CTX-M beta-lactamases in Escherichia coli from community-acquired urinary tract infections, Cambodia.
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ABSTRACT:
SUBMITTER: Ruppe E
PROVIDER: S-EPMC2687024 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A population-based study was performed to investigate the efficacy of mecillinam treatment of community-acquired urinary tract infections (CA-UTI) caused by extended-spectrum β-lactamase (ESBL) producing Escherichia coli. The study was conducted in South-Eastern Norway. Data from patients with CA-UTI caused by ESBL-producing and non-producing (random controls) E. coli were collected through interviews, questionnaires, medical records and the Norwegian Prescription Database. Treatment failure was defined as a new antibiotic prescription appropriate for UTI prescribed within two weeks after the initial antimicrobial therapy. Multivariable logistic regression analysis was performed to identify treatment agents and patient- or bacterial traits associated with treatment failure. A total of 343 patients (mean age 59) were included, of which 158 (46%) were treated with mecillinam. Eighty-one patients (24%, mean age 54) had infections caused by ESBL producing E. coli, and 41 of these patients (51%) received mecillinam as the primary treatment. Mecillinam treatment failure was observed in 18 (44%) of patients infected by ESBL-producing strains and in 16 (14%) of patients with a CA-UTI caused by ESBL non-producing strains. Multivariable analysis showed that ESBL status (odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3-7.8, p = 0.009) and increased MIC of mecillinam (OR 2.0 for each doubling value of MIC, CI 1.4-3.0, p<0.001) were independently associated with mecillinam treatment failure. This study showed a high rate of mecillinam treatment failure in CA-UTIs caused by ESBL producing E. coli. The high failure rate could not be explained by the increased MIC of mecillinam alone. Further studies addressing the use of mecillinam against ESBL-producing E. coli, with emphasis on optimal dosing and combination therapy with β-lactamase inhibitors, are warranted.
| S-EPMC3893261 | biostudies-literature
Project description:IntroductionMultidrug resistance (MDR) and emergence of extended-spectrum ?-lactamases (ESBLs) that mediate resistance to ?-lactam drugs among Escherichia coli and other uropathogens have been reported worldwide. However, there is little information on the detection of ESBLs genes in E. coli from patients with urinary tract infections (UTIs) in the Arab countries using polymerase chain reaction (PCR), and in Libya such information is lacking.MethodsAll patients attending Zawiya Teaching Hospital in Zawiya city between November 2012 and June 2013 suspected of having UTIs and from whom midstream urine samples were taken as part of the clinical workup were included in this prospective study. Samples were examined for uropathogens by standard bacteriological procedures. VITEK-2 automated microbiology system was used to identify the isolated uropathogens and determine the susceptibility of E. coli and Klebsiella spp. isolates to antimicrobials. In addition, phenotypically ESBLs-positive E. coli isolates were tested for ESBLs genes by PCR.ResultsThe present study enrolled 1,790 patients with UTIs. Uropathogens were found in 371 (20.7%) urine specimens examined. Mixed pathogens were detected in two specimens with 373 total pathogens isolated. E. coli and Klebsiella spp. were the predominant uropathogens at 55.8% (208/373) and 18.5% (69/373), respectively. Other pathogens were detected in 25.7% (96/373) of urine samples. Of the E. coli and Klebsiella spp. tested, 69.2 and 100% were resistant to ampicillin, 6.7 and 33.3% to ceftriaxone, and 23.1 and 17.4% to ciprofloxacin, respectively. MDR (resistance to ?3 antimicrobial groups) was found in 69 (33.2%) of E. coli and in 29 (42%) of Klebsiella spp. isolates. ESBLs were detected phenotypically in 14 (6.7%) of E. coli and in 15 (21.7%) of Klebsiella spp. isolates. Thirteen out of the 14 phenotypically ESBL-positive E. coli were positive for ESBL genes by PCR. bla TEM gene was detected in seven isolates, bla OXA gene in 10 isolates and bla CTX-M gene in six isolates. bla SHV gene was not detected in the present study.ConclusionThe isolation of MDR ESBL-producing uropathogens undoubtedly will limit the choices clinicians have to treat their patients with UTIs. Therefore, there is an urgent need for surveillance studies on antimicrobial resistance and prevalence of ESBLs among uropathogens to guide the clinical treatment of UTIs in Libya in the future.
