[Phytoprophylaxis of complications after extracorporeal lithotrips].

AIM: To evaluate the efficiency of the drug phytolysin (capsules) in the prevention of complications after extracorporeal lithotripsy. MATERIALS AND METHODS: A total of 15 patients diagnosed with urolithiasis and chronic pyelonephritis in the latent phase were treated. The predominant localization of radiopaque stones no larger than 20 mm in size was the collecting system. The piezoelectric lithotripsy (1-2 sessions) was performed, followed by the administration of the herbal drug Phytolysin in the dosage form of a capsule. The follow-up was carried out after 14- and 30-days using laboratory, ultrasound and x-ray methods. RESULTS: In the postoperative period, there were no cases of the pyelonephritis, which may result from a short-term disturbance of the upper urinary tract urodynamics due to the passage of stone fragments. The antibacterial, antispasmodic, diuretic and anti-inflammatory effects of Phytolysin ensured positive changes in laboratory and bacteriological tests, contributed to the prevention of postoperative complications after extracorporeal lithotripsy (renal colic, pyelonephritis), and contributed to maintaining renal blood flow within normal limits and significantly reduced the time to stone-free status. CONCLUSIONS: Our results justify the feasibility of using phytolysin in capsules in patients with urolithiasis after extracorporeal lithotripsy. The dosage form in capsules eliminates the undesirable effects associated with the specific smell and taste, that patients noted when using phytolysin in the form of a paste.

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis.

The objective of this study was to probe the effect and mechanism of Szechwan Lovage Rhizome (Chuanxiong, CX) extract on renal function (RF) and inflammatory responses (IRs) in acute pyelonephritis (APN) rats infected with Escherichia coli (E. coli). Fifteen SD rats were randomized to intervention, model and control groups. Rats in the control were fed normally without treatment, rats in the APN model were infected with E. coli, and rats in the intervention group were intragastrically administered CX extract after infection with E. coli. HE staining detected pathological changes in the kidney tissues in rats. Levels of renal function indexes and inflammatory factors (IFs) were measured by ELISA and an automatic biochemical analyzer. Besides, levels of IL-6/signal transducer and activator of transcription 3 (STAT3) pathway-related genes in rat kidney tissue were detected by qRT-PCR and western blot. the experimental results showed that IL-1ß, IL-8, TNF-α and RF levels were the highest in the model group and the lowest in the control group, with those of the intervention group in between (P<0.05). Besides, the IL-6/STAT3 axis was markedly activated in the model group but inhibited in the intervention group (P<0.05). Subsequently, activated IL-6/STAT3 signal promoted IFs (IL-1ß, IL-8 and TNF-α) and RF (BUN, Scr, ß2-MG and UA), but this effect was offset after CX treatment (P<0.05). In conclusion, CX extract could improve RF and inhibit IRs of APN rats infected with E. coli by inhibiting the IL-6/STAT3 axis, which may be a new choice for APN treatment in the future.

Sulopenem for the Treatment of Complicated Urinary Tract Infections Including Pyelonephritis: A Phase 3, Randomized Trial.

BACKGROUND: Sulopenem is a thiopenem antibiotic being developed for the treatment of multidrug-resistant infections. The availability of both intravenous (IV) and oral formulations will facilitate earlier hospital discharge. METHODS: Hospitalized adults with pyuria, bacteriuria, and signs and symptoms of complicated urinary tract infection (cUTI) were randomized to 5 days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid or 5 days of IV ertapenem followed by oral ciprofloxacin or amoxicillin-clavulanate, depending on uropathogen susceptibility. The primary end point was overall combined clinical and microbiologic response at the test-of-cure visit (day 21). RESULTS: Of 1392 treated patients, 444 and 440 treated with sulopenem and ertapenem, respectively, had a positive baseline urine culture and were eligible for the primary efficacy analyses. Extended-spectrum ß-lactamase-producing organisms were identified in 26.6% of patients and fluoroquinolone-nonsusceptible pathogens in 38.6%. For the primary end point, noninferiority of sulopenem to the comparator regimen was not demonstrated, 67.8% vs 73.9% (difference, -6.1%; 95% confidence interval, -12.0 to -.1%). The difference was driven by a lower rate of asymptomatic bacteriuria in the subgroup of ertapenem-treated patients who stepped down to ciprofloxacin. No substantial difference in overall response was observed at any other time point. Both IV and oral formulations of sulopenem were well-tolerated and compared favorably to the comparator. CONCLUSIONS: Sulopenem followed by oral sulopenem-etzadroxil/probenecid was not noninferior to ertapenem followed by oral step-down therapy for the treatment of cUTIs, driven by a lower rate of asymptomatic bacteriuria in those who received ciprofloxacin. Both formulations of sulopenem were well-tolerated. CLINICAL TRIAL REGISTRATION: NCT03357614.

[Systematic review and Meta-analysis of efficacy and safety of Ningmitai Capsules in treatment of urinary tract infection].

