The Japanese journal of antibiotics最新文献

{"title":"[Epidemiological analysis for enterococci isolated in Aichi prefecture].","authors":"Daisuke Sakanashi,&nbsp;Yuka Yamagishi,&nbsp;Takayoshi Suzuki,&nbsp;Tomoko Ohno,&nbsp;Atsuko Yamada,&nbsp;Hiroyuki Suematsu,&nbsp;Hiroshige Mikamo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We investigated vancomycin-resistant genes for clinical isolates of 353 vancomycin-resistant enterococci in the Aichi Medical University hospital and 120 vancomycin-resistant enterococci from the 8 facilities in Aichi prefecture between April 2008 and January 2013. We detected 8, 105, 21 and 4 strains of enterococci with vanA, vanB, vanC1 and vanC2/C3, respectively. Among enterococci with vancomycin-resistant genes, we detected 4, 3 and 2 enterococci of vancomycin MIC level 4 microg/mL with vanB, vanC1 and vanC2/C3, respectively. According to molecular analysis using repetitive-sequence-based PCR (rep-PCR) for enterococci with vanA or vanB genes, although there have been no similarity for Enterococcus faecium with vanA and Enterococcus faecalis with vanB, high similarity was shown among E. faecium with vanB, which might be nosocomial spread in each hospital. These results showed that molecular analysis for vancomycin-resistant genes would be useful for the management of healthcare-associated infections.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32446246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2012].","authors":"Keizo Yamaguchi,&nbsp;Yoshikazu Ishii,&nbsp;Kazuhiro Tateda,&nbsp;Morihiro Iwata,&nbsp;Naoki Watanabe,&nbsp;Masaaki Shinagawa,&nbsp;Hiroyuki Kayaba,&nbsp;Masahiko Kimura,&nbsp;Akira Suwabe,&nbsp;Mitsuo Kaku,&nbsp;Yuko Abe,&nbsp;Keiji Kanemitsu,&nbsp;Nobuyuki Taniguchi,&nbsp;Masami Murakami,&nbsp;Shigefumi Maesaki,&nbsp;Toru Kawamura,&nbsp;Fumio Nomura,&nbsp;Masaharu Watanabe,&nbsp;Harushige Kanno,&nbsp;Hajime Horiuchi,&nbsp;Yoko Tazawa,&nbsp;Shigemi Kondo,&nbsp;Shigeki Misawa,&nbsp;Hiromu Takemura,&nbsp;Hideki Nakashima,&nbsp;Takayuki Matsuto,&nbsp;Yoshinori Fujimoto,&nbsp;Shiomi Ishigo,&nbsp;Hirokazu Gotoh,&nbsp;Osamu Watanabe,&nbsp;Tetsuya Yagi,&nbsp;Nami Shimaoka,&nbsp;Hiroshige Mikamo,&nbsp;Yuka Yamagishi,&nbsp;Naohisa Fujita,&nbsp;Toshiaki Komori,&nbsp;Satoshi Ichiyama,&nbsp;Seiji Kawano,&nbsp;Akifumi Nakayama,&nbsp;Fumihiko Nakamura,&nbsp;Hisashi Kohno,&nbsp;Saori Fukuda,&nbsp;Nobuchika Kusano,&nbsp;Motoko Nose,&nbsp;Michiya Yokozaki,&nbsp;Makoto Onodera,&nbsp;Koji Murao,&nbsp;Kiyoshi Negayama,&nbsp;Tatsuya Nishimiya,&nbsp;Hitoshi Miyamoto,&nbsp;Akira Matsunaga,&nbsp;Hisae Yoshimura,&nbsp;Shigeru Kohno,&nbsp;Katsunori Yanagihara,&nbsp;Kazufumi Hiramatsu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The nationwide surveillance of antibacterial susceptibility to meropenem (MEPM) and other parenteral antibiotics against clinical isolates during 2012 in Japan was conducted. A total of 2985 strains including 955 strains of Gram-positive bacteria, 1782 strains of Gram-negative bacteria, and 248 strains of anaerobic bacteria obtained from 31 medical institutions were examined. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). 2. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous studies in 2009 or 2006. Therefore, the tendency to increase in antimicrobial resistance rates was not observed. 3. MEPM resistance against Pseudomonas aeruginosa was 17.8% (56/315 strains). Compared to our previous results, it was the lowest than that in 2006 and 2009. 4. Carbapenem-resistant Klebsiella pneumoniae, and multi-drug-resistant Acinetobacter species, which emerged in worldwide, were not observed. 5. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 6.2% (59/951 strains) in enterobacteriaceae, which increased compared with that of our previous studies in 2009 or before. Whereas, the proportion of metallo-beta-lactamase strains was 1.6% (5/315 strains) in P. aeruginosa, which was stable. In conclusion, the results from this surveillance suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 17 years passed after available for commercial use in Japan.