| S-EPMC4315781 | biostudies-literature
Project description:The treatment of urinary tract infections (UTIs) has been complicated by the emergence of multidrug-resistant, β-lactamase-expressing pathogens. As a result of the limited treatment options, patients often require hospitalization and intravenous therapy. In essence, a strong unmet need for oral antibiotics, active against extended-spectrum β-lactamase (ESBL) uropathogens has emerged. Oral carbapenems (tebipenem and sulopenem) and oral cephalosporin/β-lactamase inhibitor combinations are in various stages of clinical development for the treatment of uncomplicated and complicated UTI. Tebipenem, if approved, will be the first oral treatment for complicated UTI while sulopenem will be for uncomplicated UTI. The β-lactamase inhibitors ETX0282, VNRX7145, ARX1796, and QPX7728 are combined with cefpodoxime proxetil or ceftibuten that achieve favorable exposures in urine compared to other uropathogen-active oral cephalosporins. The combination ceftibuten-QPX7728 has potential broad-spectrum coverage against carbapenemase producers including metallo β-lactamase producers. Other novel combinations, namely cefpodoxime/ETX0282, ceftibuten/VNRX-7145, and ceftibuten/ARX1796, have also demonstrated excellent activity against Klebsiella pneumoniae carbapanemase (KPC) and OXA-48-like producers. All these agents, upon their arrival for commercial use, would strengthen the outpatient therapy.
| S-EPMC8572892 | biostudies-literature
Project description:Escherichia coli is the most common cause of urinary tract infections (UTIs). E. coli genes epidemiologically associated with UTIs are potentially valuable in developing strategies for treating and/or preventing such infections as well as differentiating uropathogenic E. coli from nonuropathogenic E. coli. To identify E. coli genes associated with UTIs in humans, we combined microarray-based and PCR-based analyses to investigate different E. coli source groups derived from feces of healthy humans and from patients with cystitis, pyelonephritis, or urosepsis. The cjrABC-senB gene cluster, sivH, sisA, sisB, eco274, and fbpB, were identified to be associated with UTIs. Of these, cjrABC-senB, sisA, sisB, and fbpB are known to be involved in urovirulence in the mouse model of ascending UTI. Our results provide evidence to support their roles as urovirulence factors in human UTIs. In addition, the newly identified UTI-associated genes were mainly found in members of phylogenetic groups B2 and/or D.
| S-EPMC3264149 | biostudies-literature
Project description:The virulence determinants of uropathogenic Escherichia coli have been studied extensively over the years, but relatively little is known about what differentiates isolates causing various types of urinary tract infections. In this study, we compared the genomic profiles of 45 strains from a range of different clinical backgrounds, i.e., urosepsis, pyelonephritis, cystitis, and asymptomatic bacteriuria (ABU), using comparative genomic hybridization analysis. A microarray based on 31 complete E. coli sequences was used. It emerged that there is little correlation between the genotypes of the strains and their disease categories but strong correlation between the genotype and the phylogenetic group association. Also, very few genetic differences may exist between isolates causing symptomatic and asymptomatic infections. Only relatively few genes that could potentially differentiate between the individual disease categories were identified. Among these were two genomic islands, namely, pathogenicity island (PAI)-CFT073-serU and PAI-CFT073-pheU, which were significantly more associated with the pyelonephritis and urosepsis isolates than with the ABU and cystitis isolates. These two islands harbor genes encoding virulence factors, such as P fimbriae (pyelonephritis-associated fimbriae) and an important immunomodulatory protein, TcpC. It seems that both urovirulence and growth fitness can be attributed to an assortment of genes rather than to a specific gene set. Taken together, urovirulence and fitness are the results of the interplay of a mixture of factors taken from a rich menu of genes.
| S-EPMC3126446 | biostudies-literature
Project description:Antibiotic resistance is a threat to public health, and uncomplicated urinary tract infections (uUTIs) are an example of this concern. This systematic review (International Prospective Register of Systematic Reviews [PROSPERO] ID: CRD42020156674) is the first to determine the prevalence of Escherichia coli resistance to fluoroquinolones in women with community-acquired uUTI. PubMed and Embase searches were conducted; 38 studies fulfilled eligibility criteria and were included in the systematic review. Within Europe, ciprofloxacin resistance in E. coli isolates varied between countries and increased in some from 2006 to 2008 and 2014 to 2016, specifically in the United Kingdom (0.5% to 15.3%), Germany (8.7% to 15.1%), and Spain (22.9% to 30.8%), although methodologies and settings were often not comparable. In Asia, there was a substantial increase in ciprofloxacin resistance during 2008 to 2014 from 25% to more than 40%. In North America, resistance to ciprofloxacin also increased between 2008 and 2017, from 4% to 12%. Data exploring different age groups did not show a consistent relationship with resistance, whereas two studies found that fluoroquinolone resistance was higher in postmenopausal women than premenopausal women. One study indicated a link between fluoroquinolone resistance and uUTI recurrence. These findings may have implications for the empirical treatment of uUTI with fluoroquinolones globally, but more data are needed to fully understand regional situations and impact patient management.