This study aims to evaluate the effectiveness and safety of Ningmitai Capsules in the treatment of urinary tract infection.To be specific, articles on the treatment of urinary tract infection with Ningmitai Capsules were retrieved from China National Know-ledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, and Web of Science(from establishment to October 2021).Eligible randomized controlled trials(RCTs) were screened out, and ROB and RevMan 5.3 of Cochrane were employed for data integration and Meta-analysis.Finally, 17 articles were included, involving 1 972 cases, with 1 045 in the experimental group and 927 in the control group.The Meta-analysis results are as follows.Ningmitai Capsules combined with conventional antibiotics was superior to sensitive antibiotics alone in the treatment of acute pyelonephritis in aspects of clinical cure rate(RR=1.94, 95%CI[1.58, 2.37], P<0.000 01), reduction in the count of red blood cells in the urine(MD=-3.22, 95%CI[-3.23,-3.21], P<0.000 01), decrease in the count of white blood cells in the urine(MD=-2.34, 95%CI[-2.59,-2.10], P<0.000 01), and time for the disappearance of the symptoms(MD_(time for urinary tract irritation disappeared)=-2.19, 95%CI[-2.69,-1.68], P<0.000 01; MD_(time for waist aches disappeared)=-3.58, 95%CI[-4.20,-2.97], P<0.000 01; MD_(time for heating disappeared)=-0.57, 95%CI[-0.81,-0.33], P<0.000 01).The combination of either cephalosporin or quinolone with Ningmitai Capsules can improve clinical cure rate of acute pyelonephritis(RR_(combined with cephalosporin)=1.94, 95%CI[1.56, 2.42], P<0.000 01; RR_(combined with quinolone)=1.91, 95%CI[1.16, 3.15], P=0.01).The clinical cure rate(RR=1.91, 95%CI[1.47, 2.49], P<0.000 01) of diabetes complicated with urinary tract infection by Ningmitai Capsules was higher than that by quinolones.The clinical cure rate(RR=1.22, 95%CI[1.09, 1.37], P=0.000 5) of non-gonococcal urethritis by Ningmitai Capsules combined with conventional tetracycline and macrolide antibiotics was higher than that by conventional antibiotics.Ningmitai Capsules combined with conventional antibiotics/Ningmitai Capsules alone was superior to conventional antibiotics alone in the treatment of urinary tract infection in terms of the clinical cure rate(RR=1.35, 95%CI[1.17, 1.56], P<0.000 1) and incidence of adverse reactions(RR=0.32, 95%CI[0.15, 0.68], P=0.003), particularly the combination with quinolone antibiotics(RR=1.30, 95%CI[1.04, 1.61], P=0.02).The main adverse reactions were mild gastrointestinal discomfort, nausea, vomiting, and dry mouth.In summary, Ningmitai Capsules combined with conventional sensitive antibiotics/Ningmitai Capsules alone can improve the clinical cure rate of patients with urinary tract infection.Ningmitai Capsules combined with conventional sensitive antibiotics can significantly reduce the time for symptom disappearance of acute pyelonephritis and down-regulate the counts of red and white blood cells in the urine compared with antibiotics alone, and no serious adverse reactions have been found.However, in light of the low proportion of quality eligible articles, experiments with rigorous design, large sample size, and complete outcome in-dexes should be carried out in the future to verify the clinical efficacy and safety of Ningmitai Capsules in the treatment of urinary tract infection.

[Modern algorithm of diagnosis and treatment of acute gestational pyelonephritis in a large industrial city].

THE PURPOSE OF THE STUDY: to develop a modern algorithm for the diagnosis and treatment of acute gestational pyelonephritis in a large industrial city and to study the possibilities of phytotherapy as an integral part of this algorithm. MATERIALS AND METHODS: The study consisted of two stages and included 629 patients treated over 12 years (2010-2021) in Perm city with a population of 1.1 million people. At the first stage, the developed algorithm for the diagnosis and treatment of acute gestational pyelonephritis in 440 pregnant women was tested. A city emergency center for patients with gestational pyelonephritis was created with 3 urologists and related specialists on duty around the clock, what accelerated hospitalization timelines by 2.1 times. The patients underwent a level 1 examination, which included ultrasound examination, urine bacteriology and other methods. Patients in serve condition underwent, a level 2 examination, which included magnetic resonance imaging (MRI), ultrasound Dopplerography (USDG) and extended laboratory tests. RESULTS: During an urgent examination, acute purulent pyelonephritis was diagnosed in 27 (6.1%) patients who underwent 13 open surgeries (11 organ-preserving, 2 nephroectomies) and 14 minimally invasive (percutaneous nephrostomy, puncture of a kidney abscess) within 2-5 hours from the moment of hospitalization. Serve obstructive pyelonephritis was diagnosed in 286 patients, the passage of urine was restored by the installation of a stent or catheterization of the ureter. Conservative antibacterial therapy was performed in 127 patients with serous non-obstructive pyelonephritis. Positive results of treatment were observed in 439 (99.8%) patients: recovery in 95%, significant improvement in 4.8%, with a mortality rate of 0.2%. Bed-day decreased by 30.4%. At the second stage, a comparative randomized study was conducted during 4 years with 189 pregnant women with acute serous pyelonephritis enrolled. In the group 1 (n=94) patients received standard therapy according to the implemented algorithm, in the group 2 (n=95) patients had 60-day use of Canephron N. In the group 2, treatment results were better: recovery was achieved in 96.8% of patients, improvement in 3.2%, the number of pregnant women with leukocyturia and bacteriuria decreased 4.1 times, which prevented the occurrence of repeated attacks of acute pyelonephritis. Compared with standard therapy, Canephron N increased glomerular filtration by 12,3%, diuresis by 14.2%, increased urea excretion function of the kidneys, sanitized the urinary tract at an earlier timelines, reduced the number of premature births and the birth of dead and premature babies. CONCLUSION: As a result of the development and implementation of an algorithm for the diagnosis and treatment of acute gestational pyelonephritis and creation of the treatment center for such patients, it was possible to reduce significantly the time of hospitalization and inpatient treatment and achieve good treatment results in 99.8% of patients. The inclusion of long-term phytotherapy with Canephron N in the treatment regimen increased the effectiveness of treatment, improved kidney function in patients, significantly reduced the number of pregnant women with leukocyturia and bacteriuria, and reduced the risk of a repeated attack of pyelonephritis.

