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Cykloserins och ceftazidim/avibaktams effekt på multiresistenta gramnegativa bakterier
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
2018 (Swedish)Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
Abstract [sv]

Multiresistenta gramnegativa bakterier (MRGN) som Escherichia coli och Pseudomonas aeruginosa utgör ett globalt hälsoproblem och på grund av resistensutveckling hos bakterierna behövs nya behandlingsalternativ. Extended Spectrum β-Lactamase (ESBL) är vanligt förekommande hos MRGN och det finns olika typer av ESBL (exempelvis ESBLoch ESBLCARBA). Gemensamt är att det finns få behandlingsalternativ för ESBL-producerande MRGN. Syftet med studien var att undersöka effekten av potentiellt nya behandlingsalternativ mot MRGN i form av cykloserin och ceftazidim tillsammans med β-laktamasinhibitorn avibaktam.

För att undersöka minimum inhibitory concentration (MIC) för cykloserin (CYK) mot E. coli (n=26) användes en egenutvecklad buljongspädningsmetod. Isolat av P. aeruginosa med och utan karbapenemasproduktion (n=25) undersöktes avseende MIC för ceftazidim/avibaktam (CZA) med två kommersiella buljongspädningsmetoder. 

För CYK låg medianen för E. coli-stammarnas MIC-värden vid 32 mg/L (16 – 64 mg/L) vilket ligger kring det epidemiologiska cut-off värdet för Mycobacterium tuberculosis (32 mg/L), för vilken CYK idag används som behandling. 

För CZA låg medianen för P. aeruginosa-stammarnas MIC-värden vid 8 mg/L (<1 - ≥8 mg/L), och 40% (2/5) av de karbapenemasproducerande isolaten var känsliga enligt kliniska brytpunkter (S≤8 mg/L).

Sammanfattningsvis visar studien att CYK har MIC-värden mot non-ESBL- och ESBL-producerande E. coli i nivå med andra patogener där preparatet används. Studien visar också att CZA kan ha effekt mot isolat med nedsatt känslighet mot meropenem eller ESBLCARBA-producerande isolat av P. aeruginosa, men isolaten måste resistensbestämmas innan behandling sätts in.

Abstract [en]

Multiresistant gramnegative bacteria (MRGN) like Escherichia coli and Pseudomonas aeruginosa, constitute a global health issue. Due to the resistance development among bacteria, new options for treatment are needed. Extended Spectrum β-Lactamase (ESBL) is common among MRGN, and there are different types of ESBLs (as ESBLand ESBLCARBA). The increasing lack of treatment alternatives is mutual for the different ESBLs. The purpose of this study was to examine cycloserine and ceftazidime with the β-lactamase-inhibitor avibactam, two potentially new options for treatments effective against MRGN. To examine the minimum inhibitory concentration (MIC) for cycloserine (CYK) against E. coli (n=26) a in-house broth microdilution-method was used. Using two commercial broth microdilution-methods, isolates of P. aeruginosa with and without carbapenemaseproduction (n=23) were examined regarding MIC for ceftazidime/avibactam (CZA). 

Regarding CYK, the median MIC-value of the E. coli-strains was 32 mg/L (16 - 64 mg/L), which is around the epidemiological cut-off-value (32 mg/L) for Mycobacterium tuberculosisfor which CYK is being used as treatment. The median of the MIC-values for CZA was 8 mg/L (<1 - ≥8 mg/L) for all P. aeruginosa-strains and 40% (2/5) of the carbapenemaseproducing isolates were sensitive according to the clinical breakpoint (S≤8 mg/L). In summary, this study shows that CYK has MIC-values against non-ESBL- and ESBL-producing E. coli at the same level as other pathogens where CYK is being used. Further, CZA may have effect against the isolates with reduced susceptibility against meropenem and ESBLCARBA-producing P. aeruginosa, although the isolates need to be susceptibility-determined before treatment. 

Place, publisher, year, edition, pages
2018. , p. 31
Keywords [sv]
Multiresistenta bakterier, buljongspädningsmetod, MIC-bestämning, ESBL, cykloserin, ceftazidim/avibaktam
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:lnu:diva-75474OAI: oai:DiVA.org:lnu-75474DiVA, id: diva2:1216039
External cooperation
Klinisk Mikrobiologi, Diagnostiskt Centrum, Kalmar Länssjukhus
Subject / course
Biomedical Laboratory Science; Biomedical Laboratory Science
Educational program
Biomedical Laboratory Science Programme, 180 credits; Biomedical Laboratory Science Programme, 180 credits
Supervisors
Examiners
Available from: 2018-06-11 Created: 2018-06-11 Last updated: 2018-06-11Bibliographically approved

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