Prevalence of common carbapenemase genes and multidrug resistance among uropathogenic Escherichia coli phylogroup B2 isolates from outpatients in Wasit Province/ Iraq.

Carbapenems are the last resort antimicrobials for the treatment of extended spectrum ß-lactamases (ESBLs) producing Enterobacteriaceae. Emergence of carbapenems resistant group B2 uropathogenic E. coli (UPEC) is a major concern because of their high virulence. Prevalence of these enzymes and multidrug resistance (MDR) among B2 UPEC isolates from Iraqi outpatients with acute urinary tract infection (UTI) was evaluated in this research. Urine cultures were performed and the isolates were identified biochemically. Escherichia coli isolates were tested for phylogroup reference by quadraplex PCR, then B2 isolates were detected for antimicrobial resistance by disc diffusion test and carbapenemase genes by PCR. Escherichia coli was the most prevalent among Gram-negative isolates (66.6%) and B2 was the most detected phylogroup among E. coli isolates (33.9%). Most of B2 isolates showed high resistance rates to tested antimicrobials, especially ß-lactams with MDR revealed in 100% of them. Whereas, low resistance rates were noted against carbapenems, aminoglycosides and nitrofurantoin. Carbapenemase genes were detected in 76.3% of B2 isolates. Of which, blaOXA-48 was the most frequent (57.8%), followed by blaPER (47.3%), blaKPC (15.7%), blaVEB and blaVIM (10.5%, for each). Whereas, blaGES and blaIMP genes were not found. Coproduction of these genes occurred among 17 isolates. The combination of blaOXA-48 and blaPER was the most frequent (41.1%). All carbapenemase producing isolates were MDR. These results revealed high prevalence of carbapenemase genes and MDR among B2 UPEC recovered in this study. In the study area. it is strongly advised to use aminoglycosides and nitrofurantoin for empirical treatment of UPEC.

Prevalence and patient related factors associated with Extended-Spectrum Beta-Lactamase producing Escherichia coli and Klebsiella pneumoniae carriage and infection among pediatric patients in Tanzania.

Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (EPE) is increasing worldwide, though less documented in low-income settings. Here we determined the prevalence of EPE infection and carriage, and patient factors associated with EPE-carriage among pediatric patients in three health care levels in Tanzania. Between January and April 2016, 350 febrile children (median age 21 months) seeking care at a university or a regional referral hospital, or a health centre in Moshi municipality, Tanzania, were included. Socio-demographic characteristics were collected using a questionnaire. Rectal swabs and blood cultures were collected from all children (n = 350) and urinary samples from 259 children at admission. ESBL-phenotype and antimicrobial susceptibility were determined for Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) isolates. Only one EPE case (E. coli) in blood and four in urine (one E. coli and three K. pneumoniae) were found, whereas (n = 90, 26%) of the children were colonized in feces (ESBL-E. coli; n = 76, ESBL-K. pneumoniae, n = 14). High resistance rates were seen in fecal ESBL-E. coli (n = 76) against trimethoprim-sulfamethoxazole (n = 69, 91%), gentamicin (n = 51, 67%), ciprofloxacin (n = 39, 51%) and chloramphenicol (n = 27, 35%) whereas most isolates were sensitive to amikacin (n = 71, 93%). Similar rates were seen for fecal ESBL-K. pneumoniae. Resistance to first line antibiotics were also very high in fecal E. coli not producing ESBL. No sociodemographic factor was associated with EPE-carriage. Children colonized with EPE were younger than 12 months (n = 43, 48%) and often treated with antibiotics (n = 40, 44%) in the previous two months. After adjustment for age children admitted to the intensive care unit had higher odds of EPE fecal carriage compared with those in the general wards (OR = 3.9, 95%CI = 1.4-10.4). Despite comparatively high rates of fecal EPE-carriage and previous antibiotic treatment, clinical EPE cases were rare in the febrile children. The very high resistant rates for the EPE and the non-ESBL producing E. coli to commonly used antibiotics are worrying and demand implementation of antibiotic stewardship programs in all levels of health care in Tanzania.

Epidemiology, Risk Factors, and Clinical Outcomes of Bloodstream Infection due to Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Hematologic Malignancy: A Retrospective Study from Central South China.

