Acute Febrile Urinary Tract Infection Research Articles

Pivmecillinam with Amoxicillin/Clavulanic acid as step down oral therapy in febrile Urinary Tract Infections caused by ESBL-producing Enterobacterales (PACUTI)

BackgroundOral treatment alternatives for febrile urinary tract infections are limited in the era of increasing antimicrobial resistance. We aim to evaluate if the combination of pivmecillinam and amoxicillin/clavulanic acid is non-inferior to current alternatives for step-down therapy in adult patients with febrile urinary tract infection.MethodsWe plan to perform an investigator-initiated non-inferiority trial. Adult hospitalised patients treated with 1–5 days of intravenous antibiotics for acute febrile urinary tract infection caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales will be randomised 1:1 to either control (7–10 days of either oral ciprofloxacin 500 mg twice daily or oral trimethoprim–sulfamethoxazole 800 mg/160 mg twice daily or intravenous ertapenem 1 g once daily, depending on sex, drug allergy, glomerular filtration rate and susceptibility testing) or intervention (10 days of pivmecillinam 400 mg three times daily and amoxicillin/clavulanic acid 500/125 mg three times daily). The primary outcome will be clinical cure 10 days (+/− 2 days) after antibiotic treatment completion. Clinical cure is defined as being alive with absence of fever and return to non-infected baseline of urinary tract symptoms without additional antibiotic treatment or re-hospitalisation (for urinary tract infection) based on a centralised allocation-blinded structured telephone interview. We plan to recruit 330 patients to achieve 90% power based on a sample size simulation analysis using a two-group comparison, one-sided alpha of 2.5%, an absolute non-inferiority margin of 10% and expecting 93% clinical cure rate and 10% loss to follow-up. The primary endpoint will be analysed using generalised estimated equations and reported as risk difference for both intention-to-treat and per protocol populations. Patients are planned to be recruited from at least 10 centres in Sweden from 2023 to 2026.DiscussionIf the combination of pivmecillinam and amoxicillin/clavulanic acid is found to be non-inferior to the control drugs there are potential benefits in terms of tolerability, frequency of interactions, outpatient treatment, side effects, nosocomial infections and drive for further antimicrobial resistance compared to existing drugs.Trial registrationNCT05224401. Registered on February 4, 2022

Elevated Urinary Hepcidin Level and Hypoferremia in Infants with Febrile Urinary Tract Infection: A Prospective Cohort Study.

To evaluate the kinetics of serum and urinary hepcidin levels along with anemia-related parameters during the infection course of infants with febrile urinary tract infection (UTI), we enrolled febrile infants aged one to four months in this prospective study. Febrile patients with UTI were allocated into Escherichia coli (E. coli) or non-E. coli groups according to urine culture results. Septic workup, blood hepcidin, iron profile, urinalysis, and urinary hepcidin-creatinine ratio were collected upon admission and 3 days after antibiotic treatment. In total, 118 infants were included. On admission, the febrile UTI group showed a significant reduction in serum iron level and a significant elevation of urinary hepcidin-creatinine ratio compared to the febrile control counterpart. Moreover, urinary hepcidin-creatinine ratio had the highest odds ratio, 2.01, in logistics regression analysis. After 3 days of antibiotic treatment, hemoglobin and the urinary hepcidin-creatinine ratio were significantly decreased. Patients with an E. coli UTI had a significantly decreased urinary hepcidin-creatinine ratio after 3 days of antibiotics treatment, whereas the non-E. coli group showed insignificant changes. Our study suggested that the urinary hepcidin-creatinine ratio elevated during acute febrile urinary tract infection and significantly decreased after 3 days of antibiotics treatment, especially in E. coli UTI.

Adjuvant corticosteroids for prevention of kidney scarring in children with acute pyelonephritis: a systematic review and meta-analysis

BackgroundAcute pyelonephritis in children may result in permanent kidney scarring that is primarily caused by inflammation during acute infection. Antibiotic therapy alone is not enough to significantly reduce kidney scarring,...