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32446244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Studies on the distribution of doripenem in pancreatic tissues, especially on the importance of the ratio in pancreatic tissue concentration of doripenem/serum concentration of doripenem].","authors":"Yu Nobuoka,&nbsp;Akihiro Tanemura,&nbsp;Yoshinori Azumi,&nbsp;Masashi Kishiwada,&nbsp;Ichiro Osawa,&nbsp;Shugo Mizuno,&nbsp;Masanobu Usui,&nbsp;Hiroyuki Sakurai,&nbsp;Masami Tabata,&nbsp;Shuji Isaji","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Doripenem (DRPM) which is injectable carbapenem antimicrobial agent is a compound with high antimicrobial activity against severe acute pancreatitis in carbapenem agents. It does not have a report of the distribution in human pancreatic tissue until now. This time, we performed examination about the distribution in pancreatic tissue of DRPM. Blood and pancreatic tissues were collected from six patients who were administered DRPM intravenously at a dose of 0.5 g after 1 hour from the start of injection. The concentration of DRPM in the serum and pancreatic tissues were measured. The concentrations of DRPM in the pancreatic tissues and serum were 0.58-5.39 microg/g and 0.02-0.24 microg/mL, respectively. DRPM distributed in pancreatic tissues sufficiently, and we could expect that DRPM was useful agent of pancreas infection in acute pancreatitis.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32325239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Efficacy and safety of levofloxacin in patients with nursing and healthcare-associated pneumonia].","authors":"Kei Yamasaki,&nbsp;Kazuhiro Yatera,&nbsp;Toshinori Kawanami,&nbsp;Yosuke Sasahara,&nbsp;Ryosuke Hata,&nbsp;Keigo Uchimura,&nbsp;Takashi Tachiwada,&nbsp;Keisuke Naito,&nbsp;Kaori Kato,&nbsp;Tsutomu Takaki,&nbsp;Ikuko Shimabukuro,&nbsp;Tomoko Shiraishi,&nbsp;Keishi Oda,&nbsp;Kanako Hara,&nbsp;Yasuo Chojin,&nbsp;Yu Suzuki,&nbsp;Kentarou Akata,&nbsp;Takaaki Ogoshi,&nbsp;Susumu Tokuyama,&nbsp;Naoyuki Inoue,&nbsp;Shingo Noguchi,&nbsp;Chinatsu Nishida,&nbsp;Takeshi Orihashi,&nbsp;Yugo Yoshida,&nbsp;Yukiko Kawanami,&nbsp;Yuusuke Taura,&nbsp;Hiroshi Ishimoto,&nbsp;Hideto Obata,&nbsp;Yukikazu Awaya,&nbsp;Tohru Tsuda,&nbsp;Chiharu Yoshii,&nbsp;Hiroshi Mukae","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32325240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of clinical bacteriological efficacy of oral antibiotics using a mechanism-based pharmacokinetic-pharmacodynamics modeling.","authors":"Kayoko Matsumoto,&nbsp;Toshie Sugano,&nbsp;Nobuo Sato,&nbsp;Takashi Ida,&nbsp;Shigeki Shibasaki","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The objective of this study was to predict the clinical bacteriological efficacy of antibiotics and to examine the pharmacodynamics (PD) characteristics of antibiotics against bacterial strains using a mechanism-based pharmacokinetic-pharmacodynamics (PK-PD) modeling developed on the basis of interaction between drug concentrations and antibacterial activities. Dynamic PD parameters (epsilon, gamma, EC50) and growth rate of organisms (lambda) were obtained from in vitro time-kill profile data of oral antibiotics, tebipenem pivoxil (TBPM-PI) and cefditoren pivoxil (CDTR-PI) against Streptococcus pneumoniae or Haemophilus influenzae. PD characteristics of both drugs against S. pneumoniae or H. influenzae were examined, which indicated TBPM was concentration-dependent as well as time-dependent, and CDTR was mainly time-dependent to exhibit their bactericidal activities. Next, we simulated TBPM and CDTR concentrations in plasma after oral administration according to the dosage regimen of each drug specified in package insert, using population pharmacokinetic parameters of both drugs in pediatric patients with infections. In addition, changes in viable in vivo bacterial counts in humans were simulated using dynamic PD parameters and mean plasma concentrations of each drug. As a result, simulated profile of viable counts of S. pneumoniae and H. influenzae were well corresponding to the bacteriological efficacy results in clinical double-blinded comparative study of TBPM-PI and CDTR-PI in oral administration to pediatric patients with acute otitis media. As mentioned in the above, it was considered to be possible to clarify the PD characteristics of TBPM and CDTR against each bacterial strain using the mechanism-based PK-PD model developed on the basis of interaction between drug concentrations and antibacterial activities, and to estimate the clinical bacteriological efficacy of those drugs.