scholarly journals Pan-resistome characterization of uropathogenic Escherichia coli and Klebsiella pneumoniae strains circulating in Uganda and Kenya isolated from 2017-2018

Author(s):  
Arun Gonzales Decano ◽  
Kerry Pettigrew ◽  
Wilber Sabiiti ◽  
Derek Sloan ◽  
Stella Neema ◽  
...  

AbstractBackgroundUrinary tract infection (UTI) develops after a pathogen adhered to the inner lining of the urinary tract. Cases of UTIs are predominantly caused by several Gram-negative bacteria and account for high morbidity in the clinical and community settings. Of greater concern are the strains carrying antimicrobial resistance (AMR)-conferring genes. The gravity of UTI is also determined by a spectrum of other virulence factors. This study represents a pilot project to investigate the burden of AMR among uropathogens in East Africa.MethodsWe examined bacterial samples isolated in 2017-2018 from in- and out-patients in Kenya (KY) and Uganda (UG) that presented with clinical symptoms of UTI. We reconstructed the evolutionary history of the strains, investigated their population structure and performed comparitive analysis their pangenome contents.ResultsWe found 55 Escherichia coli and 19 Klebsiella pneumoniae strains confirmed uropathogenic following screening for the prevalence of UTI virulence genes including fimH, iutA, feoA/B/C, mrkD and foc. We identified 18 different sequence types in E. coli population while all K. pneumoniae strains belong to ST11. The most prevalent E. coli sequence types were ST131 (26%), ST335/1193 (10%) and ST10 (6%). Diverse plasmid types were observed in both collections such as Incompatibility (IncF/IncH/IncQ1/IncX4) and Col groups. Pangenome analysis of each set revealed a total of 2,862 and 3,464 genes comprised the core genome of E. coli and K. pneumoniae population, respectively. Among these are AMR determinants including fluoroquinolone resistance-conferring genes aac(3)-Ib-cr and other significant genes: aad, tet, sul1, sul2, and cat, which are associated with aminoglycoside, tetracycline, sulfonamide and chloramphenicol resistance. Accessory genomes of both species collection were detected several β-lactamase genes, blaCTX-M, blaTEM and blaOXAor blaNDM.Overall, 93% are multi-drug resistant in the E. coli collection while 100% of the K. pneumoniae strains contained genes that are associated with resistance to 3 or more antibiotic classes.ConclusionsOur findings illustrate the abundant resistome and virulome repertoire in uropathogenic E. coli and K. pneumoniae, which are mainly disseminated via clonal and horizontal transfer, circulating in the East African region. We further demonstrate here that routine genomic surveillance is necessary for high-resolution bacterial epidemiology of these important AMR pathogens.

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1547
Author(s):  
Arun Gonzales Decano ◽  
Kerry Pettigrew ◽  
Wilber Sabiiti ◽  
Derek J. Sloan ◽  
Stella Neema ◽  
...  

Urinary tract infection (UTI) develops after a pathogen adheres to the inner lining of the urinary tract. Cases of UTIs are predominantly caused by several Gram-negative bacteria and account for high morbidity in the clinical and community settings. Of greater concern are the strains carrying antimicrobial resistance (AMR)-conferring genes. The gravity of a UTI is also determined by a spectrum of other virulence factors. This study represents a pilot project to investigate the burden of AMR among uropathogens in East Africa. We examined bacterial samples isolated in 2017–2018 from in- and out-patients in Kenya (KY) and Uganda (UG) that presented with clinical symptoms of UTI. We reconstructed the evolutionary history of the strains, investigated their population structure, and performed comparative analysis their pangenome contents. We found 55 Escherichia coli and 19 Klebsiella pneumoniae strains confirmed uropathogenic following screening for the prevalence of UTI virulence genes including fimH, iutA, feoA/B/C, mrkD, and foc. We identified 18 different sequence types in E. coli population while all K. pneumoniae strains belong to ST11. The most prevalent E. coli sequence types were ST131 (26%), ST335/1193 (10%), and ST10 (6%). Diverse plasmid types were observed in both collections such as Incompatibility (IncF/IncH/IncQ1/IncX4) and Col groups. Pangenome analysis of each set revealed a total of 2862 and 3464 genes comprised the core genome of E. coli and K. pneumoniae population, respectively. Among these are acquired AMR determinants including fluoroquinolone resistance-conferring genes aac(3)-Ib-cr and other significant genes: aad, tet, sul1, sul2, and cat, which are associated with aminoglycoside, tetracycline, sulfonamide, and chloramphenicol resistance, respectively. Accessory genomes of both species collections were detected several β-lactamase genes, blaCTX-M, blaTEM and blaOXA, or blaNDM. Overall, 93% are multi-drug resistant in the E. coli collection while 100% of the K. pneumoniae strains contained genes that are associated with resistance to three or more antibiotic classes. Our findings illustrate the abundant acquired resistome and virulome repertoire in uropathogenic E. coli and K. pneumoniae, which are mainly disseminated via clonal and horizontal transfer, circulating in the East African region. We further demonstrate here that routine genomic surveillance is necessary for high-resolution bacterial epidemiology of these important AMR pathogens.


