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Use of other antimicrobial drugs is associated with trimethoprim resistance in patients with urinary tract infections caused by E. coli.

ABSTRACT: In recent years, high frequencies of trimethoprim resistance in urinary tract infections (UTIs) caused by E. coli are have been reported. Co-resistance to other antimicrobial drugs may play a role in this increase. Therefore, we investigated whether previous use of other antimicrobial drugs was associated with trimethoprim resistance. We conducted a nested case-control study with urinary cultures with E. coli from participants of the Rotterdam Study sent in by general practitioners to the regional laboratory between 1 January 2000 and 1 April 2016. Multivariable logistic regression analysis was performed to study the association between prior prescriptions of several antimicrobial drug groups and trimethoprim resistance using individual participant data. Urinary cultures of 1264 individuals with a UTI caused by E. coli were included. When adjusted for previous other antimicrobial drug use, a history of >?3 prescriptions of extended-spectrum penicillins (OR 1.68; 95% CI 1.10-2.55) was significantly associated with trimethoprim resistance of E. coli as was the use of >?3 prescriptions of sulfonamides and trimethoprim (OR 2.22; 95% CI 1.51-3.26). The use of >?3 prescriptions of nitrofuran derivatives was associated with a lower frequency of trimethoprim resistance (OR 0.60; 95% CI 0.39-0.92), after adjustment for other antimicrobial drug prescriptions. We found that previous use of extended-spectrum penicillins is associated with trimethoprim resistance. On the contrary, previous nitrofurantoin use was associated with a lower frequency of trimethoprim resistance. Especially in individuals with recurrent UTI, co-resistance should be taken into account and susceptibility testing before starting trimethoprim should be considered.

SUBMITTER: Mulder M

PROVIDER: S-EPMC6858404 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Use of other antimicrobial drugs is associated with trimethoprim resistance in patients with urinary tract infections caused by E. coli.

Mulder M M Verbon A A Lous J J Goessens W W Stricker B H BH

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 20190907 12

In recent years, high frequencies of trimethoprim resistance in urinary tract infections (UTIs) caused by E. coli are have been reported. Co-resistance to other antimicrobial drugs may play a role in this increase. Therefore, we investigated whether previous use of other antimicrobial drugs was associated with trimethoprim resistance. We conducted a nested case-control study with urinary cultures with E. coli from participants of the Rotterdam Study sent in by general practitioners to the region ...[more]

PMID: 31494829

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Project description:Urinary tract infections (UTIs) are the most common bacterial infections requiring medical attention and a leading justification for antibiotic prescription. Trimethoprim is prescribed empirically for uncomplicated cases. UTIs are primarily caused by extraintestinal pathogenic Escherichia coli (ExPEC) and ExPEC strains play a central role in disseminating antimicrobial-resistance genes worldwide. Here, we describe the whole-genome sequences of trimethoprim-resistant ExPEC and/or ExPEC from recurrent UTIs (67 in total) from patients attending a regional Australian hospital from 2006 to 2008. Twenty-three sequence types (STs) were observed, with ST131 predominating (28 %), then ST69 and ST73 (both 7 %). Co-occurrence of trimethoprim-resistance genes with genes conferring resistance to extended-spectrum β-lactams, heavy metals and quaternary ammonium ions was a feature of the ExPEC described here. Seven trimethoprim-resistance genes were identified, most commonly dfrA17 (38 %) and dfrA12 (18 %). An uncommon dfrB4 variant was also observed. Two blaCTX-M variants were identified - blaCTX-M-15 (16 %) and blaCTX-M-14 (10 %). The former was always associated with dfrA12, the latter with dfrA17, and all blaCTX-M genes co-occurred with chromate-resistance gene chrA. Eighteen class 1 integron structures were characterized, and chrA featured in eight structures; dfrA genes featured in seventeen. ST131 H30Rx isolates possessed distinct antimicrobial gene profiles comprising aac(3)-IIa, aac(6)-Ib-cr, aph(3')-Ia, aadA2, blaCTX-M-15, blaOXA-1 and dfrA12. The most common virulence-associated genes (VAGs) were fimH, fyuA, irp2 and sitA (all 91 %). Virulence profile clustering showed ST131 H30 isolates carried similar VAGs to ST73, ST405, ST550 and ST1193 isolates. The sole ST131 H27 isolate carried molecular predictors of enteroaggregative E. coli/ExPEC hybrid strains (aatA, aggR, fyuA). Seven isolates (10 %) carried VAGs suggesting ColV plasmid carriage. Finally, SNP analysis of serial UTI patients experiencing worsening sequelae demonstrated a high proportion of point mutations in virulence factors.

