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Escherichia coli ST131 is a multidrug-resistant lineage associated with the global spread of extended-spectrum ß-lactamase-producing organisms. Particularly, ST131 clade C1 is the most predominant clade in Japan, harboring blaCTX-M-14 at a high frequency. However, the process of resistance gene acquisition and spread remains unclear. Here, we performed whole-genome sequencing of 19 E. coli strains belonging to 12 STs and 12 fimH types collected between 1997 and 2016. Additionally, we analyzed the full-length genome sequences of 96 ST131-H30 clade C0 and C1 strains, including those obtained from this study and those registered in public databases, to understand how ST131 clade C1 acquired and spread blaCTX-M-14. We detected conjugative IncFII plasmids and IncB/O/K/Z plasmids carrying blaCTX-M-14 in diverse genetic lineages of E. coli strains from the 1990s to the 2010s, suggesting that these plasmids played an important role in the spread of blaCTX-M-14. Molecular phylogenetic and molecular clock analyses of the 96 ST131-H30 clade C0 and C1 strains identified 8 subclades. Strains harboring blaCTX-M-14 were clustered in subclades 4 and 5, and it was inferred that clade C1 acquired blaCTX-M-14 around 1993. All 34 strains belonging to subclade 5 possessed blaCTX-M-14 with ISEcp1 upstream at the same chromosomal position, indicating their common ancestor acquired blaCTX-M-14 in a single ISEcp1-mediated transposition event during the early formation of the subclade around 1999. Therefore, both the horizontal transfer of plasmids carrying blaCTX-M-14 to diverse genetic lineages and chromosomal integration in the predominant genetic lineage have contributed to the spread of blaCTX-M-14.
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Ceftazidime-avibactam and cefiderocol represent two of the few alternatives for infections by KPC-producing Enterobacterales. We reported the emergence of resistance to both ceftazidime-avibactam and cefiderocol in a KPC-producing ST131-Escherichia coli (KPC-ST131-Ec) clinical isolate. Antimicrobial susceptibility testing, Fourier-transform infrared (FTIR) spectroscopy, whole-genome sequencing, and cloning experiments were performed. A KPC-49-Ec isolate resistant to ceftazidime-avibactam (MICCZA > 16/4 mg/L) and susceptible to cefiderocol (MICFDC: 2 mg/L) was recovered in a blood sample from an oncologic patient hospitalized in the medical ICU (June 2019) during ceftazidime-avibactam treatment. After 44 days, a KPC-31-Ec resistant to both ceftazidime-avibactam and cefiderocol (MICCZA > 16/4 mg/L, MICFDC: 8 mg/L) was found in a rectal sample during a second cycle of ceftazidime-avibactam treatment. Both KPC-49 (R163S) and KPC-31 (D179Y) were detected in the epidemic ST131-H30R1-Ec high-risk clone and showed a phenotype resembling that of ESBL producers. FTIR spectroscopy managed to differentiate cefiderocol-susceptible and resistant ST131-Ec isolates, and these from others belonging to different clones. After cloning and transformation experiments, KPC-49 and KPC-31 were responsible for ceftazidime-avibactam resistance (MICCZA > 16/4 mg/L) and decreased carbapenem MICs (MICMER ≤ 0.12 mg/L, MICIMI ≤ 1 mg/L). KPC-31 was also shown to be associated with increased MICs of cefiderocol (twofold and threefold dilutions over KPC-3 and KPC-49, respectively). However, mutations in proteins participating in outer membrane stability and integrity, such as TolR, could have a more relevant role in cefiderocol resistance. The effects of ceftazidime-avibactam and cefiderocol co-resistance in clinical isolates of Enterobacterales producing KPC mutants make their identification challenging for clinical laboratories.IMPORTANCEThroughout four admissions in our hospital of a single patient, different KPC-3 variants (KPC-3, KPC-49, and KPC-31) were found in surveillance and clinical ST131-Escherichia coli isolates, after prolonged therapies with meropenem and ceftazidime-avibactam. Different patterns of resistance to cefiderocol and ceftazidime-avibactam emerged, accompanied by restored carbapenem susceptibility. The inability to detect these variants with some phenotypic methods, especially KPC-31 by immunochromatography, and the expression of a phenotype similar to that of ESBL producers, posed challenge to identify these variants in the clinical microbiology laboratory. Molecular methods and whole-genome sequencing are necessary and new techniques able to cluster or differentiate related isolates could also be helpful; this is the case of Fourier-transform infrared spectroscopy, which managed in our study to discriminate isolates by cefiderocol susceptibility within ST131, and those from the non-ST131 ones.
