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resistance

  • Open Access
    Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019
    Epidemiology and Surveillance
    Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019

    Biennial therapeutic efficacy monitoring is a crucial activity for ensuring the efficacy of currently used artemisinin-based combination therapy in Angola. Children with acute uncomplicated Plasmodium falciparum infection in sentinel sites in the Benguela, Zaire, and Lunda Sul Provinces were treated with artemether-lumefantrine (AL) or artesunate-amodiaquine (ASAQ)...

    Pedro Rafael Dimbu, Roberta Horth, Ana Luísa M. Cândido, Carolina Miguel Ferreira, Felismina Caquece, Luzala Elisabeth Armando Garcia, Kialanda André, Garcia Pembele, Domingos Jandondo, Belmira José Bondo, Benjamin Nieto Andrade, Sarah Labuda, Gabriel Ponce de León, Julia Kelley, Dhruviben Patel, Samaly S. Svigel, Eldin Talundzic, Naomi Lucchi, Joana F. M. Morais, Filomeno Fortes, José Franco Martins, Mateusz M. Pluciński
  • Mutations in <em>fbiD</em> (<em>Rv2983</em>) as a Novel Determinant of Resistance to Pretomanid and Delamanid in <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>
    Editor's Pick Mechanisms of Resistance
    Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis

    The nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant...

    Dalin Rifat, Si-Yang Li, Thomas Ioerger, Keshav Shah, Jean-Philippe Lanoix, Jin Lee, Ghader Bashiri, James Sacchettini, Eric Nuermberger
  • <em>In Vitro</em> Activity Analysis of a New Polymyxin, SPR741, Tested in Combination with Antimicrobial Agents against a Challenge Set of <em>Enterobacteriaceae</em>, Including Molecularly Characterized Strains
    Susceptibility
    In Vitro Activity Analysis of a New Polymyxin, SPR741, Tested in Combination with Antimicrobial Agents against a Challenge Set of Enterobacteriaceae, Including Molecularly Characterized Strains

    The activities of azithromycin, fusidic acid, vancomycin, doxycycline, and minocycline were evaluated alone and in combination with SPR741. A total of 202 Escherichia coli and 221 Klebsiella pneumoniae isolates were selected, and they included a genome-sequenced subset (n = 267), which was...

    Rodrigo E. Mendes, Paul R. Rhomberg, Troy Lister, Nicole Cotroneo, Thomas R. Parr, Mariana Castanheira
  • Mutations Identified in the Hepatitis C Virus (HCV) Polymerase of Patients with Chronic HCV Treated with Ribavirin Cause Resistance and Affect Viral Replication Fidelity
    Antiviral Agents
    Mutations Identified in the Hepatitis C Virus (HCV) Polymerase of Patients with Chronic HCV Treated with Ribavirin Cause Resistance and Affect Viral Replication Fidelity

    Ribavirin has been used for 25 years to treat patients with chronic hepatitis C virus (HCV) infection; however, its antiviral mechanism of action remains unclear. Here, we studied virus evolution in a subset of samples from a randomized 24-week trial of ribavirin monotherapy versus placebo in chronic HCV patients, as well as the viral resistance mechanisms of the observed ribavirin-associated mutations in cell culture. Thus, we...

    Niels Mejer, Ulrik Fahnøe, Andrea Galli, Santseharay Ramirez, Ola Weiland, Thomas Benfield, Jens Bukh
  • Effect of Exposure to Chlorhexidine Residues at “During Use” Concentrations on Antimicrobial Susceptibility Profile, Efflux, Conjugative Plasmid Transfer, and Metabolism of <span class="named-content genus-species" id="named-content-1">Escherichia coli</span>
    Mechanisms of Resistance
    Effect of Exposure to Chlorhexidine Residues at “During Use” Concentrations on Antimicrobial Susceptibility Profile, Efflux, Conjugative Plasmid Transfer, and Metabolism of Escherichia coli

    There is no standardized protocol to predict the concentration levels of microbicides that are left on surfaces as a result of the use of these products, and there is no standardized method to predict the potential risk that such levels pose to emerging antibacterial resistance. The ability to distinguish between selection and adaption processes for antimicrobial resistance in bacteria and the impact of different concentrations of...

    R. Wesgate, S. Fanning, Y. Hu, J.-Y. Maillard
  • <em>In Vitro</em> Activity of Manogepix against Multidrug-Resistant and Panresistant <span class="named-content genus-species" id="named-content-1">Candida auris</span> from the New York Outbreak
    Susceptibility
    In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak

    An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several...

    YanChun Zhu, Shannon Kilburn, Mili Kapoor, Sudha Chaturvedi, Karen Joy Shaw, Vishnu Chaturvedi
  • Open Access
    Natural Polymorphisms in <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Conferring Resistance to Delamanid in Drug-Naive Patients
    Susceptibility
    Natural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-Naive Patients

    Mutations in the genes of the F420 signaling pathway of Mycobacterium tuberculosis complex, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, can lead to delamanid resistance. We searched for such mutations among 129 M. tuberculosis...

    Martina L. Reichmuth, Rico Hömke, Kathrin Zürcher, Peter Sander, Anchalee Avihingsanon, Jimena Collantes, Chloé Loiseau, Sonia Borrell, Miriam Reinhard, Robert J. Wilkinson, Marcel Yotebieng, Lukas Fenner, Erik C. Böttger, Sebastien Gagneux, Matthias Egger, Peter M. Keller
    and on behalf of the International epidemiology Databases to Evaluate AIDS (IeDEA)
  • Characterization of Large Deletion Mutants of <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Selected for Isoniazid Resistance
    Mechanisms of Resistance
    Characterization of Large Deletion Mutants of Mycobacterium tuberculosis Selected for Isoniazid Resistance

    Large genomic deletions (LGDs) (6 to 63 kbp) were observed in isoniazid-resistant Mycobacterium tuberculosis mutants derived from four M. tuberculosis strains. These LGDs had no growth defect in vitro but could be defective in intracellular growth and showed various sensitivities toward...

    Catherine Vilchèze, Rajagopalan Saranathan, Brian Weinrick, William R. Jacobs
  • Assessment of Drug Resistance during Phase 2b Clinical Trials of Presatovir in Adults Naturally Infected with Respiratory Syncytial Virus
    Antiviral Agents
    Assessment of Drug Resistance during Phase 2b Clinical Trials of Presatovir in Adults Naturally Infected with Respiratory Syncytial Virus

    This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults. Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific...

    Danielle P. Porter, Ying Guo, Jason Perry, David L. Gossage, Timothy R. Watkins, Jason W. Chien, Robert Jordan
  • Open Access
    Antileishmanial Aminopyrazoles: Studies into Mechanisms and Stability of Experimental Drug Resistance
    Mechanisms of Resistance
    Antileishmanial Aminopyrazoles: Studies into Mechanisms and Stability of Experimental Drug Resistance

    Current antileishmanial treatment is hampered by limitations, such as drug toxicity and the risk of treatment failure, which may be related to parasitic drug resistance. Given the urgent need for novel drugs, the Drugs for Neglected Diseases initiative (DNDi) has undertaken a drug discovery program, which has resulted in the identification of aminopyrazoles, a highly promising antileishmanial chemical series. Multiple...

    M. Van den Kerkhof, D. Mabille, S. Hendrickx, P. Leprohon, C. E. Mowbray, S. Braillard, M. Ouellette, L. Maes, G. Caljon

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