e. coli – ETIDIoH

#NDM-β-Lactamase-5–Producing #Escherichia coli in Companion #Animals, #USA (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / Research Letter

New Delhi Metallo-β-Lactamase-5–Producing Escherichia coli in Companion Animals, United States

Stephen D. Cole, Laura Peak, Gregory H. Tyson, Renate Reimschuessel, Olgica Ceric, and Shelley C. Rankin

Author affiliations: University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA (S.D. Cole, S.C. Rankin); Louisiana State University, Baton Rouge, Louisiana USA (L. Peak); US Food and Drug Administration, Silver Spring, Maryland, USA (G.H. Tyson, R. Reimscheussel, O. Ceric)

Abstract

We report isolation of a New Delhi metallo-β-lactamase-5–producing carbapenem-resistant Escherichia coli sequence type 167 from companion animals in the United States. Reports of carbapenem-resistant Enterobacteriaceae in companion animals are rare. We describe a unique cluster of blaNDM-5–producing E. coli in a veterinary hospital.

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; NDM1; USA.

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Restoring #colistin sensitivity in colistin-resistant #Ecoli: Combinatorial use of MarR inhibitor with efflux pump inhibitor (Sci Rep., abstract)

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

Sci Rep. 2019 Dec 25;9(1):19845. doi: 10.1038/s41598-019-56325-x.

Restoring colistin sensitivity in colistin-resistant E. coli: Combinatorial use of MarR inhibitor with efflux pump inhibitor.

Sundaramoorthy NS1, Suresh P2, Selva Ganesan S2, GaneshPrasad A1, Nagarajan S3.

Author information: 1 Center for Research on Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. 2 Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. 3 Center for Research on Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. sai@scbt.sastra.edu.

Abstract

Antibiotics like colistin are the last resort to deal with infections by carbapenem-resistant Enterobacteriaceae (CREB). Resistance to colistin severely restricts therapeutic options. To tackle this dire situation, urgent measures to restore colistin sensitivity are needed. In this study, whole-genome sequencing of colistin-resistant E. coli strain was performed and the genome analysis revealed that the strain belonged to the sequence type ST405. Multiple mutations were observed in genes implicated in colistin resistance, especially those related to the L-Ara-4-N pathway but mgrB was unmutated and mcr1-9 genes were missing. MarR inhibitor salicylate was used to re-sensitize this strain to colistin, which increased the negative charge on the cell surface especially in colistin resistant E. coli (U3790 strain) and thereby facilitated a decrease in colistin MIC by 8 fold. It is indeed well known that MarR inhibition by salicylate triggers the expression of AcrAB efflux pumps through MarA. So, in order to fully restore colistin sensitivity, a potent efflux pump inhibitor (BC1), identified earlier by this group was employed. The combination of colistin with both salicylate and BC1 caused a remarkable 6 log reduction in cell counts of U3790 in time-kill assay. Infection of muscle tissue of zebrafish with U3790 followed by various treatments showed that the combination of colistin + salicylate + BC1 was highly effective in reducing bioburden in infected muscle tissue by 4 log fold. Thus, our study shows that a combination of MarR inhibitor to enhance colistin binding and efflux pump inhibitor to reduce colistin extrusion was highly effective in restoring colistin sensitivity in colistin-resistant clinical isolate of E. coli in vitro and in vivo.

PMID: 31882661 DOI: 10.1038/s41598-019-56325-x

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Colistin; Enterobacteriaceae.

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Large #Fecal #Reservoir of #Escherichia coli Sequence Type 131-H30 Subclone Strains that Are Shared within #Households and Resemble Clinical ST131-H30 Isolates (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Large Fecal Reservoir of Escherichia coli Sequence Type 131-H30 Subclone Strains that Are Shared within Households and Resemble Clinical ST131-H30 Isolates

Muhanad Mohamed, Connie Clabots, Stephen B Porter, Tricia Bender, Paul Thuras, James R Johnson

The Journal of Infectious Diseases, jiz669, https://doi.org/10.1093/infdis/jiz669

Published: 18 December 2019

Abstract

Background

Emerging antimicrobial-resistant Escherichia coli represent mainly the nested (fluoroquinolone-resistant [FQR]) H30R and H30Rx subclones within sequence type 131 (ST131). Intestinal colonization and within-household transmission may underlie H30R’s emergence.

