Association Between #Treatment with Oral Third-Generation #Cephalosporin #Antibiotics and #Mortality #Outcomes in #Ebola Virus Disease: A Multinational Retrospective Cohort Study (Trop Med Int Health, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Trop Med Int Health. 2020 Jan 7. doi: 10.1111/tmi.13369. [Epub ahead of print]

Association Between Treatment with Oral Third-Generation Cephalosporin Antibiotics and Mortality Outcomes in Ebola Virus Disease: A Multinational Retrospective Cohort Study.

Aluisio AR1, Perera SM2, Yam D3, Garbern S1, Peters JL4, Abel L4, Cho DK4, Woldemichael D2, Kennedy SB5, Massaquoi M5, Sahr F6, Liu T3, Levine AC1.

Author information: 1 Department of Emergency Medicine, Warren Alpert Medical School of Brown University, Providence, USA. 2 International Medical Corps, Washington, DC, USA. 3 Center for Statistical Sciences, Department of Biostatistics, Brown University School of Public Health, Providence, USA. 4 Warren Alpert Medical School of Brown University, Providence, USA. 5 Ministry of Health, Monrovia, Liberia. 6 College of Medicine and Allied Health Sciences, University of Sierra Leone, Sierra Leone, Freetown.

 

Abstract

OBJECTIVE:

To evaluate the association between oral third-generation cephalosporin antibiotic treatment and mortality in Ebola Virus Disease (EVD).

METHODS:

This retrospective cohort studied EVD-infected patients admitted to five Ebola Treatment Units in Sierra Leone and Liberia during 2014-15. Empiric treatment with Cefixime 400 mg once daily for five days was the clinical protocol: however, due to resource variability, only a subset of patients received treatment. Data on sociodemographics, clinical characteristics, malaria status and Ebola viral loads were collected. The primary outcome was mortality compared between cases treated with Cefixime within 48 hours of admission to those not treated within 48 hours. Propensity scores were derived using clinical covariates. Mortality between treated and untreated cases was compared using propensity-matched conditional logistic regression and bootstrapped log-linear regression analyses to calculate an odds ratio (OR) and relative risk (RR), respectively, with associated 95% confidence intervals (CI).

RESULTS:

Of 424 cases analyzed, 360 (84.9%) met the Cefixime treatment definition. The mean age was 30.5 years and 40.3% were male. Median Cefixime treatment duration was 4 days (IQR: 3, 5). Among Cefixime-treated patients, mortality was 54.7% (95% CI: 49.6-59.8%), vs. 73.4% (95% CI: 61.5-82.7%) in untreated patients. In conditional logistic regression, mortality likelihood was significantly lower among cases receiving Cefixime (OR=0.48, 95% CI: 0.32-0.71; p=0.01). In the bootstrap analysis, a non-significant risk reduction was found with Cefixime treatment (RR=0.82, 95% CI: 0.64-1.16, p=0.11).

CONCLUSION:

Early oral Cefixime may be associated with reduced mortality in EVD and warrants further investigation.

© 2020 John Wiley & Sons Ltd.

KEYWORDS: Antibiotics; Cephalosporin; Cohort Study; Ebola Virus; Viral hemorrhagic fevers

PMID: 31912627 DOI: 10.1111/tmi.13369

Keywords: Antibiotics; Cephalosporins; Cefixime; Ebola.

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High heterogeneity of #MDR #Enterobacteriaceae #fecal levels in hospitalized patients is partially driven by intravenous #betalactams (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

High heterogeneity of multidrug-resistant Enterobacteriaceae fecal levels in hospitalized patients is partially driven by intravenous beta-lactams.

