A genome-wide association study of susceptibility to upper urinary tract infections.

BACKGROUND: Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs). METHODS: We used data from UK Biobank, The Trøndelag Health Study (HUNT), and Michigan Genomics Initiative (MGI) to conduct genome-wide association studies (GWASs) and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs. RESULTS: One genome-wide significant (P ≤ 5E-08) locus was associated with the susceptibility to upper UTI, located near TSN in the female-only analysis. Additionally, we identified suggestive (P ≤ 5E-06) loci near DNAI3 for the females, SCAMP1-AS1 for the males, and near TSN, LINC00603, and HLA-DQA2 for both sexes. In MR analyses, higher genetically predicted lifetime smoking scores were associated with an increased risk of developing upper UTI for females and both sexes (OR of 4.84, P = 4.50E-06 and OR of 2.79, P = 3.02E-05, respectively). CONCLUSIONS: We found that genetic variants near TSN was associated with the risk of upper UTIs among females. In addition, we found several genetic loci with suggestive associations with the risk of upper UTIs. Finally, MR analyses found smoking to be a potential causal risk factor for upper UTIs.

Minimally invasive techniques as a first line approach in the management of emphysematous pyelonephritis - A single centre experience.

Context: Emphysematous pyelonephritis (EPN) is a dangerous necrotizing infection of the kidney involving the diabetics with a high case fatality rate. Recent medical literature has shown shifting of treatment strategy from conventional radical approach to minimally invasive approach. Aims: The aim of our study was to assess the role of minimally invasive stepwise decompression techniques in the management of EPN and preservation of the renal unit. Settings and Design: : This was a retrospective observational study conducted from June 2017 to April 2020 at a tertiary care centre. Material and Methods: We reviewed the hospital online records of 18 patients diagnosed with EPN for patient demographics, clinical profiles, co-morbidities, laboratory and, radiological investigations, surgical interventions performed and the outcomes. The severity of EPN was graded as per the Huang classification. Patients underwent surgical interventions as per the treatment protocol and response was assessed. Statistical Analysis Used: Descriptive statistics was applied. Results: Diabetes mellitus was present in 15 (83.3%) patients along with urinary tract obstruction in 8 (44.4%) patients. Flank pain (77.7%) was the most common presenting clinical feature while Escherichia coli (55.5%) were the most common causative organism. Most patients (50%) had Type- II EPN, all of which were managed successfully by minimally invasive procedures. In total seventeen patients (94.4%) responded well while one patient (5.5%) underwent nephrectomy with no mortality. Conclusions: Renal salvage in EPN requires multidisciplinary approach including the initial medical management followed by properly selected stepwise decompressive surgical techniques. Conservative management and decompression techniques have shown to improve patient's outcome, reducing the traditional morbidity associated with nephrectomy.

A clinical decision support system improves antibiotic therapy for upper urinary tract infection in a randomized single-blinded study.

BACKGROUND: Due to increasing bacterial resistance rates choosing a correct empiric antibiotic therapy is getting more and more complex. Often medical doctors use information tools to make the right treatment choice. METHODS: One hundred sixty six participants (77 medical doctors and 89 medical students) were asked to provide a diagnosis and antibiotic therapy in a simple fictive paper case of upper urinary tract infection (UTI) in a randomized single-blinded study. Participants were randomized to one of four information tools they were allowed to use in the study or control: 1. free internet access, 2. pharmaceutical pocket guide, 3. pocket guide antibiotic therapy, 4. clinical decision support system (CDSS), and control (no information tool). The CDSS was designed for the study. The adherence to the national German UTI guideline was evaluated. RESULTS: Only 27.1% (n = 45/166) provided a correct diagnosis of upper UTI and 19.4% (n = 32/166) an antibiotic treatment recommended by national German treatment guidelines indicating their need for information tools. This result was not significantly different between medical doctors and medical students, residents and medical specialists or level of working experience. Using CDSS improved results significantly compared to conventional tools (diagnosis 57.1%; treatment recommendation 40.5%; p < 0,01). Processing time was not different between the use of CDSS and conventional information tools. CDSS users based their decision making on their assigned information tool more than users of conventional tools (73.8% vs. 48.0%; p < 0.01). Using CDSS improved the confidence of participants in their recommendation significantly compared to conventional tools (p < 0.01). CONCLUSIONS: Our study suggests that medical professionals require information tools in diagnosing and treating a simple case of upper UTI correctly. CDSS appears to be superior to conventional tools as an information source.