Methods

We screened fecal samples from 741 volunteers (383 veterans, 358 household members [including pets]) for ST131 and FQR E. coli (FQREC) and used molecular profiling to resolve unique strains. Selected strains underwent PCR-based detection of phylogroups, sequence types (STs), H30, H30Rx, and 53 virulence genes (VGs). Within-household strain sharing was compared with household, host, and bacterial characteristics. Fecal isolates were compared with clinical isolates.

Results

Colonization prevalence was 5.1% for H30R, 8% for ST131 (67% FQREC), and 10% for FQREC (52% ST131). ST131 isolates exhibited more VGs than non-ST131 isolates. Strain sharing (27% of multi-subject households, 18% of corresponding subjects) was associated with the elderly, FQREC, H30R, H30Rx, ST73, and specific VGs. Fecal ST131 and FQREC isolates resembled contemporaneous and historical clinical isolates according to all studied traits.

Conclusions

Veterans and their human household members commonly carry and extensively share FQREC, predominantly H30R, thereby likely facilitating the ST131 pandemic. Strain sharing corresponds with multiple bacterial characteristics, including FQ resistance and specific VGs, which may promote intestinal colonization and/or host-to-host transmission.

Escherichia coli, ST131, Fluoroquinolone resistance, Intestinal colonization, Strain sharing

Issue Section: Major Article

This content is only available as a PDF.

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)

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Keywords: Antibiotics; Drugs Resistance; E. Coli.

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#Antibiotic #Resistance of #Escherichia coli from #Humans and Black #Rhinoceroses in #Kenya (Ecohealth, abstract)

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

Ecohealth. 2019 Dec 7. doi: 10.1007/s10393-019-01461-z. [Epub ahead of print]

Antibiotic Resistance of Escherichia coli from Humans and Black Rhinoceroses in Kenya.

Kipkorir KC1, Ang’ienda PO1, Onyango DM1, Onyango PO2.

Author information: 1 Department of Zoology, Maseno University, Private Bag, Maseno, Kenya. 2 Department of Zoology, Maseno University, Private Bag, Maseno, Kenya. patonyango@gmail.com.

Abstract

Upsurge of antibiotic resistance in wildlife poses unprecedented threat to wildlife conservation. Surveillance of antibiotic resistance at the human-wildlife interface is therefore needed. We evaluated differences in antibiotic resistance of Escherichia coli isolates from human and the endangered black rhinoceros in Lambwe Valley, Kenya. We used standard microbiological techniques to carry out susceptibility assays using eight antibiotics of clinical and veterinary importance. Standard PCR method was used to characterize antibiotic resistance genes. There was no difference in resistance between E. coli isolates from human and those from rhinoceros (U = 25, p = 0.462). However, higher resistance in isolates from humans was noted for cotrimoxazole (p = 0.000, OR = 0.101), ceftriaxone (p = 0.005, OR = 0.113) and amoxicillin/clavulanic acid (p = 0.017, OR = 0.258), whereas isolates from rhinoceros showed higher gentamicin resistance (p = 0.001, OR = 10.154). Multi-drug resistance phenotype was 69.0% in humans and 43.3% in rhinoceros. Isolates from both species contained blaTEM, tetA, tetB, dfrA1 and sul1 genes. Resistance profiles in the two species suggest potential for cross-transfer of resistance genes or exposure to comparable selective pressure and call for a multi-sectorial action plan on surveillance of antibiotic resistance at the human-wildlife interface. Genome-wide studies are needed to explicate the direction of transfer of genes that confer antibiotic resistance at the human-wildlife interface.

KEYWORDS: Antibacterial resistance; Black rhinoceros; Escherichia coli; Kenya; Multi-drug resistance; Zoonotic

PMID: 31811599 DOI: 10.1007/s10393-019-01461-z

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Keywords: Antibiotics; Drugs Resistance; E. Coli; Wildlife; Human; Kenya.

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#Antimicrobial #resistance of commensal #Escherichia coli strains in #children of two rural communities in #Peru (Rev Peru Med Exp Salud Publica, abstract)

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

Rev Peru Med Exp Salud Publica. 2019 Jul-Sep;36(3):459-463. doi: 10.17843/rpmesp.2019.363.4366. Epub 2019 Dec 2.