Studies on Virulence and Extended-Spectrum ß-Lactamase-Producing Uropathogenic Escherichia coli Isolates and Therapeutic Effect of Fosfomycin in Acute Pyelonephritis Mice.

The understanding about virulence factors (VFs) and the drug resistance of uropathogenic Escherichia coli (UPEC) helps us understand the pathogenesis of urinary tract infections (UTIs) and make better decisions for clinical treatment. This study examined the correlation between the extended-spectrum ß-lactamases (ESBLs) phenotype and VFs in UPEC strains. In addition, we validated the therapeutic potential of fosfomycin in acute pyelonephritis mice. From May 2017 to November 2018, 22 nonduplicate E coli. strains were isolated from UTI patients. PCR was utilized to detect the distribution of virulence genes. We also analyzed the ESBL phenotype in E coli. We further evaluated the therapeutic effect of intravenous fosfomycin treatment in the acute pyelonephritis (APN) model. All 22 UPEC strains expressed the type 1 fimbriae (FimH) gene and more than 50% (12/22) of strains produced ESBLs. The detection rates of the iron acquisition-associated genes ChuT and IutA were 77.3% (n = 17) and 50% (n = 11) and those of P fimbria papA and papC genes were 45% (n = 10) and 50% (n = 11), respectively. Though the VFs were closely related with pathologenicity, the relationship between VFs and ESBLs still needs further investigation. Furthermore, intravenous fosfomycin 800 mg/kg significantly reduced the bacterial load and the inflammatory infiltration in the bladder and kidney, maintaining the structural integrity of the kidney. Intravenous fosfomycin administration can be used for the treatment of acute pyelonephritis caused by highly pathogenic and drug-resistant UPEC strains.

[Clinical and pathogenetic aspects of the treatment and prevention of pyelonephritis in children].

INTRODUCTION: Treatment of pyelonephritis in children should be combined, long-term and individual-based. The success of the therapy in children largely depends on the prompt appointment and the correct choice of antimicrobial therapy. AIM: To evaluate the efficiency of the dietary supplement "Cystenium II" in a group of children aged 7 to 14 years with a diagnosis of acute and chronic recurrent pyelonephritis in the acute phase. MATERIALS AND METHODS: A total of 60 children aged 7 to 14 years with a diagnosis of acute or chronic recurrent pyelonephritis in the acute stage were included in the study. The clinical group consisted of 30 patients (mean age 12.1+/-1.8 years), while the control group included 30 patients of mean age 11.2+/-1.7 years. In the control group patients received only standard antibiotic therapy, while in the clinical group it was combined with a dietary supplement "Cystenium II" 1 tablet 2 times a day with meals for 14 days. After the course of antibacterial treatment, the children in the clinical group continued to take the studied dietary supplement for another 14 days in order to prevent the recurrence of pyelonephritis. The results of treatment (patient's condition, presence of pain, dysuria, fever) were assessed on the 3rd, 7th, 14th day, 1 and 6 months after the start of treatment. A urinalysis was performed at the baseline, on the 7th and 14th days, as well as after 1 and 6 months. Urine culture was performed before and after antibiotic therapy at the baseline, on the 14th day, 1 and 6 months after the start of treatment. RESULTS: The main indicators of urinalysis (leukocytes, red blood cells, protein) returned to normal values in 26 (86.7%) patients of the clinical group and in 23 (76.7%) patients of the control group on the 7th day after the start of treatment. At the completion of the basic therapy (after 14 days) normal clinical parameters (absence of leukocyturia, microhematuria, proteinuria) were observed in all patients of the clinical group and in 28 (93.3%) patients of the control group. After a month of follow-up, the disturbances in urinalysis (leukocytes, red blood cells, protein) in the control group were again seen in 3 (10%) patients, as well as after 6 months. However, in the clinical group all patients had normal urinalysis (absence of leukocyturia, microhematuria, proteinuria) after 1 month and only in 1 (3.3%) case leukocyturia, as well as an increase in the number of red blood cells and protein was detected by 6 months. DISCUSSION: According to our results, the use of dietary supplements "Cystenium II" (manufactured by Akvion, Russia), due to the constituents of D-mannose (450 mg), cranberry fruit extract with a standardized activity of 500 mg (36 mg of proanthocyanidins) and vitamin C (60 mg), may cause anti-inflammatory and anti-adhesive effects (resolving of leukocyturia and bacteriuria). This allows to use the dietary supplement Cystenium II in children from 7 years of age in the combination therapy of acute pyelonephritis, as well as exacerbation of chronic pyelonephritis. The obtained results showed a high overall therapeutic efficacy of combination therapy using Cystenium II after 6 months from the start of treatment (relapse in 1 patient), in contrast to the control group (relapse in 6 patients). CONCLUSIONS: the use of dietary supplement "Cystenium II" allowed to reduce the number of repeated courses of antibiotic therapy in children during 6 months of follow-up and, most likely, reduced the frequency of development of chronic pyelonephritis after an acute inflammation. Therefore, the wide clinical use of dietary supplements "Cystenium II" for the combined treatment of acute and exacerbation of chronic pyelonephritis in children older than 7 years seems to be very reasonable.

