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Published in: Antimicrobial Resistance & Infection Control 1/2018

Open Access 01-12-2018 | Research

Extended-spectrum β-lactamase prevalence and virulence factor characterization of enterotoxigenic Escherichia coli responsible for acute diarrhea in Nepal from 2001 to 2016

Authors: Katie R. Margulieux, Apichai Srijan, Sirigade Ruekit, Panida Nobthai, Kamonporn Poramathikul, Prativa Pandey, Oralak Serichantalergs, Sanjaya K. Shrestha, Ladaporn Bodhidatta, Brett E. Swierczewski

Published in: Antimicrobial Resistance & Infection Control | Issue 1/2018

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Abstract

Background

Multidrug-resistant (MDR) Gram-negative bacterial species are an increasingly dangerous public health threat, and are now endemic in many areas of South Asia. However, there are a lack of comprehensive data from many countries in this region determining historic and current MDR prevalence. Enterotoxigenic Escherichia coli (ETEC) is a leading cause of both acute infant diarrhea and traveler’s diarrhea in Nepal. The MDR prevalence and associated resistance mechanisms of ETEC isolates responsible for enteric infections in Nepal are largely unknown.

Methods

A total of 265 ETEC isolates were obtained from acute diarrheal samples (263/265) or patient control samples (2/265) at traveler’s clinics or regional hospitals in Nepal from 2001 to 2016. Isolates were screened for antibiotic resistance, to include extended spectrum beta-lactamase (ESBL) production, via the Microscan Automated Microbiology System. ETEC virulence factors, specifically enterotoxins and colonization factors (CFs), were detected using multiplex PCR, and prevalence in the total isolate population was compared to ESBL-positive isolates. ESBL-positive isolates were assessed using multiplex PCR for genetic markers potentially responsible for observed resistance.

Results

A total of 118/265 (44.5%) ETEC isolates demonstrated resistance to ≥2 antibiotics. ESBL-positive phenotypes were detected in 40/265 isolates, with isolates from 2008, 2013, 2014, and 2016 demonstrating ESBL prevalence rates of 1.5, 34.5, 31.2, and 35.0% respectively. No difference was observed in overall enterotoxin characterization between the total ETEC and ESBL-positive populations. The CFs CS2 (13.6%), CS3 (25.3%), CS6 (30.2%), and CS21 (62.6%) were the most prevalent in the total ETEC population. The ESBL-positive ETEC isolates exhibited a higher association trend with the CFs CS2 (37.5%), CS3 (35%), CS6 (42.5%), and CS21 (67.5%). The primary ESBL gene identified was blaCTX-M-15 (80%), followed by blaSHV-12 (20%) and blaCTX-M-14 (2.5%). The beta-lactamase genes blaTEM-1 (40%) and blaCMY-2 (2.5%) were also identified. It was determined that 42.5% of the ESBL-positive isolates carried multiple resistance genes.

