Acute Uncomplicated Pyelonephritis Research Articles

Clinical Characteristics of Uncomplicated Acute Pyelonephritis Caused by Escherichia coli and Klebsiella pneumoniae.

This study compared the clinical characteristics and antimicrobial susceptibility of uncomplicated acute pyelonephritis (APN) caused by Escherichia coli and Klebsiella pneumoniae. We retrospectively reviewed the medical records of patients with uncomplicated APNs caused by E. coli and K. pneumoniae admitted to Keimyung University Dongsan Hospital between February 2014 and December 2021. We enrolled 497 patients (372 with E. coli infection, 125 with K. pneumoniae infection). Male, healthcare-associated infection, solid tumors, liver cirrhosis, chronic renal disease, solid organ transplantation, and antibiotic usage within the last 3 months were more strongly associated with K. pneumoniae uncomplicated APNs than with E. coli. Bacteremia and fever occurred more frequently in E. coli uncomplicated APNs. Antimicrobial resistance rates to piperacillin/tazobactam and carbapenem were higher in K. pneumoniae. Antimicrobial resistance rates to aztreonam and ciprofloxacin were lower in K. pneumoniae. Thirty-day mortality was more observed in K. pneumoniae group in univariate analysis, but this difference was not observed after adjustment. Male sex, ultimately fatal disease in McCabe, and prior antibiotic use within 3months were more associated with K. pneumoniae. Male, underlying diseases, and prior antibiotic use was more associated with K. pneumoniae. Further study will be needed that microbiome of each situation and the related with the distribution of the strains.

Disorder of the Microbiota and Mucosal Immunity of the Genital Tract in Women of Reproductive Age with Different Clinical Courses of Acute Uncomplicated Pyelonephritis

The research deals with the study of immuno-microbiological parallels of the genital tract in women with acute uncomplicated pyelonephritis with concomitant chronic pelvic inflammatory diseases. In addition to etiotropic antibacterial therapy, correction of the mucosal immunity state of the genital tract is crucial for the treatment of the disease and prevention of its recurrence. The purpose of the work was to investigate the contamination and state of local immunity of the genital tract in women with acute uncomplicated pyelonephritis with different clinical courses. Methods. 246 women of reproductive age suffering from acute uncomplicated pyelonephritis were studied, divided into three variants of the disease clinical course: group 1 - mild (n=105), group 2 - moderate (n=90), and group 3 - severe (n=51) courses. The scrapings of the mucous membrane of the cervical canal and washings from the vagina were obtained before the start of antimicrobial therapy. Quantitative determination of pathogens was carried out by sowing the biological material on solid nutrient environment. Identification of detached bacteria was carried out according to Bergeys. Mollicutes (Ureaplasma spp., Mycoplasma hominis) were determined by the cultural-fermentative method using test systems and the polymerase chain reaction. Vaginal washings of 121 sick women were used for immunological studies. The levels of myeloperoxidase, lysozyme, human β-defensin-2, immunoglobulins M, A, G, secretory IgA, lactoferrin, C3-component of complement, secretory component, and tumor necrosis factor-α were determined. The reference group consisted of 23 clinically healthy women. The Statistica 12.0 program package for Windows was used, and a difference of p<0.05 was considered verifi able. Results. In the majority of patients with acute uncomplicated pyelonephritis (85.6% of cases), concomitant chronic pelvic inflammatory diseases (colpitis, salpingitis, underlying medical condition of cervix) were observed. Classical bacteria were more often detected in vaginal washings of patients of all groups, while mollicutes were detected in scrapings of the mucous membrane of the cervical canal, whereas the frequency of their detection increased with increase in the pyelonephritis severity. The analysis of indicators of local immunity determined disorders of mucosal immunity of the genital tract in the form of increased levels of myeloperoxidase, IgA, and IgG relative to reference values. The highest levels of lysozyme and myeloperoxidase were determined in patients with a severe course of acute uncomplicated pyelonephritis (by 5.3 and 3.6 times more, respectively), and the content of immunoglobulins A, M, and G in patients with a mild course of the disease (by 3.2, 3.1, and 4.0 times more, respectively). An increase in the level of tumor necrosis factor-α was detected in all patients, although no significant differences from controls were found in any group, but the highest median value was recorded in patients with severe pyelonephritis. In the group of patients with a severe clinical course, the lowest median was observed for β-defensin-2, which makes it impossible to inhibit the synthesis of TNF-α and, thus, supports the inflammatory process. Conclusions. It has been proven that in women with acute uncomplicated pyelonephritis, the severity of the course probably correlates with infection of the genital tract by mollicutes, mainly in association with classical bacteria and with level of mucosal immunity disorder. The obtained results of microbiological and immunological studies of biological material collected before the start of antibacterial therapy in patients with acute uncomplicated pyelonephritis proved the need for a mandatory examination by a gynecologist to ascertain concomitant chronic pelvic inflammatory diseases and establish infection with mollicutes to provide relevant etiotropic treatment. The above is the basis for adding the data regarding laboratory examination and treatment to the management protocols of patients with acute uncomplicated pyelonephritis.

2239. Evaluating the Use of Cefuroxime for the Treatment of Outpatient Pyelonephritis at an Indian Health Service Hospital

Abstract Background In 2015, a rural Indian Health Service Hospital found itself unable to use SMX/TMP due to high E. coli resistance rates. The stewardship team decided to include cefuroxime as a first line agent for outpatient pyelonephritis to have a fluoroquinolone sparing agent. Oral B-lactams are not typically recommended over SMX/TMP or fluoroquinolones for pyelonephritis, however there is sparse literature on the use of cefuroxime. This retrospective review aims to evaluate the efficacy of cefuroxime therapy for acute uncomplicated pyelonephritis over a five-year period. Methods 528 patients with a diagnosis of pyelonephritis from January 1st, 2015 to December 31st, 2019 were screened. Data collection included 30-day reinfection rates, emergence of ESBL isolates, duration of therapy, one time IV antibiotic administration, urine culture and susceptibility, increased risk (genitourinary abnormalities and diabetes), white blood cell count, and symptoms. Pediatric patients and patients requiring hospital admission were excluded. Results 264 patients were included and 188 patients received cefuroxime therapy. Baseline characteristics included 94.5% female patients, median age of 44 years, and average duration of therapy of 11.6 days. 95% of the isolates were E. coli. 31 patients had treatment failure defined as a return to the ED with 30 days for UTI. 25 of those patients received cefuroxime and of those, 20 had a one-time IV antibiotic dose. 10 patients with treatment failure had a history of ESBL after the encounter and of those 3 patients had cefuroxime therapy. 5 patients who had treatment failure with cefuroxime had diabetes and genitourinary abnormality. Conclusion This review suggests a lower rate of bacteriological cure of acute uncomplicated pyelonephritis with cefuroxime therapy with or without a one-time IV antibiotic dose with a cephalosporin or aminoglycoside. Disclosures All Authors: No reported disclosures.

