Comparative Genomics of Antibiotic-Resistant Uropathogens Implicates Three Routes for Recurrence of Urinary Tract Infections

ABSTRACT The rise of antimicrobial resistance in uropathogens has complicated the management of urinary tract infections (UTIs), particularly in patients who are afflicted by recurrent episodes of UTIs. Antimicrobial-resistant (AR) uropathogens persistently colonizing individuals at asymptomatic time points have been implicated in the pathophysiology of UTIs. The dynamics of uropathogen persistence following the resolution of symptomatic disease are, however, mostly unclear. To further our understanding, we determined longitudinal AR uropathogen carriage and clonal persistence of uropathogenic Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae isolates in the intestinal and urinary tracts of patients affected by recurrent and nonrecurrent UTIs. Clonal tracking of isolates in consecutively collected urine and fecal specimens indicated repeated transmission of uropathogens between the urinary tract and their intestinal reservoir. Our results further implicate three independent routes of recurrence of UTIs: (i) following an intestinal bloom of uropathogenic bacteria and subsequent bladder colonization, (ii) reinfection of the urinary tract from an external source, and (iii) bacterial persistence within the urinary tract. Taken together, our observation of clonal persistence following UTIs and uropathogen transmission between the intestinal and urinary tracts warrants further investigations into the connection between the intestinal microbiome and recurrent UTIs. IMPORTANCE The increasing antimicrobial resistance of uropathogens is challenging the continued efficacy of empiric antibiotic therapy for UTIs, which are among the most frequent bacterial infections worldwide. It has been suggested that drug-resistant uropathogens could persist in the intestine after the resolution of UTI and cause recurrences following periurethral contamination. A better understanding of the transmission dynamics between the intestinal and urinary tracts, combined with phenotypic characterization of the uropathogen populations in both habitats, could inform prudent therapies designed to overcome the rising resistance of uropathogens. Here, we integrate genomic surveillance with clinical microbiology to show that drug-resistant clones persist within and are readily transmitted between the intestinal and urinary tracts of patients affected by recurrent and nonrecurrent UTIs. Thus, our results advocate for understanding persistent intestinal uropathogen colonization as part of the pathophysiology of UTIs, particularly in patients affected by recurrent episodes of symptomatic disease.

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Gut microbiota and urinary tract infections in children

Fundamental and Clinical Medicine ◽

10.23946/2500-0764-2021-6-2-24-30 ◽

2021 ◽

Vol 6 (2) ◽

pp. 24-30

Author(s):

L. A. Levanova ◽

A. A. Markovskaya ◽

L. Yu. Otdushkina ◽

Yu. V. Zakharova

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Antimicrobial Resistance ◽

Urinary Tract Infections ◽

Intestinal Microbiota ◽

Neonatal Intensive Care ◽

Intestinal Microbiome ◽

Intestinal Dysbiosis ◽

Tract Infections ◽

Klebsiella Spp

Aim. To evaluate the role of intestinal dysbiosis in the development of urinary tract infections in children admitted to a multidisciplinary hospital.Materials and Methods. We performed a bacteriological analysis of 2,694 urine samples collected from ≤ 3-years-old children who have been admitted to a multidisciplinary hospital (Kemerovo, Russian Federation). Urine specimens were inoculated by the 4-sector technique. Concurrently, we quantified the intestinal microbiota and its antimicrobial resistance in 100 children with urinary tract infections.Results. Titers of pathogenic microbes significantly differed in patients from distinct units (p = 0.02). The highest number of positive samples was detected in the neonatal pathology and neonatal intensive care units (43.8% each) as well as urology unit (37.9%). The most frequent pathogens belonged to Enterobacteriaceae family, in particular Escherichia coli, Klebsiella spp., Enterobacter spp., and Proteus spp. All studied children (100/100) suffered from intestinal dysbiosis. Titers of Bifidobacterium spp. and Lactobacillus spp. were reduced to 6 (5.0; 8.0) and 5 (4.0; 6.0) lg CFU/g, respectively. In 89.2% children, Escherichia coli lac+ levels were elevated to 9-10 lg CFU/g. Of note, 18.9% children had high Escherichia coli lac- titers [8 (6.0; 9.0) lg] and 24.3% had high Escherichia coli hly+ titers [5 (4.5; 6.0) lg] in the intestine. We have also found a high frequency (44.6%) and density [8.1 (7.0; 8.5) lg] of Klebsiella spp., in the intestinal mucosa of such patients. Notably, Enterobacter spp. and Proteus spp. were abundant [7 (5.0; 8.0) CFU/g] in the intestinal microbiota of 10.8% children. The prevalence of resistance strains in the studied setting reached 63%.Conclusions. More than 75% children with urinary tract infections suffer from intestinal dysbiosis. The microbiome of these patients was predominantly composed of Enterobacteriaceae and was characterized by high titers of Escherichia coli lac+, Klebsiella spp., Enterobacte spp., and Proteus spp. Similar profile of antimicrobial resistance in urinary and intestinal isolates of enterobacteria suggests intestinal microbiome as the main source of pathogens causing urinary tract infections in children.