Conclusion

Over 30% of ETEC isolates collected post-2013 and evaluated in this study demonstrated ESBL resistance. Persistent surveillance and characterization of enteric ETEC isolates are vital for tracking the community presence of MDR bacterial species in order to recommend effective treatment strategies and help mitigate the spread of resistant pathogens.
Literature
2.
go back to reference Lai CC, Lee K, Xiao Y, Ahmad N, Veeraraghavan B, Thamlikitkul V, Tambyah PA, Nelwan RHH, Shibl AM, Wu J-J, et al. High burden of antimicrobial drug resistance in Asia. J Glob Antimicrob Resist. 2014;2:141–7.PubMed Lai CC, Lee K, Xiao Y, Ahmad N, Veeraraghavan B, Thamlikitkul V, Tambyah PA, Nelwan RHH, Shibl AM, Wu J-J, et al. High burden of antimicrobial drug resistance in Asia. J Glob Antimicrob Resist. 2014;2:141–7.PubMed
3.
go back to reference Hawkey PM. Prevalence and clonality of extended-spectrum β-lactamases in Asia. Clin Microbiol Infect. 2008;14:159–65.PubMed Hawkey PM. Prevalence and clonality of extended-spectrum β-lactamases in Asia. Clin Microbiol Infect. 2008;14:159–65.PubMed
4.
go back to reference Jean SS, Hsueh PR. High burden of antimicrobial resistance in Asia. Int J Antimicrob Agents. 2011;37:291–5.PubMed Jean SS, Hsueh PR. High burden of antimicrobial resistance in Asia. Int J Antimicrob Agents. 2011;37:291–5.PubMed
5.
go back to reference Basnyat B, Pokharel P, Dixit S, Giri S. Antibiotic use, its resistance in Nepal and recommendations for action: a situation analysis. J Nepal Health Res Counc. 2015;13:102–11.PubMed Basnyat B, Pokharel P, Dixit S, Giri S. Antibiotic use, its resistance in Nepal and recommendations for action: a situation analysis. J Nepal Health Res Counc. 2015;13:102–11.PubMed
6.
go back to reference Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: causes and control strategies. Antimicrob Resist Infect Control. 2017;6:47.PubMedPubMedCentral Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: causes and control strategies. Antimicrob Resist Infect Control. 2017;6:47.PubMedPubMedCentral
7.
go back to reference Vernet G, Mary C, Altmann DM, Doumbo O, Morpeth S, Bhutta ZA, Klugman KP. Surveillance for antimicrobial drug resistance in under-resourced countries. Emerg Infect Dis. 2014;20:434–41.PubMedPubMedCentral Vernet G, Mary C, Altmann DM, Doumbo O, Morpeth S, Bhutta ZA, Klugman KP. Surveillance for antimicrobial drug resistance in under-resourced countries. Emerg Infect Dis. 2014;20:434–41.PubMedPubMedCentral
8.
go back to reference Qadri F, Svennerholm A-M, Faruque ASG, Sack RB. Enterotoxigenic Escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention. Clin Microbiol Rev. 2005;18:465–83.PubMedPubMedCentral Qadri F, Svennerholm A-M, Faruque ASG, Sack RB. Enterotoxigenic Escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention. Clin Microbiol Rev. 2005;18:465–83.PubMedPubMedCentral
9.
go back to reference Vila J, Saez-Lopez E, Johnson JR, Romling U, Dobrindt U, Canton R, Giske CG, Naas T, Carattoli A, Martinez-Medina M, et al. Escherichia coli: an old friend with new tidings. FEMS Microbiol Rev. 2016;40:437–63.PubMed Vila J, Saez-Lopez E, Johnson JR, Romling U, Dobrindt U, Canton R, Giske CG, Naas T, Carattoli A, Martinez-Medina M, et al. Escherichia coli: an old friend with new tidings. FEMS Microbiol Rev. 2016;40:437–63.PubMed
10.
go back to reference Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, Finlay BB. Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbiol Rev. 2013;26:822–80.PubMedPubMedCentral Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, Finlay BB. Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbiol Rev. 2013;26:822–80.PubMedPubMedCentral