Objective: To determine the epidemiology, risk factors, and prognosis of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections (BSIs) among hematology malignancy (HM) patients in China. Method: From January 2010 to June 2018, we retrospectively collected and analyzed the 449 HM patients with E. coli or K. pneumoniae BSIs from three leading hospitals in Hunan Province, China. Results: Two hundred four (45.4%) patients harbored ESBL-producing bacteremia. The proportion of ESBL-producing bacteremia increased significantly with the growth of the year, with a ratio of 34.47% in 2010-2014 to 54.7% in 2015-2018. Comparing with non-ESBL groups in HM patients, central venous catheter (odds ratio [OR] 1.717, p = 0.009), previous antibiotic exposure (OR 1.559, p = 0.035), and E. coli (OR 2.561, p ≤ 0.001) among ESBL groups were independent risk factors. No significant differences in 30-day mortality were tested in patients with BSI caused by ESBL-producing or non-ESBL-producing E. coli and K. pneumoniae (17.1% vs. 16.7%; p = 0. 893). The proportion of carbapenem used within 72 hours after the onset of bacteremia in two groups was high, which was routinely used as "last-resort drugs" in Gram-negative bacterial infections. Risk factors associated with 30-day mortality in HM patients with E. coli or K. pneumoniae bacteremia were myelodysplastic syndrome, incomplete remission of the disease, Multinational Association of Supportive Care in Cancer score <21, Pitt bacteremia score ≥4, Charlson comorbidity score >3, catheter insertion, use of vasopressors, and inappropriate antibiotics within 72 hours of BSI onset. Conclusions: The results of this study may provide some references for the whole process management of HM patients with BSIs.

Ribonucleotide Reductases: Structure, Chemistry, and Metabolism Suggest New Therapeutic Targets.

Ribonucleotide reductases (RNRs) catalyze the de novo conversion of nucleotides to deoxynucleotides in all organisms, controlling their relative ratios and abundance. In doing so, they play an important role in fidelity of DNA replication and repair. RNRs' central role in nucleic acid metabolism has resulted in five therapeutics that inhibit human RNRs. In this review, we discuss the structural, dynamic, and mechanistic aspects of RNR activity and regulation, primarily for the human and Escherichia coli class Ia enzymes. The unusual radical-based organic chemistry of nucleotide reduction, the inorganic chemistry of the essential metallo-cofactor biosynthesis/maintenance, the transport of a radical over a long distance, and the dynamics of subunit interactions all present distinct entry points toward RNR inhibition that are relevant for drug discovery. We describe the current mechanistic understanding of small molecules that target different elements of RNR function, including downstream pathways that lead to cell cytotoxicity. We conclude by summarizing novel and emergent RNR targeting motifs for cancer and antibiotic therapeutics.

Developmental loss, but not pharmacological suppression, of renal carbonic anhydrase 2 results in pyelonephritis susceptibility.

Carbonic anhydrase II knockout (Car2-/-) mice have depleted numbers of renal intercalated cells, which are increasingly recognized to be innate immune effectors. We compared pyelonephritis susceptibility following reciprocal renal transplantations between Car2-/- and wild-type mice. We examined the effect of pharmacological CA suppression using acetazolamide in an experimental murine model of urinary tract infection. Car2-/- versus wild-type mice were compared for differences in renal innate immunity. In our transplant scheme, mice lacking CA-II in the kidney had increased pyelonephritis risk. Mice treated with acetazolamide had lower kidney bacterial burdens at 6 h postinfection, which appeared to be due to tubular flow from diuresis because comparable results were obtained when furosemide was substituted for acetazolamide. Isolated Car2-/- kidney cells enriched for intercalated cells demonstrated altered intercalated cell innate immune gene expression, notably increased calgizzarin and insulin receptor expression. Intercalated cell number and function along with renal tubular flow are determinants of pyelonephritis risk.

Effect of challenge dose of plasmid-mediated extended-spectrum ß-lactamase and AmpC ß-lactamase producing Escherichia coli on time-until-colonization and level of excretion in young broilers.