A retrospective review of oral cephalosporins versus fluoroquinolones for the treatment of pyelonephritis.

BackgroundThe current Infectious Diseases Society of America guidelines for the treatment of acute uncomplicated pyelonephritis (AUP) advise caution when using oral beta-lactams due to concern for potentially inferior efficacy compared to fluoroquinolones (FQs) and trimethoprim-sulfamethoxazole; however, studies specifically evaluating the efficacy of oral cephalosporins (CPs) in AUP are limited.ObjectiveTo assess the safety and efficacy of oral CPs versus FQs for the treatment of AUP.Design, setting and participantsThis is a retrospective, chart review study conducted at a single-center, tertiary care hospital.MeasurementsThe primary endpoint was treatment failure within 30 days, defined as a change in antibiotic or return to ED or clinic due to persistent symptoms. Secondary endpoints included adverse drug reactions (ADRs) and C. difficile infection (CDI) within 30 days.ResultsOf the 343 patients included in the study, treatment failure occurred in 54/338 (16.0%) patients and was similar between oral CPs and FQs (35/229 [15.3%] vs. 19/109 [17.4%]). A higher percentage of treatment failures were observed for third generation (3GC) and first generation (1GC) CPs compared to second generation CPs (2GC) (3GC: 15/65 [23.4%]; 1GC: 11/49 [22.4%]; 2GC: 9/115 [7.8%]). Documented ADRs were low (6/343 [1.7%]) and no cases of CDI were documented.ConclusionsOral CPs appear to be as safe and effective as FQs for the treatment of AUP. Fewer treatment failures were noted with 2GCs as compared to 3GCs and 1GCs.

Comparison of antimicrobial resistance in patients with obstructive pyelonephritis associated with ureteral stones and uncomplicated pyelonephritis.

This study aimed to investigate the clinical outcomes of causative microorganisms in obstructive pyelonephritis associated with ureteral stones (OPU) and their antibiotic susceptibilities. This retrospective cohort study included female patients diagnosed with community-acquired acute pyelonephritis (APN) at a tertiary-care hospital between 2008 and 2017. A comparison of APN cases associated with the obstruction of the upper urinary tract by ureteral stones and APN cases without complications was performed. Propensity score (PS) matching was used to adjust the heterogeneity within each group. Of the 588 female patients with community-acquired APN, 107 were diagnosed with OPU and 481 with uncomplicated APN. After PS matching, Enterobacteriaceae strains isolated from OPU cases were more resistant to fluoroquinolones (51.9% vs 16.0%, P < .001). Extended-spectrum β-lactamase was detected in 22.2% and 21.0% of the Enterobacteriaceae strains isolated from OPU and uncomplicated APN cases, respectively (P = 1.000). The treatment failure rate was similar in OPU and uncomplicated APN groups (16.0% vs 21.0%, P = .545). Patients with OPU may be empirically treated with antibiotics in accordance with the treatment protocol for general pyelonephritis. Clinicians should exercise caution in prescribing fluoroquinolones for treating OPU.

Persistent Aseptic Pyelonephritis After Acute Bacterial Pyelonephritis: Possible Role of Corticosteroids

