Poster Presenter

Antibacterial Activity and Mechanism of Bacterial Resistance of the Nucleoside Analogues Gemcitabine and Zidovudine
Anne Doléans-Jordheim, Emmanuelle Bergeron, Oana Dumitrescu, Charles Dumontet, Jean Freney & Lars Petter Jordheim
France

Microbial drug resistance represents a major public-health problem, reducing the number of effective treatments of infected patients. Development of new molecules by the pharmaceutical industry is however limited because of the inevitable emergence of resistances. Therefore, using already approved drugs such as nucleoside analogues as antibiotics is tempting.

We evaluated the inhibitory activity of gemcitabine and zidovudine (AZT) towards the growth of a large collection of pathogenic bacteria, as well as frequency and mechanism of resistance.

Gemcitabine is active towards several Gram-positive bacteria (minimum inhibitory concentrations from 1 to 64 µM), and in particular Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE) strains, two of the major germs responsible for hospital-related infections and for which treatment possibilities are limited. AZT is active against Gram-negative enterobacteria such as Escherichia coli (MIC=4-16 µM). In addition, the two nucleoside analogues completely inhibited the growth of bacteria when associated with classical antibiotics such as gentamicin, oxacillin or vancomycin. Resistance frequencies were 10^-8 for gemcitabine in S. aureus and 10^-7 for AZT in E. coli. Mechanisms of resistance include genetic modifications in the genes of activating deoxynucleoside kinases. Resistant strains are still sensitive to other antibiotics, indicating that no cross resistance exist between nucleoside analogues and classical molecules.