We established silkworm infection model for developing a novel antibiotic. Silkworm model has less ethical issues and is low cost compared to mammalian model, thus allow us to use a lot of individuals for screening assay. In addition, we can evaluate therapeutic activity and toxicity of candidate samples because silkworm has similar pharmacokinetics as mammals. Using this system, we identified a novel antibiotic named “Lysocin E”. In this review article, we describe advantages of silkworm model for development of antimicrobial agents.

Nontypeable Haemophilus influenzae, one of the major causative bacteria for acute otitis media (AOM), is also considered to cause intractable otitis media including prolonged AOM and recurrent AOM in children by the mechanism of internalization of the bacteria into epithelial cells of middle ear mucosa. In this study, we visualized the dynamics of H. influenzae internalization in cultured human cells. We also examined the effects of antimicrobials, including a novel quinolone, tosufloxacin, and a cephem antibacterial agent, cefditoren, on H. influenzae internalized in cultured human cells.

The results indicated that (1) H. influenzae were internalized into human cells, (2) cefditoren has no effect on internalized H. influenzae, and (3) tosufloxacin has a bactericidal action on H. influenzae invading human cells. These data strongly support high clinical efficacy of tosufloxacin on intractable otitis media in children.

Colistin is a polypeptide antibiotic of the polymyxin family (polymyxin E) which has been reported to be active against many multidrug-resistant (MDR) Gramnegative aerobic bacteria collected across the globe. While this agent was not currently licensed in Japan, the emergence of MDR organisms has necessitated its off-label used in the country. However, colistin was approved in March, 2015. This retrospective observational report includes nine patients with MDR Gram-negative infections due to Pseudomonas aeruginosa (n=6) and Klebsiella spp. (n=3) who received intravenous colistin therapy as part of their antimicrobial regimen. The median age and duration of administration were 40 years (range 7-90) and 8 days (range 1-19). Clinical success was observed in all eight patients for whom efficacy could be evaluated. Two patients encountered colistin related adverse effects 22.2% (2/9). In both cases the nephrotoxicity and dysgeusia resolved after discontinuation of colistin therapy. In vitro studies conducted with these clinical isolates of P. aeruginosa displayed synergy with the combination of colistin plus ceftazidime, rifampicin, meropenem or aztreonam. This report provides early evidence that colistin is generally safe, effective and demonstrates in vitro synergy when used in combination for the management of MDR Gram-negative pathogens derived from Japanese patients.

We investigated the susceptibility to antibacterial agents of 186 clinical isolates of Pseudomonas aeruginosa isolated from medical facilities in Gifu, Aichi, Toyama, and Fukui prefectures from October 2013 to February 2014. MIC_50/90 of piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), aztreonam (AZT), ciprofloxacin (CPFX), levofloxacin (LVFX), amikacin (AMK) and colistin (CL) against P. aeruginosa was 8/32, 4/32, 2/8, 2/16, 1/32, 0.5/8, 0.25/4, 8/32, 0.25/8, 0.5/16, 4/8 and 1/1μg/mL respectively. Two strains of multidrug resistant P. aeruginosa were isolated (1.1%).

They were isolated from the respiratory tract, intra-abdominal, and urinary infection. The susceptible ratio against P. aeruginosa derived from intra-abdominal infection for carbapenem was lower than those from respiratory tract and urinary infection. The susceptible ratio against P. aeruginosa derived from urinary infection for penicillin, cephem, monobactam, and fluoroquinolone was lower than those from respiratory and intra-abdominal infection.

It is meaningful to pay attention to the susceptibility to antibacterial agents in each clinical specimen from infected organ.

This clinical case report concerns a pediatric patient with acute enteritis caused by multi-drug resistant Salmonella enterica serovar Blockley (Salmonella Blockley). A 3-year-old boy presented to our emergency room with a 5-day history of fever, abdominal pain, and bloody diarrhea. Stool culture tested positive for a Salmonella species, while the blood culture was negative. The patient was successfully treated with an oral antibiotic regimen of fosfomycin. The stool isolate was found to be resistant to multiple drugs, including cefpodoxime, cefotaxime, ceftazidime, and aztreonam, and was confirmed to be a CTX-M-15 extended-spectrum β-lactamase (ESBL)-producing strain of Salmonella Blockley. This is the first report of a pediatric patient in Japan with acute enteritis caused by a CTX-M-15 ESBLproducing strain of Salmonella Blockley.