Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review.

Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Gram-positive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospital-acquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections

The genesis and early developments of Aitken\u2019s process, Shanks\u2019 transformation, the \u3b5\u2013algorithm, and related fixed point methods

In this paper, we trace back the genesis of Aitken\u2019s \u3942 process and Shanks\u2019 sequence transformation. These methods, which are extrapolation methods, are used for accelerating the convergence of sequences of scalars, vectors, matrices, and tensors. They had, and still have, many important applications in numerical analysis and in applied mathematics. They are related to continued fractions and Pad\ue9 approximants. We go back to the roots of these methods and analyze the original contributions. New and detailed explanations on the building and properties of Shanks\u2019 transformation and its kernel are provided. We then review their historical algebraic and algorithmic developments. We also analyze how they were involved in the solution of systems of linear and nonlinear equations, in particular in the methods of Steffensen, Pulay, and Anderson. Testimonies by various actors of the domain are given. The paper can also serve as an introduction to this domain of numerical analysis