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Antibacterianos , Compuestos de Azabiciclo , Cefiderocol , Ceftazidima , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Escherichia coli/genética , Escherichia coli/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Carbapenémicos , Pruebas de Sensibilidad Microbiana , Klebsiella pneumoniae/genética , Proteínas Bacterianas/genética , Combinación de MedicamentosRESUMEN
An exceptional gut-colonizing ability may underlie the dramatic epidemiological success of the multidrug-resistant H30R subclone of Escherichia coli sequence type 131 (O25b:K+:H4). In order to inform the development of colonization-preventing measures, we studied systemic immune correlates of H30R intestinal colonization. Human volunteers' fecal samples were screened for H30R by selective culture and PCR. Subjects were assessed by enzyme immunoassay for serum levels of anti-O25 IgG (representing H30R) and anti-O6 IgG (representing non-H30 E. coli generally), initially and for up to 14 months. Whole blood was tested for the antigen-stimulated release of IFNγ, TNFα, IL-4, IL-10, and IL-17 after incubation with E. coli strains JJ1886 (H30R; O25b:K+:H4) or CFT073 (non-H30; O6:K2:H1). Three main findings were obtained. First, H30R-colonized subjects had significantly higher anti-O25 IgG levels than controls, but similar anti-O6 IgG levels, suggesting an IgG response to H30R colonization. Second, anti-O25 and anti-O6 IgG levels were stable over time. Third, H30R-colonized subjects exhibited a lower TNFα and IL-10 release than controls in response to strain JJ1886 (H30R) relative to strain CFT073 (non-H30R), consistent with TNFα hypo-responsiveness to H30R possibly predisposing to H30R colonization. Thus, H30R-colonized hosts exhibit a sustained serum anti-O25 IgG response and an underlying deficit in TNFα responsiveness to H30R that could potentially be addressed for colonization prevention.
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Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (blaCTX-M-15-associated) H30Rx subclone and (blaCTX-M-27-associated) C1-M27 subset within the H30R1 subclone. We assessed cefiderocol, ceftazidime-avibactam, eravacycline, and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012-2017), then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (blaCTX-M; group 1 and 9 variants), and coresistance. Percent susceptible was >95% (cefiderocol, ceftazidime-avibactam, eravacycline, carbapenems, amikacin, piperacillin-tazobactam, tigecycline), 64% to 75% (gentamicin, minocycline), or <40% (ceftazidime, levofloxacin, colistin). MICs varied significantly by multiple bacterial characteristics, in agent-specific patterns. The least-susceptible ST131 subset was the non-C1-M27 fraction within H30R1. Cefiderocol, ceftazidime-avibactam, and eravacycline MICs tended to be higher among isolates resistant (vs. susceptible) to diverse comparators. Thus, cefiderocol, ceftazidime-avibactam, and eravacycline are promising carbapenem-sparing alternatives for treating ESCREC infections, and their strength of activity varies in relation to diverse bacterial characteristics.
