Evaluation of the safety profile and intrapulmonary pharmacokinetics of intravenous fosfomycin in healthy adults.

Unlabelled: This Phase 1 trial described the intrapulmonary pharmacokinetics and safety profile of IV fosfomycin in healthy participants Fosfomycin, a broad-spectrum antibiotic mainly used to treat urinary tract infections, is being considered for treatment of more complex conditions, including lung infections, due to the emergence of multidrug-resistant (MDR) organisms. Despite its potential, the pharmacokinetics and safety profile of intravenous (IV) fosfomycin, particularly its penetration into the lower respiratory tract, are unknown. To address this gap, we conducted a Phase 1, open-label trial to assess the safety and pulmonary pharmacokinetics of IV fosfomycin in healthy participants.

Evaluation of Vancomycin Dose Needed to Achieve 24-Hour Area Under the Concentration-Time Curve to Minimum Inhibitory Concentration Ratio Greater Than or Equal to 400 Using Pharmacometric Approaches in Pediatric Intensive Care Patients.

Objectives: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

Design: Prospective population pharmacokinetic study of vancomycin.

Setting: Critically ill patients in quaternary care PICUs.

Crystal structure of bis-(β-alaninium) tetra-bromidoplumbate.

The title compound, poly[bis-(β-alaninium) [[di-bromido-plumbate]-di-μ-di-bromido]] {(CHNO)[PbBr]} or (-AlaH)PbBr, crystallizes in the monoclinic space group 2/. The (PbBr) anion is located on a general position and has a two-dimensional polymeric structure. The Pb center is holodirected.

Crystal structure of hexa-glycinium dodeca-iodo-triplumbate.

The crystal structure of hexa-glycinium tetra-μ-iodido-octa-iodido-triplumbate, (CHNO)[PbI] or (GlyH)[PbI], is reported. The compound crystallizes in the triclinic space group . The [PbI] anion is discrete and located around a special position: the central Pb ion located on the inversion center is holodirected, while the other two are hemidirected.

Safety and pharmacokinetics of antifungal agent VT-1598 and its primary metabolite, VT-11134, in healthy adult subjects: phase 1, first-in-human, randomized, double-blind, placebo-controlled study of single-ascending oral doses of VT-1598.

VT-1598 is a novel fungal CYP51 inhibitor and 1-tetrazole-based antifungal drug candidate with improved selectivity minimizing off-target binding to and inhibition of human CYP450 enzymes. Data are presented from this first clinical study in the evaluation of the safety and pharmacokinetic (PK) of single ascending doses of 40, 80, 160, 320, and 640 mg VT-1598, comprising a 160 mg cohort in both fasting and fed states. Eight healthy adults per dose were randomized to receive either oral VT-1598 or placebo (3:1).

Daily fosfomycin versus levofloxacin for complicated urinary tract infections.

Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.

Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial.

Background: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin.

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

Background: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.

Methods: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site).

Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial.

Background: Staphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15-50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S.

Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial.

Importance: Childhood community-acquired pneumonia (CAP) is usually treated with 10 days of antibiotics. Shorter courses may be effective with fewer adverse effects and decreased potential for antibiotic resistance.

Objective: To compare a short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in young children.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

Background: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19.

Methods: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA).

: A rare uropathogen.

Urinary tract infections (UTIs) are clinically and economically burdensome. Gram positive causative uropathogens are rare, and has infrequently been isolated as a causative agent for UTIs. Here, we present two cases of causing complicated urinary tract infections.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

Background: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.

Methods: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19.

Declining tuberculosis notification trend associated with strengthened TB and expanded HIV care in Swaziland.

This retrospective observational review documents the efforts of the Swaziland National Tuberculosis (TB) Control Programme between 2004 and 2014. The objective is to describe the disparity between actual declines in case notification and increases in estimated incidence. The review of policies and practices shows the most influential factors associated with the decrease in TB case notification to be an increase in access to antiretroviral therapy for co-infected TB patients, the general success of TB and human immunodeficiency virus service integration in the country and improvements in implementation of all components of directly observed treatment, active case finding, and rapid diagnosis using new technologies.

Unusual hydrogen bonding in L-cysteine hydrogen fluoride.

L-Cysteine hydrogen fluoride, or bis(L-cysteinium) difluoride-L-cysteine-hydrogen fluoride (1/1/1), 2C3H8NO2S(+)·2F(-)·C3H7NO2S·HF or L-Cys(+)(L-Cys···L-Cys(+))F(-)(F(-)...

L-Argininium phosphite - a new candidate for NLO materials.

In order to investigate the possibility of salt formation in the L-Arg-H3PO3-H2O system, single crystals of L-argininium phosphite, C6H15N4O2(+)·H2PO3(-), were prepared by evaporation of an aqueous solution containing equimolar quantities of L-arginine and phosphorous acid. The asymmetric unit contains one L-argininium(+) cation and one phosphite [HPO2(OH)](-) anion. The phosphite anions form chains parallel to [010] by O-H.

β-Alaninium tetrafluoroborate: a new salt with di-β-alaninium dimeric cation.

β-Alaninium tetrafluoroborate crystallizes in the monoclinic system (space group P21/n, Z=4). The asymmetric unit contains one β-alaninium cation and one tetrafluoroborate anion, in which the fluorine atoms are disordered. All β-alaninium cations are connected with the symmetry related cations via an inversion center, thus forming dimeric centrosymmetric β-Ala(+)···β-Ala(+) cations.

L-Methioninium picrate.

Single crystals of l-methioninium picrate were obtained by evaporation of aqueous solution containing equimolar quantities of each component. l-Methioninium picrate crystallizes in the monoclinic system (space group P21, Z=2). The asymmetric unit contains one l-methioninium cation and one picrate anion.

L-tryptophan L-tryptophanium chloride.

L-tryptophan L-tryptophanium chloride is a new salt with (A⋯A(+)) type dimeric cation. It crystallizes in the monoclinic system (space group P2(1), Z=2). The asymmetric unit contains one zwitterionic L-tryptophan molecule, one L-tryptophanium cation and one chloride anion.

On the existence of "L-threonine formate", "L-alanine lithium chloride" and "bis L-alanine lithium chloride" crystals.

We argue that the recently reported crystals "L-threonine formate" as well as "L-alanine lithium chloride" and "bis L-alanine lithium chloride" actually are the well-known crystals L-threonine and L-alanine, respectively.

Diaquaiodidotetrasarcosinepotassium: an overview of sarcosine metal halogenide structures.

The monoclinic crystal structure of tetrasarcosine potassium iodide dihydrate {or catena-poly[[potassium-tetra-μ-sarcosine-κ(4)O:O';κ(4)O:O] iodide dihydrate]}, {[K(C(3)H(7)NO(2))(4)]I·2H(2)O}(n) or Sar(4)·KI·2H(2)O (space group C2/c), comprises two crystallographically different sarcosine molecules and one water molecule on general positions, and one K(+) cation and one I(-) anion located on twofold axes. The irregular eight-coordinated K(+) polyhedra are connected into infinite chains along [001] via sarcosine molecules. This compound is the first sarcosine metal halogenide salt with a 4:1 ratio.

Reinvestigation of L-tryptophan picrate: establishment of the existence of the L-tryptophan L-tryptophanium dimeric cation.

A crystal structure redetermination of the L-tryptophan picrate crystal previously studied by Ishida et al. (Chem. Pharm.