The diagnosis and management of a patient with acute pyelonephritis.

Lower urinary tract infections account for more than 224 000 hospital admissions each year and nearly all of these have the pathophysiological possibility to develop into pyelonephritis, known clinically as an upper urinary tract infection. Acute pyelonephritis is characterised by inflammation of the renal parenchyma caused by bacteriuria ascending from the bladder, up the ureters to the kidneys. Effective history taking, combined with refined physical examination skills, are the two most powerful tools to differentiate upper and lower urinary tract infections as well as assisting the practitioner to exclude other differential diagnoses. Utilisation of these skills by the practitioner, together with the recognised presenting symptom triad of flank pain, fever and nausea in this case study, enabled the diagnosis of acute pyelonephritis to be given.

Serum soluble ST2 as a marker of renal scar in pediatric upper urinary tract infection.

BACKGROUND AND OBJECTIVES: Upper urinary tract infection is the most common serious bacterial infection in childhood. Patients with upper urinary tract infection have a risk for renal scarring with subsequent complications including hypertension, proteinuria, and progressive renal failure. However, the predictive biomarkers of renal scarring in children with upper urinary tract infection are still unknown. In this study, we evaluated whether soluble ST2 levels can be biomarkers of subsequent renal scarring in patients with upper urinary tract infection. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively studied pediatric patients with upper urinary tract infection at a tertiary center. Twenty-eight children had an upper urinary tract infection with (n = 14) and without (n = 14) renal scarring and underwent 99mtechnetium dimercaptosuccinic acid imaging. In addition, 13 control subjects were enrolled. The clinical data and serum cytokine levels, including soluble ST2 levels, were compared between those with and without renal scars. RESULTS: Serum soluble ST2 levels were significantly higher in the scar group than in the non-scar group, whereas there was no difference in the levels of serum interferon-γ, interleukin-6, interleukin-10, soluble tumor necrosis factor receptor 1, and transforming growth factor-ß between the scar and non-scar groups. The area under the curve for differentiating between the non-scar and scar groups on the basis of measurements of serum soluble ST2 was 0.79, with a sensitivity and specificity of 92.9% and 64.3%, respectively. CONCLUSION: These results suggest that serum soluble ST2 levels on admission could be a useful biomarker of subsequent renal scarring in pediatric patients with upper urinary tract infection.

Increased community-acquired upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in children and the efficacy of flomoxef and cefmetazole.

BACKGROUND: Urinary tract infections caused by extended-spectrum beta-lactamase-producing bacteria are increasing worldwide. At our hospital, the number of pediatric patients hospitalized because of an upper urinary tract infection has dramatically increased since 2016. In total, 60.5% of urinary tract infections are caused by extended-spectrum beta-lactamase-producing Escherichia coli. Such a high prevalence of extended-spectrum beta-lactamase-producing E. coli has not been detected previously in Japan. Therefore, we evaluated the clinical and bacteriologic characteristics and efficacy of antibiotics against upper urinary tract infections caused by E. coli in children. METHODS: This retrospective study surveyed 152 patients who were hospitalized in the pediatric department of Shimane Prefectural Central Hospital because of upper urinary tract infections caused by E. coli. Medical records were reviewed to examine patient characteristics. O antigens, antibiotic susceptibility, gene typing, and pulse-field gel electrophoresis were studied at the Shimane Prefectural Institute of Public Health and Environmental Science. RESULTS: Urine sample analyses showed extended-spectrum beta-lactamase types such as CTX-M-9 and plural virulence genes. We changed the primary antibiotic treatment to flomoxef or cefmetazole to treat upper urinary tract infections caused by Gram-negative bacilli. After changing treatment, the time to fever alleviation was significantly shortened. CONCLUSION: Extended-spectrum beta-lactamase-producing E. coli should be suspected in community-acquired upper urinary tract infections. Therefore, when treating patients, it is necessary to focus on antibiotic susceptibility and the prevalence of extended-spectrum beta-lactamase-producing bacteria found in each area. Flomoxef and cefmetazole are useful primary treatments for upper urinary tract infections caused by extended-spectrum beta-lactamase-producing E. coli.

Distinctive inflammatory profile between acute focal bacterial nephritis and acute pyelonephritis in children.

