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  1. Article: In Vitro Screening of a 1280 FDA-Approved Drugs Library against Multidrug-Resistant and Extensively Drug-Resistant Bacteria.

    Peyclit, Lucie / Baron, Sophie Alexandra / Hadjadj, Linda / Rolain, Jean-Marc

    Antibiotics (Basel, Switzerland)

    2022  Volume 11, Issue 3

    Abstract: Alternative strategies against multidrug-resistant (MDR) bacterial infections are suggested to clinicians, such as drug repurposing, which uses rapidly available and marketed drugs. We gathered a collection of MDR bacteria from our hospital and performed ...

    Abstract Alternative strategies against multidrug-resistant (MDR) bacterial infections are suggested to clinicians, such as drug repurposing, which uses rapidly available and marketed drugs. We gathered a collection of MDR bacteria from our hospital and performed a phenotypic high-throughput screening with a 1280 FDA-approved drug library. We used two Gram positive (Enterococcus faecium P5014 and Staphylococcus aureus P1943) and six Gram negative (Acinetobacter baumannii P1887, Klebsiella pneumoniae P9495, Pseudomonas aeruginosa P6540, Burkholderia multivorans P6539, Pandoraea nosoerga P8103, and Escherichia coli DSM105182 as the reference and control strain). The selected MDR strain panel carried resistance genes or displayed phenotypic resistance to last-line therapies such as carbapenems, vancomycin, or colistin. A total of 107 compounds from nine therapeutic classes inhibited >90% of the growth of the selected Gram negative and Gram positive bacteria at a drug concentration set at 10 µmol/L, and 7.5% were anticancer drugs. The common hit was the antiseptic chlorhexidine. The activity of niclosamide, carmofur, and auranofin was found against the selected methicillin-resistant S. aureus. Zidovudine was effective against colistin-resistant E. coli and carbapenem-resistant K. pneumoniae. Trifluridine, an antiviral, was effective against E. faecium. Deferoxamine mesylate inhibited the growth of XDR P. nosoerga. Drug repurposing by an in vitro screening of a drug library is a promising approach to identify effective drugs for specific bacteria.
    Language English
    Publishing date 2022-02-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics11030291
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi.

    Peyclit, Lucie / Yousfi, Hanane / Rolain, Jean-Marc / Bittar, Fadi

    Pharmaceuticals (Basel, Switzerland)

    2021  Volume 14, Issue 5

    Abstract: Immunodepression, whether due to HIV infection or organ transplantation, has increased human vulnerability to fungal infections. These conditions have created an optimal environment for the emergence of opportunistic infections, which is concomitant to ... ...

    Abstract Immunodepression, whether due to HIV infection or organ transplantation, has increased human vulnerability to fungal infections. These conditions have created an optimal environment for the emergence of opportunistic infections, which is concomitant to the increase in antifungal resistance. The use of conventional antifungal drugs as azoles and polyenes can lead to clinical failure, particularly in immunocompromised individuals. Difficulties related to treating fungal infections combined with the time required to develop new drugs, require urgent consideration of other therapeutic alternatives. Drug repurposing is one of the most promising and rapid solutions that the scientific and medical community can turn to, with low costs and safety advantages. To treat life-threatening resistant fungal infections, drug repurposing has led to the consideration of well-known and potential molecules as a last-line therapy. The aim of this review is to provide a summary of current antifungal compounds and their main resistance mechanisms, following by an overview of the antifungal activity of non-traditional antimicrobial drugs. We provide their eventual mechanisms of action and the synergistic combinations that improve the activity of current antifungal treatments. Finally, we discuss drug repurposing for the main emerging multidrug resistant (MDR) fungus, including the
    Language English
    Publishing date 2021-05-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph14050488
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Drug Repurposing to Fight Colistin and Carbapenem-Resistant Bacteria.

