The susceptibility of 1578 Streptococcus pneumoniae strains isolated from pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015 was tested to penicillin G (PCG), cefotaxime (CTX), ceftriaxone (CTRX), cefditoren (CDTR), meropenem (MEPM), erythromycin (EM) and levofloxacin (LVFX). Although no significant differences were observed, the percentage of strains with a minimal inhibitory concentration (MIC) of PCG of <0.1pg/mL increased from 55.5% (2011) to 64.0% (2015), whereas that of strains with MIC of ≥2μg/mL decreased from 14.8% to 9.5%. From 2011 to 2015, the percentage of strains with MIC ≤0.12ug/mL increased from 18.9% to 28.9% for CTX, from 20.5% to 30.2% for CTRX, from 29.2% to 40.9% for CDTR, and from 69.6% to 80.6% for MEPM. EM-resistant strains with MIC ≥22μg/mL accounted for as much as approximately 90% each year. One LVFX-resistant strain with MIC 8pg/mL has been detected each year since 2013.
Pneumonia ranks as the third leading cause of death in Japan. About 97% of patients who die because of pneumonia are elderly, with aspiration generally thought to be involved in the majority of cases of pneumonia in elderly. Once an elderly individual contracts pneumonia, their physical function often declines and their activities of daily living diminish with hospital admission, even in individuals with no underlying disorders. Prolonged confinement to a bed and immobility leads to weakening of the legs and back, making it difficult for elderly patients to attend daily outpatient clinics, often leading to admission to nursing facilities for the aged instead of returning to their own home, even after curative treatment for pneumonia. Most such patients repeatedly develop pneumonia and repeated antibiotic treatment enhances the risk of the emergence of resistant organisms. It is beyond doubt, therefore, that prevention of pneumonia is of vital importance in the elderly.
Influenza A and B viruses possess an enzyme "sialidase" that cleavages terminal sialic acid from glycochains. These viral sialidase proteins are highly expressed on the virus infected cells. We developed sialidase imaging probe "BTP3-Neu5Ac" that enables histochemical fluorescence staining of sialidase activity. BTP3-Neu5Ac was able to perform speedy and easy fluorescence imaging of these virus infected cells, with no needs of specific antibody and cell fixation. In addition, combination use of anti-influenza drugs (sialidase inhibitors) and BTP3-Neu5Ac resulted in selective fluorescence imaging for detection and high-efficiency isolation of drug-resistant virus. Fluorescence imaging of drug-resistant virus will be a powerful method for study of the drug-resistance mechanism, for monitoring of drug-resistant viruses. A novel tool for fluorescence imaging of viral sialidase activity is described in this review.
Colistin is a polypeptide antibiotic of the polymyxin family (polymyxin E) which has been reported to be active against many multidrug-resistant (MDR) Gram-negative 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.
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. infiuenzae 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. infiuenzae were internalized into human cells, (2) cefditoren has no effect on internalized H. influenzae, and (3) tosufloxacin has a bactericidal action on H. infiuenzae invading human cells. These data strongly support high clinical efficacy of tosuffoxacin on intractable otitis media in children.
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. MIC₅₀/₉₀ 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 1/1pg/mLrespectively. 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.
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.
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 ESBL- producing strain of Salmonella Blockley.