Genetic determinants of renal scarring in children with febrile UTI.

BACKGROUND: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. METHODS: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. RESULTS: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. CONCLUSIONS: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs.

Genome-wide association study of hemolytic uremic syndrome causing Shiga toxin-producing Escherichia coli from Sweden, 1994-2018.

Shiga toxin-producing Escherichia coli (STEC) infection can cause clinical manifestations ranging from diarrhea to potentially fatal hemolytic uremic syndrome (HUS). This study is aimed at identifying STEC genetic factors associated with the development of HUS in Sweden. A total of 238 STEC genomes from STEC-infected patients with and without HUS between 1994 and 2018 in Sweden were included in this study. Serotypes, Shiga toxin gene (stx) subtypes, and virulence genes were characterized in correlation to clinical symptoms (HUS and non-HUS), and pan-genome wide association study was performed. Sixty-five strains belonged to O157:H7, and 173 belonged to non-O157 serotypes. Our study revealed that strains of O157:H7 serotype especially clade 8 were most commonly found in patients with HUS in Sweden. stx2a and stx2a + stx2c subtypes were significantly associated with HUS. Other virulence factors associated with HUS mainly included intimin (eae) and its receptor (tir), adhesion factors, toxins, and secretion system proteins. Pangenome wide-association study identified numbers of accessory genes significantly overrepresented in HUS-STEC strains, including genes encoding outer membrane proteins, transcriptional regulators, phage-related proteins, and numerous genes related to hypothetical proteins. Whole-genome phylogeny and multiple correspondence analysis of pangenomes could not differentiate HUS-STEC from non-HUS-STEC strains. In O157:H7 cluster, strains from HUS patients clustered closely; however, no significant difference in virulence genes was found in O157 strains from patients with and without HUS. These results suggest that STEC strains from different phylogenetic backgrounds may independently acquire genes determining their pathogenicity and confirm that other non-bacterial factors and/or bacteria-host interaction may affect STEC pathogenesis.

Longitudinal follow-up on vascular morphology and function in children with kidney transplants.

AIM: Our aim was to evaluate cardiovascular risk profile in 42 children with kidney transplants (KT) at the Queen Silvia Children's Hospital, Gothenburg Sweden. METHODS: Forty-two children (7.1-18 years) with KT, time from transplantation 3.5 (0.9-13) years, were examined at inclusion and annually for three consecutive years. Eighteen matched controls were examined once. Cardiovascular phenotyping included ultra-high-frequency ultrasound (UHFUS), pulse wave velocity (PWV), and endothelial function. RESULTS: Children with KT had higher body mass index (BMI) z-score and blood pressure (BP) z-score than healthy controls (BMI z-score: 0.4 ± 1.0 and - 0.2 ± 0.9, respectively, p = 0.02; SBP z-score: 0.5 ± 0.9 and - 0.8 ± 0.7; DBP z-score: 0.7 ± 0.7 and - 0.3 ± 0.5, respectively, p < 0.001). BP z-score decreased significantly over 3 years; other vascular markers remained unchanged. PWV and carotid intima thickness (IT) were higher in children with KT compared to healthy controls. Children with pre-emptive KT had lower radial IT and dorsal pedal media thickness (MT) compared to children with preceding dialysis. CONCLUSION: Children with KT show increased cardiovascular risk parameters, not increasing over time. Children on dialysis before KT have more pronounced vascular changes than those with pre-emptive KT, suggesting pre-emptive transplantation more beneficial for cardiovascular health.

Impaired renal clearance among Swedish adolescents born preterm.

AIM: To determine whether adolescents born before 28 gestational weeks have an increased risk for renal impairment. METHODS: Swedish infants, born before 28 gestational weeks in 2001 and 2002, were identified from a local register. A total of 16 children, 12 females and 4 males, were examined at 16-17 years of age with 51 Cr-EDTA clearance. A comparison group (n = 26) was used. RESULTS: Most study participants (n = 13) had normal blood pressure; one individual had hypertension stage 1. All study participants had results within the reference interval for ionised calcium, parathyroid hormone, intact fibroblast growth factor-23 and for urinary albumin-to-creatinine ratio. Four out of 16 participants (25%) had a 51 Cr-EDTA clearance less than 90 ml/min/1.73 m2 , indicating a reduced kidney function. Measured 51 Cr-EDTA clearance values were significantly lower in the study group than in the comparison group (p = 0.0012). Five study participants (31%) were referred for further investigations. CONCLUSION: Swedish children born before 28 gestational weeks have an increased risk of renal impairment later in life, suggesting that the kidney function in these individuals should be assessed, at least once, during adolescence.