11.
go back to reference Pandey P, Bodhidatta L, Lewis M, Murphy H, Shlim DR, Cave W, Rajah R, Springer M, Batchelor T, Sornsakrin S, Mason CJ. Travelers' diarrhea in Nepal: an update on the pathogens and antibiotic resistance. J Travel Med. 2011;18:102–8.PubMed Pandey P, Bodhidatta L, Lewis M, Murphy H, Shlim DR, Cave W, Rajah R, Springer M, Batchelor T, Sornsakrin S, Mason CJ. Travelers' diarrhea in Nepal: an update on the pathogens and antibiotic resistance. J Travel Med. 2011;18:102–8.PubMed
12.
go back to reference Murphy H, Pandey P. Pathogens for travelers' diarrhea in Nepal and resistance patterns. Curr Infect Dis Rep. 2012;14:238–45.PubMed Murphy H, Pandey P. Pathogens for travelers' diarrhea in Nepal and resistance patterns. Curr Infect Dis Rep. 2012;14:238–45.PubMed
13.
go back to reference Turner SM, Scott-Tucker A, Cooper LM, Henderson IR. Weapons of mass destruction: virulence factors of the global killer enterotoxigenic Escherichia coli. FEMS Microbiol Lett. 2006;263:10–20.PubMed Turner SM, Scott-Tucker A, Cooper LM, Henderson IR. Weapons of mass destruction: virulence factors of the global killer enterotoxigenic Escherichia coli. FEMS Microbiol Lett. 2006;263:10–20.PubMed
14.
go back to reference Shah N, DuPont HL, Ramsey DJ. Global etiology of travelers' diarrhea: systematic review from 1973 to the present. Am J Trop Med Hyg. 2009;80:609–14.PubMed Shah N, DuPont HL, Ramsey DJ. Global etiology of travelers' diarrhea: systematic review from 1973 to the present. Am J Trop Med Hyg. 2009;80:609–14.PubMed
15.
go back to reference Madhavan TPV, Sakellaris H. Colonization factors of enterotoxigenic Escherichia coli. Adv Appl Microbiol. 2015;90:155–97.PubMed Madhavan TPV, Sakellaris H. Colonization factors of enterotoxigenic Escherichia coli. Adv Appl Microbiol. 2015;90:155–97.PubMed
16.
go back to reference Fleckenstein JM, Munson GM, Rasko DA. Enterotoxigenic Escherichia coli: orchestrated host engagement. Gut Microbes. 2013;4:392–6.PubMedPubMedCentral Fleckenstein JM, Munson GM, Rasko DA. Enterotoxigenic Escherichia coli: orchestrated host engagement. Gut Microbes. 2013;4:392–6.PubMedPubMedCentral
17.
go back to reference Sears CL, Kaper JB. Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion. Microbiol Rev. 1996;60:167–215.PubMedPubMedCentral Sears CL, Kaper JB. Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion. Microbiol Rev. 1996;60:167–215.PubMedPubMedCentral
18.
go back to reference Isidean SD, Riddle MS, Savarino SJ, Porter CK. A systematic review of ETEC epidemiology focusing on colonization factor and toxin expression. Vaccine. 2011;29:6167–78.PubMed Isidean SD, Riddle MS, Savarino SJ, Porter CK. A systematic review of ETEC epidemiology focusing on colonization factor and toxin expression. Vaccine. 2011;29:6167–78.PubMed
19.
go back to reference Fleckenstein JM, Hardwidge PR, Munson GP, Rasko DA, Sommerfelt H, Steinsland H. Molecular mechanisms of enterotoxigenic Escherichia coli infection. Microbes Infect. 2010;12:89–98.PubMed Fleckenstein JM, Hardwidge PR, Munson GP, Rasko DA, Sommerfelt H, Steinsland H. Molecular mechanisms of enterotoxigenic Escherichia coli infection. Microbes Infect. 2010;12:89–98.PubMed
20.
go back to reference Zhang W, Sack DA. Progress and hurdles in the development of vaccines against enterotoxigenic Escherichia coli in humans. Expert Rev Vaccines. 2012;11:677–94.PubMed Zhang W, Sack DA. Progress and hurdles in the development of vaccines against enterotoxigenic Escherichia coli in humans. Expert Rev Vaccines. 2012;11:677–94.PubMed
