d IMP-type metallo-␤-lactamase enzymes have been reported in different geographical areas and in various Gram-negative bacteria. However, the risk factors and epidemiology pertaining to IMP-type metallo-␤-lactamase-producing Enterobacter cloacae (IMP-producing E. cloacae) have not been systematically evaluated. We conducted a retrospective, matched case-control study of patients from whom IMP-producing E. cloacae isolates were obtained, in addition to performing thorough molecular analyses of the clinically obtained IMP-producing E. cloacae isolates. Unique cases with IMP-producing E. cloacae isolation were included. Patients with IMP-producing E. cloacae were matched to uninfected controls at a ratio of 1 to 3. Fifteen IMP-producing E. cloacae cases were identified, with five of the isolates being obtained from blood, and they were matched to 45 uninfected controls. All (100%) patients from whom IMP-producing E. cloacae isolates were obtained had indwelling devices at the time of isolation, compared with one (2.2%) uninfected control. Independent predictors for isolation of IMP-producing E. cloacae were identified as cephalosporin exposure and invasive procedures within 3 months. Although in-hospital mortality rates were similar between cases and controls (14.3% versus 13.3%), the in-hospital mortality of patients with IMP-producing E. cloacae-caused bacteremia was significantly higher (40%) than the rate in controls. IMP-producing E. cloacae isolates were frequently positive for other resistance determinants. The MICs of meropenem and imipenem were not elevated; 10 (67%) and 12 (80%) of the 15 IMP-producing E. cloacae isolates had a MIC of <1 g/ml. A phylogenetic tree showed a close relationship among the IMP-producing E. cloacae samples. Indwelling devices, exposure to cephalosporin, and a history of invasive procedures were associated with isolation of IMP-producing E. cloacae. Screening for carbapenemase production is important in order to apply appropriate clinical management and infection control measures.

Keywordsbiaxial kneading extruder; fused deposition modelling type three-dimensional printer; geometrical structure of three-dimensional tablet; hypromellose phthalate; rebamipide Correspondence AbstractObjectives Three-dimensional (3-D) printers are widely expected to provide a novel manufacturing method in the future to make personalized medicines in hospitals. Methods Functional filament containing 5-20% drug was prepared with rebamipide (REB; a poorly water-soluble model drug) and hypromellose phthalate (HPMCP; enteric base) at 130-170°C using a biaxial kneading extruder. Several tablet models with various internal structures were designed using computeraided design. REB-containing 3-D tablets were prepared based on these designs from filament using a fused deposition modelling type 3-D printer. Key findings Physicochemical characteristics of the filament and 3-D tablets were measured by powder X-ray diffraction and differential scanning calorimetry. The results suggested that a part of the crystalline REB dispersed into the HPMCP and transformed into an amorphous form, because crystalline REB was kneaded with melted HPMCP at 130-170°C during the preparation processes of filament and 3-D tablets. The drug-release properties of 3-D tablets were tested in both pH 1.2 and 6.8 buffers. REB was not released from the 3-D tablets at pH 1.2, but HPMCP dissolved at pH 6.8, and then REB was rapidly released from the tablet. Conclusions The dissolution of 3-D tablets in the small intestine could be controlled by the tablet geometrical structure.

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