Alteration of Platelet Indices in Young Children with Acute Pyelonephritis

Background Platelets have an important contribution in pathogenesis of different infectious and inflammatory disorders. This study was performed to identify the diagnostic value of platelet count (PLT), and platelet indices in children with acute pyelonephritis (APN). Materials and Methods In a cross sectional case control study, a total of 91 children with APN and 90 healthy control children were investigated during 2018-2019. About 3 ml EDTA blood was drawn before antibiotic treatment and investigated for white blood count (WBC), Hemoglobin level, mean corpuscular volume (MCV), platelet counts, and platelet indices including mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (PLCR) in two groups. Then, the results were compared in two groups. Results Mean age at diagnosis of patients was 34.57±30.96 months. Children with APN had significantly higher PLT, along with lower MPV, PDW and PLCR, compared to the normal healthy group. Using the best cutoff points, PLT>452000, and MPV≤7.7 had the highest sensitivity (96.67%) and specificity (92.22%) for diagnosis of APN, respectively. Based on AUC, PLT and platelet indices were accurate diagnostic markers of APN. Conclusion Based on the results, PLT and platelet indices were fast and additional tests for diagnosis of children with acute febrile urinary tract infection.

National Imaging and Antibiotic Practice Patterns in Children Presenting With Urinary Tract Infection to Community Practices: Little Impact From the American Academy of Pediatrics Guidelines?

Our objective was to use community-based, national databases to evaluate diagnostic imaging and antibiotic prophylaxis practice patterns before and after the release of the 2011 American Academy of Pediatrics guidelines for acute febrile urinary tract infection. Using the National Ambulatory and Hospital Ambulatory Medical Care Surveys, urinary tract infection encounters were identified for patients aged 2 months to 18 years. Primary outcomes were utilization of antibiotics (as proxy for prophylaxis) and diagnostic imaging during encounters. Weighted multivariate logistic regression models were used to examine the association between time period (before and after 2011) and each of the primary outcomes. Among 8 588 035 weighted encounters, adjusting for covariates, there was insufficient evidence to suggest a difference between time periods for antibiotic utilization (odds ratio = 0.66, P = .12) or diagnostic imaging (odds ratio = 1.16, P = .56). Thus, we did not find evidence of changes in antibiotic utilization or diagnostic imaging practice patterns after the release of the 2011 American Academy of Pediatrics guidelines.

Evaluation and Comparison of Urinary Cytokines for the Diagnosis of Acute Pyelonephritis

Background: The accurate diagnosis and management of febrile urinary tract infection (UTI) is a clinical challenge in the absence of specific clinical and laboratory findings in infants and young children. Objectives: The aim of this study was to identify and compare the diagnostic and therapeutic implications of recently introduced cytokines for the diagnosis of acute pyelonephritis (APN). Methods: This multicenter prospective study was performed on 37 (female/male = 6.5:1) children with symptomatic culture-proven APN and 37 (female/male = 1.6/1) age-matched febrile children without UTIs as the control group. Urine samples were obtained before antibiotic treatment in both groups and 3 - 4 days after treatment in the UTI group, and evaluated for interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) using an ELISA immunoassay kit. Results: Mean urinary IL-1α, IL-4, IL-6, and IL-8 concentrations significantly increased in the acute phase of APN compared to the control group, and decreased following antibiotic treatment. Conclusions: We recommend routine urinalysis and urine culture for the diagnosis of children with APN. Urinary IL-4 was a relatively good cytokine for the prediction and treatment-monitoring of children with acute febrile UTI.

Value of Ultrasound in Detecting Urinary Tract Anomalies After First Febrile Urinary Tract Infection in Children.

