The outbreak of multispecies carbapenemase-producing Enterobacterales associated with pediatric ward sinks: IncM1 plasmids act as vehicles for cross-species transmission.

BACKGROUND: This study describes an outbreak caused by multispecies carbapenemase-producing Enterobacterales (CPE) occurring in a pediatric ward at an academic medical center in Tokyo. METHODS: The index case involved a 1-year-old boy with Klebsiella variicola (CPE) detected in anal swabs in June 2016. The second case was Klebsiella quasipneumoniae (CPE) occurred in March 2017 followed by further spread, leading to the declaration of an outbreak in April 2017. Extensive environmental and patient microbiological sampling was performed. The relatedness of the isolates was determined using draft-whole-genome sequencing. RESULTS: CPE surveillance cultures of patients and environments were positive in 19 patients and 9 sinks in the ward. The sinks in hospital rooms uninhabited by CPE patients exhibited no positive CPE-positive specimen during the outbreak. All CPE strains analyzed using draft-whole-genome sequencing harbored blaIMP-1, except for one harboring blaIMP-11; these strains harbored identical blaIMP-1-carrying IncM1 plasmids. CPE was detected even after sink replacement; infection-control measures focused on sinks were implemented and the CPE outbreak ended after 7 months. CONCLUSIONS: Multiple bacterial species can become CPE via blaIMP-1-carrying IncM1 plasmids of the same origin and spread through sinks in a hospital ward. Thorough infection-control measures implemented as a bundle might be crucial.

Direct measurement of interactions between stimulation-responsive drug delivery vehicles and artificial mucin layers by colloid probe atomic force microscopy.

A novel thermo- and pH-sensitive nanogel particle, which is a core-shell structured particle with a poly(N-isopropylacrylamide) (p(NIPAAm)) hydrogel core and a poly(ethylene glycol) monomethacrylate grafted poly(methacrylic acid) (p(MMA-g-EG)) shell, is of interest as a vehicle for the controlled release of peptide drugs. The interactions between such nanogel particles and artificial mucin layers during both approach and separation were successfully measured by using colloid probe atomic force microscopy (AFM) under various compression forces, scan velocities, and pH values. While the magnitudes of the compression forces and scan velocities did not affect the interactions during the approach process, the adhesive force during the separation process increased with these parameters. The pH values significantly influenced the interactions between the nanogel particles and a mucin layer. A large steric repulsive force and a long-range adhesive force were measured at neutral pH due to the swollen p(MMA-g-EG) shell. On the other hand, at low pH values, the steric repulsive force disappeared and a short-range adhesive force was detected, which resulted from the collapse of the shell layer. The nanogel particles possessed a pH response that was sufficient to protect the incorporated peptide drug under the harsh acidic conditions in the stomach and to effectively adhere to the mucin layer of the small intestine, where the pH is neutral. The relationships among the nanogel particle-mucin layer interactions, pH conditions, scan velocities, and compression forces were systemically investigated and discussed.

Effect of particle size on surface modification of silica nanoparticles by using silane coupling agents and their dispersion stability in methylethylketone.

The effect of particle size on the reactivity of hexyltrimethoxysilane (C6S) with the particle surface was studied by using silica nanoparticles (SNPs) with different diameters (30 or 200 nm). In case of 30-nm SNPs, a large amount of isolated silanol was observed. On the other hand, in the case of 200-nm SNPs, the amount of hydrogen bonded silanol and hydrogen bonded water molecules at the surface of the SNPs increased. Since the hydrogen bonded silanol and the hydrogen bonded water enhanced the reaction of C6S with SNPs, the chemisorbed C6S on 200-nm SNPs was larger than that on 30-nm SNPs. Furthermore, the effects of surface modification on the dispersion stability in MEK were studied using viscosity measurements and surface force measurements by the AFM colloid probe method. The viscosity of the dilute SNPs/MEK suspension did not change by the chemisorptions of C6S; however, the viscosity of dense suspension reduced effectively by surface modification. It was estimated that the suspension viscosity reduced effectively when the mean particle surface distance in the suspension was near to the distance where the repulsive force appeared by the surface force measurements using the colloid probe AFM.

Effect of surface interaction of silica nanoparticles modified by silane coupling agents on viscosity of methylethylketone suspension.

In order to control the viscosity of a dense silica methylethylketone (MEK) suspension, the surfaces of silica nanoparticles were modified by 3-glycidoxypropyltrimethoxysilane (GPS) or hexyltrimethoxysilane (C6S) in MEK with the addition of a small amount of pH-controlled water. First, the effect of water addition on the amount of chemisorbed coupling agent was investigated. pH-controlled water enhanced the reactivity of the coupling agent in MEK. The amount of chemisorbed coupling agent increased slightly with the addition of pH 3 water and increased remarkably with the addition of pH 12 water. Next, the effect of the organic functional groups of the coupling agent, pH of the additive water, and additive amount of coupling agent on surface interaction were determined by colloid probe AFM. The steric repulsive force between the silica nanoparticles increased due to water addition, particularly when the pH was maintained at 3. The viscosity of the silica MEK suspension reduced effectively when this repulsive force appeared; however, the optimum condition for reducing the suspension viscosity was dependent on the coupling agent species. The viscosity of the dense silica MEK suspension can be controlled by the addition of small amounts of pH-controlled water and the functional groups of the coupling agent.

Microstructure control of iron hydroxide nanoparticles using surfactants with different molecular structures.

To control the morphology and crystal phase of iron oxide nanoparticles within several 10 nm in diameter, a microbial-derived surfactant (MDS) with a high carboxyl-group density and relatively low molecular weight (about 650 g/mol) or an artificially synthesized polyacrylic acid sodium salt (PAA) was added into the raw material aqueous solution before iron oxide particle synthesis by the gel-sol method. While pseudo-cubic hematite particles with a diameter of 500 nm were prepared without surfactant addition, spherical iron hydroxide nanoparticles with a diameter of 20 nm were prepared by MDS addition. In contrast, needle-type iron hydroxide nanoparticles with a length of 100 nm along the long axis were prepared by PAA addition. Complex formation due to the interaction between COO- groups in each surfactant and Fe3+ ions, as well as the template role prior to the synthesis of iron oxide in raw aqueous solution, inhibited the phase transition from iron hydroxide to hematite. Furthermore, the morphology of the iron hydroxide nanoparticles depended on the molecular structure of the surfactants.

Preparation of agglomeration-free hematite particles coated with silica and their reduction behavior in hydrogen.

To prepare silica-coated hematite particles without agglomeration, the effects of solid fraction, ion content in solution, and designed layer thickness on agglomeration and dispersion behavior after silica coating were examined. Since the ion concentration remained high in suspension after the hematite particles were prepared, these particles formed aggregates by the compression of an electric double layer on the hematite and silica layer produced a solid bridge between primary hematite particles. Silica bridge formation and agglomeration were almost completely prevented by decreasing the ion concentration and solid fraction of the hematite particles. Furthermore, the effects of the silica-layer thickness and structure on the reduction of hematite to iron under hydrogen gas flow and the iron core stability under air were discussed. When the solid fraction was low in suspension to prevent agglomeration during coating, a densely packed structure of nanoparticles formed by heterogeneous nucleation was observed on the silica-layer surface. Since this structure could not completely prevent oxide diffusion, the layer thickness was increased to 40 nm to obtain a stable iron core under air. Although a dense uniform layer was produced at a high solid fraction during coating, its thickness was reduced to 20 nm to completely reduce hematite to iron.