<1 day) after initiation of treatment. It was detected more frequently (P=0.06) and in significantly higher concentrations (P=0.046) in children with a normal (99m )Tc-dimercaptosuccinic acid scan compared with those with abnormal scans performed 3-14 days after the diagnosis of UTI, suggesting a regulatory role in fibrogenesis and outcome of pyelonephritis in childhood.

Child, Preschool↗

May we go on with antibacterial prophylaxis for urinary tract infections?

Recurrent urinary tract infections (UTIs), with or without vesicoureteric reflux (VUR), are by far the most frequent reason for long-term antibacterial prophylaxis in infants and children today. However, the strategies of antibacterial prophylaxis for the prevention of recurrent urinary tract infection are no longer universally accepted. In infants and children at risk, the benefits of antibacterial prophylaxis definitively are not yet proven by evident data. To put antibacterial prophylaxis in its place, risk groups for recurrent symptomatic infections, ascending UTI and permanent renal damage have to be defined and the efficacy of prophylaxis in these groups has to be proved by prospective randomised studies. Nevertheless, until the results of these studies are available, antibacterial prophylaxis will remain one of the most frequently practised methods to protect risk patients from pyelonephritic damage and UTI recurrences.

Anti-Bacterial Agents↗

Bladder dysfunction in children and adolescents after renal transplantation.

The underlying mechanisms of urinary-tract infections (UTI) in renal transplant recipients are still not fully understood. In otherwise healthy children, bladder dysfunction increases the susceptibility to UTI. The aim of this study was to evaluate lower-urinary-tract function in children and adolescents after renal transplantation. Sixty-eight recipients of renal transplants, 5-20 years of age and 1-15 years after transplantation, were evaluated for their bladder function with a questionnaire, uroflowmetry and bladder ultrasound, and for renal function (glomerular filtration rate) by measuring clearance of inulin or iohexol. Forty-nine patients (72%) had some type of abnormality of bladder function. Abnormal bladder capacity was found in 26%, abnormal urinary flow in 50% and residual urine in 32% of the patients. There was no significant difference in bladder or renal function in children with urinary-tract malformations compared with those with normal urinary tract. Furthermore, there was no significant difference in renal function in patients with bladder dysfunction compared with those without. The incidence of bladder dysfunction is high in children and adolescents after renal transplantation, but the clinical significance of this finding and whether there is a correlation between bladder dysfunction and UTI in these patients need to be clarified further.

Adolescent↗

Technetium-99m-dimercaptosuccinic acid renal scintigraphy in children over 5 years.

We retrospectively evaluated the frequency of renal scintigraphic abnormalities in children over 5 years admitted with a first symptomatic urinary tract infection (UTI). Among 261 children investigated, we found only 23 over 5 years having had technetium-99m-dimercaptosuccinic acid scintigraphy during the acute phase of a first UTI. Obvious scintigraphic abnormalities were detected in 14 children (15 kidneys): 12 kidneys showed focal cortical defects and 3 were small and deformed. Ultrasound was normal in 7 of the 15 kidneys with abnormal scintigraphy and in all the kidneys with normal scintigraphy. Among the 12 kidneys with focal cortical lesions, 8 kidneys returned to normal or improved considerably 2-12 months after initial work-up. In conclusion, in children over 5 years admitted with a first symptomatic UTI, the frequency of scintigraphic abnormalities is high and a strategy based only on ultrasound data would miss about 50% of the abnormal kidneys.

Acute Disease↗

Childhood reflux and urinary infection: a follow-up of 10-41 years in 226 adults.

To ascertain the outcome of childhood vesicoureteric reflux (VUR), 226 adults (37 males), mean age 27 years, were studied after 10-35 years, extended to 41 years by postal questionnaire in 161. At presentation (mean age 5 years) all had VUR (grade III-V in 68) and urinary tract infection (UTI); there was renal scarring in 85 (acquired before referral in 11 and during follow-up in 1), hypertension in 6 and impaired renal function in 5. They were managed and followed prospectively by one paediatrician; 63% of these children remained free from UTI; VUR persisted in 63 and had resolved in 69% of 193 children managed medically. At follow-up, 61% of adults had remained free from infection; 17 adults had hypertension and/or raised plasma creatinine, 16 with scarred kidneys. Their deterioration was predictable because of scar type, blood pressure or plasma creatinine levels in childhood. No new scars developed after puberty. Renal growth rates were unaffected by initial severity or persistence of VUR. On the later questionnaire, 9 further adults, mean age 38 years, had moderate hypertension. The adults with complications were those with extensive renal scarring and/or at least borderline hypertension in childhood. Those with VUR, but no scarring, and managed carefully in childhood, did not suffer serious consequences as adults. There is a need for early recognition and treatment of children with VUR and UTI to limit scar development.

Adolescent↗

Acute renal cortical scintigraphy in children with a first urinary tract infection.