Plasmid-mediated extended-spectrum ß-lactamase and AmpC ß-lactamase (ESBL/pAmpC) producing bacteria are present at all levels of the broiler production pyramid. Young birds can be found positive for ESBL/pAmpC-producing Escherichia coli shortly after arrival at farm. The aim of this study was to determine the effect of different challenge doses of ESBL/pAmpC-producing E. coli on time-until-colonization and the level of excretion in young broilers. One-day-old broilers (specific-pathogen free (SPF) and conventional Ross 308) were housed in isolators and challenged with 0.5 ml ESBL/pAmpC-producing E. coli strains of varying doses (101-105 CFU/ml). Presence and concentration (CFU/gram feces) of ESBL/pAmpC-producing E. coli and total E. coli were determined longitudinally from cloacal swabs, and in cecal content 72 h after challenge. Higher challenge doses resulted in shorter time-until-colonization. However, even the lowest dose (101 CFU/ml) resulted in colonization of the broilers which excreted >106 CFU/gram feces 72 h after inoculation. Conventional broilers were colonized later than SPF broilers, although within 72 h after challenge all broilers were excreting ESBL/pAmpC-producing E. coli. A probabilistic model was used to estimate the probability of colonization by initial inoculation or transmission. The higher the dose the higher the probability of excreting ESBL/pAmpC-producing E. coli as a result of inoculation. In conclusion, low initial doses of ESBL/pAmpC-producing E. coli can result in rapid colonization of a flock. Interventions should thus be aimed to eliminate ESBL/pAmpC-producing bacteria in the environment of the hatchlings and measures focusing at reducing colonization and transmission of ESBL/pAmpC-producing E. coli should be applied shortly after hatching.

Ribonuclease 7 Shields the Kidney and Bladder from Invasive Uropathogenic Escherichia coli Infection.

BACKGROUND: Evidence suggests that antimicrobial peptides, components of the innate immune response, protect the kidneys and bladder from bacterial challenge. We previously identified ribonuclease 7 (RNase 7) as a human antimicrobial peptide that has bactericidal activity against uropathogenic Escherichia coli (UPEC). Functional studies assessing RNase 7's contributions to urinary tract defense are limited. METHODS: To investigate RNase 7's role in preventing urinary tract infection (UTI), we quantified urinary RNase 7 concentrations in 29 girls and adolescents with a UTI history and 29 healthy female human controls. To assess RNase 7's antimicrobial activity in vitro in human urothelial cells, we used siRNA to silence urothelial RNase 7 production and retroviral constructs to stably overexpress RNase 7; we then evaluated UPEC's ability to bind and invade these cells. For RNase 7 in vivo studies, we developed humanized RNase 7 transgenic mice, subjected them to experimental UTI, and enumerated UPEC burden in the urine, bladder, and kidneys. RESULTS: Compared with controls, study participants with a UTI history had 1.5-fold lower urinary RNase 7 concentrations. When RNase 7 was silenced in vitro, the percentage of UPEC binding or invading human urothelial cells increased; when cells overexpressed RNase 7, UPEC attachment and invasion decreased. In the transgenic mice, we detected RNase 7 expression in the kidney's intercalated cells and bladder urothelium. RNase 7 humanized mice exhibited marked protection from UPEC. CONCLUSIONS: These findings provide evidence that RNase 7 has a role in kidney and bladder host defense against UPEC and establish a foundation for investigating RNase 7 as a UTI prognostic marker or nonantibiotic-based therapy.

Emergence of New Delhi Metallo-Beta-Lactamase (NDM) and Klebsiella pneumoniae Carbapenemase (KPC) Production by Escherichia coli and Klebsiella pneumoniae in Southern Vietnam and Appropriate Methods of Detection: A Cross-Sectional Study.