Ana Djukovic, Eva M. González-Barberá, Jaime Sanz, Alejandro Artacho, Iván Peñaranda, Beatriz Herrera, María Jose Garzón, Miguel Salavert, Jose Luis López-Hontangas, Karina B. Xavier, Bernhard Kuster, Laurent Debrauwer, Jean-Marc Rolain, Miguel Sanz, Joao Xavier, Carles Ubeda

DOI: 10.1128/AAC.01415-19

 

ABSTRACT

Multidrug-resistant Enterobacteriaceae (MRE) colonize the intestine asymptomatically from where they can breach into the bloodstream and cause life-threatening infections, especially in heavily colonized patients. Despite the clinical relevance of MRE colonization levels, we know little about how they vary in hospitalized patients and the clinical factors that determine those levels. Here we conducted one of the largest studies of MRE fecal levels by tracking longitudinally 133 acute leukemia patients and monitoring their MRE levels over time through extensive culturing. MRE were defined as Enterobactericeae species that acquired non-susceptibility to ≥1 agent in ≥3 antimicrobial categories. In addition, due to the selective media used, the MRE had to be resistant to third-generation cephalosporins. MRE were detected in 60% of the patients, but their fecal levels varied considerably among patients and within the same patient (>6 and 4 orders of magnitude, respectively). Multivariate analysis of clinical metadata revealed an impact of intravenous beta-lactams (i.e. meropenem and piperacillin-tazobactam), which significantly diminished the fecal MRE levels in hospitalized patients. Consistent with a direct action of beta-lactams, we found an effect only when the patient was colonized with strains sensitive to the administered beta-lactam (p<0.001) but not with non-susceptible strains. We report previously unobserved inter and intra-individual heterogeneity in MRE fecal levels, suggesting that quantitative surveillance is more informative than qualitative surveillance of hospitalized patients. In addition, our study highlights the relevance of incorporating antibiotic treatment and susceptibility data of gut colonizing pathogens for future clinical studies and in clinical decision-making.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; Cephalosporins; Enterobacteriaceae.

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#Prevalence and outcome of #bloodstream #infections due to third-generation #cephalosporin-resistant #Enterobacteriaceae in sub-Saharan #Africa: a systematic review (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Prevalence and outcome of bloodstream infections due to third-generation cephalosporin-resistant Enterobacteriaceae in sub-Saharan Africa: a systematic review

Rebecca Lester, Patrick Musicha, Nadja van Ginneken, Angela Dramowski, Davidson H Hamer, Paul Garner, Nicholas A Feasey

Journal of Antimicrobial Chemotherapy, dkz464, https://doi.org/10.1093/jac/dkz464

Published: 19 November 2019

 

Abstract

Background

The prevalence of bacterial bloodstream infections (BSIs) in sub-Saharan Africa (sSA) is high and antimicrobial resistance is likely to increase mortality from these infections. Third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae are of particular concern, given the widespread reliance on ceftriaxone for management of sepsis in Africa.

Objectives

Reviewing studies from sSA, we aimed to describe the prevalence of 3GC resistance in Escherichia coli, Klebsiella and Salmonella BSIs and the in-hospital mortality from 3GC-R BSIs.

Methods

We systematically reviewed studies reporting 3GC susceptibility testing of E. coli, Klebsiella and Salmonella BSI. We searched PubMed and Scopus from January 1990 to September 2019 for primary data reporting 3GC susceptibility testing of Enterobacteriaceae associated with BSI in sSA and studies reporting mortality from 3GC-R BSI. 3GC-R was defined as phenotypic resistance to ceftriaxone, cefotaxime or ceftazidime. Outcomes were reported as median prevalence of 3GC resistance for each pathogen.

Results

We identified 40 articles, including 7 reporting mortality. Median prevalence of 3GC resistance in E. coli was 18.4% (IQR 10.5 to 35.2) from 20 studies and in Klebsiella spp. was 54.4% (IQR 24.3 to 81.2) from 28 studies. Amongst non-typhoidal salmonellae, 3GC resistance was 1.9% (IQR 0 to 6.1) from 12 studies. A pooled mortality estimate was prohibited by heterogeneity.

Conclusions

Levels of 3GC resistance amongst bloodstream Enterobacteriaceae in sSA are high, yet the mortality burden is unknown. The lack of clinical outcome data from drug-resistant infections in Africa represents a major knowledge gap and future work must link laboratory surveillance to clinical data.