[Antimicrobial resistance of commensal Escherichia coli strains in children of two rural communities in Peru].

[Article in Spanish; Abstract available in Spanish from the publisher]

Alzamora MC1, Echevarría AC1, Ferraro VM1, Riveros MD2, Zambruni M3, Ochoa TJ1,2.

Author information: 1 Facultad de Medicina, Universidad Peruana Cayetano Heredia. Lima, Perú. 2 Instituto de Medicina Tropical Alexander von Humbolt, Universidad Peruana Cayetano Heredia. Lima, Perú. 3 Center for Infectious Diseases, University of Texas Health Science Center at Houston, Houston, Estados Unidos.

Abstract in English, Spanish

Antibiotic resistance is a major global problem. The objective of this study was to determine antibiotic resistance in commensal strains isolated from healthy children from rural communities of Moyobamba and Urubamba in Peru. This cohort study identified 179 commensal E. coli strains from 93 children, followed for six months. Thirteen antibiotics were analyzed by diffusion disk. The highest rates of resistance were for cotrimoxazole (49.1%), ampicillin (48.0%), and nalidixic acid (31.8%). An 11.6% increase in resistance was found for nalidixic acid and 6.4% for cotrimoxazole in this period; while 34.0% of the isolates were multidrug-resistant. This study supports previous findings of multidrug resistance in commensal strains in rural communities and highlights the increased rates of resistance over time. We recommend studies in larger populations with a longer follow-up.

PMID: 31800939 DOI: 10.17843/rpmesp.2019.363.4366

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Keywords: Antibiotics; Drugs Resistance; E. Coli; Peru.

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#Transmission of #ESBL-producing #Escherichia coli between #broilers and #humans on broiler #farms (J Antimicrob Chemother., abstract)

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

Transmission of ESBL-producing Escherichia coli between broilers and humans on broiler farms

Angela H A M van Hoek, Cindy Dierikx, Thijs Bosch, Leo Schouls, Engeline van Duijkeren, Michael Visser

Journal of Antimicrobial Chemotherapy, dkz507, https://doi.org/10.1093/jac/dkz507

Published: 04 December 2019

Abstract

Background

ESBL and AmpC β-lactamases are an increasing concern for public health. Studies suggest that ESBL/pAmpC-producing Escherichia coli and their plasmids carrying antibiotic resistance genes can spread from broilers to humans working or living on broiler farms. These studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these isolates.

Methods

Eleven suspected transmission events among broilers and humans living/working on eight broiler farms were investigated using whole-genome short-read (Illumina) and long-read sequencing (PacBio). Core genome MLST (cgMLST) was performed to investigate the occurrence of strain transmission. Horizontal plasmid and gene transfer were analysed using BLAST.

Results

Of eight suspected strain transmission events, six were confirmed. The isolate pairs had identical ESBL/AmpC genes and fewer than eight allelic differences according to the cgMLST, and five had an almost identical plasmid composition. On one of the farms, cgMLST revealed that the isolate pairs belonging to ST10 from a broiler and a household member of the farmer had 475 different alleles, but that the plasmids were identical, indicating horizontal transfer of mobile elements rather than strain transfer. Of three suspected horizontal plasmid transmission events, one was confirmed. In addition, gene transfer between plasmids was found.

Conclusions

The present study confirms transmission of strains as well as horizontal plasmid and gene transfer between broilers and farmers and household members on the same farm. WGS is an important tool to confirm suspected zoonotic strain and resistance gene transmission.

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.

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Keywords: Antibiotics; Drugs Resistance; Beta-lactams; E. Coli; Poultry; Human.

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LMB-1 producing #Citrobacter freundii from #Argentina, a novel player in the field of MBLs (Int J Antimicrob Agents, abstract)

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

Int J Antimicrob Agents. 2019 Nov 27. pii: S0924-8579(19)30328-0. doi: 10.1016/j.ijantimicag.2019.11.014. [Epub ahead of print]

LMB-1 producing Citrobacter freundii from Argentina, a novel player in the field of MBLs.

Dabos L1, Rodriguez CH2, Nastro M2, Dortet L3, Bonnin R4, Famiglietti A2, Iorga BI5, Vay C2, Naas T6.

