In Vitro Antibacterial Activity of Imipenem/Relebactam against Clinical Isolates in Japan.

Relebactam is a novel ß-lactamase inhibitor of Ambler class A and C ß-lactamases that has been developed in combination with imipenem/cilastatin for the treatment of carbapenem-resistant bacterial infections. In this study, we evaluated the in vitro antibacterial activity of imipenem/relebactam (IMR) against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. Two sets of antibacterial susceptibility tests were conducted according to the susceptibility testing standard of the Clinical and Laboratory Standards Institute. In the first set, antibacterial susceptibility as measured by the MIC50/90 (MIC range) of IMR was assessed for the following 61 imipenem-nonsusceptible strains: 2 Enterobacter cloacae complex (not determined [0.25 µg/mL]), 33 Klebsiella aerogenes (0.5/1 µg/mL [0.5 to 1 µg/mL]), 2 Serratia marcescens (not determined [1 to 2 µg/mL]), and 24 P. aeruginosa (2/128 µg/mL [0.25 to >128 µg/mL]). In the second set, antibacterial susceptibility was assessed for the following 8 imipenem-nonsusceptible strains: 4 Escherichia coli, 1 E. cloacae complex and 3 Klebsiella pneumoniae. The MIC ranges of IMR for these strains were 0.25 to 0.5 µg/mL, 0.5 µg/mL, and 0.5 to 16 µg/mL, respectively. The antibacterial activity of IMR was similar to or lower than that of amikacin and comparable to or greater than those of other reference drugs. In conclusion, IMR has shown antibacterial activity against clinical isolates from Japan and, therefore, is expected to become a new therapeutic option for carbapenem-resistant infections in Japan. IMPORTANCE Carbapenem-resistant Enterobacterales and carbapenem-resistant Pseudomonas aeruginosa strains pose a global threat. Antibacterial activity of imipenem/relebactam (IMR) against clinical isolates of these bacteria from several global regions has been shown; however, as yet there are no reports on Japanese isolates. In this study, we evaluated the in vitro antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. The antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales was generally comparable to that of amikacin (AMK) and comparable to or higher than those of other reference drugs tested. The antibacterial activity of IMR against imipenem-nonsusceptible P. aeruginosa isolates was lower than that of AMK but comparable to or higher than those of other drugs. These results support the use of IMR as a new treatment option for infections due to Enterobacterales and P. aeruginosa strains that are resistant to existing ß-lactams and other antibacterial agents.

In vitro activity of sitafloxacin against atypical bacteria (2009-2014) and comparison between susceptibility of clinical isolates in 2009 and 2012.

In vitro activities of sitafloxacin (STFX) along with fluoroquinolones (levofloxacin (LVFX), moxifloxacin (MFLX), garenoxacin (GRNX)) and macrolides (azithromycin, clarithromycin) against atypical bacteria (Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae) recovered from clinical specimens from 2009 to 2014 at different healthcare facilities in Japan were investigated. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) against M pneumoniae (n= 14) was 0.03µg/mL which was comparable to GRNX, 4- and 16-fold more active than MFLX and LVFX, respectively. Reduced susceptibilities of M pneumoniae (9/14 isolates) to macrolides were observed. MIC90 of STFX against L. pneumophila (n =15) was 0.004µg/mL which was 2- and 4-fold more active than GRNX/LVFX and MFLX, respectively. The minimum inhibitory concentration range of STFX against C. trachomatis (n=5) and C. pneumoniae (n=5) were from 0.015 to 0.03 and from 0.03 to 0.06µg/mL, respectively. Furthermore, differences between the activities of STFX against various clinical isolates in 2009 and those in 2012, which were already published in two articles (Jpn. J. Antibiotics 63:411- 430, 2010, 66:311-330, 2013), were also evaluated. The MIC90s of STFX against methicillin- susceptible Staphylococcus aureus (MSSA), Streptococcus spp. and Enterococcus faecalis isolated in 2012 were 4 or 8 times higher than those in 2009, however there was no difference between STFX activities against other species in 2009 and those in 2012. In conclusion, STFX showed potent activity against atypical bacteria (M pneumoniae, L. pneumophila, C. trachomatis, C. pneumoniae) and no tendency for emergence resistance to Gram- positive cocci, Gram-negative bacteria and anaerobes except MSSA, Streptococcus spp. andt. faecalis.

[In vitro activity of sitafloxacin against clinical isolates in 2012].

In vitro activity of sitafloxacin (STFX) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between January and December 2012, at different healthcare facilities in Japan was evaluated. A total of 1,620 isolates including aerobic and anaerobic organisms were available for the susceptibility testing using the microbroth dilution methods recommended by Clinical and Laboratory Standards Institute. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) was 0.5 microg/mL for methicillin-susceptible Staphylococcus aureus and was 2 times lower than that of garenoxacin (GRNX), 4 times lower than that of moxifloxacin (MFLX), and 16 times lower than that of levofloxacin (LVFX). STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90 of STFX was 0.03 microg/mL and was 2 times lower than that of GRNX, 4 times lower than that of MFLX, and 32 times lower than that of LVFX. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL and was 2 times lower than that of GRNX, 8 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX was 2 microg/mL for Enterococcus faecalis, and was 4 times lower than that of GRNX, 8 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX for Escherichia coli was 2 microg/mL, and the MIC90(s) of other 10 species of Enterobacteriaceae which were the lowest values of the quinolones tested ranged from 0.03 to 1 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 4 microg/mL and was 32 times lower than those of GRNX, MFLX and LVFX. The MIC90 of STFX for P. aeruginosa isolates recovered from respiratory infections was 4 microg/mL and was 8 to 16 times lower than those of GRNX, MFLX, and LVFX. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less, and was 4 times lower than that of GRNX, 16 times lower than that of MFLX, and 8 times lower than that of LVFX. The MIC90 of STFX was 0.015 microg/mL for Moraxella catarrhalis, and was equal to that of GRNX, 4 times lower than those of MFLX and LVFX. The MIC90(s) of STFX ranged from 0.03 to 0.25 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested. In conclusion, the activity of STFX against Gram-positive cocci was comparable or superior to those of GRNX, MFLX and LVFX. STFX showed the most potent activity against Gram-negative bacteria and anaerobic bacteria of all the antimicrobial agents tested in this study.