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Antibacterianos/farmacología , Compuestos de Azabiciclo/farmacología , Ceftazidima/farmacología , Escherichia coli , Tetraciclinas/farmacología , Adulto , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Escherichia coli/clasificación , Escherichia coli/efectos de los fármacos , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/microbiología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Adulto JovenRESUMEN
We report the emergence of an isolate belonging to the sequence type (ST)131-Escherichia coli high-risk clone with ceftazidime-avibactam resistance recovered from a patient with bacteremia in 2019. Antimicrobial susceptibility was determined and whole genome sequencing (Illumina-NovaSeq6000) and cloning experiments were performed to investigate its resistance phenotype. A KPC-3-producing E. coli isolate susceptible to ceftazidime-avibactam (MIC = 0.5/4 mg/L) and with non-wild type MIC of meropenem (8 mg/L) was detected in a blood culture performed at hospital admission. Following 10-days of standard ceftazidime-avibactam dose treatment, a second KPC-producing E. coli isolate with a phenotype resembling an extended-spectrum ß-lactamase (ESBL) producer (meropenem 0.5 mg/L, piperacillin-tazobactam 16/8 mg/L) but resistant to ceftazidime-avibactam (16/4 mg/L) was recovered. Both E. coli isolates belonged to ST131, serotype O25:H4 and sublineage H30R1. Genomics analysis showed a core genome of 5,203,887 base pair with an evolutionary distance of 6 single nucleotide polymorphisms. A high content of resistance and virulence genes was detected in both isolates. The novel KPC-49 variant, an Arg-163-Ser mutant of bla KPC-3, was detected in the isolate with resistance to ceftazidime-avibactam. Cloning experiments revealed that bla KPC-49 gene increases ceftazidime-avibactam MIC and decreases carbapenem MICs when using a porin deficient Klebsiella pneumoniae strain as a host. Both bla KPC-3 and bla KPC-49 genes were located on the transposon Tn4401a as a part of an IncF [F1:A2:B20] plasmid. The emergence of novel bla KPC genes conferring decreased susceptibility to ceftazidime-avibactam and resembling ESBL production in the epidemic ST131-H30R1-E. coli high-risk clone presents a new challenge in clinical practice.
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BACKGROUND: Although intestinal colonization precedes most extraintestinal Escherichia coli infections, colonization-promoting factors are incompletely understood. We compared within-household E. coli colonization patterns with host and bacterial traits. METHODS: Twenty-two veterans with a clinical E. coli isolate and their 46 human and animal household members underwent longitudinal fecal sampling. Distinct E. coli strains were characterized for phylogenetic background, virulence genes, antibiotic resistance, and colonization behaviors. Host and bacterial traits were assessed statistically as predictors of colonization behaviors. RESULTS: Among the 139 unique-by-household fecal E. coli strains, univariable predictors of colonization behavior included (i) host demographics, (ii) matching the index clinical isolate, and (iii) bacterial characteristics (2 phylogroups, 5 clonal lineages, 18 virulence genes, and molecular extraintestinal pathogenic E. coli status). Multivariable predictors of colonization behavior included veteran host, spouse host, matching the index clinical isolate, phylogroup F, ST73, hlyD (alpha hemolysin), hlyF (variant hemolysin), H7 fliC (flagellar variant), vat (vacuolating toxin), and iha (adhesin-siderophore). CONCLUSIONS: Host demographics, multiple bacterial "virulence" traits, and matching the index clinical isolate predicted E. coli fecal colonization behaviors. Thus, certain bacterial characteristics may promote both colonization and pathogenicity. Future interventions directed toward such traits might prevent E. coli infections both directly and by disrupting antecedent colonization.