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32325241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics of cefditoren pivoxil in non-infected adults.","authors":"Kayoko Matsumoto,&nbsp;Nobuo Sato,&nbsp;Nayu Mitomi,&nbsp;Yoshihisa Shitara,&nbsp;Shigeki Shibasaki","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Population pharmacokinetic analysis was conducted on cefditoren pivoxil (CDTR-PI), a third generation oral antibiotic to evaluate the effect of covariates on pharmacokinetic parameters. Plasma concentrations of cefditoren (CDTR, total number of sampling points: 2864) obtained from healthy adult subjects, elderlies, and subjects with renal dysfunction (287 subjects) after CDTR-PI administration as well as demographic data of those subjects were used for analysis. We conducted the population pharmacokinetic analysis of CDTR-PI using a nonlinear mixed effects modeling (NONMEM) method. A one-compartment model with a first-order absorption and lag time fitted well to plasma concentration-time curve for CDTR. The subject covariate significantly affecting pharmacokinetic parameters of CDTR-PI was demonstrated by population pharmacokinetic analysis. The absorption rate constant (ka: hr(-1)) of CDTR-PI decreased with age, total clearance adjusted by bioavailability (CL/F: L/hr/kg) increased with increasing creatinine clearance adjusted by body weight (Ccr: mL/min/kg) and volume of distribution adjusted by bioavailability (Vd/F: L/kg) decreased with increasing body weight (WT: kg). In addition, the lag time (Tlag: hr) depends on formulation (tablet or granule) of CDTR-PI and the absorption lag time of the tablet was longer than that of the granule. We could obtain the population mean parameters of CDTR-PI together with interindividual variability and intraindividual residual variability after oral administration of CDTR-PI to adult subjects. In the future, this information will enable us to simulate the plasma concentrations of CDTR in subjects with various demographic backgrounds, which contributes to future examination of the efficacy and safety of CDTR-PI.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32325242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Candida catheter related-blood stream infection].","authors":"Masako Kadowaki,&nbsp;Nobuyuki Shimono","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Candida catheter-related bloodstream infection (CRBSI) is a biofilm-related disease, which is usually refractory because antifungals show limited effect. With medical development and increase in number of compromised hosts, CRBSI became more frequent. Candida, which is one of the opportunistic pathogens, ranks the fourth causative organism of bacteremia. The onset of bacteremia is greatly associated with the presence of catheter. Repeated blood cultures and the central venous catheter (CVC) tip culture are done for the definitive diagnosis of Candida CRBSI. Additionally serological examinations such as (1 --> 3)-beta-D-glucan and mannan antigen are also useful for early diagnosis. It is important for the appropriate treatment to remove CVC, which is an artificial contaminated material, and administer antifungals promptly. As to the choice of antifungals, we should also take into account the ability of antibiofilm effect of antifungals as well as immunological state of host including neutropenia, prior administration of azoles, isolated or estimated Candida species, sensitivity against antifungals, administration route, pharmacokinetics (bioavailability, metabolic and excretion pathway, distribution) and drug interaction. As to complication of Candida bacteremia, first we should check endophthalmitis, which occurs frequently and leads to the loss of eyesight, as well as infective endocarditis, arthritis, metastatic infections such as embolic pneumonia and suppurative thrombotic phlebitis of catheter insertion site. Lastly we emphasize that the appropriate treatment based on the character of Candida bacteremia and biofilm leads to favorable prognosis.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32326373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[In vitro activity of sitafloxacin against clinical isolates in 2012].","authors":"Ayako Amano,&nbsp;Kaoru Matsuzaki,&nbsp;Naoko Kishi,&nbsp;Hideaki Koyama,&nbsp;Miyuki Hasegawa,&nbsp;Fumiaki Ikeda,&nbsp;Takuyuki Matsumoto,&nbsp;Hiroki Yamaguchi,&nbsp;Yukihiro Okutani","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32193966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetic analysis of cefditoren pivoxil in pediatric patients with infection.","authors":"Kayoko Matsumoto,&nbsp;Nobuo Sato,&nbsp;Nayu Mitomi,&nbsp;Shigeki Shibasaki","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Population pharmacokinetic analysis was conducted on cefditoren pivoxil (CDTR-PI, Brand name: MEIACT, Meiji Seika Pharma Co., Ltd.), a third generation oral antibiotic, using plasma concentrations of cefditoren (CDTR, total number of sampling points: 578) obtained from pediatric patients (153 subjects, dose: 5.62 +/- 1.62 mg/kg) after CDTR-PI administration as well as demographic data of those subjects. NONMEM (Ver. VI LEVEL 2.0) was used as software. The first-order conditional estimation (FOCE) method without interaction was employed as algorithm. A