Gemcitabine is active against clinical multiresistant Staphylococcus aureus strains and is synergistic with gentamicin

Jordheim, Lars Petter; Larbi, Sabrina Ben; Fendrich, Olivier; Ducrot, Claire; Bergeron, Emmanuelle; Dumontet, Charles; Freney, J.; Doléans-Jordheim, Anne

doi:10.1016/j.ijantimicag.2012.01.019

Cited by 26 publications

(31 citation statements)

References 10 publications

(14 reference statements)

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“…Gemcitabine, floxuridine, carmofur, and 5-fluorouracil showed significant antimicrobial activity against planktonic S. aureus with IC 50 s equal to or below the lowest concentration tested (0.6 M). The antimicrobial activity of gemcitabine against several strains of S. aureus has previously been reported by Jordheim et al (18). An average MIC of 0.9 M was reported in that study for most clinical MRSA strains, and that finding agrees very well with our observation of an IC 50 below 0.6 M. Huczynski et al (19) reported on the antimicrobial activity of floxuridine and several conjugates against several reference and clinical strains of S. aureus.…”

Section: Resultssupporting

confidence: 92%

Screening a Commercial Library of Pharmacologically Active Small Molecules against Staphylococcus aureus Biofilms

Torres

Abercrombie

Srinivasan

et al. 2016

Antimicrob Agents Chemother

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It is now well established that bacterial infections are often associated with biofilm phenotypes that demonstrate increased resistance to common antimicrobials. Further, due to the collective attrition of new antibiotic development programs by the pharmaceutical industries, drug repurposing is an attractive alternative. In this work, we screened 1,280 existing commercially available drugs in the Prestwick Chemical Library, some with previously unknown antimicrobial activity, against Staphylococcus aureus, one of the commonly encountered causative pathogens of burn and wound infections. From the primary screen of the entire Prestwick Chemical Library at a fixed concentration of 10 M, 104 drugs were found to be effective against planktonic S. aureus strains, and not surprisingly, these were mostly antimicrobials and antiseptics. The activity of 18 selected repurposing candidates, that is, drugs that show antimicrobial activity that are not already considered antimicrobials, observed in the primary screen was confirmed in dose-response experiments. Finally, a subset of nine of these drug candidates was tested against preformed biofilms of S. aureus. We found that three of these drugs, niclosamide, carmofur, and auranofin, possessed antimicrobial activity against preformed biofilms, making them attractive candidates for repurposing as novel antibiofilm therapies.

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Section: Resultssupporting

confidence: 92%

Screening a Commercial Library of Pharmacologically Active Small Molecules against Staphylococcus aureus Biofilms

Torres

Abercrombie

Srinivasan

et al. 2016

Antimicrob Agents Chemother

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“…The application limitations of some nucleoside analogues as antibiotics could be connected with their side effects and toxicity (e.g., myelosuppression or pulmonary toxicity). However, the concentrations of nucleoside analogues that inhibited the growth of bacteria were lower than those used for the treatment of cancer patients, which can reduce the problem of toxicity (Jordheim et al, 2012). The antibiotic potency of nucleoside analogues could be useful, especially in hospital settings, to treat multi-drug-resistant bacteria.…”

Section: Nucleoside Antimetabolites -Approved Antineoplastic Drugs Wimentioning

confidence: 99%

“…Additionally, treatment with gemcitabine activates the expression of several IFN-stimulated genes (including CXCL10, IRF7, IRF9, IFIT1 or DDX58), the major effectors in innate immunity . Gemcitabine has also shown antibacterial activity against grampositive bacteria, such as Enterococcus, Listeria, Bacillus, and Staphylococcus, including multi-drug-resistant strains of Staphylococcus aureus (Thomson and Lamont, 2019;Jordheim et al, 2012;Sandrini et al, 2007). Unfortunately, one study revealed that the treated strains developed resistance to gemcitabine.…”

Section: Nucleoside Antimetabolites -Approved Antineoplastic Drugs Wimentioning

confidence: 99%

“…Unfortunately, one study revealed that the treated strains developed resistance to gemcitabine. Such a phenomenon could in turn be overcome by the combination of gemcitabine and gentamicin, which showed synergistic activity and reduced the rate of resistance development (Jordheim et al, 2012). Gemcitabine did not show activity against gram-negative bacteria.…”

Section: Nucleoside Antimetabolites -Approved Antineoplastic Drugs Wimentioning

confidence: 99%

“…Myelodysplastic syndrome (2004) AdV (Alexeeva et al (2001); (Alexeeva et al, 2015) HMPV (Bösl et al, 2019) HIV-1 (Dapp et al, 2009;Rawson et al, 2016a) HIV-1 -synergy in combination with resveratrol (Rawson et al, 2016b) HIV-2 (Beach et al, 2014) RVFV ( (Clouser et al, 2012) HIV-1 -synergy in combination with decitabine (Clouser et al, 2010) MuLV (Clouser et al, 2012) HIV-2 (Beach et al, 2014) ZIKV (Kuivanen et al, 2017) Enteroviruses including poliovirus (Kang et al, 2015;Zhang et al, 2017) Enteroviruses -synergy with ribavirin (Kang et al, 2015) Rhinoviruses (Song et al, 2017) HCV (Beran et al, 2012) Coronaviruses (Dyall et al, 2014) SINV, HSV-1, FLUAV (Denisova et al, 2012) Gram-positive bacteria (Jordheim et al, 2012;Sandrini et al, 2007;…”

Section: Introductionmentioning

confidence: 99%

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Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

Pastuch-Gawołek

Gillner

Król

et al. 2019

European Journal of Pharmacology

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A B S T R A C T Nucleos(t)ide analogues play pivotal roles as antiviral, cytotoxic or immunosuppressive agents. Here, we review recent reports of nucleoside analogues that exhibit broad-spectrum activity towards multiple life-threatening RNA and DNA viruses. We also present a discussion about nucleoside antimetabolites-approved antineoplastic agents-that have recently been shown to have antiviral and/or antibacterial activity. The approved drugs and drug combinations, as well as recently identified candidates for investigation and/or experimentation, are discussed. Several examples of repurposed drugs that have already been approved for use are presented. This strategy can be crucial for the first-line treatment of acute infections or coinfections and for the management of drug-resistant strains.T against viral infections of great medical importance (e.g., herpes simplex virus (HSV), varicella zoster virus (VZV), human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV)) and/or that are known antineoplastic agents used to treat cancer. Approved nucleos(t)ide-based drugs with multi-target activity and compounds being tested in clinical trials or evaluated in preclinical assays are listed in Table 1. In this paper, the term "approval date" means the date on which the drug was approved by the US Food and Drug Administration (FDA) unless otherwise stated. G. Pastuch-Gawołek, et al. Multi-target nucleos(t)ide-based drugs in the treatment and prophylaxis of HIV, HBV and HCV infections

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