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INTRODUCTION: Eradication of asymptomatic bacteriuria (ASB) before urological procedures is important to reduce the risk for infectious complications after surgery. However, the appropriate regimen for antimicrobial treatment has not been fully determined. We experienced continuous (over 10 months) isolation of extended spectrum ß-lactamase (ESBL)-producing fluoroquinolone-resistant Escherichia coli from urine of an asymptomatic patient. The four isolates obtained (SMESC1 to 4) were international high-risk clones of O25b:H4-ST131-H30R, and originated from one strain, as revealed by the whole genome sequences. Although the patient received meropenem (MEPM) and fosfomycin (FOM), to which the strains were susceptible before the urological procedures, they could not be eradicated. METHODS: To explore the reason for the continuous isolation even after MEPM and FOM administration, antimicrobial killing of adherent and/or intracellular bacterial communities (IBC) formed by coculture of the E. coli cells and T24 bladder epithelial cells were examined. RESULTS: FOM and levofloxacin did not decrease viable E. coli cells compared with gentamicin. MEPM partly decreased them, and sitafloxacin (STFX) decreased them most potently. These observations indicate that E. coli can survive in the urinary tract under antimicrobial administration, and some antimicrobials such as FOM and MEPM cannot eradicate E. coli in uroepithelial cells. Adhesion on urinary epithelial cells and/or IBC formation might result in continuous isolation from the urinary tract and recurrence of ASB and urinary tract infections. CONCLUSIONS: The present study suggests that STFX is a promising optional agent for the eradication of ESBL-producing fluoroquinolone-resistant E. coli in the urinary tract before urological procedures.
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Infecciones por Escherichia coli , Infecciones Urinarias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Fluoroquinolonas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Urinarias/tratamiento farmacológico , beta-Lactamasas/genéticaRESUMEN
The H30Rx subclade of Escherichia coli ST131 is a clinically important, globally dispersed pathogenic lineage that typically displays resistance to fluoroquinolones and extended spectrum ß-lactams. Isolates EC233 and EC234, variants of ST131-H30Rx with a novel sequence type (ST) 8196, isolated from unrelated patients presenting with bacteraemia at a Sydney Hospital in 2014 are characterised here. EC233 and EC234 are phylogroup B2, serotype O25:H4A, and resistant to ampicillin, amoxicillin, cefoxitin, ceftazidime, ceftriaxone, ciprofloxacin, norfloxacin and gentamicin and are likely clonal. Both harbour an IncFII_2 plasmid (pSPRC_Ec234-FII) that carries most of the resistance genes on an IS26 associated translocatable unit, two small plasmids and a novel IncI1 plasmid (pSPRC_Ec234-I). SNP-based phylogenetic analysis of the core genome of representatives within the ST131 clonal complex places both isolates in a subclade with three clinical Australian ST131-H30Rx clade-C isolates. A MrBayes phylogeny analysis of EC233 and EC234 indicates ST8196 share a most recent common ancestor with ST131-H30Rx strain EC70 isolated from the same hospital in 2013. Our study identified genomic hallmarks that define the ST131-H30Rx subclade in the ST8196 isolates and highlights a need for unbiased genomic surveillance approaches to identify novel high-risk MDR E. coli pathogens that impact healthcare facilities.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Escherichia coli/epidemiología , Escherichia coli/genética , beta-Lactamasas/genética , Australia/epidemiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Escherichia coli/clasificación , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Fluoroquinolonas/farmacología , Genoma Bacteriano/genética , Humanos , Pruebas de Sensibilidad Microbiana , Filogenia , Plásmidos/genética , beta-Lactamas/farmacologíaRESUMEN
Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extraintestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical E. coli isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002 to 2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003 to 2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamase-encoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82% to 98%) after tigecycline (TGC) (99%); avibactam improved CZA's activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the Klebsiella pneumoniae carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with the beta-lactamase CTX-M for ERV. Percent susceptible also varied by global region for CZA (lower in Asia-Pacific) and by U.S. region for ERV (lower in the South and Southeast). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR E. coli in relation to multiple bacterial characteristics and geographical region.