Background Urinary tract infection (UTI) is an infection that affects part of the urinary tract. Ultrasound is a noninvasive test that can demonstrate the size and shape of kidneys, presence of dilatation of the ureters, and the existence of anatomic abnormalities. The aim of the study is to estimate the value of ultrasound in detecting urinary tract anomalies after first attack of UTI. Methods This study was conducted at the Nephrology Clinic, New Children's Hospital, Faculty of Medicine, Cairo University, from August 2012 to March 2013, and included 30 children who presented with first attack of acute febrile UTI. All patients were subjected to urine analysis, urine culture and sensitivity, serum creatinine, complete blood count, and imaging in the form of renal ultrasound, voiding cysto-urethrography, and renal scan. Results All the patients had fever with a mean of 38.96°C ± 0.44°C and the mean duration of illness was 6.23 ± 5.64 days. Nineteen patients (63.3%) had an ultrasound abnormality. The commonest abnormalities were kidney stones (15.8%). Only 2 patients who had abnormal ultrasound had also vesicoureteric reflux on cystourethrography. Sensitivity of ultrasound was 66.7%, specificity was 37.5%, positive predictive value was 21.1%, negative predictive value was 81.8%, and total accuracy was 43.33%. Conclusion We concluded that ultrasound alone was not of much value in diagnosing and putting a plan of first attack of febrile UTI. It is recommended that combined investigations are the best way to confirm diagnosis of urinary tract anomalies.

The diagnosis of febrile urinary tract infection in children may be facilitated by urinary biomarkers.

We prospectively assessed the feasibility of two urinary markers of renal injury as potential diagnostic tests for acute febrile urinary tract infection (UTI) and subsequent renal scarring. The patient cohort comprised children aged 0 to 4 years who visited the emergency room. The children were divided into three groups, namely, a febrile UTI (fUTI), febrile control (FC) and a non-febrile control (NFC) group, respectively, which were matched for sex and age. An enzyme-linked immunosorbent assay for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) was performed on urine collected from each child. The urine levels of both markers were compared between the three groups, and the diagnostic accuracy was determined based on the area under the receiver-operator characteristic curve (AUC). In the fUTI group, the predictability of subsequent renal scarring was assessed by associating urinary levels with dimercaptosuccinic acid findings 6 months after an UTI episode. Significantly elevated levels of urinary NGAL and KIM-1 were observed in the fUTI group, as well as with increased urine esterase, serum C-reactive protein, and pyuria. The AUC was 72 % for KIM-1 and 96 % for NGAL. The AUC of KIM-1 for the prediction of scarring was 71 % (p < 0.05). The diagnosis of febrile UTI and the prediction of subsequent scarring may be facilitated by assaying urine biomarkers with acceptable accuracy.

A rapid plasma neutrophil gelatinase-associated lipocalin assay for diagnosis of acute pyelonephritis in infants with acute febrile urinary tract infections: a preliminary study

In infants with febrile urinary tract infection (UTI), the accurate rapid diagnosis of acute pyelonephritis (APN) would be valuable because early aggressive treatment reduces the risk of renal scarring. The objective of the study was to evaluate whether rapid plasma neutrophil gelatinase-associated lipocalin (NGAL) assay could be used as a diagnostic biomarker of renal parenchymal injury in infants with acute febrile UTI to distinguish APN at the bedside. This prospective observational study included 47 infants, who were admitted with a first episode of acute febrile UTI. Total UTI group was divided into the Cortical defect (UTI-CD, n = 24) group and Non-cortical defect (UTI-ND, n = 23) group, according to the result of renal scan. For the Control group, 15 infants who presented a febrile episode without any focus of bacterial infection were included. On admission, the median NGAL level (106.5 [60-476] ng/mL) in the UTI-CD group was significantly higher than that (60 [60-196] ng/mL) in the UTI-ND group and that (60 [60-197] ng/mL) in the Control group and was significantly decreased to 60 [60-306] ng/mL after an antibiotic treatment. The area under the receiver operating characteristic curves was 0.748 (95% CI, 0.610-0.887; P = 0.003) for NGAL levels and 0.724 (95% CI, 0.579-0.868; P = 0.009) for CRP levels. The best cutoff of NGAL level for detection of APN was founded to be 61.0ng/mL (sensitivity, 75.0%; specificity, 78.3%). Although not a stand-alone test, the rapid determination of plasma NGAL level provides valuable information quickly, concerning the distinction of APN, for determining the clinical course of acute febrile UTI.