| S-EPMC7508571 | biostudies-literature
Project description:Urinary tract infections (UTI) affect community and healthcare patients worldwide and may have different clinical outcomes. We assessed the phylogenetic origin, the presence of 43 virulence factors (VFs) of diarrheagenic and extraintestinal pathogenic Escherichia coli, and the occurrence of hybrid strains among E. coli isolates from 172 outpatients with different types of UTI. Isolates from phylogroup B2 (46%) prevailed, followed by phylogroups A (15.7%) and B1 (12.2%), with similar phylogenetic distribution in symptomatic and asymptomatic patients. The most frequent VFs according to their functional category were fimA (94.8%), ompA (83.1%), ompT (63.3%), chuA (57.6%), and vat (22%). Using published molecular criteria, 34.3% and 18.0% of the isolates showed intrinsic virulence and uropathogenic potential, respectively. Two strains carried the eae and escV genes and one the aggR gene, which classified them as hybrid strains. These hybrid strains interacted with renal and bladder cells, reinforcing their uropathogenic potential. The frequency of UPEC strains bearing a more pathogenic potential in the outpatients studied was smaller than reported in other regions. Our data contribute to deepening current knowledge about the mechanisms involved in UTI pathogenesis, especially among hybrid UPEC strains, as these could colonize the host's intestine, leading to intestinal infections followed by UTI.
| S-EPMC8874565 | biostudies-literature
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.
| S-EPMC5895837 | biostudies-other
Project description:Objectives: The aim of this study was to assess the clonal structure, virulence potential and antibiotic susceptibility of uropathogenic Escherichia coli (UPEC) isolates causing community acquired urinary tract infection (CAUTI) in unselected primary care patients in Switzerland. Methods: We performed multilocus sequence typing, virulence factor determination, and phenotypic and genotypic antimicrobial resistance testing on 44 non-duplicate UPEC isolates. Results: Twenty-seven different sequence types (STs) were identified. Major UPEC clones were represented by 19 (43.2%) of the isolates, including E. coli ST131, ST69 (both 13.6%), ST73 (6.8%), ST10 (4.5%), ST127, ST140, (both 2.3%). Five (11.4%) isolates belonged to ST141. Aggregate virulence factor (VF) scores were highest among isolates belonging to ST127 and ST141. Overall, 50% of the isolates were susceptible to all 12 antimicrobials tested, and all isolates remained susceptible to fosfomycin and nitrofurantoin. Resistance to sulfamethoxazole and ciprofloxacin were found in 31.8, and 15.9% of the isolates, respectively. Plasmid-mediated resistance genes were detected in ST69 and ST131 and included aac(6')-Ib-cr (2.3% of all isolates) blaCTX-M-14 and blaCTX-M-15 (9%), and mph(A) (13.6%). None of the isolates tested positive for mcr-1 or mcr-2. Conclusions: Our results show that CAUTI in Switzerland is caused by a wide variety of UPEC STs for which fosfomycin remains a good treatment option. We suggest that ST141 is an emerging clone associated with UTI in the community, and warrants closer attention. Moreover, the high rate of E. coli harboring mph(A) from patients without a history of antimicrobial therapy or hospitalization indicates that UPEC is an important reservoir for mph(A).
| S-EPMC5716990 | biostudies-literature
Project description:This study determined the antimicrobial resistance profiles of Escherichia coli isolates from dogs with a presumptive diagnosis of urinary tract infection (UTI). Urine samples from 201 dogs with UTI diagnosed through clinical examination and urinalysis were processed for isolation of Escherichia coli. Colonies from pure cultures were identified by biochemical reactions (n=114) and were tested for susceptibility to 18 antimicrobials. The two most frequent antimicrobials showing resistance in Urinary E. coli isolates were oxytetracycline and ampicillin. Among the resistant isolates, 17 resistance patterns were observed, with 12 patterns involving multidrug resistance (MDR). Of the 69 tetracycline-resistant E. coli isolates, tet(B) was the predominant resistance determinant and was detected in 50.9% of the isolates, whereas the remaining 25.5% isolates carried the tet(A) determinant. Most ampicillin and/or amoxicillin-resistant E. coli isolates carried blaTEM-1 genes. Class 1 integrons were prevalent (28.9%) and contained previously described gene cassettes that are implicated primarily in resistance to aminoglycosides and trimethoprim (dfrA1, dfrA17-aadA5). Of the 44 quinolone-resistant E. coli isolates, 38 were resistant to nalidixic acid, and 6 were resistant to nalidixic acid, ciprofloxacin and enrofloxacin. Chromosomal point mutations were found in the GyrA (Ser83Leu) and ParC (Ser80Ile) genes. Furthermore, the aminoglycoside resistance gene aacC2, the chloramphenicol resistant gene cmlA and the florfenicol resistant gene floR were also identified. This study revealed an alarming rate of antimicrobial resistance among E. coli isolates from dogs with UTIs.
| S-EPMC4349538 | biostudies-literature