Author information: 1 EA7361 “Structure, dynamic, function and expression of broad spectrum β-lactamases”, Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France. 2 Departamento de Bioquímica Clinica, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. 3 EA7361 “Structure, dynamic, function and expression of broad spectrum β-lactamases”, Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; Department of Bacteriology-Hygiene, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France. 4 EA7361 “Structure, dynamic, function and expression of broad spectrum β-lactamases”, Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France. 5 CNRS, UMR3525, Paris, France. 6 EA7361 “Structure, dynamic, function and expression of broad spectrum β-lactamases”, Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; Department of Bacteriology-Hygiene, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France. Electronic address: thierry.naas@aphp.fr.

Abstract

Carbapenemase-producing Enterobacterales expressing OXA-48, KPC, NDM, VIM or IMP enzymes are increasingly reported worldwide. We have characterized LMB-1, a novel metallo-β-latamase (MBL) of Ambler class B3 from Citrobacter freundii 164 (Cf164) clinical isolate from Buenos Aires, Argentina. Cf164 displayed reduced susceptibility to carbapenems but gave inconsistent results with carbapenemase confirmatory tests, suggesting the presence of a weak carbapenemase. Analysis of WGS of Cf164 using Resfinder revealed four β-lactamase genes coding for CTX-M-8, PER-2, TEM-1 and CMY-150, a novel chromosomally-encoded CMY variant. Kinetic parameters of purified CMY-150 did not reveal any carbapenemase activity. However, CMY-150 conferred to E. coli higher MIC values for ceftazidime and aztreonam as compared to CMY-2. The in-house developed β-lactamase search software (ResMINER) in WGS data, revealed a novel subclass B3 MBL named LMB-1. LMB-1 conferred to E. coli, resistance to penicillins, to expanded-spectrum cephalosporins and reduced susceptibility to carbapenems. The blaLMB-1 gene was located on a 176-kb IncA/C2 plasmid. LMB-1 shared 99% of amino acid sequence identity with the MBL encoded in the chromosome of Rheinheimera pacifica, it’s likely progenitor. Despite repeated attempts, LMB-1 could not be purified, thus only specific activities could evidence hydrolysis of carbapenems. Here we report CMY-150, a novel CMY-2 variant that confers increased ceftazidime and aztreonam MICs to E. coli and the first description of LMB-1 in Argentina. This work underlines the need for several CPE confirmatory tests, as this novel enzyme might have been missed using only one.

KEYWORDS: CPE; Carbapenemase; Class B3 MBL; Metallo-beta-lactamase

PMID: 31785341 DOI: 10.1016/j.ijantimicag.2019.11.014

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Keywords: Antibiotics; Drugs Resistance; E. Coli; Citrobacter freundii; Carbapenem; Beta-lactams; Argentina.

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Do #vegetarians less frequently carry #ESBL/pAmpC-producing #Escherichia coli/Klebsiella pneumoniae compared with non-vegetarians? (J Antimicrob Chemother., abstract)

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

Do vegetarians less frequently carry ESBL/pAmpC-producing Escherichia coli/Klebsiella pneumoniae compared with non-vegetarians?

Anouk P Meijs, Esther F Gijsbers, Paul D Hengeveld, Christiaan Veenman, Annika M van Roon, Angela H A M van Hoek, Sabine C de Greeff, Engeline van Duijkeren, Cindy M Dierikx

Journal of Antimicrobial Chemotherapy, dkz483, https://doi.org/10.1093/jac/dkz483

Published: 25 November 2019

Abstract

Background

ESBL and plasmid-mediated AmpC (pAmpC)-producing Enterobacteriaceae are frequently found on meat products in Dutch retail, especially on poultry.

Objectives

We investigated whether vegetarians are at lower risk of carrying ESBL/pAmpC-producing Escherichia coli/Klebsiella pneumoniae (ESBL-E/K) compared with persons who consume meat.

Methods

Vegetarians, pescatarians (vegetarians who eat fish) and non-vegetarians (persons who eat meat at least three times per week) were asked to send in a faecal sample and a questionnaire. ESBL-E/K were cultured and MLSTs were determined. ESBL/pAmpC genes were analysed using PCR and sequencing. The risk of ESBL-E/K carriage in the three study groups was analysed using multivariable logistic regression.