2020 ◽  
Vol 75 (12) ◽  
pp. 3656-3664
Author(s):  
Rasmus Richelsen ◽  
Jesper Smit ◽  
Henrik Carl Schønheyder ◽  
Pavithra Laxsen Anru ◽  
Belen Gutiérrez-Gutiérrez ◽  
...  

Abstract Objectives To assess the impact of ESBL production on mortality and length of hospital stay (LOS) of community-onset infections due to Escherichia coli or Klebsiella pneumoniae. Methods A population-based cohort study including all adult patients hospitalized with a first-time community-onset E. coli or K. pneumoniae bacteraemia or urinary tract infection in the North Denmark Region between 2007 and 2017. For each bacterial agent, we computed 1 year Kaplan–Meier survival curves and cumulative incidence functions of LOS, and by use of Cox proportional hazard regression we computed HRs as estimates of 30 day and 1 year mortality rate ratios (MRRs) and LOS among patients with and without ESBL-producing infections. Results We included 24 518 cases (among 22350 unique patients), of whom 1018 (4.2%) were infected by an ESBL-producing bacterium. The 30 day cumulative mortality and adjusted MRR (aMRR) in patients with and without ESBL-producing isolates was as follows: E. coli bacteraemia (n = 3831), 15.8% versus 14.0%, aMRR = 1.01 (95% CI = 0.70–1.45); E. coli urinary tract infection (n = 17151), 9.5% versus 8.7%, aMRR = 0.97 (95% CI = 0.75–1.26); K. pneumoniae bacteraemia (n = 734), 0% versus 17.2%, aMRR = not applicable; and K. pneumoniae urinary tract infection (n = 2802), 13.8% versus 10.7%, aMRR = 1.13 (95% CI = 0.73–1.75). The 1 year aMRR remained roughly unchanged. ESBL-producing E. coli bacteraemia was associated with an increased LOS compared with non-ESBL production. Conclusions ESBL production was not associated with an increased short- or long-term mortality in community-onset infections due to E. coli or K. pneumoniae, yet ESBL-producing E. coli bacteraemia was associated with an increased LOS.


1970 ◽  
Vol 24 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Taslima Taher Lina ◽  
Sabita Rezwana Rahman ◽  
Donald James Gomes