Acute pyelonephritis (APN) is a common cause of acute kidney injury (AKI) in kidney graft recipients but only few cases of severe AKI after uncomplicated nonobstructive native kidney APN have been reported.1Jones S.R. Acute renal failure in adults with uncomplicated acute pyelonephritis: case reports and review.Clin Infect Dis. 1992; 14: 243-246https://doi.org/10.1093/clinids/14.1.243Crossref PubMed Scopus (23) Google Scholar In some of these latter, renal dysfunction persists despite appropriate antiinfectious treatment and urine sterilization.2Sqalli T.H. Hamzaoui H. Guiard E. Noel L.H. Fakhouri F. Severe renal failure in acute bacterial pyelonephritis: do not forget corticosteroids.Saudi J Kidney Dis Transplant. 2010; 21: 118-122PubMed Google Scholar, 3Kwon H.J. Yoo K.H. Kim I.Y. Lee S. Jang H.R. Kwon G.Y. Megalocytic interstitial nephritis following acute pyelonephritis with Escherichia coli bacteremia: a case report.J Korean Med Sci. 2015; 30: 110-114https://doi.org/10.3346/jkms.2015.30.1.110Crossref PubMed Scopus (2) Google Scholar, 4Husain S. Alroumoh M. Mohan P. El-Kass G. Seshan S.V. Galler M. Acute kidney injury from pyelonephritis in an elderly man: case report.Int Urol Nephrol. 2011; 43: 925-928https://doi.org/10.1007/s11255-011-0019-6Crossref PubMed Scopus (3) Google Scholar Some authors suggest the use of corticosteroids to treat inflammatory tubulointerstitial nephritis (TIN) triggered by the infection.2Sqalli T.H. Hamzaoui H. Guiard E. Noel L.H. Fakhouri F. Severe renal failure in acute bacterial pyelonephritis: do not forget corticosteroids.Saudi J Kidney Dis Transplant. 2010; 21: 118-122PubMed Google Scholar, 3Kwon H.J. Yoo K.H. Kim I.Y. Lee S. Jang H.R. Kwon G.Y. Megalocytic interstitial nephritis following acute pyelonephritis with Escherichia coli bacteremia: a case report.J Korean Med Sci. 2015; 30: 110-114https://doi.org/10.3346/jkms.2015.30.1.110Crossref PubMed Scopus (2) Google Scholar, 4Husain S. Alroumoh M. Mohan P. El-Kass G. Seshan S.V. Galler M. Acute kidney injury from pyelonephritis in an elderly man: case report.Int Urol Nephrol. 2011; 43: 925-928https://doi.org/10.1007/s11255-011-0019-6Crossref PubMed Scopus (3) Google Scholar Nevertheless, this approach is not validated by any evidence-based study and therefore not mentioned in any guideline. We aim at describing the clinicopathologic presentation, management, and outcome of such persistent TIN in patients of the Tenon Hospital nephrology and pathology departments between January 1, 2010 and December 31, 2020. Fifteen patients were studied following the case definition (see Supplementary Methods in the Supplementary Material). The initial characteristics of the patients and the initial APN are summarized in Table 1.Table 1Clinical and biological presentationCharactersticsCases (N = 15) n (%), mean ± SD, or median [IQR]At APNAt biopsyAt LFUaLast follow-up.General informationAge, yrs58 [52–64]Sex (female)8 (53.3)74.6 ± 29.1Baseline eGFR (ml/min/1.73 m2)Immunosuppression5/15 (33)Diabetes8/15 (53)≥1 severe infection predisposing factor13/15(86.7)≥1 severe infection predisposing factor8/15 (53)Urinary tract anomalies6/15 (40)Severity and complicationsHemodynamic severitybDefined as the presence of one of the following criteria: arterial blood pressure <65 mm Hg, lactataemia ≥2 mmol/l, fluid resuscitation needs ≥3000 ml in the first 24 hours of sepsis, multisystemic dysfunction.4 (26.7)NANAeGFR, ml/min/1.73 m212.9 ± 8.415 ± 9.238.3 ± 27.5KDIGO stage of AKIcAKI according to the KDIGO classification. - 10 (0)0 (0)— - 22 (13.3)2 (13.3) - 313 (86.7)13 (86.7)Kidney(s) involved - both13 (86.7) - left1 (6.7) - unknown1 (6.7)C-reactive protein, mg/l228.6 ± 100.09.0 ± 3.0—Leukocyte count, cells/μl17430 ± 54256800 ± 2750—Leucocyturia, cells/μl1 × 106 [654 × 103–1 × 106]1.5 × 104 [2.6 × 103–1 × 106]5000 ± 2200Proteinuria, g/mmolNA0.09 [0.06–0.16]—Albuminuria, mg/mmolNA15.07 [10.98–30.25]—Urinary RBP,dRBP, normal value <0.08 mg/mmol of creatinine. mg/mmolNA3.67 [1.24–10.16]—Urin culturesDurably sterileDurably sterileEscherichia coli of which10 (66.7) - WT5 (33.3) - low level penicillinase producers3 (20) - high level penicillinase producers2 (13.3)Morganella morganii WT2 (13.3)Klebsiella pneumoniae WT3 (20)TreatmentAntibiotics choice adapted to the guidelines15 (100) - Duration, wks4 ± 2Steroid therapy—11/15 (73) - Duration, wks—4.8 ± 4.0Complementary antibiotic therapy12/15 (80) - Duration, wks5.4 ± 2.7AKI, acute kidney injury; APN, acute pyelonephritis; eGFR, estimated gloerular filteration rate; IQR, interquartile range; KDIGO, Kidney Disease: Improving Global Outcomes; LFU, last follow-up; NA, not applicable; RBP, retinol-binding protein; WT, wild type.a Last follow-up.b Defined as the presence of one of the following criteria: arterial blood pressure <65 mm Hg, lactataemia ≥2 mmol/l, fluid resuscitation needs ≥3000 ml in the first 24 hours of sepsis, multisystemic dysfunction.c AKI according to the KDIGO classification.d RBP, normal value <0.08 mg/mmol of creatinine. Open table in a new tab AKI, acute kidney injury; APN, acute pyelonephritis; eGFR, estimated gloerular filteration rate; IQR, interquartile range; KDIGO, Kidney Disease: Improving Global Outcomes; LFU, last follow-up; NA, not applicable; RBP, retinol-binding protein; WT, wild type. All the infections were complicated by AKI as follows: KDIGO stage 2 in 2 of 15 patients (13%) or stage 3 in 13 of 15 patients (87%), mean estimated glomerular filtration rate (eGFR) after stabilization was 12.9 ± 8.4 ml/min per 1.73 m2, and mean eGFR loss was −57.5 ± 33 ml/min per 1.73 m2. All radiologically documented infections were bilateral except in 1 case. The documentation exclusively included ascending infections because of Enterobacteriales, mostly with Escherichia coli. All patients were treated accordingly as per the current French Infectous Diseases Society (Société de Pathologie Infectieuse de Langue Française) guidelines. Antibiotic treatment allowed resolution of the infectious symptoms and urine sterilization in all 15 cases (100%). A total of 58 (interquartile range: 28–102) days after antibiotic initiation, all patients presented persistent kidney impairment (mean eGFR of 19.6 ± 11.2 ml/min per 1.73 m2, P = 0.08). Urinary analysis was indicative of active TIN: aseptic leukocyturia >10,000 cells/μl in 14 of 15 cases (93%), and >100,000 cells/μl in 9 of 15 cases (60%). Low molecular weight proteinuria was constant (Table 1). As expected, given our case definition, kidney biopsy systematically revealed tubulo-interstitial inflammation. The infiltrate was predominantly lymphoplasmacytic in all patients. Neutrophils (sometimes clustering into microabscesses, Supplementary Figure S1B) and eosinophils were observed in 13 of 15 (86.7%) and 1 of 15 cases (6.7%) respectively among this infiltrate. Extensive inflammatory fibrosis with edema was constant (Supplementary Figure S1A). Lymphoid nodules were identified in 7 of 15 cases (46.7%) (Supplementary Figure S1D), some of them forming germinal center-like patterns. Neutrophilic intratubular casts were constant although rarely abundant (Supplementary Figure S1B). Tubulitis (Supplementary Figure S1F) was present in all biopsies except 1, mediated by neutrophils in half of the cases (Supplementary Figure S1E). Features of acute tubular necrosis (usually mild) were revealed in 13 of 15 biopsies (86.7%). There was no argument for malakoplakia, xanthogranulomatous pyelonephritis or signs of glomerulonephritis, or acute vascular involvement. Seven days Brain Heart Infusion Broth cultures of the frozen biopsy specimens did not reveal any relevant documentation. Eight patients were treated with corticosteroids (0.5 or 1 mg/kg tapered over a mean duration of 1.2 ± 1.0 months) and antibiotics (mean duration 5.4 ± 2.7 weeks), 4 patients treated with antibiotics only, and 3 treated with corticosteroids only. There were no reported side effects of corticosteroids. After a mean follow-up period of 8.7 ± 3.8 months, kidney function