Carbapenemase-producing Enterobacteriaceae (CPE) are well known to cause many serious infections resulting in increasing mortality rate, treatment cost, and prolonged hospitalization. Among the widely recognized types of carbapenemases, New Delhi ß-lactamase (NDM) and Klebsiella pneumoniae carbapenemase (KPC) are the most important enzymes. However, in Vietnam, there are only scattered reports of CPE due to the lack of simple and affordable methods that are suitable to laboratory conditions. This study aims to survey the characteristics of carbapenem-resistant E. coli and K. pneumoniae (CR-E/K) at two hospitals in Southern Vietnam and perform some simple methods to detect the two enzymes. A total of 100 CR-E/K strains were collected from clinical isolates of Gia Dinh People's Hospital and Dong Nai General Hospital, Vietnam, from November 2017 to May 2018. The patient-related information was also included in the analysis. We conducted real-time polymerase chain reaction (PCR), Modified Hodge Test (MHT), and combined disk test (CDT) on all isolates. Carbapenemase-encoding genes were detected in 47 isolates (36 NDM, 10 KPC, and one isolate harboring both genes). The E. coli strain carrying simultaneously these two genes was the first case reported here. Most of isolates were collected from patients in ICU, Infectious Disease Department, and Department of Urologic Surgery. Urine and sputum were two common specimens. The true positive rate (sensitivity, TPR) and specificity (SPC) of the imipenem-EDTA (ethylen diamine tetra acetic acid) for NDM detection and the imipenem-PBA (phenylboronic acid) for KPC detection on E. coli were 93.8%, 97.1% and 66.7%, 95.7%, respectively. Meanwhile, the imipenem-EDTA for NDM detection and the imipenem-PBA for KPC detection among K. pneumonia achieved 90.5%, 100% and 100%, 92.9% TPR and SPC, respectively. However, MHT showed low sensitivity and specificity. Our findings showed that CP-E/K were detected with high prevalence in the two hospitals. We suggest that CDT can be used as a low-priced and accurate method of detection.

Repeated Isolation of Extended-Spectrum-ß-Lactamase-Positive Escherichia coli Sequence Types 648 and 131 from Community Wastewater Indicates that Sewage Systems Are Important Sources of Emerging Clones of Antibiotic-Resistant Bacteria.

Antibiotic resistance in bacteria is an emerging problem globally. Resistant bacteria are found in human and animal microbiota, as well as in the environment. Wastewater receives bacteria from all these sources and thus can provide a measurement of abundance and diversity of antibiotic-resistant bacteria circulating in communities. In this study, water samples were collected from a wastewater pump station in a Norwegian suburban community over a period of 15 months. A total of 45 daily samples were cultured and analyzed for the presence of Escherichia coli Eighty E. coli-like colonies were collected from each daily sample and then phenotyped and analyzed for antibiotic resistance using the PhenePlate-AREB system. During the sampling period, two unique E. coli phenotypes with resistance to cefotaxime and cefpodoxime indicating carriage of extended-spectrum ß-lactamases (ESBL) were observed repeatedly. Whole-genome sequencing of 15 representative isolates from the two phenotypes identified these as two distinct clones belonging to the two globally spread E. coli multilocus sequence types (STs) ST131 and ST648 and carrying blaCTX-M-15 The number of ESBL-positive E. coli strains in the community wastewater pump station was 314 of 3,123 (10%) analyzed E. coli strains. Of the ESBL-positive isolates, 37% belonged to ST648, and 7% belonged to ST131. Repeated findings of CTX-M-15-positive ST648 and ST131 over time indicate that these STs are resident in the analyzed wastewater systems and/or circulate abundantly in the community.

Phenotypic and Genotypic Characterization of ESBL-, AmpC-, and Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli Isolates.

OBJECTIVES: Drug resistance among gram-negative bacteria is a worldwide challenge. Due to the importance of drug-resistant Klebsiella pneumoniae and Escherichia coli strains in hospital-acquired infections, we aimed to determine the phenotypic and genotypic characteristics of ESBL-, AmpC-, and carbapenemase-producing isolates obtained from hospitalized patients in Tehran and Ilam (Iran). MATERIALS AND METHODS: In total, 90 K. pneumoniae isolates and 65 E. coli isolates were collected from various infections. Phenotypic identification of bacterial isolates was performed using standard methods. Phenotypic screening of ESBL, AmpC, and carbapenemase enzymes was carried out. Detection of ESBL, AmpC, and carbapenemase genes was also performed by the PCR method. RESULTS: Phenotypic detection tests showed that 36 (40%) K. pneumoniae and 23 (35.4%) E. coli isolates were ESBL producers. Moreover, 18 (20%) and 6 (9.2%) K. pneumoniae and E. coli isolates were AmpC producers, respectively. Modified Hodge test results indicated that 39 (43.3%) K. pneumoniae and 18 (27.7%) E. coli isolates produced carbapenemase. Molecular tests showed that 40% of K. pneumoniae and 36.9% of E. coli isolates were ESBL positive. AmpC was detected in 24.4 and 13.8% of K. pneumoniae and E. coli isolates. Carbapenemase was detected in 34 (37.8%) K. pneumoniae and 13 (20%) E. coli isolates. -Conclusion: In this study, 3 K. pneumoniae isolates simultaneously carried ESBL, AmpC, and carbapenemase genes. Up-to-date strategies such as combination therapy or utilization of new antimicrobial agents might help to combat such drug-resistant organisms.