BACKGROUND: Acute focal bacterial nephritis (AFBN) is a severe form of upper urinary tract infection (UTI) with neurological manifestations and focal renal mass lesions on computed tomography (CT). Prolonged antibiotic therapy may improve the renal outcome, but the early differential diagnosis of AFBN from acute pyelonephritis (APN) is challenging. We searched for effective biomarkers of AFBN based on the pathophysiology of upper UTIs. METHODS: Of 52 upper UTI cases treated at Yamaguchi University between 2009 and 2016, 38 pediatric patients with AFBN (n=17) or APN (n=21) who underwent ultrasonography and/or CT were enrolled. The clinical data and serum cytokine concentrations were analyzed to differentiate AFBN from APN. RESULTS: AFBN patients tended to be older, and have a higher body temperature, longer febrile period, more frequent neurological symptoms, higher immature neutrophil count, lower lymphocyte count, higher procalcitonin and urine ß2-microglobulin levels. AFBN patients showed higher serum levels of IFN-γ, IL-6, IL-10 and soluble TNF-receptor 1 (sTNFR1) (all p<0.05). Although the cytokine levels were variably correlated among each other, multiple logistic regression analysis revealed that combination of IFN-γ and IL-6 levels were most relevant for distinguishing AFBN from APN. The discriminant power of the logistic equation was 0.86 in terms of the area under the curve by the ROC analysis. CONCLUSIONS: Circulating 4 out of 7 cytokines in AFBN patients were at higher levels compared with those in APN patients. IFN-γ and IL-6 levels might most effectively distinguish AFBN from APN.

Acute focal bacterial nephritis is associated with invasive diagnostic procedures - a cohort of 138 cases extracted through a systematic review.

BACKGROUND: Acute focal bacterial nephritis (AFBN) is a rare disease currently described only in case reports and small case series. In this study we summarize the clinical features of AFBN as has been documented in the literature and draw recommendations on the proper diagnosis and therapy. METHODS: A systematic literature review was undertaken in PUBMED, Web of Science and The Cochrane Library online databases for relevant literature on AFBN in adults. RESULTS: Literature review revealed a total of 38 articles according to our inclusion criteria, of which we could extract data from 138 cases of AFBN. Fever (98%) and flank pain (80%) were most commonly reported symptoms. E. coli was the most frequent pathogen. Diagnosis was set by CT and/or MRI (52%) with or without sonography or by sonography alone (20%) as well as by sonography combined with IVU. In total, sonography was applied in 83% of cases. All but one patient received antibiotic treatment. Kidney lesions were occasionally mistaken for neoplasms or renal abscesses and as a result, cases were subjected to percutaneous puncture (12.3%), surgical exploration (5.1%) and partial or radical nephrectomy (4.4%). Four cases (2.9%) developed a renal abscess. CONCLUSIONS: The diagnosis of AFBN is set by characteristic clinico-radiological findings. Differential diagnoses of this interstitial bacterial infection include renal abscess and tumor. Correct diagnosis is occasionally impeded by atypical symptoms. Invasive diagnostic and therapeutic procedures should be limited as the majority of cases respond well to conservative treatment.

Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for blaCTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of blaCTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice.

[Experimental modeling of acute pyelonephritis].

Acute pyelonephritis (AP) predominates among inflammatory infection kidney affections. In accordance to international classifications, AP is an upper urinary tract infection, subdivided into non-complicated (non-obstructive) and complicated (obstructive) forms. The clinical significance of AP presently is defined by the conditions frequent occurrence and its progression into chronic kidney disease. For a limited number of pathogens the involvement in AP is considered proven: representatives of the Enterobacteriaceae family (E.coli, Klebsiella spp., Proteus spp., etc.), Pseudomonas spp., a number of gram-positive microorganisms (S.aureus, Enterococcus spp.). Beside that, over the last 3 decades there have been rare publications in the world literature describing clinical cases of AP caused by microorganisms not readily cultivated on standard mediums (mostly anaerobic). This was accompanied by an idea that AP might develop in case of kidney invasion not only by aerobic, but also by anaerobic microorganisms, which is practically not taken into account in current clinical practice. In this regard it was deemed feasible to perform an analysis of experimental disease models to refine the discussion points of the disease etiology, to do so an attempt of all-encompassing study in the Russian and English literature databases (linical Key, MEDLINE, PubMed, HighWire Press, The Cochrane Library, BioMed Central, Central scientific medical library of the I.M. Sechenov Moscow medical academy, Russian State Library). A total of 356 literature sources have been studied, of which 41 were selected for the current review.