This prospective study, performed in 101 children with a first symptomatic urinary tract infection (UTI), evaluates the diagnostic value of clinical, biological, and ultrasound parameters in detecting children with acute renal infection documented by dimercaptosuccinic acid (DMSA) scintigraphy. In children with a positive DMSA scan, mean C-reactive protein (CRP) was higher than in children with a normal DMSA scan (114+/-64 vs. 67+/-38 mg/dl, mean+/-SD, P=0.0002). The sensitivity and specificity of CRP was 64% and 68%, respectively. In children with severe kidney involvement, mean CRP and white blood count (WBC) were higher than in children with mild/moderate disease (151+/-83 vs. 92+/-55 mg/dl for CRP, P=0.0149; 20,100+/-6,854 vs. 15,023+/-6,145 WBC/ mm3 for WBC, P=0.0131). The sensitivity and specificity was 85% and 20% for CRP, and 77% and 18% for WBC, respectively. One or more areas of abnormal cortical echogenicity were documented in 3% of kidneys with positive DMSA scans. Dilatation of the collecting system was observed in 24% of kidneys. The sensitivity and specificity of ultrasonography was 27% and 89%, respectively. In conclusion, clinical, biological, and ultrasound parameters do not accurately distinguish cystitis from pyelonephritis in children with UTI and do not identify children with severe renal damage. Accordingly, we recommend that DMSA scan should be added to the initial work-up of children with UTI.

Adolescent↗

The multiple functions of Tamm-Horsfall protein in human health and disease: a mystery clears up.

Tamm-Horsfall protein (THP) is exclusively produced by renal tubular cells of the distal loop of Henle and is the most abundant urinary protein in mammals. The physiological function of THP has remained elusive for over half a century; however, new lines of research position it as a central antimicrobial molecule combating urinary tract infection (UTI). Furthermore, the genetic basis of familial juvenile hyperuricemic nephropathy (FJHN), glomerulocystic kidney disease (GCKD) and autosomal dominant medullary cystic kidney disease 2 (MCKD2) has been recently attributed to mutations within the THP gene. In these clinical conditions misfolded THP accumulates in the tubular cells, ultimately leading to overt renal insufficiency. UTI is the most common nonepidemic bacterial infection in humans, where both innate and adaptive components of the immune system as well as the bladder epithelium are involved in its prevention and clearance. Since the urogenital tract is devoid of typical physical barriers such as mucus or a ciliated epithelium, soluble mediators with potent anti-bacterial capabilities might exist. Recently, genetic ablation of the THP gene was shown to lead to severe infection and lethal pyelonephritis in experimental models of UTI. In addition, mounting evidence indicates that, beyond simply a direct antimicrobial activity, THP is a potent immunoregulatory molecule that induces specific THP-directed cell-mediated immunity. In light of these novel findings the particular role of THP as a specialized defense molecule in the urinary tract is discussed.

Humans↗

Optimal diagnostic testing for urinary tract infection in young children.

Urinary tract infection (UTI) is a major concern in young febrile children. Current recommendations favor use of urine obtained by bladder catheterization or aspiration, but opinion varies as to the best ancillary tests to predict a positive culture and guide initial management. The utility of dipstick leukocyte esterase, blood, and nitrite; unspun urine leukocyte count; gram stain of cytocentrifuged urine; and standard spun sediment examination was evaluated in 142 febrile, < 5-year-old children seen in the Emergency Department, 25 of whom had culture-proven UTI. Using sensitivity and negative predictive values as criteria for performance, unspun urine leukocyte count and gram stain of cytocentrifuged urine used in parallel was the best approach but still failed to detect some UTI. Analysis of the nature of the specimens evaluated provided explanation of differences from previous observations. Adoption of this modified approach to prediction of urinary tract infection appears to improve prediction but has operational implications and creates potential problems for the laboratory.

Bacteriological Techniques↗

Evaluation of antibacterial efficacy of drugs for urinary tract infections by genotyping based on pulsed-field gel electrophoresis (PFGE).

We attempted to determine whether the same bacterium isolated from patients with urinary tract infections (UTI) before and after treatment with antimicrobial agents was of the same strain ("persisted") or of a different strain ("changed"). Furthermore, to verify the effectiveness of antimicrobial agents for UTI, we investigated whether bacterial strains could be classified as persisted or changed based on their electrophoretic patterns in pulsed-field gel electrophoresis (PFGE). We examined eight species of bacteria ( Enterococcus avium, Staphylococcus epidermidis, Pseudomonas fluorescens, Serratia marcescens, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, and Escherichia coli), consisting of 41 strains (19 pairs isolated before and after treatment with antimicrobial agents) isolated from patients with complicated UTI. It was concluded that all bacteria were unchanged, based on the clinical effect on bacteriuria. The chromosomal DNA of these bacteria was digested with restriction enzymes and classified based on their electrophoretic pattern in PFGE. A comparison of the patterns of the fragments revealed that 14 pairs were indistinguishable before and after treatment, 3 pairs were closely related, 1 pair was possibly related, and 1 pair was different. These results demonstrated that 18 pairs of isolates (indistinguishable, closely related, and possibly related) were highly likely to be continued infections by the same strain, and that 1 pair (different) had been replaced by another strain. Based on these results, we believe that bacterium genotyping by PFGE is a more effective method for evaluating the antibacterial efficacy of antimicrobial agents.