Transcriptome analysis of beta-lactamase genes in diarrheagenic Escherichia coli.

Beta (ß)-lactamases are the most important agents that confer drug resistance among gram-negative bacteria. Continuous mutations in ß-lactamases make them remarkably diverse. We carried out the transcriptome analysis of 10 ß-lactamase genes of Extended-Spectrum ß-lactamases (ESBL), Metallo ß-lactamases (MBL), and AmpC ß-lactamases (ABL) in drug-resistant and sensitive diarrheagenic E. coli (DEC) isolates obtained from children up to 5 years of age. Out of the 10 ß-lactamase genes, four belonged to ESBL (TEM, SHV, CTX, and OXA); three to MBL (NDM-1, IMP, and VIM); and three to ABL (ACT, DHA and CMY) class of genes. The different categories of DEC were estimated for ß-lactamases production using a set of conventional phenotypic tests, followed by detection of their messenger RNA (mRNA) expression. The study revealed a direct correlation between mRNA expression of these genes and the presence of antibiotic resistance; also corroborated by mutation analysis of the AmpC promoter region. All the 10 ß-lactamase genes showed a significant increase in their expression levels in resistant isolates, compared to those of the sensitive isolates, indicating their possible role in the disease pathogenesis. Increase in mRNA expression of ß-lactamase genes, and thereby virulence, may be due to multifactorial parameters causing phenotypic as well as genotypic changes. Our study highlights the necessity of instantaneous detection of ß-lactamase gene expression to curb the overwhelming threat posed by emergence of drug resistance amongst the commensal E. coli strains in children from developing countries for larger public health interest.

Novel blaCTX-M variants and genotype-phenotype correlations among clinical isolates of extended spectrum beta lactamase-producing Escherichia coli.

The rapid emergence of multiresistant microbial pathogens, dubbed superbugs, is a serious threat to human health. Extended spectrum beta lactamase (ESBL)-producing Escherichia coli is a superbug causing worldwide outbreaks, necessitating timely and accurate tracking of resistant strains. Accordingly, this study was designed to investigate the spread of ESBL-producing Escherichia coli isolates, to analyze the effect of different genotypic and phenotypic factors on in vitro resistance patterns, and to assess the diagnostic value of commonly used ESBL genetic markers. For that purpose, we cultured 250 clinical isolates and screened their susceptibility to beta-lactam antibiotics. Among 12 antibiotics screened, only imipenem seems to have remained resilient. We subsequently analyzed the ESBL phenotype of Escherichia coli isolates and examined potential associations between their resistance phenotypes and patient-related factors. ESBL genotyping of 198 multiresistant isolates indicated that 179 contained at least one blaCTX-M gene. As we statistically dissected the data, we found associations between overall resistance and body site / type of disease. Additionally, we confirmed the diagnostic value of testing both blaCTX-M-1 and blaCTX-M-15 in providing better prediction of overall resistance. Finally, on sequencing the amplification products of detected blaCTX-M genes, we discovered two novel variants, which we named blaCTX-M-14.2 and blaCTX-M-15.2.

The Relative Impact of Community and Hospital Antibiotic Use on the Selection of Extended-spectrum Beta-lactamase-producing Escherichia coli.