Results

Prevalence of ESBL-E/K carriage was 8.0% in vegetarians (63/785; 95% CI 6.3–10.1), 6.9% in pescatarians (27/392; 95% CI 4.8–9.8) and 3.8% in non-vegetarians (14/365; 95% CI 2.3–6.3). Multivariable analysis showed an OR for ESBL-E/K carriage of 2.2 for vegetarians (95% CI 1.2–4.0) and 1.6 for pescatarians (95% CI 0.8–3.2) compared with non-vegetarians. The predominant MLST was E. coli ST131 and the most common ESBL genes were blaCTX-M-15, blaCTX-M-27, blaCTX-M-14 and blaCTX-M-1 in all diet groups. Independent risk factors for ESBL-E/K carriage were travel to Africa/Latin America/Asia (OR 4.6; 95% CI 2.8–7.7) in the past 6 months and rarely/never washing hands before food preparation (OR 2.5; 95% CI 1.2–5.0).

Conclusions

Vegetarians and pescatarians did not have a lower risk of ESBL-E/K carriage compared with non-vegetarians, indicating that eating meat is not an important risk factor for ESBL-E/K carriage.

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Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; E. Coli; Klebsiella pneumoniae; Food Safety.

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#Bloodstream #infections caused by #Escherichia coli carrying #mcr-1 gene in hospitalized patients in northern #Italy from 2012 to 2018 (Infection, abstract)

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

Infection. 2019 Nov 22. doi: 10.1007/s15010-019-01377-4. [Epub ahead of print]

Bloodstream infections caused by Escherichia coli carrying mcr-1 gene in hospitalized patients in northern Italy from 2012 to 2018.

Mariani B1, Corbella M2,3, Merla C1,4, Tallarita M1,4, Piralla A1, Girello A1, Castelli M5, Bracchi C6, Marone P1, Cambieri P1.

Author information: 1 UOC Microbiologia e Virologia, Fondazione IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100, Pavia, Italy. 2 UOC Microbiologia e Virologia, Fondazione IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100, Pavia, Italy. m.corbella@smatteo.pv.it. 3 Servizio Epidemiologia Clinica e Biometria, Direzione Scientifica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. m.corbella@smatteo.pv.it. 4 Scuola di Specializzazione in Microbiologia e Virologia, Università degli Studi di Pavia, Pavia, Italy. 5 Dipartimento di Bioscienze, Centro Romeo ed Enrica Invernizzi Ricerca Pediatrica, Università degli Studi di Milano, Milan, Italy. 6 Unità di analisi del rischio ed epidemiologia genomica, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Parma, Italy.

Abstract

PURPOSE:

The recurrence of multi-drug resistant (MDR) pathogens to the latest antibiotics and the limited development of new antibacterial agents have reduced the options for the treatment of severe infections. The reintroduction of old antibiotics, such as colistin, represents an effective strategy, since the latest antibiotics are over-consumed and ineffective against MDR pathogens. In 2015, Liu (Lancet Infect Dis 16:161-168, 2016) reported Escherichia coli (E. coli) isolates carrying plasmid-mediated colistin resistance gene mcr-1. The first of mcr-1 positive colistin-resistant (col-R) E. coli from a human blood culture was observed in 2012 in Latin America, while in Italy was reported for the first time by our center in 2016. The present study aimed to describe the prevalence of mcr-1 positive col-R strains in E. coli-related bloodstream infection among patients hospitalized in Fondazione IRCCS Policlinico San Matteo in Pavia, Italy, from 2012 to 2018, including the three cases already published.

METHODS:

All col-R E. coli strains isolated from blood cultures collected during the study period were analyzed. The minimal inhibitory concentration of colistin was determined using broth microdilution and detection of mcr-1 and mcr-2 genes was performed by PCR. The sequence type of E. coli mcr-1 positive was determined according to Multilocus sequence typing.

RESULTS:

Out of 1557 samples, 14 strains (0.90%) were col-R. and positive for the presence of the mcr-1 gene, with no mcr-2 detected. The most common ST was ST10 (n = 3), followed by ST410 (n = 2). The remaining strains exhibited different MLST profiles, indicating that they were genetically unrelated.

CONCLUSIONS:

Proper reporting of the presence of mcr-1 genes is an essential component to anticipate the spread of colistin resistance. This public health issue is particularly alarming in Italy due to the consistent circulation of MDR bacteria.