    Peyclit, Lucie / Baron, Sophie Alexandra / Rolain, Jean-Marc

    Frontiers in cellular and infection microbiology

    2019  Volume 9, Page(s) 193

    Abstract: The emergence of new resistance mechanisms, the failure of classical antibiotics in clinic, the decrease in the development of antibiotics in the industry are all challenges that lead us to consider new strategies for the treatment of infectious diseases. ...

    Abstract The emergence of new resistance mechanisms, the failure of classical antibiotics in clinic, the decrease in the development of antibiotics in the industry are all challenges that lead us to consider new strategies for the treatment of infectious diseases. Indeed, in recent years controversy has intensified over strains resistant to carbapenem and/or colistin. Various therapeutic solutions are used to overcome administration of last line antibiotics. In this context, drug repurposing, which consists of using a non-antibiotic compound to treat multi-drug resistant bacteria (MDR), is encouraged. In this review, we first report what may have led to drug repurposing. Main definitions, advantages and drawbacks are summarized. Three major methods are described: phenotypic, computational and serendipity. In a second time we will focus on the current knowledge in drug repurposing for carbapenem and colistin-resistant bacteria with different studies describing repurposed compounds tested on Gram-negative bacteria. Furthermore, we show that drug combination therapies can increase successful by drug repurposing strategy. In conclusion, we discuss the pharmaceutical industries that have little interest in reprofiling drugs due to lack of profits. We also consider what a clinician might think of the indications of these uncommon biologists to treat MDR bacterial infections and avoid therapeutic impasses.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Carbapenems/pharmacology ; Colistin/pharmacology ; Databases, Factual ; Drug Combinations ; Drug Repositioning/methods ; Drug Resistance, Multiple, Bacterial/drug effects ; Gram-Negative Bacteria/drug effects ; Humans
    Chemical Substances Anti-Bacterial Agents ; Carbapenems ; Drug Combinations ; Colistin (Z67X93HJG1)
    Keywords covid19
    Language English
    Publishing date 2019-06-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2019.00193
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Fatal Pandoraea nosoerga infection after combined liver-lung transplantation for cystic fibrosis: a recontamination by the pre-transplantation strain.

    Peyclit, Lucie / Baron, Sophie Alexandra / Reynaud-Gaubert, Martine / Cassir, Nadim / Rolain, Jean-Marc

    European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

    2021  Volume 40, Issue 11, Page(s) 2403–2406

    Abstract: A 26-year-old girl with a longstanding colonization by Pandoraea nosoerga underwent liver-lung transplantation for cystic fibrosis (CF) in 2018. Her brother also suffering from CF was also colonized by P. nosoerga. Despite appropriate perioperative ... ...

    Abstract A 26-year-old girl with a longstanding colonization by Pandoraea nosoerga underwent liver-lung transplantation for cystic fibrosis (CF) in 2018. Her brother also suffering from CF was also colonized by P. nosoerga. Despite appropriate perioperative antibiotic therapy, she had post-transplant bacteremic pneumonia caused by extensively drug-resistant P. nosoerga. Drug repurposing was used to optimize treatment options. The cause of post-transplant contamination was studied by comparative whole-genome sequencing including pre- and post-transplant strains and her brother's strains. Post-transplant contamination appeared to be due to her own pre-transplant strain, emphasizing the urgent need to study and implement effective decontamination protocols before transplantation.
    MeSH term(s) Adult ; Anti-Bacterial Agents/therapeutic use ; Burkholderiaceae/genetics ; Burkholderiaceae/isolation & purification ; Burkholderiaceae/physiology ; Cystic Fibrosis/surgery ; Fatal Outcome ; Female ; Gram-Negative Bacterial Infections/drug therapy ; Gram-Negative Bacterial Infections/microbiology ; Gram-Negative Bacterial Infections/mortality ; Humans ; Liver/surgery ; Liver Transplantation/adverse effects ; Lung/microbiology ; Lung/surgery ; Lung Transplantation/adverse effects ; Postoperative Complications/drug therapy ; Postoperative Complications/microbiology ; Postoperative Complications/mortality
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2021-04-08
    Publishing country Germany
    Document type Case Reports ; Journal Article
    ZDB-ID 603155-9
    ISSN 1435-4373 ; 0934-9723 ; 0722-2211
    ISSN (online) 1435-4373
    ISSN 0934-9723 ; 0722-2211
    DOI 10.1007/s10096-021-04235-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: IgM triplet in neonatal diagnosis by immunoblotting and its potential use as a diagnostic marker for congenital toxoplasmosis.