Keywords: Antibiotics; Drugs Resistance; Cephalosporins; Enterobacteriaceae; Bacteremia; Africa region.

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#Bloodstream #infections caused by #Escherichia coli in #onco-haematological patients: #Risk #factors and #mortality in an #Italian prospective survey (PLOS One, abstract)

[Source: PLOS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Bloodstream infections caused by Escherichia coli in onco-haematological patients: Risk factors and mortality in an Italian prospective survey

Enrico Maria Trecarichi , Gabriele Giuliano, Chiara Cattaneo, Stelvio Ballanti, Marianna Criscuolo, Anna Candoni, Francesco Marchesi, Marica Laurino, Michelina Dargenio, Rosa Fanci, Mariagiovanna Cefalo, Mario Delia, Angelica Spolzino,  [ … ], for the Haematologic Malignancies Associated Bloodstream Infections Surveillance (HEMABIS) registry–Sorveglianza Epidemiologica Infezioni Fungine in Emopatie Maligne (SEIFEM) group, Italy

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Published: October 29, 2019 / DOI: https://doi.org/10.1371/journal.pone.0224465

 

Abstract

Bloodstream infections (BSIs) remain life-threatening complications in the clinical course of patients with haematological malignancies (HM) and Escherichia coli represent one of the most frequent cause of such infections. In this study, we aimed to describe risk factors for resistance to third generation cephalosporins and prognostic factors, including the impact of third generation cephalosporins resistance, in patients with HM and BSIs caused by E. coli. Three hundred forty-two cases of E. coli BSIs were collected during the study period (from January 2016 to December 2017). The percentage of resistance to third generation cephalosporins was 25.7%. In multivariate analysis, the variables recent endoscopic procedures, culture-positive surveillance rectal swabs for multidrug-resistant bacteria, antibiotic prophylaxis with fluoroquinolones, and prolonged neutropenia were independently associated with bloodstream infections caused by a third generation cephalosporins resistant E. coli. The overall 30-day mortality rate was 7.1%. Cox regression revealed that significant predictors of mortality were acute hepatic failure, septic shock, male sex, refractory/relapsed HM, and third generation cephalosporins resistance by E. coli isolate. In conclusion, resistance to third generation cephalosporins adversely affected the outcomes of bloodstream infections caused by E. coli in our cohort of HM patients. We also found a significant correlation between prophylaxis with fluoroquinolones and resistance to third generation cephalosporins by E. coli isolates.

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Citation: Trecarichi EM, Giuliano G, Cattaneo C, Ballanti S, Criscuolo M, Candoni A, et al. (2019) Bloodstream infections caused by Escherichia coli in onco-haematological patients: Risk factors and mortality in an Italian prospective survey. PLoS ONE 14(10): e0224465. https://doi.org/10.1371/journal.pone.0224465

Editor: Peter Gyarmati, University of Illinois College of Medicine, UNITED STATES

Received: June 3, 2019; Accepted: October 14, 2019; Published: October 29, 2019

Copyright: © 2019 Trecarichi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Data cannot be made publicly available due to ethical restrictions imposed by Italian legislation and ethic committees of the study coordinating center and of any other participating centers. For additional information, please contact the corresponding author, Professor Enrico M Trecarichi (em.trecarichi@unicz.it) or the ethic committee of the study coordinating center (Fondazione Policlinico Universitario Agostino Gemelli IRCCS – Università Cattolica del Sacro Cuore; E-mail: comitato.etico@policlinicogemelli.it).

Funding: The author(s) received no specific funding for this work.

Competing interests: EMT has been a speaker at accredited educational courses funded by unrestricted grants from Pfizer and Mattioli 1885. MT has been a scientific advisor/consultant for Angelini, Gilead, MSD, Nordic Pharma, and Roche, and speaker/chairman at accredited educational courses funded by unrestricted grants from Astellas, Gilead, MSD, and Pfizer. LP received honoraria for Advisory Board from Gilead Sciences, MSD, Pfizer, Jazz, Janssen, Menarini and Cidara, and has been speaker for Gilead Sciences, MSD, Pfizer, Celgine, Novartis, Astellas Pharma. MD received honoraria for Advisory Board from Honoraria from MSD, Gilead, and Pfizer. AB received honoraria for Advisory Board from Gilead, Pfizer, MSD, and Jazz. None of the other authors has any conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Keywords: Antibiotics; Drugs Resistance; E. Coli; Fluoroquinolones; Cephalosporins; Cancer; Italy.