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Antibacterianos , Escherichia coli , Antibacterianos/farmacología , Asia , Compuestos de Azabiciclo/farmacología , Carbapenémicos/farmacología , Ceftazidima/farmacología , Cefalosporinas , Combinación de Medicamentos , Escherichia coli/genética , Europa (Continente) , América Latina , Pruebas de Sensibilidad Microbiana , Filogenia , Tetraciclinas , Estados Unidos , beta-Lactamasas/genética , CefiderocolRESUMEN
Escherichia coli ST131, with its multidrug-resistance-associated H30R1 and H30Rx clonal subsets within the H30R subclone, causes most antimicrobial-resistant E. coli infections. The activity of ceftazidime-avibactam (CZA) against ST131 strains is undefined. We determined CZA MICs for 595 E. coli clinical isolates from 24 Veterans Affairs Medical Centers (2010-2011). Resistance status and MICs were compared with study resistance category (fluoroquinolone-susceptible, fluoroquinolone-resistant, and extended-spectrum beta-lactamase (ESBL)-producing); ST131, H30R1, and H30Rx status; blaCTX-M-15-like genotype; and MICs for piperacillin-tazobactam, levofloxacin, gentamicin, ceftazidime, and meropenem. Proportion resistant ranged from zero (CZA, meropenem) to 61% (levofloxacin). MICs generally increased by resistance category (from fluoroquinolone-susceptible through fluoroquinolone-resistant to ESBL), clonal subgroup (from non-ST131-H30 through H30R1 to H30Rx), and blaCTX-M-15-like status. CZA MICs were slightly but significantly greater in association with resistance (or elevated MICs) to each comparator yet remained in the susceptible range. CZA was reliably active and outperformed noncarbapenem comparators, so it should prove useful as a carbapenem-sparing alternative.
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Antibacterianos/farmacología , Compuestos de Azabiciclo/farmacología , Ceftazidima/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Veteranos/estadística & datos numéricos , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/genética , Fluoroquinolonas/farmacología , Genotipo , Hospitales de Veteranos , Humanos , Pruebas de Sensibilidad Microbiana , Prevalencia , Estados Unidos/epidemiología , beta-Lactamasas/genética , beta-Lactamas/farmacologíaRESUMEN
BACKGROUND: The pandemic spread of antibiotic resistance increases the likelihood of ineffective empirical therapy. The recently emerged fluoroquinolone-resistant Escherichia coli sequence type (ST) 131-H30R subclone (H30) is a leading cause of multidrug-resistant urinary tract infection (UTI) and bloodstream infection worldwide. METHODS: We studied the relative impact of H30 on the likelihood that bacteria isolated from urine of urgent care patients would be resistant to the empirically prescribed antibiotic regimen for UTI. RESULTS: Of 750 urinalysis-positive urine samples from urgent care patients with suspected UTI, 306 (41%) yielded E. coli, from 35 different clonal groups (clonotypes). H30 predominated (14% prevalence overall), especially among older patients (age ≥70 years: 26%) and those with diabetes (43%) or urinary catheterization (60%). Resistance to the empirically selected antibiotic regimen occurred in 16% (40/246) of patients overall, 28% (20/71) of older patients, 30% (8/27) of patients with diabetes, 60% (3/5) of catheterized patients, and 71% (22/30) of those with H30. H30's contribution to such mismatched antibiotic selection was 55% overall, 70% among older patients, and 100% among patients with diabetes or a urinary catheter. Among patients with ≥2 of these factors (older age, diabetes, or urinary catheter), 24% of all urinalysis-positive urine samples yielded H30, with a 92% likelihood of resistance to the selected empirical therapy. CONCLUSIONS: The multidrug-resistant H30 subclone of E. coli ST131 is responsible for the great majority of mismatched empirical antibiotic prescriptions for suspected UTI at an urgent care clinic among patients ≥70 years old or with diabetes or urinary catheterization.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Escherichia coli/microbiología , Infecciones Urinarias/microbiología , Escherichia coli Uropatógena/efectos de los fármacos , Anciano , Antibacterianos/administración & dosificación , Prescripciones de Medicamentos , Femenino , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Prevalencia , Estudios RetrospectivosRESUMEN