Rotula aquatica Lour. mitigates oxidative stress and inflammation in acute pyelonephritic rats.

The current study evaluates the efficacy of methanolic extract of Rotula aquatica Lour. (MERA) against inflammatory changes associated with acute pyelonephritis. The antioxidant enzymes such as SOD, CAT, GPx, GR and oxidative stress markers like GSH content, malondialdehyde (MDA) level, nitrate level, reactive oxygen species (ROS) level and renal toxicity markers were evaluated in this study. The mRNA level expression of Toll-like receptor 4 (TLR-4), nuclear transcription factor kappa B (NF-κB), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and Tamm Horsfall protein (THP) were studied by RT-PCR analysis. The oral administration of MERA increases the antioxidant enzyme status in pyelonephritis rat. The elevated levels of oxidative stress markers in pyelonephritic rats were ameliorated by the administration of MERA at 100 mg/kg and 200 mg/kg bwt of the rat. The mRNA level expression of major genes were restored to normal level by MERA.

Antimicrobial resistance profiles and genes in uropathogenic Enterobacteriaceae in reproductive-age women in St. Petersburg, Russia: implication for treatment of pyelonephritis in pregnancy.

BACKGROUND: Urinary tract infections (UTIs) are common in women, and during pregnancy can cause significant morbidity. Growing and greatly varying antimicrobial resistance (AMR) of Enterobacteriaceae, responsible for most UTIs, necessitates regular local AMR surveillance. In obstetric population, where beta-lactams are the mainstay for treatment of severe UTIs, particular focus should be placed on beta-lactam resistance. This study aimed to evaluate AMR rates and frequency of extended spectrum beta-lactamase (ESBL) and carbapenemase genes in uropathogenic Enterobacteriaceae among reproductive-age women in St. Petersburg, Russia. MATERIALS/METHODS: Urine samples were collected from consecutive reproductive-age women, who attended the D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology from October 2017 to November 2019, and cultured according to routine procedures. Susceptibility to antibiotics and ESBL production was determined using the disc diffusion method according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. All urine samples and Enterobacteriaceae isolates were tested for ESBL and carbapenemase genes using real-time PCR. RESULTS: Enterobacteriaceae were detected in 91 (56 pregnant and 35 non-pregnant) of 119 (76%) included women. The vast majority of Enterobacteriaceae strains were susceptible to nitrofurantoin, fosfomycin and meropenem (99-100%). The frequency of strains susceptible to penicillins and cephalosporins ranged from 59% to 82%; 78% of strains were susceptible to ciprofloxacin. ESBL production was phenotypically detected in 15 (16%) Enterobacteriaceae strains, with CTX-M genes revealed in all cases. In all corresponding urine samples, CTX-M genes were also detected. The remaining 104 urine samples were negative for CTX-M genes. In none of the isolates and urine samples, carbapenemase genes were present. CONCLUSIONS: The frequency of ESBL producing Enterobacteriaceae was relatively high (16%), with CTX-M genes detected in all cases in both urine and urine cultures. Rapid PCR detection of CTX-M genes directly in urine samples from women with pyelonephritis can be valuable for timely informing treatment choices.

Protective Effects of Omega-3 Fatty Acids Supplementation Against Renal Parenchymal Scarring in Children with Acute Pyelonephritis: Results of a Pilot Clinical Trial.