21.
go back to reference Zhang W, Sack DA. Current progress in developing subunit vaccines against Enterotoxigenic Escherichia coli-associated diarrhea. Clin Vaccine Immunol. 2015;22:983–91.PubMedPubMedCentral Zhang W, Sack DA. Current progress in developing subunit vaccines against Enterotoxigenic Escherichia coli-associated diarrhea. Clin Vaccine Immunol. 2015;22:983–91.PubMedPubMedCentral
22.
go back to reference Tribble DR. Resistant pathogens as causes of traveller's diarrhea globally and impact(s) on treatment failure and recommendations. J Travel Med. 2017;24:S6–S12.PubMedPubMedCentral Tribble DR. Resistant pathogens as causes of traveller's diarrhea globally and impact(s) on treatment failure and recommendations. J Travel Med. 2017;24:S6–S12.PubMedPubMedCentral
23.
go back to reference Rossolini GM, D'Andrea MM, Mugnaioli C. The spread of CTX-M-type extended-spectrum β-lactamases. Clin Microbiol Infect. 2008;14:33–41.PubMed Rossolini GM, D'Andrea MM, Mugnaioli C. The spread of CTX-M-type extended-spectrum β-lactamases. Clin Microbiol Infect. 2008;14:33–41.PubMed
25.
go back to reference Kassakian SZ, Mermel LA. Changing epidemiology of infections due to extended spectrum β-lactamase producing bacteria. Antimicrob Resist Infect Control. 2014;3:9.PubMedPubMedCentral Kassakian SZ, Mermel LA. Changing epidemiology of infections due to extended spectrum β-lactamase producing bacteria. Antimicrob Resist Infect Control. 2014;3:9.PubMedPubMedCentral
26.
go back to reference Kumar P, Bag S, Ghosh TS, Dey P, Dayal M, Saha B, Verma J, Pant A, Saxena S, Desigamani A, et al. Molecular insights into antimicrobial resistance traits of multidrug resistant enteric pathogens isolated from India. Sci Rep. 2017;7:14468.PubMedPubMedCentral Kumar P, Bag S, Ghosh TS, Dey P, Dayal M, Saha B, Verma J, Pant A, Saxena S, Desigamani A, et al. Molecular insights into antimicrobial resistance traits of multidrug resistant enteric pathogens isolated from India. Sci Rep. 2017;7:14468.PubMedPubMedCentral
27.
go back to reference Pitout JD, Laupland KB. Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008;8:159–66.PubMed Pitout JD, Laupland KB. Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008;8:159–66.PubMed
28.
go back to reference Pitout JD. Enterobacteriaceae that produce extended-spectrum β-lactamases and AmpC β-lactamases in the community: the tip of the iceberg? Curr Pharm Des. 2013;19:257–63.PubMed Pitout JD. Enterobacteriaceae that produce extended-spectrum β-lactamases and AmpC β-lactamases in the community: the tip of the iceberg? Curr Pharm Des. 2013;19:257–63.PubMed
29.
go back to reference Pan H, Zhang J, Kuang D, Yang X, Ju W, Huang Z, Guo J, Li Y, Zhang P, Shi W, et al. Molecular analysis and antimicrobial susceptibility of enterotoxigenic Escherichia coli from diarrheal patients. Diagn Microbiol Infect Dis. 2015;81:126–31.PubMed Pan H, Zhang J, Kuang D, Yang X, Ju W, Huang Z, Guo J, Li Y, Zhang P, Shi W, et al. Molecular analysis and antimicrobial susceptibility of enterotoxigenic Escherichia coli from diarrheal patients. Diagn Microbiol Infect Dis. 2015;81:126–31.PubMed
30.
go back to reference Mendez Arancibia E, Pitart C, Ruiz J, Marco F, Gascón J, Vila J. Evolution of antimicrobial resistance in enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli causing traveller's diarrhoea. J Antimicrob Chemother. 2009;64:343–7.PubMed Mendez Arancibia E, Pitart C, Ruiz J, Marco F, Gascón J, Vila J. Evolution of antimicrobial resistance in enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli causing traveller's diarrhoea. J Antimicrob Chemother. 2009;64:343–7.PubMed