Antibiotic resistance in urinary tract infection (UTI) is a growing public health problem in the world. In this study, a total of 182 uropathogens were isolated from patients with symptoms of urinary tract infection (UTI). Escherichia coli (88%) was the most prevalent isolate, while Klebsiella pneumoniae was recovered from 12% cases. The male/female ratio was 1:3. About 56% female and 51% male patients belonged to the age group >40 years. The antibiotic resistance rates of the isolates to fifteen different drugs were investigated. E. coli and K. pneumoniae showed variable pattern of susceptibility. The percentage of resistance to different drugs was higher in E. coli isolates compared to that of K. pneumoniae. Among the total number of isolates about 87% were resistant to at least three commonly used antibiotics. All the isolates were sensitive to imipenem. Analysis of the plasmid DNA had shown that the plasmid pattern was very diverse in both E. coli and K. pneumoniae. All the isolates contained multiple numbers of plasmid ranging from 1.0 to >140 MDa. Middleranged plasmids (30 to 80 MDa), the transferable resistance plasmids, were found to be present in 86% E. coli and 85% K. pneumoniae isolates. The strong association observed between plasmid profiles and drug resistance patterns suggest that plasmids other than the common plasmids may have epidemiological significance. The presence of class 1 and class 2 integrons were also investigated. A relatively high occurrence of class 1 integrons, that are associated with lateral transfer of antibacterial resistance genes, was observed in K. pneumoniae (88%) than in E. coli isolates (54%). Class 2 integrons were not found in any of the E. coli and K. pneumoniae isolates. These results show the high rate of drug resistance and the presence of high rate of transferable elements in these MDR isolates. Keywords: Uropathogens, Escherichia coli, Klebsiella pneumoniae, Multidrug-resistant (MDR) bacteria, Plasmid profiles, IntegronsDOI: http://dx.doi.org/10.3329/bjm.v24i1.1231 Bangladesh J Microbiol, Volume 24, Number 1, June 2007, pp 19-23


1998 ◽  
Vol 66 (7) ◽  
pp. 3059-3065 ◽  
Author(s):  
David E. Johnson ◽  
C. Virginia Lockatell ◽  
Robert G. Russell ◽  
J. Richard Hebel ◽  
Michael D. Island ◽  
...  

ABSTRACT Urinary tract infection, most frequently caused byEscherichia coli, is one of the most common bacterial infections in humans. A vast amount of literature regarding the mechanisms through which E. coli induces pyelonephritis has accumulated. Although cystitis accounts for 95% of visits to physicians for symptoms of urinary tract infections, few in vivo studies have investigated possible differences between E. coli recovered from patients with clinical symptoms of cystitis and that from patients with symptoms of pyelonephritis. Epidemiological studies indicate that cystitis-associated strains appear to differ from pyelonephritis-associated strains in elaboration of some putative virulence factors. With transurethrally challenged mice we studied possible differences using three each of the most virulent pyelonephritis and cystitis E. coli strains in our collection. The results indicate that cystitis strains colonize the bladder more rapidly than do pyelonephritis strains, while the rates of kidney colonization are similar. Cystitis strains colonize the bladder in higher numbers, induce more pronounced histologic changes in the bladder, and are more rapidly eliminated from the mouse urinary tract than pyelonephritis strains. These results provide evidence that cystitis strains differ from pyelonephritis strains in this model, that this model is useful for the study of the uropathogenicity of cystitis strains, and that it would be unwise to use pyelonephritis strains to study putative virulence factors important in the development of cystitis.


Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 181
Author(s):  
Soo Tein Ngoi ◽  
Cindy Shuan Ju Teh ◽  
Chun Wie Chong ◽  
Kartini Abdul Jabar ◽  
Shiang Chiet Tan ◽  
...  

The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of β-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established β-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76–80%), ticarcillin-clavulanate (58–76%), and piperacillin-tazobactam (48–50%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 µg/mL to 128 µg/mL) for both species. The ESBL genes blaCTX-M and blaTEM were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas blaSHV was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Shan Huang ◽  
Wan-Chen Tsai ◽  
Jia-Jie Li ◽  
Pao-Yu Chen ◽  
Jann-Tay Wang ◽  
...  