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Acute lower urinary tract infections: aetiology, antimicrobial resistance patterns and treatment results

10.26226/morressier.56d6be72d462b80296c97225 ◽

2016 ◽

Author(s):

Ilknur Erdem

Keyword(s):

Urinary Tract ◽

Antimicrobial Resistance ◽

Urinary Tract Infections ◽

Lower Urinary Tract ◽

Treatment Results ◽

Resistance Patterns ◽

Tract Infections ◽

Lower Urinary

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Surveillance of antimicrobial susceptibility of aerobic and facultative Gram-negative bacilli isolated from patients with urinary tract infections in China: 2010-2014 study for monitoring antimicrobial resistance trends (SMART)

10.26226/morressier.56d5ba2cd462b80296c969c5 ◽

2016 ◽

Author(s):

Qiwen Yang

Keyword(s):

Urinary Tract ◽

Antimicrobial Resistance ◽

Urinary Tract Infections ◽

Antimicrobial Susceptibility ◽

Gram Negative ◽

Tract Infections

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FDA approves new antibacterial drug to treat complicated urinary tract infections as part of ongoing efforts to address antimicrobial resistance

Case Medical Research ◽

10.31525/cmr-21c764f ◽

2019 ◽

Author(s):

Keyword(s):

Urinary Tract ◽

Antimicrobial Resistance ◽

Urinary Tract Infections ◽

Antibacterial Drug ◽

Tract Infections

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Faculty Opinions recommendation of Antimicrobial resistance in community-acquired urinary tract infections in Paris in 2015.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734641212.793554303 ◽

2018 ◽

Author(s):

Seung-Ju Lee

Keyword(s):

Urinary Tract ◽

Antimicrobial Resistance ◽

Urinary Tract Infections ◽

Tract Infections

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1675. Epidemiology of Urinary Tract Infections in the United States, 2009 - 2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1853 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S823-S823

Author(s):

Kendra Foster ◽

Linnea A Polgreen ◽

Brett Faine ◽

Philip M Polgreen

Keyword(s):

United States ◽

Urinary Tract ◽

Klebsiella Pneumoniae ◽

Urinary Tract Infections ◽

Proteus Mirabilis ◽

Antibiotic Use ◽

The United States ◽

Drug Resistant ◽

E Coli ◽

Tract Infections

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures

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Antimicrobial Resistance Among Uropathogens That Cause Childhood Community-acquired Urinary Tract Infections in Central Israel

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0000000000001373 ◽

2017 ◽

Vol 36 (1) ◽

pp. 113-115 ◽

Cited By ~ 3

Author(s):

Renata Yakubov ◽

Machiel van den Akker ◽

Kaba Machamad ◽

Amit Hochberg ◽

Erez Nadir ◽

...

Keyword(s):

Urinary Tract ◽

Antimicrobial Resistance ◽

Urinary Tract Infections ◽

Tract Infections

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Urinary Tract Infections Caused by Multi-Drug Resistant Proteus mirabilis: Risk Factors and Clinical Outcomes

Infection ◽

10.1007/s15010-009-8460-5 ◽

2009 ◽

Vol 38 (1) ◽

pp. 41-46 ◽

Cited By ~ 38

Author(s):

K. Cohen-Nahum ◽

L. Saidel-Odes ◽

K. Riesenberg ◽

F. Schlaeffer ◽

A. Borer

Keyword(s):

Risk Factors ◽

Urinary Tract ◽

Clinical Outcomes ◽

Urinary Tract Infections ◽

Proteus Mirabilis ◽

Drug Resistant ◽

Tract Infections

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Single Clinical Isolates from Acute Uncomplicated Urinary Tract Infections Are Representative of Dominant In Situ Populations

mBio ◽

10.1128/mbio.01064-13 ◽

2014 ◽

Vol 5 (2) ◽

Cited By ~ 18

Author(s):

Dana Willner ◽

Serene Low ◽

Jason A. Steen ◽

Narelle George ◽

Graeme R. Nimmo ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Clinical Isolates ◽

Content Type ◽

E Coli ◽

Strain Diversity ◽

Amplicon Pyrosequencing ◽

Culture Independent ◽

Tract Infections

ABSTRACTUrinary tract infections (UTIs) are one of the most commonly acquired bacterial infections in humans, and uropathogenicEscherichia colistrains are responsible for over 80% of all cases. The standard method for identification of uropathogens in clinical laboratories is cultivation, primarily using solid growth media under aerobic conditions, coupled with morphological and biochemical tests of typically a single isolate colony. However, these methods detect only culturable microorganisms, and characterization is phenotypic in nature. Here, we explored the genotypic identity of communities in acute uncomplicated UTIs from 50 individuals by using culture-independent amplicon pyrosequencing and whole-genome and metagenomic shotgun sequencing. Genus-level characterization of the UTI communities was achieved using the 16S rRNA gene (V8 region). Overall UTI community richness was very low in comparison to other human microbiomes. We strain-typedEscherichia-dominated UTIs using amplicon pyrosequencing of the fimbrial adhesin gene,fimH. There were nine highly abundantfimHtypes, and each UTI sample was dominated by a single type. Molecular analysis of the corresponding clinical isolates revealed that in the majority of cases the isolate was representative of the dominant taxon in the community at both the genus and the strain level. Shotgun sequencing was performed on a subset of eightE. coliurine UTI and isolate pairs. The majority of UTI microbial metagenomic sequences mapped to isolate genomes, confirming the results obtained using phylogenetic markers. We conclude that for the majority of acute uncomplicatedE. coli-mediated UTIs, single cultured isolates are diagnostic of the infection.IMPORTANCEIn clinical practice, the diagnosis and treatment of acute uncomplicated urinary tract infection (UTI) are based on analysis of a single bacterial isolate cultured from urine, and it is assumed that this isolate represents the dominant UTI pathogen. However, these methods detect only culturable bacteria, and the existence of multiple pathogens as well as strain diversity within a single infection is not examined. Here, we explored bacteria present in acute uncomplicated UTIs using culture-independent sequence-based methods.Escherichia coliwas the most common organism identified, and analysis ofE. colidominant UTI samples and their paired clinical isolates revealed that in the majority of infections the cultured isolate was representative of the dominant taxon at both the genus and the strain level. Our data demonstrate that in most cases single cultured isolates are diagnostic of UTI and are consistent with the notion of bottlenecks that limit strain diversity during UTI pathogenesis.

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