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Characterization of #cefotaxime #resistant #urinary #Escherichia coli from primary care in South-West #England 2017–18 (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Characterization of cefotaxime-resistant urinary Escherichia coli from primary care in South-West England 2017–18

Jacqueline Findlay, Virginia C Gould, Paul North, Karen E Bowker, Martin O Williams, Alasdair P MacGowan, Matthew B Avison

Journal of Antimicrobial Chemotherapy, dkz397, https://doi.org/10.1093/jac/dkz397

Published: 20 September 2019

 

Abstract

Objectives

Third-generation cephalosporin-resistant Escherichia coli from community-acquired urinary tract infections are increasingly reported worldwide. We sought to determine and characterize the mechanisms of cefotaxime resistance employed by urinary E. coli obtained from primary care, over 12 months, in Bristol and surrounding counties in South-West England.

Methods

Cefalexin-resistant E. coli isolates were identified from GP-referred urine samples using disc susceptibility testing. Cefotaxime resistance was determined by subsequent plating onto MIC breakpoint plates. β-Lactamase genes were detected by PCR. WGS was performed on 225 isolates and analyses were performed using the Center for Genomic Epidemiology platform. Patient information provided by the referring general practices was reviewed.

Results

Cefalexin-resistant E. coli (n = 900) isolates were obtained from urines from 146 general practices. Following deduplication by patient approximately 69% (576/836) of isolates were cefotaxime resistant. WGS of 225 isolates identified that the most common cefotaxime-resistance mechanism was blaCTX-M carriage (185/225), followed by plasmid-mediated AmpCs (pAmpCs) (17/225), AmpC hyperproduction (13/225), ESBL blaSHV variants (6/225) or a combination of both blaCTX-M and pAmpC (4/225). Forty-four STs were identified, with ST131 representing 101/225 isolates, within which clade C2 was dominant (54/101). Ciprofloxacin resistance was observed in 128/225 (56.9%) of sequenced isolates, predominantly associated with fluoroquinolone-resistant clones ST131 and ST1193.

Conclusions

Most cefalexin-resistant E. coli isolates were cefotaxime resistant, predominantly caused by blaCTX-M carriage. The correlation between cefotaxime resistance and ciprofloxacin resistance was largely attributable to the high-risk pandemic clones ST131 and ST1193. Localized epidemiological data provide greater resolution than regional data and can be valuable for informing treatment choices in the primary care setting.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Cephalosporins; Fluoroquinolones; E. Coli; UTI; Cefalexin; Cefotaxime; UK; England.

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In vitro #bactericidal activity of #amoxicillin combined with different #cephalosporins against #endocarditis-associated #Enterococcus faecalis clinical isolates (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

In vitro bactericidal activity of amoxicillin combined with different cephalosporins against endocarditis-associated Enterococcus faecalis clinical isolates

Nathan Peiffer-Smadja, Elena Guillotel, David Luque-Paz, Naouale Maataoui, F-Xavier Lescure, Vincent Cattoir

Journal of Antimicrobial Chemotherapy, dkz388, https://doi.org/10.1093/jac/dkz388

Published: 08 September 2019

 

Abstract

Background

The combination of amoxicillin with cefazolin could be an interesting regimen for the empirical therapy of severe infective endocarditis, but its activity against enterococci is unknown.

Objectives

To evaluate in vitro the bactericidal activity of the combination of amoxicillin with different cephalosporins including cefazolin.

Methods

Combinations of amoxicillin (at MIC × ¼) with cefazolin, cefotaxime, ceftriaxone, cefepime, ceftaroline or ceftobiprole (at the mean free plasma concentration) were studied using time–kill experiments for 10 endocarditis-associated Enterococcus faecalis strains and 2 reference strains.