AbstractNew Delhi metallo-β-lactamase (NDM) had been reported to be the predominant carbapenemase among Escherichia coli in Taiwan. However, studies focusing on the clonal background and epidemiology of plasmids carrying NDM genes were limited. Between 2016 and 2018, all clinical E. coli and Klebsiella pneumoniae isolates that were non-susceptible to ertapenem, meropenem, and imipenem were tested for carbapenemase-encoding genes (CEGs) and antimicrobial susceptibilities. Molecular typing was performed on all carbapenemase-producing isolates. Whole genome sequencing (WGS) was performed on all NDM-positive E. coli isolates. Twenty-three (29.5%) of 78 carbapenem non-susceptible E. coli and 108 (35.3%) of 306 carbapenem non-susceptible K. pneumoniae isolates carried CEGs. The most prevalent CEGs in carbapenemase-producing E. coli (CPEc) were blaNDM (39.1%) and blaIMP-8 (30.4%), while that in carbapenemase-producing K. pneumoniae was Klebsiella pneumoniae carbapenemase (KPC) (72.2%). Fifteen sequence types were identified among 23 CPEc, and 55.6% of NDM-positive E. coli isolates belonged to ST410. WGS showed ST410 isolates were highly clonal and similar to those from other countries. All NDM-5-positive E. coli isolates carried identical IncX3 plasmid harboring blaNDM-5 but no other antimicrobial resistance (AMR) genes. In each of the four NDM-1-positive E. coli isolates, the blaNDM-1 was present in a ∼ 300 kb IncHI2/IncHI2A plasmid which carried an array of AMR genes. NDMs are the most prevalent carbapenemase among CPEc in Taiwan. Awareness should be raised as the prevalence of NDM-positive E. coli might increase rapidly with IncX3 plasmid and globally distributed strain ST410 being the potential vectors for wide dissemination.


2021 ◽  
Vol 9 (7) ◽  
pp. 1501
Author(s):  
Gabriella Piatti ◽  
Laura De Ferrari ◽  
Anna Maria Schito ◽  
Anna Maria Riccio ◽  
Susanna Penco ◽  
...  

Urinary tract infections are often polymicrobial and are mainly due to uropathogenic Escherichia coli (UPEC). We previously demonstrated a link among clinical fluoroquinolone susceptible E. coli reducing in vitro urothelial interleukin-8 (CXCL8) induced by E. coli K-12, polymicrobial cystitis, and pyuria absence. Here, we evaluated whether fifteen clinical fluoroquinolone susceptible UPEC were able to reduce CXCL8 induced by Enterococcus faecalis that had been isolated from the same mixed urines, other than CXCL8 induced by E. coli K-12. We also evaluated the connection between fluoroquinolone susceptibility and pathogenicity by evaluating the immune modulation of isogenic gyrA, a mutant UPEC resistant to ciprofloxacin. Using the 5637 bladder epithelial cell line, we observed that lower CXCL8 induced the most UPEC isolates than K-12 and the corresponding E. faecalis. During coinfections of UPEC/K-12 and UPEC/E. faecalis, we observed lower CXCL8 than during infections caused by K-12 and E. faecalis alone. UPEC strains showed host–pathogen and pathogen–pathogen interaction, which in part explained their persistence in the human urinary tract and coinfections, respectively. Mutant UPEC showed lower modulating activity with respect to the wildtypes, confirming the connection between acquired fluoroquinolone resistance and the decrease of innate microbial properties.


Doctor Ru ◽  
2021 ◽  
Vol 20 (10) ◽  
pp. 48-53
Author(s):  
N.A. Belykh ◽  
◽  
S.V. Tereschenko ◽  
N.A. Anikeeva ◽  
S.S. Kantutis ◽  
...  

Study Objective: To study a spectrum of uropathogens and their sensitivity to antimicrobials in urinary tract infections (UTIs) in children in Ryazan and Ryazan Region. Study Design: retrospective study. Materials and Methods. We conducted a retrospective local laboratory monitoring of urinary microflora and analysed its sensitivity to antimicrobials in 111 patients aged 2 months to 17 years old who were undergoing traditional UI therapy in 2020. The study group comprised 75 (67.6%) girls and 36 (32.4%) boys. Pathogen isolation and type identification were performed using urine specimens collected in sterile disposable plastic containers prior to antimicrobial therapy. Material was delivered for analysis within 2 hours from collection. For testing of pathogen sensitivity to antimicrobials, we used the phenotyping diffusion test and an analytical test for carbapenems inactivation. Study Results. Prevailing causative agents of UIs were Escherichia coli (50.4%) and Klebsiella pneumoniae (14.4%). Resistance determinants were found in 9.0% and 2.7% of Е. соli and K. pneumoniae urological strains, respectively. The main mechanism of resistivity was production of wide spectrum plasmid β-lactamases. The highest activity in E. coli was demonstrated by generation III–IV cephalosporins, aminoglycosides, fosfomicin (100%), nitrofurantoin (91.3%), and aminopenicillins (76.1–86.9%). For K. pneumoniae, generation III–IV cephalosporins and aminoglycosides were most potent (100%). All resistant pathogens were sensitive to cefoperazone sulbactam, meropenem, imipenem, aminoglycosides (100%); tigecycline, nitrofurantoin, and fosfomicin were most potent against E. coli. Conclusion. Children with UIs in Ryazan Region had mostly gram-negative bacteria in their urine (85.6%), Enterobacteralеs (81.1%) being a prevailing type. Antimicrobials resistance determinants were quite rare (17.8%) in these urine isolates; all of them were class A ЕSBL producers. These characteristic features of antibiotic resistance of uropathogenic enterobacteria strains allow using β-lactam antibiotics in empiric initial treatment and emphasising the need in patient-specific selection of antimicrobials. Keywords: antibacterial therapy, antibiotic resistance, children, urinary tract infections, Escherichia coli, Klebsiella pneumoniae.