Renal infarction versus pyelonephritis in a woman presenting with fever and flank pain.

Patients with fever, flank pain, and dysuria frequently are encountered in the emergency department. Acute pyelonephritis is the most likely diagnosis; however, its clinical and radiologic presentation consistently overlap with that of acute renal infarction. Ultrasound is unable to distinguish early infarction from nonabscessed acute pyelonephritis. Hence, computed tomography or magnetic resonance imaging are needed. We report the case of a 68-year-old woman who presented with fever, flank pain, and dysuria, along with respiratory distress and tachycardia. Elevated values for inflammatory indexes suggested a diagnosis of acute pyelonephritis, and subsequent contrast-enhanced computed tomography showed hypodense wedge-shaped areas in both kidneys. However, the presence of a thin rim of capsular enhancement (cortical rim sign), the absence of perirenal inflammatory changes, and the location of the lesions apart from defined calyces suggested the alternative diagnosis of renal infarction. The underlying cause was not identified until an episode of acute dyspnea revealed paroxysmal arrhythmia. Our case demonstrates that a thorough knowledge of the imaging findings of renal infarction and acute pyelonephritis is essential to correctly making the diagnosis.

Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection-- 7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Acute pyelonephritis is a frequent cause of morbidity, with a wide variation in duration of therapy. We performed a systematic review of all randomized controlled trials (RCTs) comparing ≤7 days treatment with a longer course. METHODS: Electronic databases were searched to identify RCTs that assessed adults treated for pyelonephritis, comparing a 7 day or shorter versus longer therapy. Primary outcome was clinical failure at the end of the long treatment arm (EOT). Secondary outcomes included clinical failure at the end of follow-up (EOF), microbiological failure, all-cause mortality, the development of resistance and adverse events. RESULTS: Clinical failure at EOT did not significantly differ between the two treatment arms [relative risk (RR) 0.63, 95% CI 0.33-1.18, I(2) = 41%]. Results did not differ when including studies comparing only fluoroquinolones, reducing the heterogeneity (RR 0.76, 95% CI 0.49-1.17, I(2) = 0%). We found no difference between the short and long treatment arms regarding clinical failure at EOF, even in a small subgroup of bacteraemic patients. No difference was found between the arms regarding microbiological failure at EOF, except in a subgroup of studies with a high percentage of patients with urogenital abnormalities, where microbiological failure at EOF was significantly higher in the short treatment arm (RR 1.78, 95% CI 1.02-3.10, I(2) = 21%). Adverse events were similar between the arms. CONCLUSIONS: Seven days of treatment for acute pyelonephritis is equivalent to longer treatment in terms of clinical failure and microbiological failure, including in bacteraemic patients. In patients with urogenital abnormalities, the evidence, although weak, suggests that longer treatment is required.

Percutaneous drainage for non-operative management of emphysematous pyelonephritis: Clinical characteristics and predictors of success.

Emphysematous pyelonephritis (EPN) is a necrotizing renal infection that can rapidly progress without urgent intervention. The purpose of this study was to evaluate the safety and efficacy of percutaneous nephrostomy (PN) in the management of EPN, as well as the relationship of outcomes with initial classification by the Huang-Tseng classification system and other prognostic factors such as thrombocytopenia. A retrospective review of medical records revealed seven patients with EPN treated with PN. Thirty-day survival rate was 86%, with the only mortality due to an arrhythmia secondary to underlying cardiomyopathy rather than a complication from EPN or PN. A single nephrostomy procedure served as definitive treatment in 3 patients (43%). Reintervention due to recurrence of EPN symptoms was required in 4 patients (57%), all of which initially presented with Class 3 disease or higher. Two of these four patients required nephrectomy, while the other two were successfully managed with a second drainage procedure without further recurrence of symptoms. PN appears to be a safe and generally effective management option for EPN, especially in patients who are considered poor surgical candidates. PN may serve as definitive treatment in hemodynamically stable patients with lower class of disease. In patients with higher class of disease, PN may be definitive treatment in patients who lack additional risk factors such as thrombocytopenia or serve as an effective bridge to nephrectomy.

Comparison of mild encephalopathy with reversible splenial lesion with and without acute focal bacterial nephritis.

