The Experts below are selected from a list of 281352 Experts worldwide ranked by ideXlab platform

Pamela Yeh - One of the best experts on this subject based on the ideXlab platform.

  • antibiotic Combination Therapy against resistant bacterial infections synergy rejuvenation and resistance reduction
    2020
    Co-Authors: Anthony R M Coates, James K L Holt, Pamela Yeh
    Abstract:

    Introduction: Anti-Microbial Resistance (AMR) is a pandemic which threatens modern medicine. There is a lack of effective drug treatment due to the slow pace, high cost and low achievable sales prices of new antibiotic monotherapies. New hope comes in the shape of antibiotic Combination Therapy, which although used by mother nature, is under-explored and could provide the solution to AMR.Areas covered: We performed a search of Pubmed and Medline using the keywords 'Combination Therapy', 'antimicrobial resistance' for articles between 1930 and 2019, as supplemented with other relevant references to our knowledge. We have reviewed the theoretical considerations for Combination development and examine the existing and future clinical indications of Combination therapies. We have discussed the potential of antibiotic Combinations to provide therapeutic synergy, rejuvenating the effectiveness of old antibiotics to which the bacteria had developed resistance previously. We have examined the current thinking and evidence on resistance reduction using Combination therapies, with a review on toxicity and drug-drug antagonism.Expert opinion: Antibiotic Combination Therapy, exploiting synergies, old-drug rejuvenation and resistance reduction could provide the solution to AMR. The number of pharmaceutical companies in this area is likely to expand, bringing promising Combinations to the bedside, to save millions of lives worldwide.

Leonard Leibovici - One of the best experts on this subject based on the ideXlab platform.

  • Combination Therapy for carbapenem resistant gram negative bacteria
    2014
    Co-Authors: M Paul, Johan W. Mouton, Yehuda Carmeli, Emanuele Durantemangoni, Evelina Tacconelli, Ursula Theuretzbacher, Cristina Mussini, Leonard Leibovici
    Abstract:

    Carbapenem-resistant Gram-negative bacteria (CR-GNB) represent an increasing hazard in healthcare settings. A central question concerning the treatment of invasive infections caused by CR-GNB involves the use of Combination Therapy. Potential advantages of Combination Therapy include improved efficacy due to synergy, while the disadvantages include adverse events and increased antibiotic use with a potential drive towards resistance. Several observational studies have examined whether Combination Therapy offers an advantage over colistin/ polymyxin monoTherapy. We highlight the inherent limitations of these studies related to their observational design and sample size to show why they do not at present provide an answer to the question of Combination versus monoTherapy.This distinction is important to guide clinical practice until solid evidence has been obtained and to enable the recruitment of patients into randomized controlled trials. A few randomized controlled trials examining specific Combinations have recently been completed or are ongoing. Currently, however, there is no evidence-based support for mostCombination therapies against CR-GNB, including colistin/carbapenem Combination Therapy.

Lisa L. Maragakis - One of the best experts on this subject based on the ideXlab platform.

  • Combination Therapy for treatment of infections with gram-negative bacteria
    2012
    Co-Authors: Pranita D Tamma, Sara E Cosgrove, Lisa L. Maragakis
    Abstract:

    Combination antibiotic Therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric Combination Therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued Combination Therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of Combination antibiotic Therapy stems from the increased likelihood of choosing an effective agent during empiric Therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monoTherapy versus Combination antimicrobial Therapy for the treatment of infections with Gram-negative bacteria.

Ram I Mahato - One of the best experts on this subject based on the ideXlab platform.