KEYWORDS: Blood stream infection; Colistin resistance; Drug resistance; Escherichia coli; mcr-1 gene

PMID: 31758437 DOI: 10.1007/s15010-019-01377-4

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Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; E. Coli; Italy.

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Long-term #impact of an #educational #antimicrobial #stewardship programme in primary care on #infections caused by #ESBL #Escherichia coli in the community… (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Long-term impact of an educational antimicrobial stewardship programme in primary care on infections caused by extended-spectrum β-lactamase-producing Escherichia coli in the community: an interrupted time-series analysis

Germán Peñalva, MSEd, Rocío Fernández-Urrusuno, PhD, José María Turmo, MD, Rocío Hernández-Soto, PhD, Ignacio Pajares, MD, Lucía Carrión, MD, Inmaculada Vázquez-Cruz, PhD, Blanca Botello, MD, Beatriz García-Robredo, PhD, Manuel Cámara-Mestres, PharmD, Juan Carlos Domínguez-Camacho, PharmD, Manuel María Aguilar-Carnerero, PharmD, José Antonio Lepe, PhD, Marina de Cueto, PhD, María Carmen Serrano-Martino, PhD, María Carmen Domínguez-Jiménez, PhD, Ana Domínguez-Castaño, MD, José Miguel Cisneros, PhD on behalf of the PIRASOA-FIS team †

Published: November 22, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30573-0

Summary

Background

There is little evidence on the ecological effect and sustainability of antimicrobial stewardship programmes (ASPs) in primary-care settings. We aimed to determine whether a multimodal, educational ASP would be sustainable in the long-term and reduce the incidence of infections caused by extended-spectrum β-lactamase-producing Escherichia coli in the community by optimising antibiotic use.

Methods

We did this quasi-experimental intervention study in 214 primary health centres of four primary health-care districts in Andalusia, Spain. Local multidisciplinary teams, comprised of general practitioners, paediatricians, primary-care pharmacists, and epidemiologists, were created in each district and implemented a multimodal, education-based ASP. The core activity of the programme consisted of regular one-to-one educational interviews between a reference interviewing physician and prescribing physicians from each centre on the appropriateness of their most recent (same or preceding day) antibiotic prescriptions based on a structured questionnaire. Appropriate prescribing was defined as compliance of all checklist items with the reference guidelines. An average of five educational interviews were scheduled per prescriber per study year. We did an interrupted time-series analysis to assess the effect of the intervention on quarterly antibiotic use (prescription and collection by the patient) and quality of prescriptions (as defined daily doses per 1000 inhabitants per day) and incidence per 1000 inhabitants of E coli producing extended-spectrum β-lactamase (ESBL) isolated from urine samples.

Findings

The study was done between January, 2012, and December, 2017, in a pre-intervention period of 2012–13 and an intervention period of 2014–17. Throughout the study period, there were 1387 physicians (1116 general practicioners and 271 paediatricians) in the included health centres serving a mean population of 1 937 512 people (299 331 children and 1 638 181 adults). 24 150 educational interviews were done over the 4 years. Inappropriate antibiotic prescribing was identified in 1794 (36·5%) of 4917 educational interviews in 2014 compared with 1793 (26·9%) of 6665 in 2017 (p<0·0001). The intervention was associated with a sustained reduction in the use of ciprofloxacin (relative effect −15·9%, 95% CI −23·9 to −8·0) and cephalosporins (−22·6%, −35·9 to −9·2), and a sustained increase in the use of amoxicillin (22·2%, 6·4 to 38·0) and fosfomycin trometamol (6·1%, 2·6 to 9·6). The incidence density of ESBL-producing E coli decreased by −0·028 cases per 1000 inhabitants (95% CI −0·034 to −0·021) after the start of the programme, reversing the pre-intervention increase and leading to a relative reduction of −65·6% (−68·2 to −63·0) 4 years later.

Interpretation

Our data suggest that implementation of a multimodal ASP in primary care that is based on individual educational interviews improves the use of antibiotics and results in a sustained significant reduction of infections by ESBL-producing E coli in the community. This information should encourage the implementation of ASPs in primary care.

Funding

Instituto de Salud Carlos III, Spanish Government (PI14/01523).

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Keywords: Antibiotics; Drugs Resistance; Society; Spain; E. Coli; Beta-lactams.

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