Antibiotic stewardship programs have traditionally focused on reducing hospital antibiotic use. However, reducing community antibiotic prescribing could have substantial impacts in both hospital and community settings. We developed a deterministic model of transmission of extended-spectrum beta-lactamase-producing Escherichia coli in both the community and hospitals. We fit the model to existing, national-level antibiotic use and resistance prevalence data from Sweden. Across a range of conditions, a given relative change in antibiotic use in the community had a greater impact on resistance prevalence in both the community and hospitals than an equivalent relative change in hospital use. However, on a per prescription basis, changes in antibiotic use in hospitals had the greatest impact. The magnitude of changes in prevalence were modest, even with large changes in antimicrobial use. These data support the expansion of stewardship programs/interventions beyond the walls of hospitals, but also suggest that such efforts would benefit hospitals themselves.

[Evaluation of susceptibility and response to therapy with piperacillin-tazobactam in patients with infections caused by Escherichia coli with extended-spectrum ß-lactamase (ESBL) CTX-M]. / Evaluación de susceptibilidad y respuesta al tratamiento con piperacilina/tazobactam en pacientes con infecciones por Escherichia coli productoras de ß-lactamasas de espectro extendido (BLEE) CTX-M.

BACKGROUND: Carbapenems are the preferred ß-lactamics for treatment for infections caused by enterobacteria producing extended-spectrum ß-lactamases (ESBL); however, clinical studies show effectiveness of piperacillin/tazobactam in certain infections by Escherichia coli ESBL producers. AIM: To determine the clinical and micro-biological cure with piperacillin/tazobactam in patients with infections caused by E. coli ESBL producers, CTXM type. METHODS: Retrospective descriptive study with adults hospitalized in a university hospital. We included urinary tract infections (UTI), intra-abdominal infections (IAI), soft tissue infections (STI) and/or bacteremia. RESULTS: We studied 40 patients, where 65% corresponded to UTI, 25% to IAI and 10% were STI. The overall clinical cure was achieved in 89.4%, with the best results in the ITU (100%), followed by STI (80%) and 70% in IAI. The 85% of the strains had minimum inhibitory concentrations (MIC) ≤8 µg/ml and 70% with MIC ≤4 µg/mL, however the rate of failure were high in intra-abdominal infections with high inocula or not controlled; CTX-M-15 was found in the 62.5%. CONCLUSIONS: Piperacillin/tazobactam was efficient to obtain clinical and microbiological cure in patients with infections caused by ESBL producers but susceptible E. coli, especially in UTI and STI and to a lesser extent in IAI.

Accelerated Aging and Clearance of Host Anti-inflammatory Enzymes by Discrete Pathogens Fuels Sepsis.

Sepsis is a life-threatening inflammatory syndrome accompanying a bloodstream infection. Frequently secondary to pathogenic bacterial infections, sepsis remains difficult to treat as a singular disease mechanism. We compared the pathogenesis of murine sepsis experimentally elicited by five bacterial pathogens and report similarities among host responses to Gram-negative Salmonella and E. coli. We observed that a host protective mechanism involving de-toxification of lipopolysaccharide by circulating alkaline phosphatase (AP) isozymes was incapacitated during sepsis caused by Salmonella or E. coli through activation of host Toll-like receptor 4, which triggered Neu1 and Neu3 neuraminidase induction. Elevated neuraminidase activity accelerated the molecular aging and clearance of AP isozymes, thereby intensifying disease. Mice deficient in the sialyltransferase ST3Gal6 displayed increased disease severity, while deficiency of the endocytic lectin hepatic Ashwell-Morell receptor was protective. AP augmentation or neuraminidase inhibition diminished inflammation and promoted host survival. This study illuminates distinct routes of sepsis pathogenesis, which may inform therapeutic development.

Extended-spectrum ß-lactamase-producing E. coli septicemia among rectal carriers in the ICU.