In recent years, besides the widespread occurrence of extended-spectrum ß-lactamase (ESBL)- and/or plasmid-mediated AmpC (pAmpC)-producing Enterobacteriaceae in both healthcare and community settings of humans, the third-generation cephalosporin (3GC)-resistant microbes have also been reported from companion animals worldwide. Here, we characterized ESBL- and/or pAmpC-producing Enterobacteriaceae clinical isolates from companion animals. Among the 487 clinical isolates mainly from urine of dogs and cats between May and September 2016, 104 non-repetitive isolates were resistant to the 3GC, and they consisted of 81 of 381 (21.3%) Escherichia coli, 21 of 50 (42.0%) Klebsiella pneumoniae, and 2 of 56 (3.6%) Proteus mirabilis isolates. In the 81 E. coli, the predominant bla genes were blaCTX-M-27 and blaCMY-2 (nâ¯=â¯15 each), followed by blaCTX-M-15 (nâ¯=â¯14), blaCTX-M-14 (nâ¯=â¯10), and blaCTX-M-55 (nâ¯=â¯5). In 21 K. pneumoniae, 10 bla gene types including blaCTX-M-15 (nâ¯=â¯4), blaCTX-M-2 (nâ¯=â¯4), and blaCTX-M-14 (nâ¯=â¯3) were found. The blaCTX-M-2 was identified in 2 P. mirabilis. Twenty-four of the 42 E. coli belonging to phylogroup B2 were O25b-ST131 clone, mostly associated with uropathogenic E. coli pathotype, and 22 isolates of this clone were identified as specific H30R subclone. High prevalence of the blaCTX-M-27-harboring isolates were noted among the H30R/non-Rx lineage (13/19, 68.4%) (pâ¯< â¯0.05). The genetic environment of blaCTX-M-27 of most isolates of this lineage was identical to that of human isolates, but unique flanking genetic structures were also identified. Newly emerging virulent lineage B2-non-O25b-ST1193 was also confirmed in 5 isolates. The fosA3 and/or armA genes were detected in E. coli and K. pneumoniae isolates. These data suggest that companion animals serve as a potential reservoir of antimicrobial resistant E. coli and K. pneumoniae. This also has considerable veterinary importance, since urinary tract infections are an important disease causing therapeutic challenges worldwide.
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Antibacterianos/farmacología , Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana Múltiple , Infecciones por Enterobacteriaceae/veterinaria , Enterobacteriaceae/genética , beta-Lactamasas/genética , Animales , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/microbiología , Gatos , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/microbiología , Perros , Enterobacteriaceae/efectos de los fármacos , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Escherichia coli/genética , Japón/epidemiología , Klebsiella pneumoniae/genética , Pruebas de Sensibilidad Microbiana , Mascotas/microbiología , Prevalencia , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiologíaRESUMEN
Antimicrobial-resistant Escherichia coli are a concern for military health services. We studied 100 extended-spectrum beta-lactamase (ESBL)-producing and non-producing E. coli clinical and surveillance isolates from military personnel and civilians at Brooke Army Medical Center (2007-2011). Major E. coli lineages, most prominently ST10 (24%), ST131 (16%), and ST648 (8%), were distributed much as reported for other North American populations. ST131, represented mainly by its resistance-associated ST131-H30 clonal subset, was uniquely associated with a clinical origin, regardless of ESBL status. Thus, clonal background predicted resistance phenotype and clinical versus surveillance origin, and these findings could assist military clinicians and epidemiologists.