Results

The combinations amoxicillin/cefazolin, amoxicillin/cefotaxime, amoxicillin/ceftriaxone and amoxicillin/cefepime were synergistic at 12 and 24 h against 12/12 strains and amoxicillin/ceftobiprole and amoxicillin/ceftaroline against 10/12 strains. The combination amoxicillin/cefepime was bactericidal at 24 h against 9/12 strains, the combination amoxicillin/cefazolin against 8/12 strains, the combinations amoxicillin/ceftaroline, amoxicillin/cefotaxime and amoxicillin/ceftobiprole against 7/12 strains and the combination amoxicillin/ceftriaxone against 6/12 strains.

Conclusions

The combination amoxicillin/cefazolin is as synergistic and bactericidal in vitro as amoxicillin/cefotaxime or amoxicillin/ceftriaxone against E. faecalis.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Amoxicillin; Cephalosporins; Endocarditis; Enterococcus faecalis.

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Polyclonal #gut #colonization with extended-spectrum #cephalosporin- and/or #colistin-resistant #Enterobacteriaceae: a normal status for #hotel employees on the island of #Zanzibar, Tanzania (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Polyclonal gut colonization with extended-spectrum cephalosporin- and/or colistin-resistant Enterobacteriaceae: a normal status for hotel employees on the island of Zanzibar, Tanzania

Thomas Büdel, Esther Kuenzli, Mathieu Clément, Odette J Bernasconi, Jan Fehr,Ali Haji Mohammed, Nadir Khatib Hassan, Jakob Zinsstag, Christoph Hatz,Andrea Endimiani

Journal of Antimicrobial Chemotherapy, dkz296, https://doi.org/10.1093/jac/dkz296

Published: 30 July 2019

 

Abstract

Objectives

For low-income countries, data regarding the intestinal colonization with extended-spectrum cephalosporin-resistant (ESC-R) and colistin-resistant (CST-R) Enterobacteriaceae in the community are still scarce. Here, we investigated this phenomenon by analysing hotel employees in Zanzibar.

Methods

During June to July 2018, rectal swabs from 59 volunteers were screened implementing selective enrichments and agar plates. Species identification was achieved using MALDI-TOF MS. Strains were characterized using microdilution panels (MICs), microarray, PCRs for mcr-1/-8, repetitive extragenic palindromic-PCR (rep-PCR) and WGS.

Results

Colonization prevalence with ESC-R-, CST-R- and mcr-1-positive Enterobacteriaceae were 91.5%, 66.1% and 18.6%, respectively (average: 2.2 strains per volunteer). Overall, 55 ESC-R Escherichia coli (3 also CST-R), 33 ESC-R Klebsiella pneumoniae (1 also CST-R), 17 CST-R E. coli and 21 CST-R K. pneumoniae were collected. The following main resistance genes were found: ESC-R E. coli (blaCTX-M-15-like, 51.0%), ESC-R K. pneumoniae (blaCTX-M-9-like, 42.9%), CST-R E. coli (mcr-1, 55%) and CST-R K. pneumoniae (D150G substitution in PhoQ). ESBL-producing E. coli mainly belonged to ST361, ST636 and ST131, whereas all those that were mcr-1 positive belonged to ST46 that carried mcr-1 in a 33 kb IncX4 plasmid. ESBL-producing K. pneumoniae mainly belonged to ST17, ST1741 and ST101, whereas CST-R strains belonged to ST11.

Conclusions

We recorded remarkably high colonization prevalence with ESC-R and/or CST-R Enterobacteriaceae in hotel staff. Further research in the local environment, livestock and food chain is warranted to understand this phenomenon. Moreover, as Zanzibar is a frequent holiday destination, attention should be paid to the risk of international travellers becoming colonized and thereby importing life-threatening pathogens into their low-prevalence countries.

Keywords: Enterobacteriaceae; Antibiotics; Drugs Resistance; Cephalosporins; Colistin; MCR1; Tanzania.

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