The aim of this study was to identify risk factors for extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E coli) bloodstream infection (BSI) among carriers hospitalized between March 2011 and June 2016 at the ICU of the West China Hospital.The cases were patients with at least 1 episode of ESBL-producing E coli BSI within 1 week after a positive rectal swab. Controls were selected randomly 1:2 among ESBL-producing E coli rectal carriers who did not develop BSI.Among 19,429 ICU patients, 9015 (46.4%) had a positive rectal swab for ESBL-producing E coli. Of them, 42 (0.5%) were diagnosed with ESBL-producing E coli BSI. The in-hospital mortality was higher for the BSI patients compared with controls (19.1% vs. 6.0%, P = .031). In the past 72 hours, patients in case group were more likely to use penicillin (odds ratio [OR] = 12.076; 95% confidence interval [CI]: 1.397-104.251, P = .02), cephalosporin (OR = 6.900; 95% CI: 1.493-31.852, P = .01), and carbapenem (OR = 5.422; 95% CI: 1.228-23.907, P = .03) as compared to patients in control group. Also, when compared to patients in control group, patients in case group were likely to stay for a longer time in ICU before positive rectal swab test (OR = 1.041, 95% CI: 1.009-1.075, P = .01) and have higher maximum body temperature before positive rectal swab (OR = 8.014; 95% CI: 2.408-26.620, P = .001).Bacteremia owing to ESBL-producing E coli was associated with high antimicrobial exposure, hospital stay, and maximum body temperature.

Evaluación de susceptibilidad y respuesta al tratamiento con piperacilina/tazobactam en pacientes con infecciones por Escherichia coli productoras de β -lactamasas de espectro extendido (BLEE) CTX-M / Evaluation of susceptibility and response to therapy with piperacillin-tazobactam in patients with infections caused by Escherichia coli with extended-spectrum β -lactamase (ESBL) CTX-M

Resumen Introducción: En las infecciones por enterobacterias productoras de β-lactamasas de espectro extendido (BLEE), los β-lactámicos preferidos para tratamiento son los carbapenémicos. Sin embargo, estudios clínicos muestran eficacia de piperacilina/tazobactam en ciertas infecciones por Escherichia coli productoras de BLEE. Objetivo: Determinar la cura clínica y microbiológica con piperacilina/tazobactam en pacientes con infecciones por E. coli productoras de BLEE, tipo CTX-M. Materiales/Métodos: Estudio descriptivo, retrospectivo, con adultos internados en un hospital universitario. Incluimos infecciones del tracto urinario (ITU), intra-abdominales (IIA) e infecciones de tejidos blandos (ITB). Resultados: Estudiamos 40 pacientes, donde 65% correspondían a ITU, 25% IIA y 10 % ITB. La cura clínica global se logró en 89,4%, con mejores resultados en las ITU (100%), seguidas de ITB (80%) e IIA (70%). El 85% de las cepas tenía concentraciones inhibitorias mínimas (CIM) ≤ 8 μg/mL y 70% con CIM ≤ 4 μg/mL. La tasa de fracaso fue mayor en las infecciones con inóculos altos intraabdominales. La BLEE del tipo CTX-M-15 se encontró en 62,5%. Conclusiones: Piperacilina/tazobactam logró cura clínica y microbiológica, en pacientes con infecciones por E. coli productoras de BLEE susceptibles, especialmente en ITU e IPB y en menor medida en IIA.

Background: Carbapenems are the preferred β-lactamics for treatment for infections caused by enterobacteria producing extended-spectrum β-lactamases (ESBL); however, clinical studies show effectiveness of piperacillin/tazobactam in certain infections by Escherichia coli ESBL producers. Aim: To determine the clinical and micro-biological cure with piperacillin/tazobactam in patients with infections caused by E. coli ESBL producers, CTXM type. Methods: Retrospective descriptive study with adults hospitalized in a university hospital. We included urinary tract infections (UTI), intra-abdominal infections (IAI), soft tissue infections (STI) and/or bacteremia. Results: We studied 40 patients, where 65% corresponded to UTI, 25% to IAI and 10% were STI. The overall clinical cure was achieved in 89.4%, with the best results in the ITU (100%), followed by STI (80%) and 70% in IAI. The 85% of the strains had minimum inhibitory concentrations (MIC) ≤8 μg/ml and 70% with MIC ≤4 μg/mL, however the rate of failure were high in intra-abdominal infections with high inocula or not controlled; CTX-M-15 was found in the 62.5%. Conclusions: Piperacillin/tazobactam was efficient to obtain clinical and microbiological cure in patients with infections caused by ESBL producers but susceptible E. coli, especially in UTI and STI and to a lesser extent in IAI.