Predictive Factors for Acute Renal Cortical Scintigraphic Lesion and Ultimate Scar Formation in Children With First Febrile Urinary Tract Infection

We assessed predictive factors for acute renal cortical scintigraphic lesion and ultimate scar formation in children with a first febrile urinary tract infection. A total of 89 girls and 138 boys with a first febrile urinary tract infection were included in the study. We analyzed radiological (ultrasound, dimercapto-succinic acid scintigraphy, voiding cystourethrogram), clinical (age, gender, peak fever, therapeutic delay time) and laboratory (complete blood count with differential count, absolute neutrophil count, blood urea nitrogen, creatinine, urinalysis, Gram's stain, culture, C-reactive protein, erythrocyte sedimentation rate) variables. Dimercapto-succinic acid scintigraphy was performed within 5 days and at 6 months after diagnosis of urinary tract infection. Voiding cystourethrogram was performed after the acute phase of the urinary tract infection. Predictive factors for acute scintigraphic lesion and ultimate scar formation were assessed using logistic regression analysis. Of 227 patients enrolled 140 had a refluxing and 87 a nonrefluxing urinary tract infection. On logistic regression analysis therapeutic delay time (p = 0.001) and presence of reflux (p = 0.011) were predictive of acute scintigraphic lesion and ultimate scar formation (p = 0.001 and p = 0.0001, respectively) in children with a first febrile urinary tract infection. Since vesicoureteral reflux is the common risk factor for acute scintigraphic lesion and ultimate scar formation, voiding cystourethrogram must be considered as an initial study in patients with acute febrile urinary tract infection.

A Perinephric Abscess Due to Escherichia coli Complicating an Acute Febrile Urinary Tract Infection in a Young Child

A perinephric abscess is an uncommon entity, especially in children. Most cases arise as a complication of a urinary tract infection. The most common organisms implicated in perinephric abscesses are gram-negative uropathogens and Staphylococcus aureus. The insidious onset of nonspecific protean symptoms in cases of perinephric abscesses requires that the clinician maintain a high index of suspicion to prevent a delay in diagnosis. Perinephric abscesses are associated with significant morbidity and mortality. A case of a perinephric abscess complicating an acute febrile urinary tract infection in a pediatric patient is presented, followed by a review of the literature.

Genetic markers and acute febrile urinary tract infection in the 1st year of life.

Blood groups ABO, MN, Rhesus, P, and Lewis, salivary ABH secretion, and at the HLA DQ alpha locus were studied in 65 Caucasian children of both sexes diagnosed as having acute febrile urinary tract infection in the 1st year of life, as well as in 60 Caucasian control children. No differences were observed between patients and controls. Results from patients with normal urinary tracts were also similar to those from patients with primary vesicoureteral reflux. We could not confirm previous findings suggesting different susceptibility to urinary tract infection based on phenotypes of several genetic markers.

Is there a single most appropriate imaging workup of a child with an acute febrile urinary tract infection?

Is there a single most appropriate imaging workup of a child with an acute febrile urinary tract infection?

Reflux nephropathy, urinary tract infection, and voiding disorders.

Urinary tract infection (UTI), vesicoureteral reflux (VUR), and certain voiding disorders result in renal damage. In the past few years, the increasing use of 99mTc-dimercaptosuccinic acid renal scans, urodynamic testing, and antenatal sonography have helped shed light on the interrelationship of these disorders. Renal parenchymal involvement during acute febrile UTI and subsequent renal scarring are quite commonly observed in the absence of VUR, suggesting that the presence of reflux is not a prerequisite for renal damage. In infants with gross VUR, renal damage is often present at birth even before the development of any UTI. High intravesical pressures during bladder filling and voiding are commonly observed in infants with gross VUR, reflecting an underlying voiding dysfunction. High voiding detrusor pressures are also commonly observed in infants presenting with symptomatic UTI who do not have VUR. Children with dysfunctional voiding states are at risk for development of VUR and UTI. Renal damage in these children may occur in the absence of one or the other. This review elucidates how voiding dysfunction predisposes children to bacterial colonization of the bladder, the development or perpetuation of VUR, and renal damage.