31.
go back to reference Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptiblity testing - 28th edition. Wayne: Clinical and Laboratory Standards Institute; 2017. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptiblity testing - 28th edition. Wayne: Clinical and Laboratory Standards Institute; 2017.
32.
go back to reference Rodas C, Iniguez V, Qadri F, Wiklund G, Svennerholm AM, Sjoling A. Development of multiplex PCR assays for detection of enterotoxigenic Escherichia coli colonization factors and toxins. J Clin Microbiol. 2009;47:1218–20.PubMedPubMedCentral Rodas C, Iniguez V, Qadri F, Wiklund G, Svennerholm AM, Sjoling A. Development of multiplex PCR assays for detection of enterotoxigenic Escherichia coli colonization factors and toxins. J Clin Microbiol. 2009;47:1218–20.PubMedPubMedCentral
33.
go back to reference Dallenne C, Da Costa A, Decre D, Favier C, Arlet G. Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae. J Antimicrob Chemother. 2010;65:490–5.PubMed Dallenne C, Da Costa A, Decre D, Favier C, Arlet G. Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae. J Antimicrob Chemother. 2010;65:490–5.PubMed
34.
go back to reference Pitout JD, Nordmann P, Laupland KB, Poirel L. Emergence of Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) in the community. J Antimicrob Chemother. 2005;56:52–9.PubMed Pitout JD, Nordmann P, Laupland KB, Poirel L. Emergence of Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) in the community. J Antimicrob Chemother. 2005;56:52–9.PubMed
35.
go back to reference Baral P, Neupane S, Marasini BP, Ghimire KR, Lekhak B, Shrestha B. High prevalence of multidrug resistance in bacterial uropathogens from Kathmandu, Nepal. BMC Res Notes. 2012;5:38.PubMedPubMedCentral Baral P, Neupane S, Marasini BP, Ghimire KR, Lekhak B, Shrestha B. High prevalence of multidrug resistance in bacterial uropathogens from Kathmandu, Nepal. BMC Res Notes. 2012;5:38.PubMedPubMedCentral
36.
go back to reference Khadgi S, Timilsina U, Shrestha B. Plasmid profiling of multidrug resistant Escherichia coli strains isolated from urinary tract infection patients. BMC Res Notes. 2013;5:38. Khadgi S, Timilsina U, Shrestha B. Plasmid profiling of multidrug resistant Escherichia coli strains isolated from urinary tract infection patients. BMC Res Notes. 2013;5:38.
37.
go back to reference Parajuli NP, Maharjan P, Parajuli H, Joshi G, Paudel D, Sayami S, Khanal PR. High rates of multidrug resistance among uropathogenic Escherichia coli in children and analyses of ESBL producers from Nepal. Antimicrob Resist Infect Control. 2017;6:9.PubMedPubMedCentral Parajuli NP, Maharjan P, Parajuli H, Joshi G, Paudel D, Sayami S, Khanal PR. High rates of multidrug resistance among uropathogenic Escherichia coli in children and analyses of ESBL producers from Nepal. Antimicrob Resist Infect Control. 2017;6:9.PubMedPubMedCentral
38.
go back to reference Ansari S, Nepal HP, Gautam R, Shrestha S, Neopane P, Gurung G, Chapagain ML. Community acquired multi-drug resistant clinical isolates of Escherichia coli in a tertiary care center of Nepal. Antimicrob Resist Infect Control. 2015;4:15.PubMedPubMedCentral Ansari S, Nepal HP, Gautam R, Shrestha S, Neopane P, Gurung G, Chapagain ML. Community acquired multi-drug resistant clinical isolates of Escherichia coli in a tertiary care center of Nepal. Antimicrob Resist Infect Control. 2015;4:15.PubMedPubMedCentral
39.
