Personal clinical history predicts antibiotic resistance of urinary tract infections.
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ABSTRACT:
SUBMITTER: Yelin I
PROVIDER: S-EPMC6962525 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Personal clinical history predicts antibiotic resistance of urinary tract infections.
Yelin Idan I Snitser Olga O Novich Gal G Katz Rachel R Tal Ofir O Parizade Miriam M Chodick Gabriel G Koren Gideon G Shalev Varda V Kishony Roy R
Nature medicine 20190704 7
Antibiotic resistance is prevalent among the bacterial pathogens causing urinary tract infections. However, antimicrobial treatment is often prescribed 'empirically', in the absence of antibiotic susceptibility testing, risking mismatched and therefore ineffective treatment. Here, linking a 10-year longitudinal data set of over 700,000 community-acquired urinary tract infections with over 5,000,000 individually resolved records of antibiotic purchases, we identify strong associations of antibiot ...[more]
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Project description:Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline.
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Project description: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.
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| S-EPMC5423680 | biostudies-literature
Project description:BackgroundUrinary tract infections (UTIs) affect up to 150 million individuals annually worldwide, mainly due to Escherichia coli (E. coli) and Klebsiella. The emergence and spread of multidrug-resistant (MDR) bacteria are increasing, representing one of the biggest threats for human health. The objective of our study was to describe antimicrobial patterns of resistance and identify risk factors associated with MDR uropathogens.MethodsWe conducted a cross-sectional study in 296 patients with community-acquired UTI who underwent clinical and microbiologic analysis, and clinical associations to MDR uropathogens were investigated. Findings. Microbiological analysis included E. coli (55%), ESBL-E. coli (26%), Enterococcus (6%), Klebsiella (5%), and others (8%). Higher frequencies of MDR bacteria were found among ESBL-E. coli, with resistance to ampicillin (100%), ceftriaxone (96%), gentamicin (57%), ciprofloxacin (89%), and TMP/SMX (53%). However, they were sensitive to fosfomycin (6.6%), nitrofurantoin (1.3%), and carbapenems (0%). Fosfomycin MIC90 for ESBL-E. coli was 5.78??g/mL. The only clinical variable with significant association to ESBL producers was the presence of comorbidities: hypertension and type 2 diabetes mellitus with an OR (95%CI) of 2.5(1.3 - 4.9)(p < 0.01) and 2.8(1.2 - 6.7)(p < 0.05), respectively.ConclusionsIn the majority of cases, resistance rates to commonly prescribed antimicrobials in UTIs were high, except for fosfomycin, nitrofurantoin, and carbapenems. To provide appropriate treatment, both the identification of risk factors and the uropathogen would be important. An active surveillance in UTIs in the community is required since the proportion of ESBL producers is increasing.
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Project description:Gram-negative uropathogenic Escherichia coli (UPEC) bacteria are a causative pathogen of urinary tract infections (UTIs). Previously developed antivirulence inhibitors of the type 1 pilus adhesin, FimH, demonstrated oral activity in animal models of UTI but were found to have limited compound exposure due to the metabolic instability of the O-glycosidic bond (O-mannosides). Herein, we disclose that compounds having the O-glycosidic bond replaced with carbon linkages had improved stability and inhibitory activity against FimH. We report on the design, synthesis, and in vivo evaluation of this promising new class of carbon-linked C-mannosides that show improved pharmacokinetic (PK) properties relative to O-mannosides. Interestingly, we found that FimH binding is stereospecifically modulated by hydroxyl substitution on the methylene linker, where the R-hydroxy isomer has a 60-fold increase in potency. This new class of C-mannoside antagonists have significantly increased compound exposure and, as a result, enhanced efficacy in mouse models of acute and chronic UTI.
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Project description:Introduction. The alarming rise in urinary tract infection (UTI) antimicrobial resistance has resulted from a combination of high prevalence, low specificity and the lack of a rapid, point-of-care (POC) antibiotic susceptibility test (AST), which has led to the overuse/inappropriate use of antibiotics.Aim. This study aimed to evaluate the performance of a rapid POC phenotypic AST device in reporting susceptibility information within 2 h.Methodology. Instrument calibration was performed with model bacteria and fluorescent microbeads to determine the dynamic range and limit of detection for quantifying concentrations of bacteria and demonstrate the ability to rapidly differentiate susceptible and resistant model bacteria. We then evaluated 30 presumptive UTI-positive patient urine samples in a clinical pilot study using a panel of 5 common UTI antibiotics plus a growth control and compared our results to the hospital standard of care AST.Results. Our device was able to robustly detect and quantify bacteria concentrations from 50 to 105 colony-forming units (c.f.u.) ml-1. The high sensitivity of this measurement technique enabled the device to differentiate between susceptible and resistant model bacteria with 100 % specificity over a 2 h growth period. In the clinical pilot study, an overall categorical agreement (CA) of 90.7 % was observed (sensitivity=91.4 %, specificity=88.9 %, n=97) with performance for individual drugs ranging from 85 % CA (ceftazidime) to 100 % (nitrofurantoin).Conclusions. By reducing the typical timeframe for susceptibility testing from 2-3 days to 2 h, our POC phenotypic AST can provide critical information to clinicians prior to the administration of antibiotic therapy.