  • Combination Therapy of paclitaxel and cyclopamine polymer drug conjugates to treat advanced prostate cancer
    2017
    Co-Authors: Ruinan Yang, Goutam Mondal, Di Wen, Ram I Mahato
    Abstract:

    Repeated treatments with chemotherapeutic agent(s) fail due to cancer stem cells (CSCs) and chemoresistance regulated by microRNAs (miRNA) whose expression alters owing to dysfunctional signaling pathways including Hedgehog (Hh) signaling. We previously demonstrated the Combination of Hh inhibitor cyclopamine (CYP) and paclitaxel (PTX) effectively inhibit PTX-resistant cells and side population, a cell fraction rich in CSCs. In this study, we synthesized mPEG-b-PCC-g-PTX-g-DC (P-PTX) and mPEG-b-PCC-g-CYP-g-DC (P-CYP) polymer-drug conjugates, which they self-assembled into micelles. The Combination of P-PTX and P-CYP alleviated PTX resistance and suppressed tumor colony formation. Further, Combination Therapy inhibited Hh signaling and up-regulated tumor suppressor miRNAs. We established orthotopic prostate tumor in nude mice and there was significant tumor growth inhibition in the group treated with the Combination Therapy of P-PTX and P-CYP compared with monoTherapy. In conclusion, this Combination Therapy of P-PTX and P-CYP has the potential to treat chemoresistant prostate cancer.

  • Combination Therapy of antiandrogen and xiap inhibitor for treating advanced prostate cancer
    2012
    Co-Authors: Michael K Danquah, Charles B Duke, Renukadevi Patil, Duane D Miller, Ram I Mahato
    Abstract:

    Purpose Overexpression of the androgen receptor (AR) and anti-apoptotic genes including X-linked inhibitor of apoptosis protein (XIAP) provide tumors with a proliferative advantage. Therefore, our objective was to determine whether novel antiandrogen (CBDIV17) and XIAP inhibitor based Combination Therapy can treat advanced prostate cancer.

Yoshihiro Kawaoka - One of the best experts on this subject based on the ideXlab platform.

  • triple Combination Therapy of favipiravir plus two monoclonal antibodies eradicates influenza virus from nude mice
    2020
    Co-Authors: Maki Kiso, Yoshihiro Kawaoka, Seiya Yamayoshi
    Abstract:

    Prolonged treatment of immunocompromised influenza patients with viral neuraminidase (NA) inhibitors is required, because the immune system of such patients fails to eradicate the viruses. Here, we attempted to eradicate influenza virus from the respiratory organs of nude mice, which is a model of immunocompromised hosts, by using Combination Therapy of the viral polymerase inhibitor favipiravir and monoclonal antibodies (mAbs) against the receptor-binding site (RBS) and stem of viral hemagglutinin (HA). Although monoTherapy or Combination Therapy of two antivirals (two mAbs or favipiravir plus a mAb) suppressed virus replication, they failed to eradicate viruses from nude mice. In contrast, the triple Combination Therapy of favipiravir plus anti-Stem and anti-RBS mAbs completely stopped virus replication in nude mice, resulting in virus clearance. Triple Combination approaches should be considered for the treatment of human immunocompromised patients with severe influenza. Kiso et al. develop Combination Therapy of the viral polymerase inhibitor favipiravir and monoclonal antibodies against the receptor-binding site and stem of viral hemagglutinin. They show that triple, but not double, Combination Therapy is able to eradicate the influenza virus from nude mice. Their work provides insights on therapeutic options for immunocompromised patients.

  • Combination Therapy with neuraminidase and polymerase inhibitors in nude mice infected with influenza virus
    2018
    Co-Authors: Maki Kiso, Seiya Yamayoshi, Tiago J S Lopes, Mutsumi Ito, Makoto Yamashita, Noriko Nakajima, Hideki Hasegawa, Gabriele Neumann, Yoshihiro Kawaoka
    Abstract:

    Background Treatment of immunocompromised, influenza virus-infected patients with the viral neuraminidase inhibitor oseltamivir often leads to the emergence of drug-resistant variants. Combination Therapy with compounds that target different steps in the viral life cycle may improve treatment outcomes and reduce the emergence of drug-resistant variants. Methods Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or Combinations thereof. Results Combination Therapy for 28 days increased survival times compared with monoTherapy, but the animals died after treatment was terminated. Mono- and Combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor-resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors. Conclusions Collectively, our data demonstrate that Combination Therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor-resistant variants.