Diffusion tensor imaging based multiparametric characterization of renal lesions in infants with urinary tract infections: an explorative study.

BACKGROUND: Conventional diffusion weighted imaging (DWI) is a promising non-invasive tool in the evaluation of infants with symptomatic urinary tract infections (UTI). The use of multiparametric diffusion tensor imaging (DTI) provides further information on renal pathology by reflecting renal microstructure. However, its potential to characterize and distinguish between renal lesions, such as acute pyelonephritic lesions, permanent renal damages or dysplastic changes has not been shown. This study aimed to evaluate the potential of multiparametric DTI for characterization of renal lesions with purpose to distinguish acute pyelonephritis from other renal lesions in young infants with their first UTI. METHODS: Nine kidneys in seven infants, age 1.0-5.6 months, with renal lesions i.e. uptake reductions, on acute scintigraphy performed after their first UTI, were included. The DTI examinations were performed during free breathing without sedation. The signal in the lesions and in normal renal tissue was measured in the following images: b0, b700, apparent diffusion coefficient (ADC), and fractional anisotropy (FA). In addition, DTI tractographies were produced for visibility. RESULTS: There was a difference between lesions and normal tissue in b700 signal (197 ± 52 and 164 ± 53, p = 0.011), ADC (1.22 ± 0.11 and 1.45 ± 0.15 mm2/s, p = 0.008), and FA (0.18 ± 0.03 and 0.30 ± 0.10, p = 0.008) for all nine kidneys. Six kidneys had focal lesions with increased b700 signal, decreased ADC and FA indicating acute inflammation. In three patients, the multiparametric characteristics of the lesions were diverging. CONCLUSION: Multiparametric DTI has the potential to further characterize and distinguish acute pyelonephritis from other renal lesions in infants with symptomatic UTI.

A scoring system for predicting downgrading and resolution of high-grade infant vesicoureteral reflux.

AIM: Aim of the study was to provide a scoring system for predicting downgrading and resolution of infantile high-grade vesicoureteral reflux (VUR). METHODS: Eighty-nine infants (65 boys) with high-grade VUR (grade 4-5) diagnosed at median age 2.5 months and followed to 39 months had repeated investigations of VUR grade, renal damage/function and bladder function. Recurrent urinary tract infections (UTIs) were registered. Risk variables collected at 1 year were analysed as independent factors for spontaneous resolution to grades ≤2 and 0, using univariable/multivariable logistic regression. RESULTS: A scoring system was built with a total of 14 points from four independent risk factors (sex, breakthrough UTI, type of renal damage and subnormal glomerular filtration rate). Children with persistent VUR (grade 3-5) had higher scores compared with the group with spontaneous resolution (grade 0-2) (mean 7.9 vs. 4.5, P < .0001). A score of ≥8 points indicated a low probability of VUR resolution (≤14%). The model was considered excellent based on area under the ROC curve (0.82) and showed satisfactory internal validity. CONCLUSION: This model provides a practical tool in the management of infants born with high-grade reflux. High scores at one year of age indicate a high risk of persistent dilated reflux.

Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation. METHODS: A retrospective study of 58 children aged 1-17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log10 Geq/ml in > 50% of the samples during ≥ 6 months. RESULTS: At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5-6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7-13). CONCLUSIONS: CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.

A 3-year longitudinal study of skeletal effects and growth in children after kidney transplantation.