    Peyclit, Lucie / Villard, Odile / Paris, Luc / Fricker-Hidalgo, Hélène / Houzé, Sandrine / Cimon, Bernard / Deleplancque, Anne-Sophie / Tournus, Céline / Pelloux, Hervé / Villena, Isabelle / Pomares, Christelle / L'Ollivier, Coralie

    Parasite (Paris, France)

    2023  Volume 30, Page(s) 19

    Abstract: Primary infection during pregnancy by the protozoan Toxoplasma gondii can be worrisome because transmission to the fetus may lead to congenital toxoplasmosis (CT). Neonatal diagnosis is usually performed by serological profile comparison of the mother ... ...

    Title translation La triplette IgM dans le diagnostic néonatal par immunoblot et son utilisation potentielle comme marqueur diagnostique de la toxoplasmose congénitale.
    Abstract Primary infection during pregnancy by the protozoan Toxoplasma gondii can be worrisome because transmission to the fetus may lead to congenital toxoplasmosis (CT). Neonatal diagnosis is usually performed by serological profile comparison of the mother and newborn. As previously reported in 2012 by C. L'Ollivier et al., three IgM bands at 75, 90 and 100 kDa called the "IgM triplet" has caught our attention and seems to be pathognomonic of CT. This retrospective multicenter study involved nine reference laboratories included in the French National Reference Center for Toxoplasmosis network and concerned determining the specificity and sensitivity of this IgM triplet. On this basis, we were able to propose a new read of the comparison of IgG and IgM immunoblot profiles of mother and infant to increase the sensitivity of this diagnostic marker. The effect of the trimester of pregnancy at the time of infection, but also of maternal treatment with pyrimethamine/sulfadiazine/folinic acid on the presence of this IgM triplet in the infant, could be studied. The presence of the triplet appears pathognomonic for the diagnosis of CT, and it increased the sensitivity of the immunoblot assay from 55.04% to 72.48%. As a result, it would be wise to enhance conventional immunoblot reading by adding the presence of the three IgM bands in the infant pattern for neonatal diagnosis of CT.
    MeSH term(s) Pregnancy ; Infant, Newborn ; Infant ; Female ; Humans ; Toxoplasmosis, Congenital/diagnosis ; Antibodies, Protozoan ; Immunoblotting ; Toxoplasmosis/diagnosis ; Toxoplasma ; Immunoglobulin M
    Chemical Substances Antibodies, Protozoan ; Immunoglobulin M
    Language English
    Publishing date 2023-06-02
    Publishing country France
    Document type Multicenter Study ; Journal Article
    ZDB-ID 1187629-3
    ISSN 1776-1042 ; 1252-607X
    ISSN (online) 1776-1042
    ISSN 1252-607X
    DOI 10.1051/parasite/2023020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Zidovudine: A salvage therapy for mcr-1 plasmid-mediated colistin-resistant bacterial infections?

    Peyclit, Lucie / Baron, Sophie A / Yousfi, Hanane / Rolain, Jean-Marc

    International journal of antimicrobial agents

    2018  Volume 52, Issue 1, Page(s) 11–13

    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Colistin/pharmacology ; Drug Resistance, Bacterial/drug effects ; Drug Resistance, Bacterial/genetics ; Enterobacteriaceae/drug effects ; Enterobacteriaceae/genetics ; Enterobacteriaceae/isolation & purification ; Enterobacteriaceae Infections/drug therapy ; Enterobacteriaceae Infections/microbiology ; Escherichia coli Proteins/genetics ; Humans ; Microbial Sensitivity Tests ; Plasmids/drug effects ; Salvage Therapy/methods ; Zidovudine/pharmacology ; Zidovudine/therapeutic use
    Chemical Substances Anti-Bacterial Agents ; Escherichia coli Proteins ; MCR-1 protein, E coli ; Zidovudine (4B9XT59T7S) ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2018-03-23
    Publishing country Netherlands
    Document type Editorial
    ZDB-ID 1093977-5
    ISSN 1872-7913 ; 0924-8579
    ISSN (online) 1872-7913
    ISSN 0924-8579
    DOI 10.1016/j.ijantimicag.2018.03.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: SCA Medium: A New Culture Medium for the Isolation of All