stabilized or improved in all patients (mean eGFR variation to biopsy was +18.7 ± 21.6 ml/min per 1.73 m2, P = 0.02). However, renal function often remained severely hampered (mean eGFR was 38.3 ± 27.5 ml/min per 1.73 m2, mean eGFR loss to baseline was −27.3 ± 10.8 ml/min per 1.73 m2). By the end of the study follow-up, 9 of 15 patients (60%) presented stage IV or V chronic kidney disease compared with none before APN onset. Urinary signs of active TIN regressed in all treated patients (leukocyturia at last follow-up of 5000 interquartile range [5000–113,250] cells/μl, median variation of −35,000 interquartile range [0–156,000] cells/μl). One patient died after 2 months of follow-up; and a second patient died after 12 months of follow-up. The second patient was treated with steroid therapy from the third to the fifth month of follow-up. Better renal outcome (i.e., last follow-up eGFR >30 ml/min per 1.73 m2) was associated with early steroid treatment initiation (≤65 days), higher baseline eGFR, and per-AKI eGFR in a univariate analysis (Supplementary Table S1). The presence of lymphoid nodules tended to be associated with a worse outcome. We further compared the patients’ renal function according to corticosteroid exposure (Supplementary Figure S1). Baseline, APN, and kidney biopsy eGFR were not significatively different but last follow-up eGFR was significatively higher in the corticosteroid group (45.8 ± 28.1 vs. 17.5 ± 10.1 ml/min per 1.73 m2, P = 0.01). All patients presented conditions known to be associated with severe infections (Table 1). One-third of the patients matched our definition of immunosuppression (5 of 15, 33.3%), 13 of 15patients (86.7%) presented ≥1 severe infection predisposing factors, and 8 of 15 (53%) presented ≥2 severe infection predisposing factors. Nonsteroidal anti-inflammatory drugs consumption at initial APN was found in 4 of 15 patients (26.7%). A total of 6 of 15 (40%) patients presented urinary tract anomalies, including 5 (33.3%) with urinary catheters at APN onset. We herein present a report on 15 patients who were treated at our institution for severe AKI because of bilateral pyelonephritis, and presenting persistent kidney impairment several weeks or even months after appropriate antibiotic therapy and urine sterilization. Urinary analysis and kidney biopsy revealed lymphoplasmacytic and neutrophilic TIN. A second prolonged antibiotic challenge and/or corticosteroid treatment allowed partial kidney function improvement in some cases. Overall prognosis was poor because 60% of the patients recovered <50% of their initial eGFR and developed stage IV to V chronic kidney disease within 1 year after AKI. Some rare cases were reported in the literature.1Jones S.R. Acute renal failure in adults with uncomplicated acute pyelonephritis: case reports and review.Clin Infect Dis. 1992; 14: 243-246https://doi.org/10.1093/clinids/14.1.243Crossref PubMed Scopus (23) Google Scholar, 2Sqalli T.H. Hamzaoui H. Guiard E. Noel L.H. Fakhouri F. Severe renal failure in acute bacterial pyelonephritis: do not forget corticosteroids.Saudi J Kidney Dis Transplant. 2010; 21: 118-122PubMed Google Scholar, 3Kwon H.J. Yoo K.H. Kim I.Y. Lee S. Jang H.R. Kwon G.Y. Megalocytic interstitial nephritis following acute pyelonephritis with Escherichia coli bacteremia: a case report.J Korean Med Sci. 2015; 30: 110-114https://doi.org/10.3346/jkms.2015.30.1.110Crossref PubMed Scopus (2) Google Scholar but this is the first case series describing the biological, histologic, and clinical presentation and evolution since Richet and Mayaud’s5Richet G. Mayaud C. The course of acute renal failure in pyelonephritis and other types of interstitial nephritis.Nephron. 1978; 22: 124-127https://doi.org/10.1159/000181432Crossref PubMed Scopus (8) Google Scholar description in 1978. In this study, most cases were attributed to drug allergy or toxicities but may have been misclassified because of the absence of preexisting data. There is no mention of steroid use, and only 1 patient recovered their baseline kidney function (Supplementary Table S2). Subsequent reports show a positive outcome with steroid use but publication bias is very likely (Supplementary Table S2). Given the small sample size and the retrospective nature of this study, it is not possible to draw definitive conclusions. The long delay between AKI and renal biopsy, and the recovery kinetics are not indicative of acute tubular necrosis (Supplementary Figure S1). Histologic and clinical presentations are not indicative of immuno-allergic nephritis. There were no extrarenal features that suggest corticosteroid sensitive systemic disease associated interstitial nephritis. Although it is coherent with high range leukocyturia and low molecular weight proteinuria, APN histologic natural course is not known. Therefore, we cannot affirm that the interstitial inflammation we describe is specific. As suggested by Richet and Mayaud5Richet G. Mayaud C. The course of acute renal failure in pyelonephritis and other types of interstitial nephritis.Nephron. 1978; 22: 124-127https://doi.org/10.1159/000181432Crossref PubMed Scopus (8) Google Scholar in 1978, we believe this entity could correspond to persistenting autonomous tubulo-interstitial inflammation, resembling pyelonephritis but aseptic, which is persistent aseptic pyelonephritis. A mechanistic lead could be that in some patients with pathogen clearance altering factors, tubulo-interstitial inflammation does not regress despite effective antibiotic therapy. The lymphoid nodules found in half of the patients could be a hallmark of this inflammatory autonomous process. Concomitant evolution of leukocyturia, eGFR, and possible corticosteroid efficiency support this hypothesis. Prevalence is not known but it is likely underestimated. Initial presentation can easily be mistaken for ATN. Persistent aseptic pyelonephritis occurring after unilateral APN, without AKI in most of the cases, most likely goes unnoticed. Larger prospective studies are required. Prompt delay to treatment seems important to prevent definitive kidney scarring. If corticosteroid efficiency were confirmed, biomarker development allowing early ATN or persistent aseptic pyelonephritis discrimination would be highly relevant. Even though we believe this entity is postinfectious, further studies are needed to determine if complementary antibiotic therapy can be avoided. We suggest systematic monitoring of leukocyturia and urinary low molecular weight protein in all patients who are treated for APN–related AKI. Patients who present persistent aseptic leukocyturia, proteinuria and kidney failure should be referred to a nephrologist to discuss kidney biopsy and potential subsequent corticosteroid and/or antibiotic treatment. All the authors declare no conflict of interest. No specific funding was needed for this study. The authors would like to thank the Professor J. Tourret for his valuable help. Download .docx (1.33 MB) Help with docx files Supplementary File (Word) Supplementary Methods. Figure S1. Histological presentation. Interstitial fibrosis with chronic inflammatory infiltrate (HESx50) (A). Intratubular casts of altered neutrophils (HESx400) (B). Interstitial clustering of neutrophils forming a microabscess (HESx400) (C). Interstitial nodular organization of lymphocytes (HESx200) (D). Neutrophilic tubulitis (HESx400) (E). Severe tubulitis with tubulorrhexis (tubular membrane rupture) (HESx400) (F). Inflammation in the adipose tissue outside the renal capsule (perinephritis) (HESx50) (G). Table S1. Factors associated with renal outcome Table S2. Literature reporting potential persisting aseptic pyelonephritis Corrigendum to Persistent Aseptic Pyelonephritis After Acute Bacterial Pyelonephritis: Possible Role of Corticosteroids Kidney International Reports, Volume 7, Issue 8, August 2022, Pages 1897-1900Kidney International ReportsPreviewThe authors regret that the affiliations in this article originally read: Full-Text PDF Open Access