Project description:Escherichia coli is the leading cause of urinary tract infections (UTIs) in children and adults. The gastrointestinal tract is the primary reservoir of uropathogenic E. coli, which can be acquired from a variety of environmental exposures, including retail meat. In the current study, we used a novel statistical-genomic approach to estimate the proportion of pediatric UTIs caused by foodborne zoonotic E. coli strains. E. coli urine isolates were collected from DC residents aged 2 months to 17 years from the Children's National Medical Center Laboratory, 2013-2014. During the same period, E. coli isolates were collected from retail poultry products purchased from 15 sites throughout DC. A total of 52 urine and 56 poultry isolates underwent whole-genome sequencing, core genome phylogenetic analysis, and host-origin prediction by a Bayesian latent class model that incorporated data on the presence of mobile genetic elements (MGEs) among E. coli isolates from multiple vertebrate hosts. A total of 56 multilocus sequence types were identified among the isolates. Five sequence types-ST10, ST38, ST69, ST117, and ST131-were observed among both urine and poultry isolates. Using the Bayesian latent class model, we estimated that 19% (10/52) of the clinical E. coli isolates in our population were foodborne zoonotic strains. These data suggest that a substantial portion of pediatric UTIs in the Washington DC region may be caused by E. coli strains originating in food animals and likely transmitted via contaminated poultry meat.IMPORTANCEEscherichia coli UTIs are a heavy public health burden and can have long-term negative health consequences for pediatric patients. E. coli has an extremely broad host range, including humans, chickens, turkeys, pigs, and cattle. E. coli derived from food animals is a frequent contaminant of retail meat products, but little is known about the risk these strains pose to pediatric populations. Quantifying the proportion of pediatric UTIs caused by food-animal-derived E. coli, characterizing the highest-risk strains, and identifying their primary reservoir species could inform novel intervention strategies to reduce UTI burden in this vulnerable population. Our results suggest that retail poultry meat may be an important vehicle for pediatric exposure to zoonotic E. coli strains capable of causing UTIs. Vaccinating poultry against the highest-risk strains could potentially reduce poultry colonization, poultry meat contamination, and downstream pediatric infections.

Project description:BackgroundThere are still no detailed data about the burden of bacterial antimicrobial resistance (AMR) in urinary tract infections (UTI). Concrete knowledge of global and regional bacterial AMR data is crucial for developing informed programs and policies to control bacterial AMR and for prudent use of antibiotics to optimize antibiotic therapy in patients with UTI. This study aimed to provide comprehensive global and regional estimates for the AMR burden of UTI in 2019.MethodsData were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), including death, disability-adjusted life-years (DALYs), year lived with disability (YLD), and years of life lost (YLL) for bacterial AMR in UTI for 7 GBD super-regions, 21 regions, 14 pathogens, 13 antibiotic classes, and 66 pathogen-antibiotic combinations in 2019. The estimates were based on two counterfactual scenarios: drug-susceptible infection and no infection.ResultsGlobally, there were 64.89 thousand deaths (95% uncertainty interval [UI]: 45.86-93.35) attributed to and 0.26 million deaths (95% UI: 0.18-0.36) associated with bacterial AMR in UTI in 2019. Among regions, the all-age death rates were higher in southern Latin America, tropical Latin America, and Europe and lower in sub-Saharan Africa. Escherichia coli and Klebsiella pneumoniae accounted for more than 50% of deaths attributable to and associated with AMR, and resistance was high among multiple types of antibiotic class, including fluoroquinolones, carbapenems, and third-generation cephalosporins. There were 2 pathogen-drug combinations that caused more than 6000 resistance-attributable deaths: third-generation cephalosporin-resistant Escherichia coli and fluoroquinolone-resistant Escherichia coli.ConclusionsAMR in UTI is an unignorable health problem, both for the management of urology disease and for global antibiotic resistance. Special tailored strategies, including enhanced surveillance and rational use of antibiotics, should be developed for different regions according to the region-specific pathogen-antibiotic situations and resources.

Dataset Information

Use of other antimicrobial drugs is associated with trimethoprim resistance in patients with urinary tract infections caused by E. coli.

Publications

Use of other antimicrobial drugs is associated with trimethoprim resistance in patients with urinary tract infections caused by E. coli.

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