AIM: This trial aimed to determine if supplementation with omega-3 fatty acids as an adjunct therapy to antibiotic treatment can have protective effects against renal scar formation after acute pyelonephritis (APN) in pediatric patients. BACKGROUND: Current evidence points out that besides antibiotic treatment, early administration of antioxidant and anti-inflammatory compounds may be effective in reducing the occurrence of renal damage following APN in children. OBJECTIVE: The main endpoint of the trial was the comparison of the development of renal scarring formation after APN in an omega-3 fatty acids-treated group and in a control-treated group. METHODS: This prospective randomized, controlled trial study was conducted from March 2016 to May 2018 on 60 children with a diagnosis APN in a tertiary hospital in Iran. After the diagnosis of APN based on the clinical signs and symptoms, urine analysis, urine culture, and dimercaptosuccinic acid renal scan (DMSA scan), the patients were randomly allocated into either the control group (n=30 patients: received standard antibiotic treatment only) or the intervention group (n=30 patients: received standard antibiotic-treatment in combination with oral omega-3 fatty acids based on the children's weight for three consecutive days). A second DMSA scan was performed for the patients at a minimum of six months after treatment. The development of renal scars was evaluated by comparing the baseline DMSA scan lesions with the follow-up DMSA scan lesions. RESULTS: Fifty patients, including 26 and 24 individuals in the control and intervention groups, respectively, completed the entire course of the study. Renal parenchymal involvement based on the baseline DMSA scan was similar in the two groups (p-value =0.85, 0.90, and 0.53 regarding the right, left, and both kidney units together, respectively). Although comparison of the follow-up DMSA scan lesions to the baseline DMSA scan lesions considering the right and left kidneys as separate units between two groups did not reach the significant level, when considering both left and right kidney units together, results showed a statistically significant difference between groups in favor of the intervention group (p-value =0.04). CONCLUSION: Although preliminary, the results of this study showed that administration of omega-3 fatty acids, a natural supplement with well-known anti-inflammatory and antioxidant properties, as an adjunct therapy to standard antibiotic treatment might significantly reduce the incidence of the occurrence renal scarring following APN in children. Confirmation of these results requires further studies.

Caracterización clínica y epidemiológica de pacientes con diagnóstico de Pielonefritis Aguda en el Hospital Militar Central, en el periodo de Enero de 2019 a Septiembre de 2022 / Clinical and epidemiological characterization of patients diagnosed with Acute Pyelonephritis at the Central Military Hospital, from January 2019 to September 2022

Antecedentes: Las infecciones de vías urinarias son patologías que representan una importante causa de morbi - mortalidad. Los individuos con comorbilidades usualmente son los más afectados. Los agentes etiológicos más frecuentes son Enterobacterias. El tratamiento inicialmente es empírico, en base a la epidemiología y la sensibilidad conocida de los antibióticos. En la Pielonefritis aguda es obligatoria la comprobación de la sensibilidad a los antibióticos mediante la realización de cultivos urinarios. En la actualidad, ha aumentado la prevalencia de enfermedades urinarias causadas por bacterias multirresistentes. Objetivo: Se caracterizó clínica y epidemiológicamente a los pacientes con diagnóstico de Pielonefritis Aguda en el Hospital Militar Central, en el periodo comprendido entre Enero de 2019 a Septiembre de 2022. Metodología: Se realizó un estudio descriptivo, transversal, retrospectivo y se determinó las características clínicas, los datos de laboratorio­microbiológicos, tratamientos farmacológicos y estudios de imagen renal, por medio de la revisión de expedientes de pacientes con diagnóstico de Pielonefritis aguda ingresados en el periodo de estudio. Resultados: La Pielonefritis aguda afecta frecuentemente a pacientes entre 30 y 65 años, del sexo femenino, con Hipertensión Arterial y Diabetes Mellitus, las manifestaciones clínicas más comunes la fiebre y el dolor lumbar, con elevación de reactantes de fase aguda leucograma y PCR, el agente principalmente reportado fue E. coli y el tratamiento frecuentemente utilizado fue la combinación de Ceftriaxona y Amikacina, los pacientes fueron hospitalizados por 10 días en su mayoría. Este estudio, enfatiza en las características del paciente con Pielonefritis Aguda para brindar un tratamiento adecuado.

Background: Urinary tract infections are pathologies that represent an important cause of morbimortality. Individuals with comorbidities are usually the most affected. The most frequent etiological agents are Enterobacteria. Treatment is initially empirical, based on the epidemiology and known sensitivity of antibiotics. In acute pyelonephritis, it is mandatory to verify sensitivity to antibiotics by performing urinary cultures. At present, the prevalence of urinary diseases caused by multiresistant bacteria has increased. Objective: Patients diagnosed with Acute Pyelonephritis at the Central Military Hospital were characterized clinically and epidemiologically, in the period from January 2019 to September 2022. Methodology: A descriptive, cross-sectional, retrospective study was carried out and the clinical characteristics, laboratory-microbiological data, pharmacological treatments and renal imaging studies were determined, by reviewing the records of patients diagnosed with acute pyelonephritis admitted to the hospital. study period. Results: Acute Pyelonephritis frequently affects female patients between 30 and 65 years of age, with Arterial Hypertension and Diabetes Mellitus, the most common clinical manifestations being fever and low back pain, with elevation of acute phase reactants, leukogram and PCR, the leucograma agent mainly reported was E coli and the treatment frequently used was the combination of Ceftriaxone and Amikacin, the majority of patients were hospitalized for 10 days. This study emphasizes the characteristics of the patient with Acute Pyelonephritis to provide adequate treatment.

Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis.

BACKGROUND: The clinical-stage drug candidate EBL-1003 (apramycin) represents a distinct new subclass of aminoglycoside antibiotics for the treatment of drug-resistant infections. It has demonstrated best-in-class coverage of resistant isolates, and preclinical efficacy in lung infection models. However, preclinical evidence for its utility in other disease indications has yet to be provided. Here we studied the therapeutic potential of EBL-1003 in the treatment of complicated urinary tract infection and acute pyelonephritis (cUTI/AP). METHODS: A combination of data-base mining, antimicrobial susceptibility testing, time-kill experiments, and four murine infection models was used in a comprehensive assessment of the microbiological coverage and efficacy of EBL-1003 against Gram-negative uropathogens. The pharmacokinetics and renal toxicology of EBL-1003 in rats was studied to assess the therapeutic window of EBL-1003 in the treatment of cUTI/AP. FINDINGS: EBL-1003 demonstrated broad-spectrum activity and rapid multi-log CFU reduction against a phenotypic variety of bacterial uropathogens including aminoglycoside-resistant clinical isolates. The basicity of amines in the apramycin molecule suggested a higher increase in positive charge at urinary pH when compared to gentamicin or amikacin, resulting in sustained drug uptake and bactericidal activity, and consequently in potent efficacy in mouse infection models. Renal pharmacokinetics, biomarkers for toxicity, and kidney histopathology in adult rats all indicated a significantly lower nephrotoxicity of EBL-1003 than of gentamicin. INTERPRETATION: This study provides preclinical proof-of-concept for the efficacy of EBL-1003 in cUTI/AP. Similar efficacy but lower nephrotoxicity of EBL-1003 in comparison to gentamicin may thus translate into a higher safety margin and a wider therapeutic window in the treatment of cUTI/API. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Infecciones del Tracto Urinario: métodos diagnósticos, tratamiento empírico y multirresistencia en una Unidad de Adultos Área de Emergencias / Urinary Tract Infections: diagnostic methods, empirical treatment and multidrug resistance in an Adult Emergency Area Unit

INTRODUCCIÓN. Las infecciones del tracto urinario por variedad de bacterias uropatógenas multiresistentes se deben al uso de tratamiento empírico o automedicación. OBJETIVO. Describir en las infecciones de tracto urinario los métodos diagnósticos, tratamiento empírico y la multirresistencia. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, retrospectivo. Población y muestra de 73 Historias Clínicas de pacientes atendidos en la Unidad de Adultos Área de Emergencias del Hospital de Especialidades Carlos Andrade Marín en el período enero a diciembre 2018. Se incluyeron pacientes mayores de 18 años, de ambos sexos, con diagnóstico clínico y por laboratorio de infección del tracto urinario superior e inferior. La información se obtuvo mediante la base de datos AS400, y se procesó en Epi-info y Excel. RESULTADOS. El 71,23% (52; 73) de mujeres tuvieron infección del tracto urinario. Escherichia coli fue frecuente en un 48,39% (15; 31), con mayor resistencia al Clotrimoxazol. El tratamiento empírico con Ciprofloxacino fue utilizado en 27,40% (20; 73). DISCUSIÓN: Se observó controversia en los tipos de estudios de imagen solicitados para el diagnóstico acorde a la clase de infección de tracto urinario así como el tratamiento empírico por factores propios de cada localidad que evitaron resistencia. CONCLUSIÓN. Escherichia coli se aisló de manera frecuente y registró mayor resistencia al Clotrimoxazol; el principal antibiótico prescrito como tratamiento empírico fue la Ciprofloxacina; el examen más solicitado fue la Urotomografía.

INTRODUCTION. Urinary tract infections due to a variety of multi-resistant uropathogenic bacteria are due to the use of empirical treatment or self-medication. OBJECTIVE. Describe diagnostic methods, empirical treatment and multidrug resistance in urinary tract infections. MATERIALS AND METHODS. Observational, descriptive, retrospective study. Population and sample of 73 Medical Records of patients treated in the Emergency Area Adult Unit of the Carlos Andrade Marín Specialty Hospital in the period january to december 2018. Patients older than 18 years of age, of both sexes, with clinical diagnosis and due to upper and lower urinary tract infection laboratory. The information was obtained through the AS400 database, and was processed in Epi-info and Excel. RESULTS. 71,23% (52; 73) of women had urinary tract infection. Escherichia coli was frequent in 48,39% (15; 31), with greater resistance to Clotrimoxazole. Empirical treatment with Ciprofloxacin was used in 27,40% (20; 73). DISCUSSION: Controversy was observed in the types of imaging studies requested for diagnosis according to the class of urinary tract infection as well as the empirical treatment due to factors specific to each locality that prevented resistance. CONCLUSION. Escherichia coli was frequently isolated and showed greater resistance to Clotrimoxazole; the main antibiotic prescribed as empirical treatment was Ciprofloxacin; the most requested examination was the Urotomography.

Appropriateness of Antibiotic Prescriptions for Urinary Tract Infections.