This prospective study investigated growth and skeletal development for 3 years after kidney transplantation in pediatric patients, 3.4-15.0 years of age. Growth, BMD, bone resorption markers (CTX and TRACP5b), bone formation markers (PINP, ALP, and osteocalcin), PTH, and vitamin D were assessed at start, 3, 12, and 36 months after transplantation. Median GFR was 63 (range 37-96) mL/min/1.73 m2 after 3 years. The median height SDS increased from -1.7 to -1.1, and median BMI SDS increased from -0.1 to 0.6 over 3 years, which shows that transplantation had a favorable outcome on growth. Fat mass increased after transplantation at all time points, whereas lean mass increased after 1 year and 3 years. Total BMC increased at all time points. No changes were observed for total BMD. Bone resorption markers decreased initially after 3 months and remained stable throughout the study, whereas the bone formation markers decreased initially, but successively increased over the study period. In conclusion, this study demonstrates that height SDS and BMI SDS increased, along with the increased formation markers that reveal a positive bone acquisition after kidney transplantation, which was reflected by the significant increase in total body BMC.

Long-term study showed that vaccination protected paediatric renal transplant recipients from life-threatening varicella zoster virus.

AIM: Renal transplant patients are particularly susceptible to highly contagious diseases due to their reduced immunity. We studied transplant recipients to gauge their varicella zoster virus (VZV) serology status over time and the outcome of any VZV infections. METHOD: This retrospective study comprised 85 children who underwent renal transplants in Gothenburg, Sweden, from 1986 to 2014, at a mean age of eight (1-18) years. The children's medical records were reviewed and 47 had the VZV infection pre-transplant and 38 had been vaccinated pre-transplant. Clinical outcomes were available for 85 children and serology results for 72. RESULTS: At transplantation, the VZV seropositivity rate was 50% in the vaccination group and 94% in the infection group and the antibody titres were significantly lower in the vaccination group (p = 0.031). During the median follow-up period of five years post-transplant, 28% of the vaccinated children and 97% of the infection group remained seropositive and the varicella infection affected eight children: one in the infection group and seven in the vaccination group. The herpes zoster was observed in two children in the infection group. CONCLUSION: This study demonstrated that VZV vaccination protected from symptomatic infections to a lesser extent than natural infection, but provided effective protection from life-threatening disease.

Urine neutrophil gelatinase-associated lipocalin and other biomarkers in infants with urinary tract infection and in febrile controls.

BACKGROUND: Urine biomarkers are commonly used in the evaluation of acute kidney injury, and are gaining attention as tools for studying urinary tract infections (UTIs). We analyzed neutrophil gelatinase-associated lipocalin (NGAL) and seven other urine biomarkers to evaluate their usefulness in the diagnosis of UTI in infants. METHODS: Eight urine biomarkers were analyzed in 108 infants with UTI. Controls were 64 febrile children without UTI and 13 healthy children. Logistic regression and construction of receiver operating characteristic (ROC) curves were performed for UTI patients versus febrile controls for all biomarkers. RESULTS: The best biomarkers to differentiate between UTI and febrile controls were NGAL and interleukin 8 (IL8). Urine NGAL in absolute concentration and adjusted for creatinine had a sensitivity of 93% and 96% and a specificity of 95% and 100% for diagnosing UTI, with a cut-off concentration of 38 ng/mL and 233 ng/mg respectively. CONCLUSIONS: Urine biomarkers, particularly NGAL, can aid in the diagnosis of UTI among febrile infants. The results suggest that in infants with fever and high NGAL, UTI is most likely, whereas in infants with fever and low NGAL, other causes of fever should be looked for.

Urinary tract infection in small children: the evolution of renal damage over time.

BACKGROUND: Our objective was to analyze the evolution of kidney damage over time in small children with urinary tract infection (UTI) and factors associated with progression of renal damage. METHODS: From a cohort of 1003 children <2 years of age with first-time UTI, a retrospective analysis of 103 children was done. Children were selected because of renal damage at index 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy at least 3 months after UTI, and a late DMSA scan was performed after at least 2 years. Damage was classified as progression when there was a decline in differential renal function (DRF) by ≥4%, as regression when there was complete or partial resolution of uptake defects. RESULTS: Of 103 children, 20 showed progression, 20 regression, and 63 remained unchanged. There were no differences between groups regarding gender or age. In the progression group, 16/20 (80%) children had vesicoureteral reflux (VUR) grade III-V and 13 (65%) had recurrent UTI. In multivariable regression analysis, both VUR grade III-V and recurrent UTI were associated with progression. In the regression group, 16/20 (80%) had no VUR or grade I-II, and two (10%) had recurrent UTI. CONCLUSIONS: Most small children with febrile UTI do not develop renal damage and if they do the majority remain unchanged or regress over time. However, up to one-fifth of children with renal damage diagnosed after UTI are at risk of renal deterioration. These children are characterized by the presence of VUR grades III-V and recurrent febrile UTI and may benefit from follow-up.