| S-EPMC7440674 | biostudies-literature
Project description:ImportanceEmpirical antibiotic prescribing in nursing homes (NHs) is often suboptimal. The potential for antibiograms to improve empirical antibiotic decision-making in NHs remains poorly understood.ObjectiveTo determine whether providing NH clinicians with a urinary antibiogram improves empirical antibiotic treatment of urinary tract infections (UTIs).Design, setting, and participantsThis was a survey study using clinical vignettes. Participants were recruited via convenience sampling of professional organization listservs of NH clinicians practicing in the US from December 2021 through April 2022. Data were analyzed from July 2022 to June 2023.InterventionsRespondents were randomized to complete vignettes using a traditional antibiogram (TA), a weighted-incidence syndromic combination antibiogram (WISCA), or no tool. Participants randomized to antibiogram groups were asked to use the antibiogram to empirically prescribe an antibiotic. Participants randomized to the no tool group functioned as controls.Main outcomes and measuresEmpirical antibiotic selections were characterized as microbiologically (1) active and (2) optimal according to route of administration and spectrum of activity.ResultsOf 317 responses, 298 (95%) were included in the analysis. Duplicate responses (15 participants), location outside the US (2 participants), and uninterpretable responses (2 participants) were excluded. Most respondents were physicians (217 respondents [73%]) and had over 10 years of NH practice experience (155 respondents [52%]). A mixed-effects logistic model found that use of the TA (odds ratio [OR], 1.41; 95% CI, 1.19-1.68; P < .001) and WISCA (OR, 1.54; 95% CI, 1.30-1.84; P < .001) were statistically superior to no tool when choosing an active empirical antibiotic. A similarly constructed model found that use of the TA (OR, 1.94; 95% CI, 1.42-2.66; P < .001) and WISCA (OR, 1.7; 95% CI, 1.24-2.33; P = .003) were statistically superior to no tool when selecting an optimal empirical antibiotic. Although there were differences between tools within specific vignettes, when compared across all vignettes, the TA and WISCA performed similarly for active (OR, 1.09; 95% CI, 0.92-1.30; P = .59) and optimal (OR, 0.87; 95% CI, 0.64-1.20; P = .69) antibiotics.Conclusions and relevanceProviding NH clinicians with a urinary antibiogram was associated with selection of active and optimal antibiotics when empirically treating UTIs under simulated conditions. Although the antibiogram format was not associated with decision-making in aggregate, context-specific effects may have been present, supporting further study of syndromic antibiograms in clinical practice.
| S-EPMC10753399 | biostudies-literature
Project description:IntroductionRecurrent urinary tract infections (rUTI) largely contribute to antibiotic use in older adults. Understanding the genetic characteristics of Escherichia coli (E.coli) is needed to identify patients at risk for recurrence. The aim of this study was to obtain a greater understanding of the genetics of E. coli rUTI in nursing home residents.MethodsThis is a secondary analysis of a multicenter Dutch nursing home study (PROGRESS). E. coli strains from residents with a suspected UTI and positive urine culture were analyzed using antimicrobial susceptibility testing and whole-genome sequencing (WGS). Same-strain recurrences were identified by single-nucleotide polymorphism (SNP) analysis.ResultIn total, 121 E. coli strains were analyzed using WGS, of which 54 belonged to a rUTI episode. One third of E. coli rUTI episodes were caused by the same strain (n = 18, 33.3%). Same-strain recurrence occurred anywhere between 30 and 434 days after the index UTI, caused by sequence types (ST): ST12, ST23, ST73, ST131, ST453, ST538 and ST2522, in seven nursing home residents. In both single UTI and rUTI, antimicrobial resistance rates were low.ConclusionRecurrent UTI in nursing home residents are caused by same-strain E. coli as well as due to different E. coli strains or other uropathogens. Same-strain recurrence can occur over 400 days after the index UTI, suggesting that some strains have the ability to colonize the bladder or gut for longer periods.
| S-EPMC9686610 | biostudies-literature