EspH Suppresses Erk by Spatial Segregation from CD81 Tetraspanin Microdomains.

Enteropathogenic Escherichia coli (EPEC) belongs to a group of enteric human pathogens known as attaching-and-effacing (A/E) pathogens, which utilize a type III secretion system (T3SS) to translocate a battery of effector proteins from their own cytoplasm into host intestinal epithelial cells. Here we identified EspH to be an effector that prompts the recruitment of the tetraspanin CD81 to infection sites. EspH was also shown to be an effector that suppresses the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) signaling pathway at longer infection times. The inhibitory effect was abrogated upon deletion of the last 38 amino acids located at the C terminus of the protein. The efficacy of EspH-dependent Erk suppression was higher in CD81-deficient cells, suggesting that CD81 may act as a positive regulator of Erk, counteracting Erk suppression by EspH. EspH was found within CD81 microdomains soon after infection but was largely excluded from these domains at a later time. Based on our results, we propose a mechanism whereby CD81 is initially recruited to infection sites in response to EspH translocation. At a later stage, EspH moves out of the CD81 clusters to facilitate effective Erk inhibition. Moreover, EspH selectively inhibits the tumor necrosis factor alpha (TNF-α)-induced Erk signaling pathway. Since Erk and TNF-α have been implicated in innate immunity and cell survival, our studies suggest a novel mechanism by which EPEC suppresses these processes to promote its own colonization and survival in the infected gut.

Caspase-8 Collaborates with Caspase-11 to Drive Tissue Damage and Execution of Endotoxic Shock.

The execution of shock following high dose E. coli lipopolysaccharide (LPS) or bacterial sepsis in mice required pro-apoptotic caspase-8 in addition to pro-pyroptotic caspase-11 and gasdermin D. Hematopoietic cells produced MyD88- and TRIF-dependent inflammatory cytokines sufficient to initiate shock without any contribution from caspase-8 or caspase-11. Both proteases had to be present to support tumor necrosis factor- and interferon-ß-dependent tissue injury first observed in the small intestine and later in spleen and thymus. Caspase-11 enhanced the activation of caspase-8 and extrinsic cell death machinery within the lower small intestine. Neither caspase-8 nor caspase-11 was individually sufficient for shock. Both caspases collaborated to amplify inflammatory signals associated with tissue damage. Therefore, combined pyroptotic and apoptotic signaling mediated endotoxemia independently of RIPK1 kinase activity and RIPK3 function. These observations bring to light the relevance of tissue compartmentalization to disease processes in vivo where cytokines act in parallel to execute diverse cell death pathways.

Risk factors of urinary tract infection caused by extended spectrum ß-lactamase-producing Escherichia coli in emergency department.

OBJECTIVES: The incidence of urinary tract infection (UTI) due to extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli has increased over recent years. Initial empirical therapy is often ineffective for these resistant isolates resulting in prolonged hospitalization and increased mortality. This study was conducted to determine the risk factors of UTI caused by ESBL E. coli in the emergency department (ED). METHODS: This is a retrospective case-control study at a university hospital in Korea with UTI patients who visited ED between June 2015 and December 2016. We compared case patients with ESBL E. coli UTI (n = 50) to control patients with non-ESBL-producing E. coli UTI (n = 100), which were matched for age and sex. Multivariate logistic regression analysis was used to explore risk factors. RESULTS: Our study showed that hospital-acquired infection (OR = 3.86; 95% CI = 1.26-11.8; p = .017), prior UTI within 1 year (OR = 3.26; 95% CI = 1.32-8.05; p = .010), and underlying cerebrovascular disease (OR = 3.24; 95% CI = 1.45-7.25; p = .004) were independent risk factors for acquisition of ESBL-producing E. coli. Notably, 35 (70%) out of 50 case patients had community-acquired infection, and 68% and 54% of ESBL E. coli were resistance to ciprofloxacin and trimethoprim-sulfamethoxazole, respectively. On the contrary, 98% of ESBL E. coli was susceptible to amikacin. CONCLUSION: The main risk factors identified in our study should be considered when treating UTI patients in ED. Amikacin may improve the outcome of empirical treatment without increasing carbapenem utilization.