Peritoneal dialysis impairs nitric oxide homeostasis and may predispose infants with low systolic blood pressure to cerebral ischemia.

BACKGROUND & PURPOSE: Infants on chronic peritoneal dialysis (PD) have an increased risk of developing neurological morbidities; however, the underlying biological mechanisms are poorly understood. In this clinical study, we investigated whether PD-mediated impairment of nitric oxide (NO) bioavailability and signaling, in patients with persistently low systolic blood pressure (SBP), can explain the occurrence of cerebral ischemia. METHODS & RESULTS: Repeated blood pressure measurements, serial neuroimaging studies, and investigations of systemic nitrate and nitrite levels, as well as NO signaling, were performed in ten pediatric patients on PD. We consistently observed the loss of both inorganic nitrate (-17 ± 3%, P < 0.05) and nitrite (-34 ± 4%, P < 0.05) during PD, which may result in impairment of the nitrate-nitrite-NO pathway. Indeed, PD was associated with significant reduction of cyclic guanosine monophosphate levels (-59.4 ± 15%, P < 0.05). This reduction in NO signaling was partly prevented by using a commercially available PD solution supplemented with l-arginine. Although PD compromised nitrate-nitrite-NO signaling in all cases, only infants with persistently low SBP developed ischemic cerebral complications. CONCLUSIONS: Our data suggests that PD impairs NO homeostasis and predisposes infants with persistently low SBP to cerebral ischemia. These findings improve current understanding of the pathogenesis of infantile cerebral ischemia induced by PD and may lead to the new treatment strategies to reduce neurological morbidities.

Urinary tract infection pattern in adult women followed from childhood.

BACKGROUND: The aim of this study was to describe the pattern of urinary tract infection (UTI) and bladder function in women who had experienced recurrent UTI in childhood, with and without consequent renal damage, and followed for three to four decades. METHODS: A population-based cohort of women who had been followed from the first UTI in childhood and previously studied at a median age of 27 years was studied at a median age of 41 years. Renal damage was evaluated by (99m)Tc-dimercaptosuccinic acid scan. Clinical data were collected on the pattern of recurrent UTIs and bladder function. RESULTS: A total of 86 women were investigated, of whom 58 had suffered renal damage and 28 were without. Febrile UTI in adulthood had occurred in 22 patients, once in 15 women and twice or more in seven women. There was a change in the infection pattern over time, evident already in childhood, that was characterized by a decrease in UTI frequency and a shift from febrile to non-febrile infections. A significant association was found between renal damage and febrile UTI (p = 0.046), and between abnormal bladder function and recurrent non-febrile UTI (p = 0.002). There was no relationship between persisting vesicoureteral reflux (VUR) and proneness to either symptomatic UTI (p = 0.99) or febrile UTI in adulthood (p = 0.14). CONCLUSIONS: Among this study cohort there was a continuously decreasing rate of febrile UTI in adulthood. Persisting VUR was not related to UTI in adulthood. Abnormal bladder function was related to non-febrile UTI but not to febrile UTI.

Urinary tract infection in infants: the significance of low bacterial count.

BACKGROUND: In national guidelines for urinary tract infection (UTI) in children, different cut-off levels for defining bacteriuria are used. In this study, the relationship between bacterial count in infant UTI and inflammatory parameters, frequency of vesicoureteral reflux (VUR), kidney damage, and recurrent UTI was analyzed. METHODS: We conducted a population-based retrospective study of 430 infants age <1 year with symptomatic UTI diagnosed by suprapubic aspiration. Clinical and laboratory parameters, findings on voiding cystourethrography and (99m)technetium dimercapto-succinic acid scintigraphy, and frequency of recurrence were related to bacterial count at the index UTI. RESULTS: Eighty-three (19%) infants had bacterial counts <100,000 colony-forming units (CFU)/ml and 347 (81%) had ≥100,000 CFU/ml. There was similar frequency of VUR (19% in both groups), kidney damage (17 and 23%, p = 0.33) and recurrent UTI (6 and 12%, p = 0.17) in the low and high bacterial group. Non-E. coli species were more prevalent (19 versus 6%, p = 0.0006) and mean C-reactive protein was lower (50 vs. 79 mg/l, p <0.0001) in the low bacteria group. CONCLUSIONS: UTI with low bacterial count is common and of importance since it may be associated with VUR and renal damage. Non-E. coli species and low inflammatory response were more prevalent in UTI with low bacterial count.