AAUS guideline for acute uncomplicated pyelonephritis

Patients with acute uncomplicated pyelonephritis often show impaired immune function that aggravates infectious diseases. Some of the therapeutic recommendations for UTIs have been revised recently, partly because of the emergence of antibiotic resistant bacteria such as quinolone-resistant Escherichia coli and Extended spectrum beta-lactamase (ESBL) producing bacteria, mainly E. coli and Klebsiella pneumoniae, which vary from country to country or between regions in frequency of emergence and spread. An era of antimicrobial resistance (AMR) has arrived, where the use of antibiotics should be reconsidered.Several newly established antimicrobial agents are commercially available for the treatment of resistant bacteria, such as penicillins or cephalosporins with beta-lactamase inhibitors. This new edition of Asian Association of UTI & STI (AAUS) guideline for acute uncomplicated pyelonephritis includes new recommendations for antibiotic use based on changing trends in antibiotic resistance.

Increasing rates of extended-spectrum B-lactamase-producing Escherichia coli and Klebsiella pneumoniae in uncomplicated and complicated acute pyelonephritis and evaluation of empirical treatments based on culture results.

Increasing rates of extended-spectrum beta-lactamase (ESBL) producing E. coli and K. pneumoniae over time made empirical treatment complicated. Knowing local antimicrobial resistance patterns of common pathogens can make it easier to decide on empirical antibiotics. We aimed to investigate the prevalence and risk factors of ESBL positivity of E. coli and K. pneumoniae strains in uncomplicated and complicated pyelonephritis acquired in community and healthcare associations and to evaluate the appropriateness of empirical treatment. Adult patients hospitalized with diagnosis of community-acquired or healthcare-associated uncomplicated/complicated pyelonephritis initiated empirical antimicrobial therapy were included in the study. Appropriateness of empirical treatment at 48-72h based on culture resultsand treatment modifications were evaluated. A total of 369 uncomplicated (94) and complicated (275) episodes of pyelonephritis were evaluated. The most common agents wereE. coli(71.0%) andK. pneumoniae(17.7%),and the ESBL-production rate was 64.4%, and higher in healthcare-associated pyelonephritis (P 0.013). Being of healthcare-associated infection, previous antibiotic use, and presence of urinary catheters were independent risk factors for ESBL-producing E. coli and K. pneumoniae (P 0.009, < 0.001, and 0.024, respectively). The treatment inappropriateness was mostly associated with use of ceftriaxone (56.3%) (P < 0.001). Treatment has escalated in 41.5% of ceftriaxone-initiated patients, in only 8.8% and 9.5% ertapenem and piperacillin-tazobactam-initiated patients, respectively. ESBL-production rates are quite high even in community-acquired infections. The use of broad-spectrum antibiotics covering ESBL-producing pathogens to increase the appropriateness of empirical treatment and then narrowing treatment based on culture results appears a better and life-saving choice.

Levoximed in the Treatment of Acute Uncomplicated Pyelonephritis in Different Phases of Menstrual Cycle

Despite the progress in the field of etiology, pathogenesis and development of new methods of diagnosis and treatment of urinary tract infections (UTI), they remain among of the most common bacterial diseases in women. Women are predisposed to UTI due to anatomical and physiological features (fluctuations in sex hormones levels during the menstrual cycle, pregnancy and childbirth), playing the role both in normal and pathological conditions (gynecological diseases and operations). The objective: to evaluate the clinical and bacteriological efficacy of levofloxacin in women with uncomplicated acute pyelonephritis (uAP) with the onset of the disease in different phases of the ovarian-menstrual cycle (OMC). Materials and methods. The study was conducted at urological departments of the Olexandrivska Clinical Hospital, Kyiv. 82 women of reproductive age were hospitalized for uAP. All of them underwent standard diagnostic procedures and were treated with levofloxacin. The Group-1 comprised 59 women with uAP, diagnosed in the period from the 20th to the 5th day of OMC. The Group-2 included 23 women with uAP, developed in the period from the 6th to the 19th day of OMC. Results. In women with uAP overall clinical efficacy of levofloxacin was 93% and bacteriological efficacy – 91.5%. In Group-2 in women with mild course both clinical and bacteriological effectiveness of treatment were 100%. Conclusion. The use of antibiotics with a broad spectrum of action, targeting most microorganisms and protozoa, reduces the reduces the costs associated with treatment and rehabilitation of women of childbearing potential. Levofloxacin demonstrates good efficacy, tolerability and safety in the complex treatment of acute uncomplicated pyelonephritis, which allows the use of this drug in clinical practice.

Molecular Epidemiology of Multidrug-Resistant Uropathogenic Escherichia coli O25b Strains Associated with Complicated Urinary Tract Infection in Children.

Background: Uropathogenic Escherichia coli (UPEC) has increased the incidence of urinary tract infection (UTI). It is the cause of more than 80% of community-acquired cystitis cases and more than 70% of uncomplicated acute pyelonephritis cases. Aim: The present study describes the molecular epidemiology of UPEC O25b clinical strains based on their resistance profiles, virulence genes, and genetic diversity. Methods: Resistance profiles were identified using the Kirby–Bauer method, including the phenotypic production of extended-spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs). The UPEC serogroups, phylogenetic groups, virulence genes, and integrons were determined via multiplex PCR. Genetic diversity was established using pulsed-field gel electrophoresis (PFGE), and sequence type (ST) was determined via multilocus sequence typing (MLST). Results: UPEC strains (n = 126) from hospitalized children with complicated UTIs (cUTIs) were identified as O25b, of which 41.27% were multidrug resistant (MDR) and 15.87% were extensively drug resistant (XDR). The O25b strains harbored the fimH (95.23%), csgA (91.26%), papGII (80.95%), chuA (95.23%), iutD (88.09%), satA (84.92%), and intl1 (47.61%) genes. Moreover, 64.28% were producers of ESBLs and had high genetic diversity. ST131 (63.63%) was associated primarily with phylogenetic group B2, and ST69 (100%) was associated primarily with phylogenetic group D. Conclusion: UPEC O25b/ST131 harbors a wide genetic diversity of virulence and resistance genes, which contribute to cUTIs in pediatrics.