INTRODUCTION: Urinary tract infections (UTI) are a common indication for antibiotic use in the emergency department (ED). With antibiotic resistance on the rise, it is essential that antibiotics be prescribed appropriately for UTIs. Our objective was to evaluate the appropriateness of antibiotic prescriptions by ED providers for uncomplicated cystitis and pyelonephritis. METHODS: We conducted a retrospective study of females ages 2-50 years seen in an academic ED from January 2017 to April 2018 diagnosed with UTI. We assessed the appropriateness of discharge antibiotic prescriptions, as determined by adherence to clinical practice guidelines, best evidence for the particular indication (cystitis vs pyelonephritis for children and adults), and the local antibiogram. RESULTS: A total of 421 patients were included in this study. Of these, 60 children and 198 adults were diagnosed with cystitis, and 47 children and 116 adults were diagnosed with pyelonephritis. Treatment in the absence of true infection was common, with culture-confirmed UTI occurring in only 17/50 (34%) of children and 60/129 (47%) of adults diagnosed with cystitis, and 23/40 (58%) of children and 58/87 (67%) of adults diagnosed with pyelonephritis, among patients who had urine cultures. The type of antibiotic prescribed was appropriate in 53/60 (88%) of children and 135/198 (68%) of adults with cystitis, and 38/47 (81%) of children and 53/116 (46%) of adults with pyelonephritis. The most common inappropriate antibiotic types were beta-lactams in adults (n = 92), nitrofurantoin for pyelonephritis (n = 16), and amoxicillin (n = 15). Dosing and duration errors were also common, occurring in 122/279 (44%) of prescriptions of an appropriate antibiotic type. The frequency of errors in the type of antibiotic prescribed was similar among provider types (attending physician, resident physician, and advanced practice clinician; p = 0.926). CONCLUSION: This study reveals room for improvement in antibiotic prescription practices across provider cohorts in the ED for the management of uncomplicated cystitis and pyelonephritis in females.

Acute on chronic kidney disease in cats: Etiology, clinical and clinicopathologic findings, prognostic markers, and outcome.

BACKGROUND: Chronic kidney disease (CKD) and acute decompensation of CKD (ACKD) are common in cats. OBJECTIVES: To characterize the etiology, clinical and clinicopathologic findings, and the short- and long-term prognosis of feline ACKD. ANIMALS: One hundred cats with ACKD. METHODS: Retrospective study, search of medical records for cats with ACKD. RESULTS: Common clinical signs included anorexia (85%), lethargy (60%), weight loss (39%), and vomiting (27%). Suspected etiologies included ureteral obstruction (11%), renal ischemia (9%), pyelonephritis (8%), others (6%), or unknown (66%). Hospitalization duration was longer in survivors versus nonsurvivors (median = 7 days, range = 2-26 versus median = 3 days, range = 2-20, respectively, P < .001). The survival rate to discharge was 58%. Age, serum creatinine, urea, and phosphorous concentrations were higher and venous blood pH was lower in nonsurvivors. However, only serum phosphorus remained associated with the short-term outcome in the multivariable model (P = .02; 95% confidence interval = 1.03-1.39). Survivors had a median survival time of 66 days after discharge. Serum creatinine concentrations at presentation as well as at discharge were associated with long-term survival (P < .002 for both). CONCLUSIONS: The short-term prognosis of ACKD is comparable to acute kidney injury, while the long-term prognosis is guarded.

Diabetes mellitus increases mortality in acute pyelonephritis patients: a population study based on the National Health Insurance Claim Data of South Korea for 2010-2014.

OBJECTIVE: Diabetes mellitus has been suspected to increase mortality in acute pyelonephritis (APN) patients and the goal of this study is to verify this suspicion with a large data set based on almost the entire population of South Korea. METHODS: A nationwide cohort study was conducted using a South Korean Health Insurance Review and Assessment Service claim database. We collected demographic and clinical information including comorbidities of patients with APN as the primary discharge diagnosis during 2010-2014. Then we compared the in-hospital mortality and recurrence of APN across the diabetes and non-diabetes groups. RESULTS: Among 845,656 APN patients, 12.4% had diabetes mellitus. The median age was 65 in the diabetes group, which was much higher than 47 in the non-diabetes group; the female proportion was 91-92% in both groups. The in-hospital mortality rate was higher in the diabetes group (2.6/1000 events in the diabetes group vs. 0.3/1000 in the non-diabetes group, P < 0.001). When covariates (age, sex, and the modified Charlson comorbidity index) were controlled with panel logistic regression, diabetes was still associated with a higher in-hospital mortality in APN patients (OR 2.66, 95% CI 2.19-3.23). The increasing effect of diabetes on in-hospital mortality of APN patients varied greatly with age: the effect was large for age 15-49 (OR 15.06, 95% CI 5.27-43.05), slightly smaller for age 50-64 (OR 12.17, 95% CI 5.71-25.92), and much smaller for age ≥ 65 (OR 2.10, 95% CI 1.72-1.92). CONCLUSIONS: Our data indicate that the mortality of APN is higher in the patients with diabetes and this effect becomes stronger for young patients.