Obstetrical outcome in women with urinary tract infections in childhood.

INTRODUCTION: Urinary tract infections (UTI) during childhood can result in permanent renal damage, with possible implications for future pregnancies. The aim of this prospective study was to investigate pregnancy outcomes in women followed after their first UTI in childhood. MATERIAL AND METHODS: A cohort of 72 parous women was followed from their first UTI in childhood up to a median age of 41 years. Clinical data were obtained from antenatal and hospital records. Renal damage was evaluated by a (99m) Tc-dimercaptosuccinic acid scan. Pregnancy blood pressure (BP), complications and UTIs were compared between women with and without renal damage. RESULTS: All women completed the investigations, 48 with and 24 without renal damage. No woman, irrespective of presence or absence of renal damage, was diagnosed with hypertension before the first pregnancy. Pregnancy-related hypertension was diagnosed in 10 of 151 pregnancies, all in women with renal damage. Preeclampsia occurred in four women. Women with renal damage had significantly higher systolic BP measured at the last antenatal visit of their first pregnancy, compared with women without renal damage (p = 0.005). During subsequent pregnancies both systolic and diastolic BP were significantly higher in women with than without renal damage (p = 0.02 and p = 0.03, respectively). CONCLUSION: In this population-based follow-up study we found a large proportion of women with renal damage after UTI in childhood. Women with renal damage had significantly higher BP during pregnancy compared with women without renal damage. Pregnancy-related hypertension was recorded only in women with renal damage. However, pregnancy complications, including preeclampsia, were few.

Long-term, low-dose prophylaxis against urinary tract infections in young children.

Urinary tract infection (UTI) affects about 2 % of boys and 8 % of girls during the first 6 years of life with Escherichia coli as the predominant pathogen. Symptomatic UTI causes discomfort and distress, and carries a risk of inducing renal damage. The strong correlation between febrile UTI, dilating vesicoureteral reflux (VUR), and renal scarring led to the introduction of antibiotic prophylaxis for children with VUR to reduce the rate of UTI recurrence. It became common practice to use prophylaxis for children with VUR and other urinary tract abnormalities. This policy has been challenged because of a lack of scientific support. Now, randomized controlled studies are available that compare prophylaxis to no treatment or placebo. They show that children with normal urinary tracts or non-dilating VUR do not benefit from prophylaxis. Dilating VUR may still be an indication for prophylaxis in young children. After the first year of life, boys have very few recurrences and do not benefit from prophylaxis. Girls with dilating VUR, on the other hand, are more prone to recurrences and benefit from prophylaxis. There has been a decline in the use of prophylaxis due to questioning of its efficacy, increasing bacterial resistance, and a propensity to low adherence to medication. Alternative measures to reduce UTI recurrences should be emphasized. However, in selected patients carefully followed, prophylaxis can protect from recurrent UTI and long-term sequelae. 1. There is a strong correlation between UTI, VUR, and renal scarring. 2. Children with normal urinary tracts or non-dilating VUR do not benefit from prophylaxis. 3. Young children, mainly girls, with dilating VUR are at risk of recurrent UTI and acquired renal scarring and seem to gain from antibiotic prophylaxis. 4. Increasing bacterial resistance and low adherence with prescribed medication is a major obstacle to successful antibiotic prophylaxis.

Renal function in adult women with urinary tract infection in childhood.

