uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Radical reduction of cephalosporin use at a tertiary hospital after educational antibiotic intervention during an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
Show others and affiliations
2011 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 66, no 5, 1161-1167 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: During an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae at our hospital, we performed an educational antibiotic intervention aimed at reducing prescriptions of second- and third-generation cephalosporins and preventing increased use of fluoroquinolones and carbapenems. In this report, we describe the implementation strategy used and evaluate the intervention effect according to Cochrane recommendations. Methods: New recommendations for empirical intravenous antibiotic treatment were communicated to prescribers throughout the hospital by infectious diseases physicians working with Strama (the Swedish strategic programme against antibiotic resistance). No restrictive measures were used. The intervention effect was analysed with interrupted time series (ITS) regression analysis of local and national monthly antibiotic sales data. Results: A radical immediate and sustained reduction was demonstrated for the cephalosporins targeted in the intervention, whereas consumption of piperacillin/tazobactam and penicillin G increased substantially. Fluoroquinolone and carbapenem use was essentially unchanged. The ESBL outbreak subsided and no increased resistance to piperacillin/tazobactam was detected in K. pneumoniae, Escherichia coli or Pseudomonas aeruginosa blood isolates during the 2.5 year follow-up. Conclusions: Our study clearly demonstrates that an educational intervention can have an immediate and profound effect on antibiotic prescription patterns at a large tertiary hospital. ITS regression analysis of local and national antibiotic sales data was valuable to readily assess the immediate and sustained effects of the intervention.

Place, publisher, year, edition, pages
2011. Vol. 66, no 5, 1161-1167 p.
Keyword [en]
interrupted time series, ESBLs, piperacillin/tazobactam
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-152851DOI: 10.1093/jac/dkr053ISI: 000289584000031OAI: oai:DiVA.org:uu-152851DiVA: diva2:414130
Available from: 2011-05-02 Created: 2011-05-02 Last updated: 2013-02-11Bibliographically approved
In thesis
1. Multidrug-Resistant Escherichia coli and Klebsiella pneumoniae: Treatment, Selection and International Spread
Open this publication in new window or tab >>Multidrug-Resistant Escherichia coli and Klebsiella pneumoniae: Treatment, Selection and International Spread
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The prevalence of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum beta-lactamases (ESBLs) and carbapenemases is increasing worldwide. Therapeutic options for infections with these bacteria are limited not only by the production of ESBLs and carbapenemases, which confer resistance to cephalosporins and carbapenems, but also by frequent co-resistance to other antibiotics. The overall aim of this thesis was to obtain a better understanding of multidrug-resistant E. coli and K. pneumoniae in relation to epidemiology, selection and susceptibility to antibiotic therapy.

In a prospective study ESBL-producing E. coli was found to spread easily through international travel. Twenty-four of 100 Swedes travelling outside Northern Europe acquired ESBL-producing E. coli in the intestinal flora. The risk was highest for travelers visiting India and those suffering from gastroenteritis during travel.

To minimize selection of ESBL-producing K. pneumoniae during a hospital outbreak with these bacteria, an educational antibiotic intervention was performed at Uppsala University Hospital in 2006. The primary aim of the intervention was to reduce the consumption of parenteral cephalosporins. An immediate and radical reduction of cephalosporins was demonstrated with interrupted time series analysis. The outbreak declined during 2007 and no increased resistance to replacement antibiotics was detected.

The impact of ESBL production on the antibacterial activity of ertapenem was studied in time-kill experiments. It was shown that porin-deficient subpopulations with reduced susceptibility to ertapenem frequently emerged in ESBL-producing E. coli during exposure to ertapenem at concentrations simulating human pharmacokinetics.

Further, the antibacterial effects of antibiotic combinations against four strains of K. pneumoniae producing carbapenemases of the metallo-beta-lactamase type were studied in time-kill experiments. Double and triple combinations of aztreonam, fosfomycin, meropenem, rifampin and colistin at clinically relevant static concentrations were effective despite that the bacteria were frequently resistant to the individual drugs. These results indicate that there is a largely unexplored potential of antibiotic combination therapy for multidrug-resistant K. pneumoniae.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 71 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 840
Escherichia coli, Klebsiella pneumoniae, extended-spectrum beta-lactamases, carbapenemases, metallo-beta-lactamases, synergy, antibiotic interventions
National Category
Infectious Medicine Microbiology in the medical area
urn:nbn:se:uu:diva-182897 (URN)978-91-554-8537-5 (ISBN)
Public defence
2012-12-15, Gustavianum, Auditorium minus, Akademigatan 3, Uppsala, 09:00 (Swedish)
Available from: 2012-11-23 Created: 2012-10-18 Last updated: 2015-09-30Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Tängdén, ThomasEriksson, Britt-MarieMelhus, ÅsaCars, Otto
By organisation
Infectious DiseasesClinical BacteriologyUCR-Uppsala Clinical Research Center
In the same journal
Journal of Antimicrobial Chemotherapy
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 213 hits
ReferencesLink to record
Permanent link

Direct link