Можливості ранньої діагностики нефросклерозу в дітей віком до 3 років у періоді повної ремісії гострого неускладненого пієлонефриту

Актуальність. Після встановлення діагнозу пієлонефриту в дитини одним із провідних завдань є безпосередня оцінка того, якою мірою запальний процес призвів до склерозування тканини нирок та формування хронічної хвороби нирок. Провідне місце відводиться маркерам недиференційованої дисплазії сполучної тканини та склерозування гломерулярної частини нефронів у дітей, якими є показник вмісту оксипроліну, рівень креатиніну та глікозаміногліканів у добовій сечі. Мета дослідження: рання діагностика нефросклерозу в дітей до 3 років, хворих на гострий неускладнений пієлонефрит, без анатомічних природжених вад розвитку органів сечовидільної системи у періоді його повної ремісії. Матеріали та методи. Обстежено 65 дітей раннього віку з гострим пієлонефритом у періоді повної ремісії, у яких після нефроурологічного обстеження не було виявлено анатомічних вад розвитку органів сечовидільної системи. Дітям проводилося загальноклінічне обстеження, визначались маркери функціонального стану тубулярного епітелію та гломерулярної частини нефронів, оксипролін у сечі, виконувались тести уринолізису. Результати та обговорення. Тести уринолізису вказують на більшу частоту екскреції всіх показників у сечі дітей основної групи порівняно із здоровими дітьми. Рівень креатиніну в сечі дітей з пієлонефритом був зниженим у 21,5 % обстежених порівняно з 2,5 % здорових дітей. У 9,2 % дітей з пієлонефритом у сечі відмічалось підвищення рівня оксипроліну, що є маркером дисфункції сполучної тканини в паренхімі нирок. Аналіз екскреції глікозаміногліканів показує, що в дітей з пієлонефритом усіх вікових груп вона не була вірогідно підвищена. Висновки. З метою прогнозування формування та ранньої діагностики нефросклерозу в дітей раннього віку з пієлонефритом рекомендовано використовувати такі маркери, як результати тестів урінолізису, рівень екскреції креатиніну та оксипроліну в добовій сечі. Рекомендовано застосування методів корекції виявлених змін.

Renal Parenchymal Hypoxia in Young Children in the Period of Complete Remission of Acute Uncomplicated Pyelonephritis without Renal Impairment

Introduction. After establishing the diagnosis of pyelonephritis, there is a need to determine, whether renal parenchymal hypoxia remains in the period of remission. The least studied methods up to now are functional ones, which allow to verify the presence and degree of tissue hypoxia in secondary pyelonephritis and to evaluate the results of the medical measures to restore kidney function. Objective: to clarify the presence of renal parenchymal hypoxia and membrane destruction of the renal epithelium in young children with pyelonephritis without anatomic congenital malformations of the urinary system during its remission.Materials and methods of the study. The study involved 65 children with acute uncomplicated pyelonephritis, who after nephro-urological examination did not reveal anatomical malformations of the urinary system. General clinical examination was carried out, markers of tissue hypoxia and morphofunctional state of cell membranes of renal epithelium were determined.Discussion of the study results. The ability of urine to prevent crystal formation was significantly reduced to oxalates and phosphates in 40.0 and 47.7 % of the surveyed children. In one-third of children with pyelonephritis, oxalate excretion was significantly higher than in healthy children, hypophosphaturia was detected in 52.3 % of cases and the tendency to reduce the excretion of urates in 10.8 % of pediatric patients with pyelonephritis. The content of lipid peroxidation products in urine was increased in 41.5 % of the surveyed children with pyelonephritis, and appearance of polar lipids was observed in 46.2 % of patients.Conclusions. To predict the formation and for the purpose of early diagnosis of renal parenchymal hypoxia and the processes of nephrothelial membrane destruction in young children with pyelonephritis, it is recommended to use such markers, as indicators of urine ability to prevent crystal formation, daily excretion of salts, excretion of lipid peroxidation products and polar lipids in the urine. It is recommended to apply the methods to correct these changes.

Clinical Pharmacokinetics and Pharmacodynamics of Cefiderocol.

Cefiderocol is a new broad-spectrum cephalosporin antibiotic with promising activity against various Gram-negative bacteria including carbapenem-resistant strains. A chlorocatechol group in the C-3 side chain provides cefiderocol with a siderophore activity, improving its stability against β-lactamases and facilitating the transportation of cefiderocol across outer bacterial membranes. Cefiderocol shows linear pharmacokinetics over a broad range of clinically relevant doses, with unchanged renal excretion constituting the main route of elimination. Geometric means (coefficient of variation) of the volume of distribution and clearance in individuals with normal kidney function were 15.8 (15%) L and 4.70 (27%) L/h, respectively. In patients with end-stage renal disease, clearance was 1.10 (24%) L/h. Time above the minimum inhibitory concentration is the main predictor of efficacy. There is no evidence for clinically relevant interactions of cefiderocol with other drugs mediated by metabolizing enzymes or drug transporters. Simulations based on population pharmacokinetic modeling suggest that dosing regimens should be adjusted based on kidney function to optimize therapeutic exposure to cefiderocol. Clinical efficacy trials indicated that cefiderocol is non-inferior to imipenem/cilastatin in the treatment of complicated urinary tract infections and acute uncomplicated pyelonephritis, and to meropenem in the treatment of nosocomial pneumonia. In the one study currently available, cefiderocol performed similarly to the best available therapy in the treatment of severe carbapenem-resistant Gram-negative infections regarding clinical and microbiological efficacy. In summary, cefiderocol shows favorable pharmacokinetic/pharmacodynamic properties and an acceptable safety profile, suggesting that cefiderocol might be a viable option to treat infections with bacteria resistant to other antibiotics.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01063-5.

Sociodemographic factors and uncomplicated pyelonephritis in women aged 15-50 years: a nationwide Swedish cohort register study (1997-2018)

Objective: To study the relationship between sociodemographic factors and pyelonephritis.Methods: A nationwide open cohort study consisting of 2,052,873 women (76.2% Swedish-born) aged 15-50 years was conducted (1997-2018). The outcome was the first event of acute uncomplicated pyelonephritis diagnosed in primary healthcare settings in relation to the sociodemographic factors. Cox regression models were used in the analyses.Results: The study identified 40,724 cases. In the fully adjusted model, women from non-Western countries had a higher risk of pyelonephritis compared to Swedish-born women. Women from Latin America/the Caribbean had the highest risk (Hazard ratio = 1.60; 95% CI 1.49-1.72), followed by Eastern Europe (HR = 1.26; 95% CI 1.21-1.32) and the Middle East/North Africa (HR = 1.25; 95% CI 1.19-1.30). Low education, low income, urban living, and young age were also associated with higher risks of pyelonephritis.Conclusion: This study presents novel risk factors associated with pyelonephritis. Women from non-Western countries and with low socioeconomic status might disproportionately suffer from this serious infection. This might be due to biological predispositions and the fact that immigrant women do not acquire the same level of health or might receive less healthcare compared to native women, even in the presence of universal healthcare.

