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Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae and trends in antibiotic consumption in a county of Sweden
Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
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2010 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 42, no 11-12, 831-838 p.Article in journal (Refereed) Published
Abstract [en]

In the last decade extended-spectrum beta-lactamase (ESBL)-producing bacteria have become an increasing problem. Our aims were to investigate the prevalence of ESBL-producing Enterobacteriaceae and trends in antibiotic use in the county of Ostergotland, Sweden. From 2002 through 2007 there were 224 ESBL-producing Escherichia coli and 23 Klebsiella pneumoniae isolates with an ESBL-phenotype identified among all Enterobacteriaceae isolated at the clinical laboratory. Trends in antibiotic consumption expressed as defined daily doses (DDD) per 1000 inhabitants and day (DID) were studied. The prevalence of ESBL-producing isolates among Enterobacteriaceae in our region is still low (andlt; 1%). Patients with ESBL-producing E. coli increased significantly (p andlt; 0.001) from 5 in y 2002 to 47 in y 2007. CTX-M group 1 was the dominant enzyme group in both E. coli and K. pneumoniae. Antibiotic susceptibility testing of ciprofloxacin, gentamicin and trimethoprim-sulfamethoxazole revealed that 58% of E. coli and 50% of K. pneumoniae isolates were multi-resistant. Antibiotic use remained unchanged from 2001 through 2009, but there was a trend towards increased use of drugs with low ESBL selection potential, which was probably due to the increased prevalence of ESBL producers.

Place, publisher, year, edition, pages
Informa Healthcare , 2010. Vol. 42, no 11-12, 831-838 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-63145DOI: 10.3109/00365548.2010.498017ISI: 000284168300006OAI: oai:DiVA.org:liu-63145DiVA: diva2:376674
Available from: 2010-12-13 Created: 2010-12-13 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Extended-spectrum beta-lactamase producing Enterobacteriaceae: aspects on detection, epidemiology and multi-drug resistance
Open this publication in new window or tab >>Extended-spectrum beta-lactamase producing Enterobacteriaceae: aspects on detection, epidemiology and multi-drug resistance
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Beta-lactam antibiotics are the largest and most commonly used group of antimicrobial agents in Sweden as well as world-wide. They show very good tolerability and many of the drugs can be administrated orally. Bacteria expressing extended-spectrum beta-lactamases (ESBLs), enzymes hydrolysing penicillins and cephalosporins, may not respond to therapy using some of these antibiotics. The isolates are also often co-resistant to other antimicrobial agents, thus further limiting treatment options. Often parenterally administrated carbapenems is one of few safe treatment options left.

In this thesis we have investigated the occurrence of ESBL producing Enterobacteriaceae in clinical isolates from Östergötland, Sweden, from 2002 until end of 2007 and the occurrence of multiresistance among ESBL producing E. coli. During these investigations we developed a simple method well suited for high-throughput analysis, for detection and sub typing of common ESBL genes.

During the six year period, the prevalence of ESBL producing Enterobacteriaceae in Östergötland was very low, <1%, but increasing. The number of patients with ESBL producing E. coli increased significantly from 5 to 47 per year; K. pneumoniae remained between one and four per year. The genes found were dominated by CTX-M group 1 (67%), followed by group 9 (27%). There has been no reason to suspect an outbreak of nosocomial origin. The total consumption of antimicrobial agents was 10.7-12.1 DID per year in primary care; 1.14-1.30 DID per year in hospital care.

Of eight oral agents tested, only three showed a generally high susceptibility; mecillinam (91%), nitrofurantoin (96%) and fosfomycin (99%). The corresponding figures for the fifteen tested parenterally administrated drugs were; amikacin (96%), tigecycline (99%), colistin (99%) and ≥99% susceptibility for the carbapenems.

Sixty eight percent of the isolates were multiresistant. The most common multiresistance pattern was ESBL phenotype with decreased susceptibility to trimethoprim, trimethoprimsulfamethoxazole, ciprofloxacin, gentamicin and tobramycin. A significant difference in susceptibility between CTX-M groups, in favor of group 9 over group 1, was seen for many of the antibiotics tested; amoxicillin-clavulanic acid, aztreonam, cafepime, ceftibuten, ceftazidime, ciprofloxacin, gentamicin, piperacillin-tazobactam, temocillin, and tobramycin.