BACKGROUND: The risk of deterioration of renal function in patients with urinary tract infection (UTI)-associated renal damage over several decades is incompletely known but of importance in regard to follow-up. METHODS: A population-based cohort of women followed from their first UTI in childhood was studied at median age of 27 years and now at 41 years. Renal damage was evaluated by (99m)Tc-dimercaptosuccinic acid scan and glomerular filtration rate (GFR) by (51)Cr-edetic acid clearance. Extent of individual kidney damage was graded as class 1 to 3. RESULTS: Eighty-six women completed the investigation, 58 with renal damage, and 28 without. Of those with damage, one had chronic kidney disease (CKD) stage 3, 14 stage 2, and 43 stage 1. Women with bilateral damage had lower GFR than those with no or unilateral damage (p < 0.0001). Women with class 3 damage had numerically but not significantly lower GFR than the others with damage (p = 0.07). Between the two studies there was significant decrease of GFR in the group with bilateral damage (p = 0.01). CONCLUSIONS: Women with UTI-associated renal damage had remarkably well preserved renal function, but those with bilateral or severe individual kidney damage may be considered for regular monitoring of GFR and blood pressure.

Urinary tract infection in small outpatient children: the influence of age and gender on resistance to oral antimicrobials.

UNLABELLED: Urinary tract infection (UTI) is a common bacterial disease in small children in which treatment with antimicrobials is used. The worldwide increase of bacterial resistance to these drugs is threatening the efficacy of such treatment and may increase the risk for long-term damage. The aim of this retrospective study was to analyse the development of resistance to oral antimicrobials over a 10-year period in an unselected outpatient population of small children with first-time UTI. The patient material included 494 boys and 512 girls below 2 years of age with community acquired symptomatic UTI. Escherichia coli bacteria were isolated in 96 % of girls and 89 % of boys (p < 0.0001). The overall resistance of E. coli was 14 % to trimethoprim and below 1 % to cefadroxil and nitrofurantoin. Over the 10-year period, the trimethoprim resistance of E. coli increased from 5 to 17 % but remained unchanged to cefadroxil and nitrofurantoin. E. coli resistance to trimethoprim was related to age: 11 % below and 19 % above 9 months (p < 0.01). The increase in resistance over time and with age was found only in girls. CONCLUSION: The increasing resistance of E. coli to trimethoprim makes this drug less suitable for empiric treatment of UTI. Young children with UTI seem predisposed to early development of resistance. Therefore, surveillance of resistance to antimicrobials with special regard to age and gender is recommended.

Prevalence and Characteristics of Plasmid-Encoded Serine Protease EspP in Clinical Shiga Toxin-Producing Escherichia coli Strains from Patients in Sweden.

Shiga toxin-producing Escherichia coli (STEC) infection can cause a broad spectrum of symptoms spanning from asymptomatic shedding to mild and bloody diarrhea (BD) and even life-threatening hemolytic-uremic syndrome (HUS). As a member of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, EspP has the ability to degrade human coagulation factor V, leading to mucosal bleeding, and also plays a role in bacteria adhesion to the surface of host cells. Here, we investigated the prevalence and genetic diversity of espP among clinical STEC isolates from patients with mild diarrhea, BD, and HUS, as well as from asymptomatic individuals, and assessed the presence of espP and its subtypes in correlation to disease severity. We found that 130 out of 239 (54.4%) clinical STEC strains were espP positive, and the presence of espP was significantly associated with BD, HUS, and O157:H7 serotype. Eighteen unique espP genotypes (GTs) were identified and categorized into four espP subtypes, i.e., espPα (119, 91.5%), espPγ (5, 3.8%), espPδ (4, 3.1%), and espPε (2, 1.5%). espPα was widely distributed, especially in strains from patients with BD and HUS, and correlated with serotype O157:H7. Serogroup O26, O145, O121, and O103 strains carried espPα only. Ten GTs were identified in espPα, and espPα/GT2 was significantly associated with severe disease, i.e., BD and HUS. Additionally, espP was strongly linked to the presence of eae gene, and the coexistence of espPα and stx2/stx2a + stx2c was closely related to HUS status. To sum up, our data demonstrated a high prevalence and genetic diversity of the espP gene in clinical STEC strains in Sweden and revealed an association between the presence of espP, espP subtypes, and disease severity. espP, particularly the espPα subtype, was prone to be present in more virulent STEC strains, e.g., "top-six" serotypes strains.