OBJECTIVE: Clinically mild encephalitis/encephalopathy with a reversible lesion (MERS) is characterized by reversible lesions with transiently-reduced diffusion in the splenium of the corpus callosum on magnetic resonance imaging. Recently, cases of MERS with accompanying acute focal bacterial nephritis (AFBN) have been reported in children. This study aimed to clarify the clinical features of MERS with AFBN. METHODS: A retrospective study of patients with MERS was conducted at Nagano Children's Hospital, Japan, from April 2013 to March 2018. The clinical signs and laboratory findings of MERS patients with AFBN (AFBN group) and without AFBN (non-AFBN group) were measured and compared. RESULTS: Of 12 patients diagnosed as having MERS, 3 were also found to have AFBN. Seven of the 9 patients without AFBN were associated with infectious agents, including rotavirus and influenza viruses. No patient received steroids or intravenous immunoglobulin therapy, and none displayed neurological sequelae. Serum C-reactive protein (CRP) levels were significantly higher in the AFBN group than in the non-AFBN group (14.7 mg/dL versus 0.8 mg/dL, P = 0.009). AFBN group patients were also significantly older (97 months versus 27 months, P = 0.018) and experienced significantly less frequent seizures (33% versus 100%, P = 0.045). The mean duration of neurological symptoms was significantly longer in the AFBN group than in the non-AFBN group (4 days versus 1.7 days, P = 0.013). CONCLUSIONS: Pediatric patients with AFBN often present with non-specific findings, such as fever and abdominal pain. Pediatricians should be aware of the possibility of AFBN in the clinical setting of MERS, particularly when the patient exhibits inexplicably high CRP.

Emphysematous pyelonephritis: Changing trend of clinical spectrum, pathogenesis, management and outcome.

OBJECTIVE: To highlight changing trend of clinical spectrum, comparing management options and predictors of outcome of emphysematous pyelonephritis. MATERIAL AND METHODS: This study included patients who were diagnosed as emphysematous pyelonephritis between August, 2001 to July, 2015. We excluded other possible causes of gas in renal system. Baseline patient characteristics, clinical spectrum, serum and urinary biochemical parameters, radiological findings, management and outcomes were recorded. Patients were classified as "responders" and "non-responders". RESULTS: We studied a total of 74 patients and categorised them as responders (62 patients) and non-responders (12 patients). Women outnumbered men constituting 62.16% of the study population (M: F; 1: 1.6). Fever was the most common presenting symptom followed by flank pain. Diabetes mellitus (85.14%) was the most common comorbidity followed by urolithiasis (32.43%). Escherichia coli was the commonest organism grown in urine culture (79.73%). Non-responders had distinct laboratory findings relative to responders as low hemoglobin (7.8±2.1/11.2±3.2 g/dL; p=0.0007), thrombocytopenia (91.67% vs. 11.29%; p=0.0001), proteinuria >3 g/L (50% vs. 6.45%; p=0.0008) and positive blood culture (100% vs. 67.74%; p=0.0288). CONCLUSION: Advanced age, higher body mass index, renal impairment, thrombocytopenia, altered sensorium, shock at presentation can be used as scores for poor prognosis. Emphysematous pyelonephritis management requires multidisciplinary collaboration including hydration and electrolyte management, broad spectrum antibiotics, strict glycaemic control, effective urinary drainage and lastly it may require emergency nephrectomy as a salvage procedure.

Validation of Cefazolin as Initial Antibiotic for First Upper Urinary Tract Infection in Children.

To validate the policy of administering cefazolin (CEZ) as a first-line antibiotic to children who are hospitalized with their first febrile urinary tract infection (UTI), we evaluated microbial susceptibility to CEZ and the efficacy of CEZ. The 75 enrolled children with febrile UTI were initially treated with CEZ. Switching CEZ was not required in 84% of the patients. The median fever duration, prevalence of bacteremia, prevalence of UTI caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli, and median duration of hospitalization were significantly higher in the CEZ-ineffective group. The risks of vesicoureteral reflux, indication of operation, and renal scarring are not increased, even when CEZ is ineffective as a first-line antibiotic. CEZ is effective in more than 80% of pediatric patients with their first febrile UTI, but it should be switched to appropriate antibiotics considering sepsis or the ESBL-producing Enterobacteriaceae pathogen, when fever does not improve within 72 hours.

Acute lobar nephritis in children: Not so easy to recognize and manage.

Acute lobar nephritis (ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children.