Bacteria↗

Molecular epidemiological studies of Staphylococcus aureus in urinary tract infection.

In recent years, the increasing incidence of urinary tract infection (UTIs) caused by Staphylococcus aureus has been noted at the urology ward, Okayama University Hospital. We investigated the molecular epidemiological characteristics of 139 UTI isolates, including 45 methicillin-sensitive S. aureus (MSSA) and 94 methicillin-resistant S. aureus (MRSA), collected over a 10-year period from 1990 to 1999. The antibiotic resistance genes ( mecA, aph(3')-III, aac(6')-aph(2"), ant(4')-I) and the toxin genes (tst, sea, seb, and sec) were detected by using multiplex polymerase chain reaction (PCR). Since 1996, the prevalence of the ant(4')-I, tstand secgenes has increased markedly in coagulase type II S. aureus possessing the mecA gene (MRSA). The presence of toxin genes in MRSA was higher than that in MSSA; 66.0% and 26.7% for tst, 7.4% and 4.4% for sea, 24.5% and 8.9% for seb, and 66.0% and 28.9% for sec, respectively. In the review of medical records, it was found that febrile episodes occurred in 12 of 72 patients with monomicrobial UTI caused by S. aureus. For the febrile patients, S. aureus isolates with both the tst and sec genes were found significantly more often (11 of 12; 91.7%) than those without the tst and sec genes ( P = 0.0484). Molecular typing of MRSA isolates, by using random amplified polymorphic DNA analysis and pulsed-field gel electrophoresis analysis, revealed no apparent clonality of these isolates over the 10 years, suggesting that most of the recent MRSA infections are not due to cross-infection in the urology ward.

Aminoglycosides↗

Urinary tract infections in the frail elderly: issues for diagnosis, treatment and prevention.

Urinary tract infections (UTIs) are among the most common infections in frail elderly adults, whether they are community dwelling, live in long term care facilities (LTCFs) or are hospitalized. UTIs cause substantial morbidity and mortality in frail elderly men and women. While many major risk factors in these individuals may not be modifiable, improved attention to incontinence management, judicious use of antimicrobials and urinary catheters, and, in women, appropriate use of topical estrogen may be useful in reducing UTIs. Future strategies may also include the appropriate use of new urinary catheter technology and emerging vaccines.

Aged↗

Cost reduction after introduction of a multidisciplinary infectious disease service at a German university hospital.

BACKGROUND: In 1997 an infectious disease service (IDS) similar to those in the US was established at a university hospital in Munich, Germany. PATIENTS AND METHODS: We assessed the economic impact of the new policy by performing a cost comparison analysis. Inpatients with pneumonia, skin infections/cellulitis, urinary tract infections (UTI) and bacteremia/sepsis were assigned to two groups: patients from a 6-month period after the establishment of the IDS (post-IDS group) were compared with similar patients before the implementation of the ID-service (pre-IDS group). Costs of microbiological investigation (MB), antibiotic treatment (AB), clinical imaging (CI), total costs and length of antibiotic therapy were analyzed. RESULTS: Patients with UTIs in the post-IDS group had 39% fewer MBs (p<0.05) than patients in the pre-IDS group, resulting in a 33% decrease in average MB costs (p<0.05). In the total group, in which subgroups with pneumonia, skin infection and UTI were summarized, the post-IDS group had 37% fewer MBs (p<0.05) resulting in MB cost reductions of 34% (p<0.05). There were no significant differences in expenditures for AB and CI and in the average length of antibiotic therapy. CONCLUSION: This study shows that continuous consultation by an IDS does not increase diagnostic and treatment costs, but results in significant cost reductions.

Aged↗

Urinary tract infections in women.

Urinary tract infection (UTI) is one of the most frequent diseases in medical practice. Some definitions and epidemiology of UTI and bacteriuria are discussed, as well as host susceptibility and defense mechanisms. Aspects of infection in young women and in the elderly are reported, emphasizing microbiological, clinical and therapeutic aspects. Finally, epidemiologic and clinical aspects of fungal UTI are discussed.

Adolescent↗

Urinary tract infection and hip fracture.

A routine audit revealed that in 25 per cent of patients with proximal femoral fracture, hospital stay was complicated by urinary tract infection (UTI). A prospective study was undertaken to investigate the relationship of UTI to fracture type, timing of surgery and the effect of perioperative antibiotics. Eighty-eight patients were investigated over a 4-month period with urine specimens obtained at time of operation and 48 h from operation. Of the patients, all female, 12.5 per cent had positive urine cultures at the time of operation. Of all patients, 42 per cent had positive urine cultures 48 h after operation. Females with intra-capsular fractures were more likely to have positive cultures both pre- and post-operatively (P < 0.005). Age (P < 0.05) and operative delay beyond 48 h (P < 0.05) were also found to predispose to infection. All patients except one who had urinary infection at the time of surgery had post-operative urine infection with the same organism. Present audit methods have significantly under estimated the presence of UTI in these patients. Fracture type and operative delay would appear to be the most significant determinants of a positive urine culture 48 h after operation. Prophylactic antibiotics appear to be ineffective in eradicating pre-existing or preventing early post-operative infection.

Adult↗