one-compartment model with first-order absorption was used as a pharmacokinetic model. As the result of analysis, the following population pharmacokinetic parameters were obtained for CDTR. Population mean parameters: ka (hr(-1)) = 0.527, CL/F (L/hr/kg) = -0.474 x Scr + 0.82, Vd/F (L/kg) = 0.77, Tlag (hr) = 0.282 x (1+0.435 x NAT) (NAT: 0 = Japan, 1 = USA, interindividual variability: omega (ka) = 17.23%, omega (CL/F) = 33.02%, omega (Vd/F) = 86.66%, intraindividual residual variability: sigma = 0.428 microg/mL. Bayes estimation was carried out for each subject using the final model to calculate secondary parameters such as C(max), T(max), AUC, and t1/2. C(max) and AUC increased significantly with dose. However, T(max) was approximately 2hours and t1/2 was approximately 1 hour at any dose level, showing no significant dose-dependent changes. When CDTR-PI was administered orally to a child, a significant increase was noted in plasma CDTR concentrations, suggesting high efficacy. In addition, pharmacokinetics of CDTR were simulated in patients with renal impairment using the final model. As a result, a delay in T(max) and increases in AUC, C(max), and t1/2 were presumed with increased Scr, and the degrees of such increases were also quantitatively estimated. As mentioned above, the population pharmacokinetic parameters of CDTR were obtained, which is sure contribute to simulation of its plasma concentrations in patients with various backgrounds and to speculation of its efficacy and safety.</p>","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32193842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2006)].","authors":"Hajime Goto,&nbsp;Hideki Takeda,&nbsp;Shin Kawai,&nbsp;Akira Suwabe,&nbsp;Suguru Watanabe,&nbsp;Mitsuhiro Okazaki,&nbsp;Yugo Ashino,&nbsp;Kaoru Shimada,&nbsp;Nobuki Aoki,&nbsp;Tetsuo Sato,&nbsp;Yasuo Honma,&nbsp;Takeshi Mori,&nbsp;Kouichiro Kudo,&nbsp;Haruhito Sugiyama,&nbsp;Shigemi Kondo,&nbsp;Tsukasa Tanaka,&nbsp;Kenji Kido,&nbsp;Kunihiko Yoshimura,&nbsp;Toyoko Oguri,&nbsp;Makoto Yamamoto,&nbsp;Yoshitaka Nakamori,&nbsp;Hiroshi Inoue,&nbsp;Kohei Yamauchi,&nbsp;Midori Sumitomo,&nbsp;Shigeatsu Endo,&nbsp;Toshihide Nakadate,&nbsp;Mikio Oka,&nbsp;Yoshihiro Kobashi,&nbsp;Naoki Saita,&nbsp;Katsunori Yanagihara,&nbsp;Akira Kondou,&nbsp;Junichi Matsuda,&nbsp;Michiko Nakano,&nbsp;Shigeru Kohno,&nbsp;Satoru Oikawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>From October 2006 to September 2007, we collected the specimen from 356 patients with lower respiratory tract infections in 14 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 414 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 407 strains were examined. The isolated bacteria were: Staphylococcus aureus 64, Streptococcus pneumoniae 96, Haemophilus influenzae 87, Pseudomonas aeruginosa (non-mucoid) 52, P. aeruginosa (mucoid) 11, Klebsiella pneumoniae 20, and Moraxella catarrhalis 44. Of 64 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 27 (42.2%) and 37 (57.8%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 microg/ml or less. Against MRSA, vancomycin and linezolid showed the most potent activity and inhibited the growth of all the strains at 1 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 microg/ml or less. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.125 and 0.5 microg/ml, respectively. In contrast, there were high-resistant strains (MIC: over 128 microg/ml) for erythromycin (45.8%) and clindamycin (20.8%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 microg/ml or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 microg/ml. Against P. aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90 was 2 microg/ml. Against K. pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 microg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 microg/ml or less. The approximately half the number (50.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 49.2% and 28.1% of all the respiratory infections, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. pneumoniae (29.2%), S. aureus (20.8%), and H. influenzae (12.9%). H. influenzae (25.0%) and P. aeruginosa (21.7%) also were frequently isolated from the patients with chronic bronchitis. Before the antibacterial agent administration, the bacteria frequently isolated from the patients were S. pneumoniae (27.5%) and H. influenzae (22.5%). The bacteria frequently isolated from the patients treated with macrolides was P. aeruginosa, and its isola","PeriodicalId":22536,"journal":{"name":"The Japanese journal of antibiotics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32193843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}