Этиология и патогенез острых пиелонефритов у детей

Introduction. Acute pyelonephritis in children takes a leading place among the reasons for hospitalization. Objective. To study the epidemiological, anamnestic, diagnostic and clinical features of the course of pyelonephritis in children. Materials and methods. We have carried out a retrospective study of case histories of 142 children admitted to the urology department of the Emergency hospital №2 (Tomsk) with a diagnosis of acute pyelonephritis. Results. According to the results of our study, children of both sexes of young age (up to 1 year оf age) suffer from acute complicated pyelonephritis, whereas acute uncomplicated pyelonephritis is typical for girls over 3 years old. The sensitivity of ultrasound examination of the kidneys in acute pyelonephritis was 76.8%. The vast majority (96,8%) of acute uncomplicated pyelonephritis were caused by Escherichia coli. Escherichia coli was the cause of acute complicated pyelonephrities only in 30.8% of patients, Pseudomonas aeruginosa was ranked in second in frequency (15.4%), and Enteroccoccus faecalis was ranked third (11.5%). The following antibiotics retained their effectiveness among all the identified causative flora of uncomplicated pyelonephritis: fosfomycin, furagin, gentamicin, amikacin. Only amikacin showed absolute efficiency (100%) in the group of complicated pyelonephritis. 90% of bacteria showed sensitivity to fosfomycin, and 88.5% to cefepime and ertapenem. For children with acute pyelonephritis, the acute phase process of cytomegalovirus, Ebstein-Barr viral infections, previous herpes simplex virus infection, as well as contact with Chlamydia trachomatis, Ureaplasma urealуticum and Mycoplasma hominis are specific. Conclusion. The results of the study indicate the dynamics in the etiology and pathogenesis of acute pyelonephritis in children and a need for an annual monitoring in order to correct therapy.

1687. Omadacycline in Female Adults With Acute Pyelonephritis: Results from a Randomized, Double-Blind, Adaptive Phase 2 Study

BackgroundOmadacycline (OMC) is a novel intravenous (IV) and oral aminomethylcycline, approved in the USA for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in adults. We present data from a randomized, adaptive dose–response phase 2 study of OMC in adult females with acute pyelonephritis (AP).MethodsFemales aged ≥ 18 y with acute uncomplicated pyelonephritis were initially randomized to 1 of 4 once-daily regimens of OMC vs once-daily standard regimen of IV-to-oral levofloxacin (LEV) (total therapy: 7–10 days) (NCT03757234); the randomization algorithm was subsequently adapted by the data monitoring committee (DMC; blinded to the investigators) following interim analyses of efficacy in the microbiological-intent-to-treat (micro-ITT) population (Table 1). Efficacy was assessed for noninferiority according to investigator’s assessment of clinical response (IACR) and microbiological response at post-therapy evaluation (PTE; Day 21) and end of therapy (EOT). Treatment-emergent adverse events (TEAEs) were assessed. Results were reviewed by the DMC.Table 1 Results201 patients were randomized. Baseline characteristics were similar across groups (Table 2). Among patients with an identified pathogen, the most common species was E. coli. For IACR at both EOT and PTE, no OMC group met noninferiority to LEV (Figure 1), as the lower limit of the 95% CI for the treatment difference exceeded −10% (range −12.4% to −34.8%). Responses at PTE were consistent with those at EOT. Microbiological responses in each OMC group were generally lower than LEV. OMC was well tolerated; 36.2% and 32.4% of OMC- and LEV-treated patients had ≥ 1 TEAE. The most frequently reported TEAEs (≥ 5%) in the OMC the LEV groups, respectively, were headache (10.2% vs 6.8%), asymptomatic bacteriuria (6.3% vs 1.4%), diarrhea (2.4% vs 6.8%), and nausea (5.5% vs 6.8%).Table 2 Figure ConclusionIn this adaptive, phase 2 study, clinical success was high for both groups, although no OMC group met criteria for noninferiority to levofloxacin in AP, potentially due to pharmacokinetic/pharmacodynamic drivers of efficacy for AP. Omadacycline was well tolerated, with a safety profile consistent with its current labeling. Further evaluation is warranted to further understand the outcomes of this study.DisclosuresJ. Scott Overcash, MD, FACEP, Paratek Pharmaceuticals, Inc. (Scientific Research Study Investigator) Evan Tzanis, BS, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Amy Manley, BS, Paratek Pharmaceuticals, Inc. (Employee) Courtney Kirsch, BS, Paratek Pharmaceuticals, Inc. (Employee) Alisa W. Serio, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Tiffany White, PhD, ContraFact Corporation (Consultant, (ended Feb 2020))Facile Therapeutics (Consultant)Paratek Pharmaceuticals, Inc. (Employee) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Surya Chitra, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Paul B. Eckburg, MD, AN2 Therapeutics (Consultant)Bugworks Research (Consultant)Curza (Advisor or Review Panel member)Paratek Pharmaceuticals, Inc. (Consultant)SNIPR Biome (Consultant)Spero Therapeutics (Consultant)

1302. Cefiderocol Population Pharmacokinetics and Probability of Target Attainment in Plasma and Epithelial Lining Fluid in Patients with Pneumonia, Bloodstream Infection/Sepsis, or Complicated Urinary Tract Infections

BackgroundCefiderocol (CFDC) is a novel siderophore cephalosporin with activity against a broad range of Gram-negative bacteria. The aim of this study was to perform population pharmacokinetic (PopPK) analysis and evaluate probability of target attainment (PTA) in plasma and epithelial lining fluid (ELF) based on a modeling and simulation approach.MethodsPopPK analysis in plasma was conducted using 3427 concentration data from 425 patients with pneumonia, bloodstream infection/sepsis (BSI/sepsis), complicated urinary tract infection (cUTI), or acute uncomplicated pyelonephritis in 3 Phase 2 or 3 studies (NCT03032380, NCT02714595, and NCT02321800), and 91 subjects without any infection in Phase 1 studies. In addition, intrapulmonary modeling was conducted using ELF concentration data from 7 pneumonia patients (NCT03862040) and 20 healthy subjects. Monte-Carlo simulations were performed by generating 1000 virtual patients for each infection site (pneumonia, BSI/sepsis, or cUTI) to predict PTA for 75% of time for which free drug concentration in plasma or ELF (only pneumonia patients) exceeds the minimum inhibitory concentration (MIC; 0.25–16 µg/mL) over dosing interval following CFDC 2 g q8h infused over 3 hours with dose adjustment based on renal function, including augmented renal clearance.ResultsThe developed PopPK model described the plasma and ELF CFDC concentrations. Creatinine clearance, body weight, infection site, and albumin concentration were statistically significant covariates on CFDC PK in plasma. There were no clinically significant differences in CFDC plasma exposure based on infection site or with/without ventilation. The penetration ratio of ELF to free plasma in pneumonia patients (0.340) was 1.3-fold higher than that in healthy subjects (0.263). As shown in the table below, plasma PTA was >90% against MICs ≤4 μg/mL, regardless of infection site and renal function. ELF PTA in pneumonia patients was >90% against MICs ≤2 μg/mL and >85% against MICs ≤4 μg/mL, regardless of renal function.Table. Probability of Target Attainment for 75% fT>MIC or 75% fT>MIC,ELF ConclusionThe recommended dosing regimen (2 g, q8h, 3-hr infusion) adjusted by renal function provided adequate exposure to CFDC in patients with infections caused by Gram-negative pathogens, irrespective of infection site and renal function.DisclosuresTakayuki Katsube, PhD, Shionogi & Co., Ltd. (Employee) Nao Kawaguchi, BPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Toshihiro Wajima, PhD, Shionogi & Co., Ltd. (Employee) David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support)