The morphological features and developmental changes of the philtral dimple: a guide to surgical intervention in cases of cleft lip.

OBJECTIVE: This study was undertaken to analyse in detail the morphological features of the philtral dimple and the developmental changes of philtral morphology, including a comparison with patients with a cleft lip. PATIENTS AND PARTICIPANTS: Fifty-five normal Japanese adults, seventy-five children and fifteen patients with complete unilateral cleft lip were referred for analysis. DESIGN: 3D facial data were acquired with a non-contacting laser scanner. We calculated the desired linear and angular components, defining the features of the philtrum with analysing software. RESULTS: The philtral dimple was morphologically expressed by the two different deepest points in the horizontal and sagittal sectional view, respectively. These decreased with age and did not show any correlation. In contrast, philtral measurements on the X-Y coordinates increased during the course of development. Most of the linear and angular variables in the patients with the cleft lip had exhibited greater values than the normal subjects, reflecting the deformed philtral morphology. CONCLUSIONS: To obtain an optimally natural philtral construction accompanied by a symmetrical lip in cleft surgery, it is critical to take into consideration both the geometric features of the philtral depth and age-appropriate morphological features of the philtrum as objective criteria.

Comprehensive evaluation of three-dimensional philtral morphology.

This study was designed to evaluate detailed philtral morphology involving sex and racial differences and to clarify the objective parameters related to subjective judgments regarding the clarity of the philtrum. Fifty-five Japanese and 20 Mexican normal subjects aged 24 to 40 years were recruited, and three-dimensional facial data were acquired using a noncontacting optical surface scanner. The visual classification of the philtral column morphology in Japanese adults using facial photographs revealed that the predominant philtral column shape was different by sex. The three-dimensional anthropometric data showed significant sex differences, which were reflected in the more pronounced visual impression of the philtrum in men. A comparative study between Japanese and Mexican women also revealed certain racial differences. Furthermore, both the philtral depth and central angle of Cupid's bow were extracted as explanatory variables related to the subjective judgments for the clarity of the philtrum. These results suggest that the comprehensive evaluation of philtral morphologic features by three-dimensional analysis is a useful means of identifying the ideal parameters in philtral construction in cleft surgery.

[In vitro activity of sitafloxacin against clinical isolates in 2009].

In vitro activity of sitafloxacin (STFX) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between January and December 2009, at different healthcare facilities in Japan was evaluated. A total of 1,620 isolates including aerobic and anaerobic organisms was available for the susceptibility testing using the microbroth dilution methods recommended by Clinical Laboratory Standard Institute. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) was 0.06 microg/mL for methicillin-susceptible Staphylococcus aureus and was equal to that of garenoxacin (GRNX), 2 times lower than that of moxifloxacin (MFLX), and 8 times lower than that of levofloxacin (LVFX). STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90s of STFX ranged from 0.03 to 0.06 microg/mL and were 1 to 2 times lower than those of GRNX, 2 to 4 times lower than those of MFLX, and 16 to 32 times lower than those of LVFX. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL and was 2 times lower than that of GRNX, 4 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX was 0.25 microg/mL for Enterococcus faecalis, and was 2 times lower than those of GRNX and MFLX, and 8 times lower than that of LVFX. The MIC90 of STFX for E. coli was 2 microg/mL, and the MIC90s of other 10 species of Enterobacteriaceae which were the lowest values of the quinolones tested ranged from 0.03 to 1 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 8 microg/mL and was 16 times lower than those of GRNX, MFLX and LVFX. The MIC90 of STFX for P aeruginosa isolates recovered from respiratory infections was 2 microg/mL and was 32 times lower than those of GRNX and MFLX, and 16 times lower than that of LVFX. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less, and was 2 to 4 times lower than those of GRNX, 8 times lower than those of MFLX, and 4 times lower than those of LVFX. The MIC90 of STFX was 0.008 microg/mL for Moraxella catarrhalis, and was 2 times lower than that of GRNX, 8 times lower than those of MFLX and LVFX. The MIC90s of STFX ranged from 0.015 to 0.12 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested. In conclusion, the activity of STFX against Gram-positive cocci was comparable or superior to those of GRNX, MFLX and LVFX. STFX showed the most potent activity against Gram-negative bacteria and anaerobic bacteria of all the antimicrobial agents tested in this study.

A mouse and embryonic stem cell derived from a single embryo.

Embryonic stem cells (ESCs) are a good material for the study of mammalian development, production of genetically modified animals, and drug discovery because they proliferate infinitely while maintaining a multilineage differentiation potency and a normal karyotype. However, ethical considerations limit the use of human embryos for the establishment of ESCs. Recently, ESCs have been produced from blastomeres divided by biopsy in mice and humans. The method is expected to be less controversial because it does not destroy the embryo. However, no one has yet produced both a pup and an ESC from a single embryo. Here, we describe the production of individual/ESC pairs from each of three embryos out of 20 attempts, and is thus considered efficient. Blastomere-derived ESC could differentiate some types of tissues and contribute to chimera mouse. These results show that each blastomere at two-cell stage possesses pluripotency and separated blastomeres maintain viability to develop to a pup or pluripotent ESC.