In conclusion this thesis shows that the prevalence of ESBL producing Enterobacteriaceae in Östergötland was very low but increasing, and the total consumption of antimicrobial agents was stable. A majority of the isolates were multiresistant and a significant difference in susceptibility between CTX-M groups, in favor of group 9 over group 1, was seen for many of the antimicrobial agents tested.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 53 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1300
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76134 (URN)978-91-7519-938-2 (ISBN)
Public defence
2012-04-26, Berzeliussalen, ingång 65, plan 09, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-03-28 Created: 2012-03-28 Last updated: 2012-03-28Bibliographically approved
2. Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae: Antibiotic consumption, Detection and Resistance Epidemiology
Open this publication in new window or tab >>Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae: Antibiotic consumption, Detection and Resistance Epidemiology
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

ESBL-producing Enterobacteriaceae are emerging worldwide and they are frequently multi-drug resistant, thus limiting treatment options for infections caused by these pathogens.

The overall aim of the thesis was to investigate ESBL-producing Enterobacteriaceae in a Swedish county.

First, we developed a molecular method, a multiplex PCR assay for identification of SHV, TEM and CTX-M genes in clinical isolates of Enterobacteriaceae with an ESBL phenotype.

From 2002 until the end of 2007 all isolates of ESBL-producing Enterobacteriaceae in Östergötland, Sweden were further investigated. The prevalence of ESBL-producing Enterobacteriaceae was low, <1%, but increasing,while the antibiotic consumption remained unchanged. CTX-M enzymes, particularly CTX-M group 1, dominate in our region as well as in the rest of Europe.

Furthermore, we have investigated antimicrobial susceptibility by performing MIC-testing in a large, well-characterized population of CTX-M-producing E. coli. Only three oral antimicrobial agents (fosfomycin, nitrofurantoin and mecillinam) demonstrated susceptibility above 90%. High susceptibility, >90%, was also demonstrated for carbapenems, colistin, tigecycline and amikacin. Sixty-eight per cent of ESBL-producing E. coli was multi-resistant, and the most common multi-resistance pattern was the ESBL phenotype with decreased susceptibility to trimethoprim, trimethoprim-sulfamethoxazole, ciprofloxacin, gentamicin and tobramycin. Isolates belonging to CTX-M group 9 are generally more susceptible to antibiotics than the CTX-M group 1-producing E. coli.

Finally, a prospective multicentre case-control study examined the prevalence of ESBL-producing Enterobacteriaceae in faecal samples before and after travel abroad and the risk factors of acquisition. Sixty-eight of 226 travellers (30%) had ESBL-producing Enterobacteriaceae in the faecal flora. The geographical area visited had the highest impact on acquisition, with highest the risk for travellers visiting the Indian subcontinent, followed by Asia and Africa north of the equator. Also, acquisition of ESBL-producing Enterobacteriaceae during travel is associated with abdominal symptoms such as diarrhoea. Age also seemed to affect the risk of acquiring ESBL-producing Enterobacteriaceae, the highest risks were found among travellers ≥ 65 years.

This thesis has contributed to increased understanding of the epidemiology of ESBL-producing Enterobacteriaceae and their susceptibility to both beta-lactam and non-beta-lactam agents.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 69 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1394
Keyword
Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae, Antibiotic consumption, Detection Methods, Multiplex PCR, Resistance Epidemiology, Multi-resistance, E. coli, ESBL, fecal carriage, faecal carriage, travel
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-104216 (URN)10.3384/diss.diva-104216 (DOI)978-91-7519-404-2 (ISBN)
Public defence
2014-04-11, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Funder
County Council of Östergötland
Available from: 2014-02-11 Created: 2014-02-11 Last updated: 2014-03-04Bibliographically approved

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Östholm Balkhed, ÅseTärnberg, MariaNilsson, MaudJohansson, AnitaHanberger, HåkanMonstein, Hans-JurgNilsson, Lennart E

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Östholm Balkhed, ÅseTärnberg, MariaNilsson, MaudJohansson, AnitaHanberger, HåkanMonstein, Hans-JurgNilsson, Lennart E
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Clinical MicrobiologyFaculty of Health SciencesDepartment of Infectious Diseases in ÖstergötlandDepartment of Clinical MicrobiologyInfectious DiseasesDepartment of Infectious Diseases in ÖstergötlandDepartment of Molecular Biological Techniques
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