1267. Comparative activity of omadacycline against extended-spectrum beta-lactamase positive and negative Escherichia coli and Klebsiella pneumoniae strains recovered from urine specimens

BackgroundOmadacycline (OMC) is a novel tetracycline (TET) derivative antibiotic with activity against TET-resistant Enterobacterales. OMC is available in both oral and intravenous formulations and is has been studied as a treatment of uncomplicated urinary tract infection (UTI) and acute pyelonephritis. The purpose of this study was to evaluate OMC activity against extended-spectrum beta-lactamase (ESBL) positive and negative Enterobacterales strains recovered from urine specimens.MethodsUrine samples from patients with suspected UTI were quantitatively plated onto blood agar and MacConkey agar plates in the microbiology lab of Wake Forest Baptist Medical Center. After overnight incubation, colonies were identified to the species level by MALDI-TOF system. Susceptibility testing was performed for isolates of E. coli and K. pneumoniae. OMC and TET susceptibility testing was performed by disk diffusion and gradient strip methodologies. Results were interpreted in accordance with the Clinical and Laboratory Standards Institute (CLSI) or Food and Drug Administration breakpoints. Isolates were tested in triplicate. ESBL screening and susceptibility testing to oral antibiotics commonly prescribed for UTI were performed by the MicroScan WalkAway System. Susceptibility rates and MIC50/90 were calculated and subsets of isolates were analyzed using descriptive statistics.ResultsA total of 204 isolates, including 102 E. coli and 102 K. pneumoniae, were tested. All but 1 isolate (99.5%) exhibited categorical agreement in results generated by the strip (Table 1) and disk (data not shown) methods and this was considered a minor error involving an intermediate result. OMC MIC90 for E. coli and K. pneumoniae were 6 µg/mL and >32 µg/mL, respectively. OMC displayed increased susceptibility rates compared to TET regardless of isolate species or ESBL positivity (Table 2).Table 1. Omadacycline Minimum Inhibitory Concentrations (MICs, µg/mL) Table 2. Susceptibilities of Oral Antibiotics Used to Treat UTI (% S) ConclusionOMC exhibits promising antimicrobial activity against TET-resistant and ESBL-positive E. coli and K. pneumoniae. OMC displays superior activity to ESBL positive E. coli when compared to ESBL positive K. pneumoniae. These data support the development of OMC as a much needed option in the treatment of UTI caused by resistant Enterobacterales.Disclosures Tyler J. Stone, PharmD, Paratek (Research Grant or Support) Abdullah Kilic, MD, Paratek (Grant/Research Support) John Williamson, PharmD, Paratek (Research Grant or Support) Elizabeth Palavecino, MD, Paratek (Grant/Research Support)Paratek (Grant/Research Support)

Infectious and Inflammatory Diseases of the Urinary System

Urinary tract infections are the most common bacterial lesions of humans. About 150 million cases of these diseases are registered annually in the world. About 95 % of urinary tract infections occur when bacteria migrate ascending from the urethra to the bladder, and in acute uncomplicated pyelonephritis, from the ureter to the kidney. An increased risk of developing urinary tract infections is observed in infants, the elderly, pregnant women, patients with spinal cord injuries, diabetes mellitus, multiple sclerosis, immunodeficiency diseases, structural abnormalities of the kidneys and urinary tract. The autumn-winter period is a traditional season of development and exacerbation of diseases of the urinary system. This is facilitated by a high risk of hypothermia, a relative decrease in physical activity, a change in the drinking regime and a partial decrease in the body's defenses against colds. The main and most common inflammatory diseases of the urinary system include urethritis, cystitis, pyelonephritis. Due to the anatomical features of the structure of the urethra (the urethra of men is longer and narrower than that of women), urethritis of various etiologies are more common in the stronger sex. Women, for the most part, suffer from cystitis, since the causative agents of infection easily bypass the short and relatively wide urethra and immediately enter the bladder, where they find fairly favorable conditions for reproduction [5].

Clinical and computed tomography factors associated with sepsis in women with clinically uncomplicated pyelonephritis.

Sepsis is major determinants of prognosis in acute pyelonephritis (APN). This study aimed to assess factors associated with the development of sepsis among patients with clinically uncomplicated APN. We examined 463 patients presenting to our hospital without complications. We assessed clinical factors including demographic and laboratory features. Renal and extrarenal features on computed tomography (CT) were also analyzed. Risk factors of sepsis are assessed. The study included 361 patients without (78.0%) and 102 patients with sepsis (22.0%). Crude and attributable mortality rates were 3.9% and 2.0% versus 1.4% and 0.6%, respectively, among patients with and without sepsis. Clinical risk factors for sepsis were age >65years (odds ratio [OR] 1.79, P=0.02), absence of flank pain (OR 1.59, P=0.04), absence of costovertebral tenderness (OR 1.89, P=0.03), diabetes mellitus (OR 2.25, P=0.02), bacteremia (OR 2.8, P=0.01), C-reactive protein level >100mg/L (OR 1.42, P=0.02), and lack of previous APN history (OR 1.76, P=0.04). APN grade IV (OR 3.16, P=0.01), high grade hydronephrosis (OR 1.50, P=0.03), diffuse peritoneal thickening (OR 4.12, P=0.01), and acute interstitial pulmonary edema (OR 3.73, P=0.01) were the CT features predictive of septic shock. Although uncomplicated APN was largely non-fatal, several clinical and CT features could lead to sepsis. Our findings may be useful for predicting sepsis risk and deciding whether intravenous antibiotic treatment and intensive management should be initiated for uncomplicated APN.