go back to reference Sharma AR, Bhatta DR, Shrestha J, Banjara MR. Antimicrobial susceptibility pattern of Escherichia coli isolated from urinary tract infected patients attending Bir hospital. Nepal J Sci Technol. 2013;14:177–84. Sharma AR, Bhatta DR, Shrestha J, Banjara MR. Antimicrobial susceptibility pattern of Escherichia coli isolated from urinary tract infected patients attending Bir hospital. Nepal J Sci Technol. 2013;14:177–84.
40.
go back to reference Arcilla MS, van Hattem JM, Haverkate MR, Bootsma MCJ, van Genderen PJJ, Goorhuis A, Grobusch MP, Lashof AMO, Molhoek N, Schultsz C, et al. Import and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study. Lancet Infect Dis. 2017;17:78–85.PubMed Arcilla MS, van Hattem JM, Haverkate MR, Bootsma MCJ, van Genderen PJJ, Goorhuis A, Grobusch MP, Lashof AMO, Molhoek N, Schultsz C, et al. Import and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study. Lancet Infect Dis. 2017;17:78–85.PubMed
41.
go back to reference Hijazi SM, Fawzi MA, Ali FM, Abd El Galil KH. Prevalence and characterization of extended-spectrum β-lactamases producing Enterobacteriaceae in healthy children and associated risk factors. Ann Clin Microbiol Antimicrob. 2016;15:3.PubMedPubMedCentral Hijazi SM, Fawzi MA, Ali FM, Abd El Galil KH. Prevalence and characterization of extended-spectrum β-lactamases producing Enterobacteriaceae in healthy children and associated risk factors. Ann Clin Microbiol Antimicrob. 2016;15:3.PubMedPubMedCentral
43.
go back to reference Sherchan JB, Hayakawa K, Miyoshi-Akiyama T, Ohmagari N, Kirikae T, Nagamatsu M, Tojo M, Ohara H, Sherchand JB, Tandukar S. Clinical epidemiology and molecular analysis of extended-spectrum-beta-lactamase-producing Escherichia coli in Nepal: characteristics of sequence types 131 and 648. Antimicrob Agents Chemother. 2015;59:3424–32.PubMedPubMedCentral Sherchan JB, Hayakawa K, Miyoshi-Akiyama T, Ohmagari N, Kirikae T, Nagamatsu M, Tojo M, Ohara H, Sherchand JB, Tandukar S. Clinical epidemiology and molecular analysis of extended-spectrum-beta-lactamase-producing Escherichia coli in Nepal: characteristics of sequence types 131 and 648. Antimicrob Agents Chemother. 2015;59:3424–32.PubMedPubMedCentral
44.
go back to reference Pokhrel RH, Thapa B, Kafle R, Shah PK, Tribuddharat C. Co-existence of β-lactamases in clinical isolates of Escherichia coli from Kathmandu, Nepal. BMC Res Notes. 2014;7:694.PubMedPubMedCentral Pokhrel RH, Thapa B, Kafle R, Shah PK, Tribuddharat C. Co-existence of β-lactamases in clinical isolates of Escherichia coli from Kathmandu, Nepal. BMC Res Notes. 2014;7:694.PubMedPubMedCentral
45.
go back to reference Sidjabat HE, Paterson DL. Multidrug-resistant Escherichia coli in Asia: epidemiology and management. Expert Rev Anti-Infect Ther. 2015;13:575–91.PubMed Sidjabat HE, Paterson DL. Multidrug-resistant Escherichia coli in Asia: epidemiology and management. Expert Rev Anti-Infect Ther. 2015;13:575–91.PubMed
46.
go back to reference Carattoli A. Plasmids and the spread of resistance. Int J Med Microbiol. 2013;303:298–304.PubMed Carattoli A. Plasmids and the spread of resistance. Int J Med Microbiol. 2013;303:298–304.PubMed
Metadata
Title
Extended-spectrum β-lactamase prevalence and virulence factor characterization of enterotoxigenic Escherichia coli responsible for acute diarrhea in Nepal from 2001 to 2016
Authors
Katie R. Margulieux
Apichai Srijan
Sirigade Ruekit
Panida Nobthai
Kamonporn Poramathikul
Prativa Pandey
Oralak Serichantalergs
Sanjaya K. Shrestha
Ladaporn Bodhidatta
Brett E. Swierczewski
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Antimicrobial Resistance & Infection Control / Issue 1/2018
Electronic ISSN: 2047-2994
DOI
https://doi.org/10.1186/s13756-018-0377-2

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