Determination of MIC and Disk Diffusion Quality Control Guidelines for Meropenem–Vaborbactam, a Novel Carbapenem/Boronic Acid β-Lactamase Inhibitor Combination

Meropenem–vaborbactam is a carbapenem/cyclic boronic acid β-lactamase inhibitor combination primarily active against Gram-negative bacilli, including those harboring class A serine carbapenemases such as Klebsiella pneumoniae carbapenemase (KPC). A Clinical and Laboratory Standards Institute M23-A4 (Tier 2) quality control study established broth microdilution and disk diffusion ranges for reference strains. Two KPC-producing K. pneumoniae ATCC strains are recommended for quality control testing

In vitro activity of iclaprim and comparator agents against Listeria monocytogenes clinical isolates from 2012 to 2018

Objectives: This study examined the in vitro activity of iclaprim and comparators against 40 Listeria monocytogenes clinical isolates mostly (95%) from patients with bloodstream infection (BSI) from the USA, Australia/New Zealand, Latin America and Europe collected between 2012–2018. Methods: Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI criteria. Results: The iclaprim MIC90 value for all L. monocytogenes was 0.015 μg/mL. The MIC50/90 values for iclaprim were 4-fold lower than trimethoprim, the only FDA-approved dihydrofolate reductase inhibitor, against all L. monocytogenes. Conclusion: Iclaprim demonstrated lower MIC values than trimethoprim against a collection (2012–2018) of L. monocytogenes clinical isolates mostly from patients with BSI from the USA, Australia/New Zealand, Latin America and Europe

Crystallographic and optical study of LiNb1 − x Ta x O3

Powders of lithium niobate-tantalate across the full compositional range have been made and crystals grown using a lithium vanadate flux growth technique. The Li-content of a lithium tantalate crystal has been determined using the zero-birefringence temperature and Curie measurements, confirming the Li content is between that of congruent and stoichiometric crystals. X-ray diffraction measurements show the Nb/Ta displacement and octahedral tilt both decrease as the Ta content is increased. This also results in a decrease in the lattice parameters from lithium niobate to lithium tantalate. Birefringence measurements on the crystals as a function of temperature have been used to determine the point that the crystals become zero-birefringent, and by comparison with the structural studies have confirmed that it is not related to a phase transition and the structures remain polar through the zero-birefringence points.</jats:p

Growth of LiNb1−xTaxO3 solid solution crystals

The growth of single crystals of solid solutions of LiNbO3 and LiTaO3 has been studied by using a number of different techniques: Czochralski pulling, Top-Seeded Solution Growth, flux growth from LiBO2 and LiVO3, and by optical floating zone. Crystals with homogenous Li, Ta and Nb compositions were obtained by several techniques. Analysis of local and average compositions of Ta, Nb and Li by Raman spectroscopy, birefringence imaging and X-ray diffraction, in addition to EDAX, is described. The effects of replacing Nb by Ta and of Li non-stoichiometry on the lattice parameters and the compositional disorder over the whole composition range 0 ≤ x ≤ 1 are discussed

In Vitro and In Vivo Activities of PD 0305970 and PD 0326448, New Bacterial Gyrase/Topoisomerase Inhibitors with Potent Antibacterial Activities versus Multidrug-Resistant Gram-Positive and Fastidious Organism Groups

PD 0305970 and PD 0326448 are new bacterial gyrase and topoisomerase inhibitors (quinazoline-2,4-diones) that possess outstanding in vitro and in vivo activities against a wide spectrum of bacterial species including quinolone- and multidrug-resistant gram-positive and fastidious organism groups. The respective MICs (μg/ml) for PD 0305970 capable of inhibiting ≥90% of bacterial strains tested ranged from 0.125 to 0.5 versus staphylococci, 0.03 to 0.06 versus streptococci, 0.25 to 2 versus enterococci, and 0.25 to 0.5 versus Moraxella catarrhalis, Haemophilus influenzae, Listeria monocytogenes, Legionella pneumophila, and Neisseria spp. PD 0326448 MIC(90)s were generally twofold higher versus these same organism groups. Comparative quinolone MIC(90) values were 4- to 512-fold higher than those of PD 0305970. In testing for frequency of resistance, PD 0305970 and levofloxacin showed low levels of development of spontaneous resistant mutants versus both Staphylococcus aureus and Streptococcus pneumoniae. Unlike quinolones, which target primarily gyrA and parC, analysis of resistant mutants in S. pneumoniae indicates that the likely targets of PD 0305970 are gyrB and parE. PD 0305970 demonstrated rapid bactericidal activity by in vitro time-kill testing versus streptococci. This bactericidal activity carried over to in vivo testing, where PD 0305970 and PD 0326448 displayed outstanding Streptococcus pyogenes 50% protective doses (PD(50)s) (oral dosing) of 0.7 and 3.6 mg/kg, respectively (ciprofloxacin and levofloxacin PD(50)s were >100 and 17.7 mg/kg, respectively). PD 0305970 was also potent in a pneumococcal pneumonia mouse infection model (PD(50) = 3.2 mg/kg) and was 22-fold more potent than levofloxacin