Author(s):  
Saskia-Camille Flament-Simon ◽  
Marie-Hélène Nicolas-Chanoine ◽  
Vanesa García ◽  
Marion Duprilot ◽  
Noémie Mayer ◽  
...  

Escherichia coli is the main pathogen responsible for extraintestinal infections. A total of 196 clinical E. coli consecutively isolated during 2016 in Spain (100 from Lucus Augusti hospital in Lugo) and France (96 from Beaujon hospital in Clichy) were characterized. Phylogroups, clonotypes, sequence types (STs), O:H serotypes, virulence factor (VF)-encoding genes and antibiotic resistance were determined. Approximately 10% of the infections were caused by ST131 isolates in both hospitals and approximately 60% of these infections were caused by isolates belonging to only 10 STs (ST10, ST12, ST58, ST69, ST73, ST88, ST95, ST127, ST131, ST141). ST88 isolates were frequent especially in Spain while ST141 isolates significantly predominated in France. The 23 ST131 isolates displayed four clonotypes: CH40-30, CH40-41, CH40-22 and CH40-298. Only 13 (6.6%) isolates were carriers of ESBL enzymes. However, 37.2% of the isolates were multidrug-resistant (MDR). Approximately 40% of the MDR isolates belonged to only four of the dominant clones (B2-CH40-30-ST131, B2-CH40-41-ST131, C-CH4-39-ST88 and D-CH35-27-ST69). Among the remaining MDR isolates two isolates belonged to B2-CH14-64-ST1193 i.e the new global emergent MDR clone. To our knowledge, it is the first identification of this emergent clone in Spain. Moreover, a hybrid ExPEC/enteroaggregative isolate belonging to A-CH11-54-ST10 clone was identified.


2020 ◽  
Vol 8 (3) ◽  
pp. 32
Author(s):  
Elie S. Sokhn ◽  
Ali Salami ◽  
Ali El Roz ◽  
Lamis Salloum ◽  
Hisham F. Bahmad ◽  
...  

Background: Urinary tract infections (UTIs) are major healthcare problems that are usually treated empirically. However, antimicrobial resistance has been increasing across many settings. This study aims to elucidate the antibiotic resistance profiles of three common uropathogens, Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Proteus mirabilis (P. mirabilis) and compare between extended spectrum beta-lactamase (ESBL) and non-ESBL strains among Lebanese patients. Methods: This retrospective study was conducted at multiple tertiary healthcare centers in South Lebanon, between January and September 2017, including 551 patients of all age groups. Demographic, clinical, and laboratory data of patients were collected and analyzed statistically. Results: The prevalence of UTI in Lebanon was highest in adults between 19 and 64 years (44%). E. coli was the predominant uropathogenic organism (67.1%) followed by K. pneumoniae (10%) and P. mirabilis (3.7%). ESBL represented 32.9% of the UTI agents. The three common uropathogens studied were found to be most susceptible to imipenem (100%) and meropenem (100%). Interestingly, 115 (25.1%) out of the 458 E. coli isolates were resistant to more than eight antibiotics while 107 (23.4%) were susceptible to all antibiotics studied. Conclusions: Our study underlined the importance of adequate antimicrobial prescription for UTIs in Lebanon to avoid multidrug resistance.


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