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Infecciones por Escherichia coli/microbiología , Escherichia coli/aislamiento & purificación , Antibacterianos/uso terapéutico , Farmacorresistencia Microbiana/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Infecciones por Escherichia coli/tratamiento farmacológico , Hospitales Militares , Humanos , Personal Militar , Epidemiología Molecular/métodos , Tipificación de Secuencias Multilocus/métodos , beta-Lactamasas/genéticaRESUMEN
The H30 strain of Escherichia coli sequence type 131 (ST131-H30) is a recently emerged, globally disseminated lineage associated with fluoroquinolone resistance and, via its H30Rx subclone, the CTX-M-15 extended-spectrum beta-lactamase (ESBL). Here, we studied the clonal background and resistance characteristics of 109 consecutive recent E. coli clinical isolates (2015) and 41 historical ESBL-producing E. coli blood isolates (2004 to 2011) from a public tertiary care center in California with a rising prevalence of ESBL-producing E. coli isolates. Among the 2015 isolates, ST131, which was represented mainly by ST131-H30, was the most common clonal lineage (23% overall). ST131-H30 accounted for 47% (8/17) of ESBL-producing, 47% (14/30) of fluoroquinolone-resistant, and 33% (11/33) of multidrug-resistant isolates. ST131-H30 also accounted for 53% (8/14) of dually fluoroquinolone-resistant, ESBL-producing isolates, with the remaining 47% comprised of diverse clonal groups that contributed a single isolate each. ST131-H30Rx, with CTX-M-15, was the major ESBL producer (6/8) among ST131-H30 isolates. ST131-H30 and H30Rx also dominated (46% and 37%, respectively) among the historical ESBL-producing isolates (2004 to 2011), without significant temporal shifts in relative prevalence. Thus, this medical center's recently emerging ESBL-producing E. coli strains, although multiclonal, are dominated by ST131-H30 and H30Rx, which are the only clonally expanded fluoroquinolone-resistant, ESBL-producing lineages. Measures to rapidly and effectively detect, treat, and control these highly successful lineages are needed. IMPORTANCE The ever-rising prevalence of resistance to first-line antibiotics among clinical Escherichia coli isolates leads to worse clinical outcomes and higher health care costs, thereby creating a need to discover its basis so that effective interventions can be developed. We found that the H30 subset within E. coli sequence type 131 (ST131-H30) is currently, and has been since at least 2004, the main E. coli lineage contributing to key resistance phenotypes-including extended-spectrum-beta-lactamase (ESBL) production, fluoroquinolone resistance, multidrug resistance, and dual ESBL production-plus-fluoroquinolone resistance-at a United States tertiary care center with a rising prevalence of ESBL-producing E. coli isolates. This identifies ST131-H30 as a target for diagnostic tests and preventive measures designed to curb the emergence of multidrug-resistant E. coli isolates and/or to blunt its clinical impact.
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BACKGROUND: The reservoir of pathogenic ciprofloxacin-resistant Escherichia coli remains unknown. METHODS: We conducted a prospective cohort study of 80 healthy twins and their mothers to determine the frequency of excretion of ciprofloxacin-resistant, potentially pathogenic E. coli. Stool specimens were cultured selectively for ciprofloxacin-resistant gram-negative bacteria. Isolates were categorized on the basis of additional resistance and virulence profiles. We also prospectively collected clinical metadata. RESULTS: Fifteen children (19%) and 8 mothers (20%) excreted ciprofloxacin-resistant E. coli at least once. Overall, 33% of 40 families had at least 1 member whose stool specimen yielded ciprofloxacin-resistant E. coli on culture. Fifty-seven submitted stool specimens (2.8%) contained such organisms; clones ST131-H30 and ST405 accounted for 52 and 5 of the positive specimens, respectively. Length of hospital stay after birth (P = .002) and maternal colonization (P = .0001) were associated with subsequent childhood carriage of ciprofloxacin-resistant E. coli; antibiotic use, acid suppression, sex, mode of delivery, and maternal perinatal antibiotic use were not. Ciprofloxacin-resistant E. coli were usually resistant to additional antibiotic classes, and all had virulence genotypes typical of extraintestinal pathogenic E. coli. CONCLUSIONS: Healthy children and their mothers commonly harbor ciprofloxacin-resistant E. coli with pathogenic potential.