Collaboration between Institute of Microbial Chemistry and Meiji Seika Pharma has a long history in the field of research and development of novel aminoglycoside antibiotics. In this review article, summary of selected output from the above collaboration is disclosed and discovery and biological activities of a novel aminoglycoside antibiotic generated from the collaboration, TS2037, are described. TS2037 exhibited stronger in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa compared with all clinically useful aminoglycoside antibiotics. Moreover the clinical efficacy of TS2037 against MRSA or P. aeruginosa infection was estimated by evaluation in application of clinical isolates. Strong protective effects of TS2037 against systemic infections in mice caused by MRSA or P. aeruginosa are also reported.

Therapeutic hypothermia is the recommended regimen for adult subjects after cardiac arrest and in neonates with hypoxic ischemic encephalopathy. Remedies are needed to negate side effects or to provide sedation during hypothermia. However, changes in the pharmacokinetics of drugs have been reported under hypothermic conditions. The mechanisms responsible for changes in the pharmacokinetics of drugs under hypothermic conditions have not been clarified fully. To optimize the medication during therapeutic hypothermia, we need to clarify the factor affecting drug disposition. The factor affecting drug disposition under hypothermia is described in this review.

Clinically isolated Pseudomonas aeruginosa, Acinetobacter spp., and Enterobacteriaceae were collected from 17 Japanese medical institutions in 2012. The susceptibilities of these isolates against carbapenems were compared among each bacterial strains. The susceptibility rates of 123 P. aeruginosa strains against meropenem, doripenem and imipenem were 79.7, 83.7 and 72.4%, respectively. The susceptibility rates of 968 Enterobacteriaceae strains against meropenem, doripenem and imipenem were 99.6, 99.5 and 75.4%, respectively. In the case of 91 Acinetobacter spp. strains, the same susceptibility rate, 97.8%, was shown in each three carbapenems. During the past 21 years, the carbapenem-resistant rates of P. aeruginosa were comparable with that of 2012, although the rates increased temporally in 2002 and in 2010. The resistant rate for doripenem was the lowest among the three carbapenems through these 21 years. For 11 years from 2002 to 2012, multidrug-resistant rate of P. aeruginosa and carbapenemresistant rate of Enterobacteriaceae ranged from 1.1 to 5.8% and from 0.0 to 0.7%, respectively, and there was no significant increase during these 11 years. These resistant strains were found to carry bla_IMP or blaVIM metallo-beta-lactamase genes. Multidrug-resistant Acinetobacter spp. strains were isolated only in 2010 with the rate of 4.7% and bla_OXA-58 was detected.

From April 2014 to January 2015, we investigated the prevalence of antimicrobial resistant Enterobacteriaceae isolated from feces in healthy volunteers who is Japanese medical student. Eighty-six Enterobacteriaceae were isolated from 50 specimens obtained from 40 students. Escherichia coli accounted for 63% (54/86) of isolated Enterobacteriaceae, which were most common species. There are no resistant isolates to 3^rd generation cephalosporins and/or quinolones except E. coli. In addition, there were no students whom new drug-resistant isolates were detected after hospital training. The quinolone-resistant E. coli accounted for 26% (14/54) of isolated E. coli, it accounted for 30% when they included two non-susceptible strains. Extended-spectrum β-lactamase (ESBL)-producing E. coli strains were isolated 5 strains from 4 students, the strains accounted for 5.8% of all of isolates, 9.3% of all E. coli isolates, and 10% of all students. ESBL producing E. coli consisted of two kinds of genotype; those were CTX-M-14 and CTX-M-27. The pulsed field gel electrophoresis( PFGE) patterns of 5 ESBL-producing E. coli strains including isolates from same student showed quite different each other.

These results showed that quinolone-resistant E. coli and ESBL-producing E. coli had already spread through the healthy adult. It is considered that surveillance of drug resistant isolates in healthy students gives students the common recognition for drug resistance. It is important to tell students using this data that anyone can become a drug-resistant bacterial carrier or an infected patient.