Renal cortical scintigraphy in the diagnosis of acute pyelonephritis

Comparative clinical studies have shown renal cortical scintigraphy, using technetium-99m (99mTc)-labeled glucoheptonate or dimercaptosuccinic acid (DMSA), to be significantly more sensitive than either intravenous pyelography or renal sonography in the diagnosis of acute pyelonephritis. However, due to uncertainties about the diagnostic accuracy of the clinical and laboratory parameters used in these studies, true sensitivity of renal cortical scintigraphy was unknown. Therefore, we evaluated the accuracy of [99mTc]DMSA scintigraphy in the diagnosis of experimentally induced acute pyelonephritis in piglets using strict histopathologic criteria as the standard of reference. The sensitivity and specificity of the DMSA scan for the diagnosis of acute pyelonephritis were 91% and 99%, respectively, with an overall 97% agreement between the scintigraphic and histopathologic findings. Based on the results of this experimental study, we used the [99mTc]DMSA scan as the standard of reference for the diagnosis of acute pyelonephritis, and conducted a prospective clinical study of 94 children hospitalized with the diagnosis of acute febrile urinary tract infection (UTI). The aims of this study were (1) to determine the relationship among vesicoureteral reflux, P-fimbriated Escherichia coli, acute pyelonephritis, and renal scarring, and (2) to evaluate the diagnostic reliability of the clinical and laboratory parameters commonly used in the diagnosis of acute pyelonephritis. We documented acute pyelonephritis in 62 (66%) of 94 patients. Vesicoureteral reflux was demonstrated in 29 (31%) of the total group and in only 23 (37%) of 62 patients with acute pyelonephritis. The prevalence of P-fimbriae in the E coli isolates was 64% in the patients with acute pyelonephritis and 78% in those with a normal DMSA scan. Even in patients without reflux, P-fimbriae were found in 71% of isolates from the patients with acute pyelonephritis and in 75% of those with a normal renal scan. Follow-up DMSA scans were obtained in 33 patients with acute pyelonephritis in 38 kidneys. We found complete resolution of the acute inflammatory changes in 58% of the involved kidneys and renal scarring in the remaining 42%, including 40% of the kidneys associated with reflux and 43% of those without reflux.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal Function in Acute Febrile Urinary Tract Infection in Children: Pathophysiologic Aspects on the Reduced Concentrating Capacity

Few studies of renal function in acute pyelonephritis in man have been published. In one of these, Winberg [1] reported a reduced concentrating capacity, a finding later confirmed by others [2, 3]. The concentrating defect was proposed to be due to a damage of distal and collecting tubules [1, 4]. The concentrating capacity normalized within 4 to 6 weeks after treatment of the infection [1]. This seemingly rapid reversibility, which also can be demonstrated in experimental pyelonephritis [5], suggested a more transient defect than can be explained by structural damage. In experimental pyelonephritis in the rat [6–8], other explanations for the reduced concentrating ability have arisen. Among these explanations are an increased solute load per nephron due to a reduced nephron mass, a diminution of the tonicity of the medullary interstitium, or a failure to achieve osmotic equilibration. Keeping the above statement in mind, we have set the aim of the present study to further evaluate renal function by more accurate clearance studies in children with acute febrile urinary tract infections.

Renal function in acute febrile urinary tract infection in children: Pathophysiologic aspects on the reduced concentrating capacity

In an attempt to elucidate the reduced concentrating capacity in acute pyelonephritis, we studied the renal function in 14 children, 5 to 16 years of age. Clearance of inulin, PAH, and free water, urinary sodium excretion, and maximal urine osmolality after 18 hours of thirst have been determined at and within 10 months after infection. Glomerular filtration rate and renal plasma flow were found to be increased during infection and normalized after infection. Urinary sodium excretion, distal sodium delivery, and maximal urine osmolality were decreased during infection and increased afterwards. Kidney size was also increased during infection. It is postulated that the reduced concentrating capacity is due to a washout effect mediated by an increased medullary blood flow and to a low distal tubular sodium delivery.