Multidrug-Resistant Escherichia coli and Klebsiella pneumoniae: Treatment, Selection and International Spread
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
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
Infectious Medicine Microbiology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-182897ISBN: 978-91-554-8537-5OAI: oai:DiVA.org:uu-182897DiVA: diva2:563708
2012-12-15, Gustavianum, Auditorium minus, Akademigatan 3, Uppsala, 09:00 (Swedish)
Johansson, Anders, Docent
Cars, Otto, Professor
List of papers