Is Piperacillin-Tazobactam Effective for the Treatment of Pyelonephritis Caused by Extended-Spectrum ß-Lactamase-Producing Organisms?

BACKGROUND: Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum ß-lactamase (ESBL)-producing organisms. METHODS: We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain. RESULTS: There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09). CONCLUSIONS: TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Comparative Pharmacokinetics of Gallic Acid, Protocatechuic Acid, and Quercitrin in Normal and Pyelonephritis Rats after Oral Administration of a Polygonum capitatum Extract.

Polygonum capitatum Buch.-Ham. ex D. Don is traditionally used by Hmong for the treatment of urinary tract infections and pyelonephritis. Information regarding the pharmacokinetic behavior of the extract in the condition of pyelonephritis is lacking. In the present study, we aimed to compare the pharmacokinetic properties of gallic acid (GA), protocatechuic acid (PCA), and quercitrin (QR)-the main bioactive constituents in the herb-in normal and pyelonephritis rats. The plasma samples were collected at various time points after administration of a single dose of Polygonum capitatum extract. The plasma level of GA, PCA, and QR at the designed time points was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and drug concentration versus time plots were constructed to estimate the pharmacokinetic parameters. The AUC(0-t), AUC(0-∞), MRT(0-t), and CL of GA, PCA, and QR in pyelonephritis rats was significantly different from those of the normal rats. The results indicated that the three constituents have higher rate of uptake and slower rate of elimination in the rats with pyelonephritis, suggesting altered rate and extent of drug metabolism.

Unexpected Activity of Oral Fosfomycin against Resistant Strains of Escherichia coli in Murine Pyelonephritis.

Fosfomycin tromethamine activity is well established for oral treatment of uncomplicated lower urinary tract infections, but little is known about its potential efficacy in pyelonephritis. Ascending pyelonephritis was induced in mice infected with 6 strains of Escherichia coli (fosfomycin MICs, 1 µg/ml to 256 µg/ml). The urine pH was 4.5 before infection and 5.5 to 6.0 during infection. Animals were treated for 24 h with fosfomycin (100 mg/kg of body weight subcutaneously every 4 h), and the CFU were enumerated in kidneys 24 h after the last fosfomycin injection. Peak (20.5 µg/ml at 1 h) and trough (3.5 µg/ml at 4 h) levels in plasma were comparable to those obtained in humans after an oral dose of 3 g. Fosfomycin treatment significantly reduced the bacterial loads in kidneys (3.65 log10 CFU/g [range, 1.83 to 7.03 log10 CFU/g] and 1.88 log10 CFU/g [range, 1.78 to 5.74 log10 CFU/g] in start-of-treatment control mice and treated mice, respectively; P < 10-6). However, this effect was not found to differ across the 6 study strains (P = 0.71) or between the 3 susceptible and the 3 resistant strains (P = 0.09). Three phenomena may contribute to explain this unexpected in vivo activity: (i) in mice, the fosfomycin kidney/plasma concentration ratio increased from 1 to 7.8 (95% confidence interval, 5.2, 10.4) within 24 h in vitro when the pH decreased to 5, (ii) the fosfomycin MICs for the 3 resistant strains (64 to 256 µg/ml) decreased into the susceptible range (16 to 32 µg/ml), and (iii) maximal growth rates significantly decreased for all strains and were the lowest in urine. These results suggest that local fosfomycin concentrations and physiological conditions may favor fosfomycin activity in pyelonephritis, even against resistant strains.

Trend of antibiotics usage for acute pyelonephritis in Korea based on national health insurance data 2010-2014.

BACKGROUND: The objective of this study is to describe the changes in prescribing practices of antibiotics to treat acute pyelonephritis (APN) in Korea. METHODS: The claim data base of the Health Insurance Review and Assessment Service in Korea was used to select patients with ICD-10 codes N10 (acute tubulo-interstitial nephritis) or N12 (tubulo-interstitial nephritis, not specified as acute nor chronic) as the primary discharge diagnosis during 2010-2014. Consumption of each class of antibiotics was converted to Defined Daily Dose (DDD)/event. RESULTS: Throughout the five-year period, the average antibiotic consumption were 11.3 DDD per inpatient event and 6.0 DDD per outpatient event. The annual average antibiotic consumption increased for inpatients (P = 0.002), but remained stable for outpatients (P = 0.066). The use of parenteral antibiotics increased for inpatients (P < 0.001), but decreased for outpatients (P = 0.017). As for the the antibiotic classes, 3rd generation cephalosporins (3rd CEPs) was the most commonly prescribed (41.4%) for inpatients, followed by fluoroquinolones (FQs) (28.5%); for outpatient, FQs (54.8%) was the most commonly prescribed, followed by 3rd CEPs (13.1%). The use of 3rd CEPs (P < 0.001), beta-lactam/beta-lactamase inhibitors (P = 0.007), and carbapenems (P < 0.001) increased substantially for the treatment of hospitalized APN patients. In particular, carbapenems use increased 3.1-fold over the 5 years. CONCLUSIONS: Prescription of broad-spectrum antibiotics increased much for the treatment of APN in Korea during 2010-2014.