Cell-wall-inhibiting antibiotic combinations with activity against multidrug-resistant Klebsiella pneumoniae and Escherichia coli

AbstractThe increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is rapidly limiting the options for effective antibiotic therapy. Systematic studies on combinations of already available antibiotics that could provide an effective treatment against MDR bacteria are needed. We tested combinations of antibiotics that target one important physiological function (peptidoglycan synthesis) at several steps, and studied Enterobacteriaceae (Klebsiella pneumoniae and Escherichia coli) for which multidrug resistance associated with ESBL-producing plasmids has become a major problem. To measure the effectiveness of antibiotics alone and in combination, we used checkerboard assays, static antibiotic concentration time-kill assays, and an improved in-vitro kinetic model that simulates human pharmacokinetics of multiple simultaneously administered antibiotics. The target strains included an MDR K. pneumoniae isolate responsible for a recent major hospital outbreak. A double combination (fosfomycin and aztreonam) and a triple combination (fosfomycin, aztreonam and mecillinam) were both highly effective in reducing bacterial populations in all assays, including the in vitro kinetic model. These combinations were effective even though each of the MDR strains was resistant to aztreonam alone. Our results provide an initial validation of the potential usefulness of a combination of antibiotics targeting peptidoglycan synthesis in the treatment of MDR Gram-negative bacteria. We suggest that a combination of fosfomycin with aztreonam could become a useful treatment option for such infections and should be further studied

General formalism for vibronic Hamiltonians in tetragonal symmetry and beyond

We derive general expansion formulas in vibrational coordinates for all bimodal Jahn-Teller and pseudo-Jahn-Teller Hamiltonians in tetragonal symmetry. Symmetry information of all the vibronic Hamiltonian matrix elements is fully carried by up to only 4 eigenvalues of symmetry operators. This problem-to-eigenvalue reduction enables us to handle thousands of vibronic problems in one work. The derived bimodal formulas can be easily extended to cover problems with one or more than two vibrational modes. They lay a solid foundation for future vibronic coupling studies of tetragonal systems. More importantly, the efficient derivation can be applied to handle (pseudo-)Jahn-Teller Hamiltonians for all problems with one principal symmetry axis

VHEGEN: A vibronic Hamiltonian expansion generator for trigonal and tetragonal polyatomic systems

An increasing number of studies in Jahn–Teller and pseudo-Jahn–Teller effects have revealed the importance of vibronic Hamiltonians with high order expansions in vibrational coordinates. This motivates us to present VHEGEN (V-ibronic H-amiltonian E-xpansion GEN-erator), a Python package that is capable of symbolically generating arbitrarily high order expansion formulas for the vibronic Hamiltonians. The program covers all >6000 bimodal Jahn–Teller and pseudo-Jahn–Teller problems in trigonal and tetragonal symmetries. The generated expansions are correct, complete, and concise. VHEGEN is a useful program for future studies in Jahn–Teller and pseudo-Jahn–Teller effects. Program summary: Program Title: VHEGEN Program Files doi: http://dx.doi.org/10.17632/7t5p6snkd7.1 Licensing provisions: GPLv3 Programming language: Python Nature of problem: Obtaining correct, complete, and concise high-order expansions of Jahn–Teller and pseudo-Jahn–Teller Hamiltonians in a case-by-case manner is a laborious and error-prone task. Solution method: We present a Python package to automate the utilization of our recently developed formalisms in obtaining any possible trigonal and tetragonal bimodal (pseudo-)Jahn–Teller vibronic Hamiltonian expanded to arbitrary order in vibrational coordinates

Cardiovascular Nursing and Climate Change: A Call to Action From the CSANZ Cardiovascular Nursing Council

Online published-ahead-of-print 1 December 2022This Call to Action aims to provide key considerations for cardiovascular nursing, related to climate and environmental impacts. Strategies to optimise nursing preparation, immediate response and adaptation to climate emergencies are crucial to ensure those at greatest risk, including First Nations peoples, are protected from potentially avoidable harm. Professionals who manage climate consequences must also understand the impact of their care on the root cause of the problem.Sally C. Inglis, Caleb Ferguson, Rebecca Eddington, Julee McDonagh, Chris J. Aldridge, Kimberley Bardsley, Dion Candelaria, Y.Y. Chen, Robyn A. Clark, Elizabeth Halcomb, Jeroen M. Hendriks, Louise D. Hickman, Rochelle Wynn