    Ibrahim, Ahmad / Peyclit, Lucie / Abdallah, Rim / Khelaifia, Saber / Chamieh, Amanda / Rolain, Jean-Marc / Bittar, Fadi

    Journal of fungi (Basel, Switzerland)

    2021  Volume 7, Issue 6

    Abstract: ... Candida ... ...

    Abstract Candida auris
    Language English
    Publishing date 2021-05-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2784229-0
    ISSN 2309-608X ; 2309-608X
    ISSN (online) 2309-608X
    ISSN 2309-608X
    DOI 10.3390/jof7060433
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Inactivation of thymidine kinase as a cause of resistance to zidovudine in clinical isolates of Escherichia coli: a phenotypic and genomic study.

    Peyclit, Lucie / Ben Khedher, Maryem / Zerrouki, Lotfi / Diene, Seydina M / Baron, Sophie Alexandra / Rolain, Jean-Marc

    The Journal of antimicrobial chemotherapy

    2020  Volume 75, Issue 6, Page(s) 1410–1414

    Abstract: Objectives: The antiviral zidovudine has been recently identified as an active drug against resistant Enterobacteriaceae, but prevalence of resistance to this compound remains unknown. The aim was to estimate the prevalence of clinical Escherichia coli ... ...

    Abstract Objectives: The antiviral zidovudine has been recently identified as an active drug against resistant Enterobacteriaceae, but prevalence of resistance to this compound remains unknown. The aim was to estimate the prevalence of clinical Escherichia coli isolates resistant to zidovudine and to decipher the mechanism of zidovudine resistance.
    Methods: We screened 537 isolates on zidovudine-containing agar plates and studied their thymidine kinase (tdk) gene sequences, the putative target involved in zidovudine resistance. Moreover, sequence analysis of 633 complete genomes of E. coli was performed to investigate mutation in the tdk gene. A comparative genomic analysis was done on an in vitro zidovudine-resistant mutant.
    Results: After screening on our medium containing 2.7 mg/L (10 μM) zidovudine, nine strains had a zidovudine MIC >26.7 mg/L. The gene was absent in three isolates, inactivated by an IS (IS1X2 and ISApl1) in two isolates and mutated in four isolates. A genomic analysis of 633 E. coli genomes showed heterogeneity of the tdk gene sequence, with 27 different sequences. Among them, three genomes showed an inactivation of the gene (IS, stop codon and no tdk gene sequence). The in vitro mutant E. coli had 27 SNPs in eight genes of the core genome compared with the initial strain.
    Conclusions: Our study reports zidovudine-resistant clinical isolates of E. coli, presumably related to tdk inactivation. Diversity of Tdk in bacterial genomes can be large. Other mechanisms need to be considered in zidovudine resistance. The use of zidovudine in antibiotic-resistant infections needs to be in combination and should be tested before clinical administration.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Drug Resistance, Bacterial/genetics ; Escherichia coli/genetics ; Escherichia coli Infections ; Escherichia coli Proteins ; Genomics ; Humans ; Microbial Sensitivity Tests ; Thymidine Kinase/genetics ; Zidovudine/pharmacology
    Chemical Substances Anti-Bacterial Agents ; Escherichia coli Proteins ; Zidovudine (4B9XT59T7S) ; Thymidine Kinase (EC 2.7.1.21)
    Language English
    Publishing date 2020-02-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dkaa057
    Database MEDical Literature Analysis and Retrieval System OnLINE

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