The Japanese journal of antibiotics (Jpn J Antibiot)

Publications in this journal

• Article: [Efficacy and safety of levofloxacin to non-gonorrheal urethritis].

  Shoichi Onodera, Yasuhiko Onoe, Takahide Hosobe, Tetsuro Kato, Masaki Yoshida
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  ABSTRACT: We investigated the efficacy and safety of levofloxacin (LVFX) 500mg once a day in patients with non-gonorrheal urethritis. Men, aged 20 years or older, with urethritis symptoms, and detection of Chlamydia trachomatis (C. trachomatis) or Mycoplasma genitalium (M. genitalium) by a microbiological examination were eligible for this study. Patients were administered LVFX 500mg, orally, once a day and the dosage period was seven days. We assumed 22 patients for a safety and efficacy analysis. In 22 patients, 17 patients had urethritis with C. trachomatis, 4 patients urethritis with M. genitalium, and one patient mixed infection of C. trachomatis and M. genitalium. In the clinial study, the primary endpoint was set as the bacteriological eradication rate at two to four weeks after completion of treatment. The bacterial eradication rate in the urethritis was 86.4% (19/22). The bacterial eradication rate in the urethritis with C. trachomatis, M. genitalium, and mixed infection of C. trachomatis and M. genitalium were 94.1% (16/17), 50.0% (2/4), 100% (1/1), respectively. A significant difference was not recognized among the three groups. The clinical efficacy at two to four weeks after completion of treatment was 90.9% (20/22). The clinical efficacy rates in the urethritis with C. trachomatis, M. genitalium, and mixed infection of C. trachomatis and M. genitalium were 100% (17/17), 50.0% (2/4), 100% (1/1), respectively. The efficacy rate of urethritis with M. genitalium was significantly low. No adverse drug reactions were observed. These results suggest that once-a-day levofloxacin (500mg) is effective and safe treatment for non-gonorrheal urethritis.
  The Japanese journal of antibiotics 12/2012; 65(6):399-409.
• Article: [In vitro activity of doripenem against strains from pediatric diseases and strains causing purulent meningitis].

  Merime Ohta, Shinsuke Toba, Akinobu Ito, Rio Nakamura, Masakatsu Tsuji
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  ABSTRACT: This study evaluated the in vitro activity of doripenem (DRPM) against 200 Streptococcus pneumoniae and 197 Haemophilus influenzae from children and adults in 2007, 50 H. influenzae type b in 2006, 20 Listeria monocytogenes in 1990-2005, 23 Neisseria meningitidis in 2007-2009 and 83 Bordetella pertussis in 1989-2003. All strains were isolated from Japanese clinical facilities. We also investigated in vitro activity of other carbapenems (meropenem, imipenem, panipenem, biapenem), cephems (ceftriaxone, cefotaxime), ampicillin and clarithromycin. The all MICs were determined by a broth micro dilution method or an agar dilution method according to CLSI. The MIC90(s) of DRPM against S. pneumoniae and H. influenzae from children were 0.25 microg/mL, 1 microg/mL, respectively, which were similar to strains from adults. These results suggested that antibacterial activity of DRPM is not variable by patient's age. DRPM also showed excellent activities against H. influenzae type b, L. monocytogenes and N. meningitidis, which cause purulent meningitis, and B. pertussis causing whooping cough more than the other carbapenems. DRPM showed superior activities against serious strains of pediatric infection diseases.
  The Japanese journal of antibiotics 12/2012; 65(6):381-98.
• Article: [Bactericidal effect of levofloxacin injection in combination with meropenem against Pseudomonas aeruginosa using an in vitro simulation model with a hollow fiber system].

  Saori Uoyama, Hiroko Kanda, Kumi Yoshida, Kazuki Hoshino
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  ABSTRACT: An in vitro human plasma concentration simulation model with a hollow fiber system was established and used to evaluate the bactericidal effect of levofloxacin (LVFX) 500mg q.d. in combination with meropenem (MEPM) 1000mg t.i.d. against Pseudomonas aeruginosa. Six clinical isolates of P. aeruginosa which had MEPM MICs of 2 - 16 microg/mL, LVFX MICs of 2 microg/mL, and fractional inhibitory concentration (FIC) indices by the in vitro checkerboard method of 0.625-1 were used. In the treatment with MEPM alone, initial viable counts (10(6)-10(7) CFU/ mL) decreased, but did not reach below the detection limit (100 CFU/mL) and the regrowth of bacteria was observed. In the treatment with LVFX alone, viable counts decreased once below the detection limit, although increased after treatment for 24 hours. On the other hand, in the treatment with LVFX-MEPM combination, more potent bactericidal effects were observed compared to LVFX or MEPM alone in all strains. Especially, in the strains with MEPM MICs of 2 and 4 microg/mL, viable counts rapidly decreased below the detection limit and no regrowth was observed until 24 hours. These results suggested that LVFX-MEPM has a potential to be an effective combination against P. aeruginosa by synergistic rapid bactericidal action in clinical settings, even in the strain against which no significant synergy is confirmed by the traditional in vitro checkerboard method.
  The Japanese journal of antibiotics 12/2012; 65(6):355-63.
• Article: [Efficacy and safety of sitafloxacin in patients with urinary tract infections].

  Takuyuki Matsumoto, Hiroki Yamaguchi, Kazuhiro Uchino, Megumi Takahashi, Hiroko Kodama, Satoko Hamajima, Rie Yonemochi, Sachiko Fujita, Atsushi Takita, Naoki Yamanouchi, Tomoo Shiozawa, Yukihiro Okutani
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  ABSTRACT: Sitafloxacin (STFX, Gracevit 50mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was carried out over the 2 years between December 2008 and November 2010. We studied the efficacy and safety of STFX in 1,452 patients with urinary tract infections (cystitis, pyelonephritis, urethritis). The total efficacy rate for urinary tract infections was 91.4% (1,235/1,351 patients). Efficacy rates, classified by the type of infection, were: uncomplicated cystitis 95.9% (466/486 patients), complicated cystitis 87.2% (511/586 patients), uncomplicated pyelonephritis 96.1% (49/51 patients), complicated pyelonephritis 93.5% (145/155 patients), and urethritis 87.7% (64/73 patients). Efficacy rates were 86.0% (49/57 patients) for non-responders to cephems and 77.4% (48/62 patients) for non-responders to quinolones. The eradication rate of indicated strains was 90.5% (545/602 strains). The eradication rates of major causative bacteria were; Escherichia coli 92.7% (294/317 isolates), Enterococcus faecalis 86.0% (43/50 isolates), Pseudomonas aeruginosa 66.7% (16/24 isolates), Klebsiella pneumoniae 95.2% (20/21 isolates), and Chlamydia trachomatis 88.9% (8/9 isolates). The incidence of adverse drug reactions (ADRs) was 2.71% (37/1,365 cases). Major ADRs were diarrhoea (0.88%, 12 cases) and hepatic function disorders (0.51%, 7 cases). A serious ADR (hepatic function abnormality) was observed in 1 case, and the hepatic function in this patient returned to normal after treatment with STFX was discontinued. In conclusion, these results suggest that STFX is a useful antibacterial agent with an efficacy rate of 91.4% against urinary tract infections, with a minimum efficacy rate of 87.2% (against complicated cystitis), and has no serious problems in its safety profile.
  The Japanese journal of antibiotics 12/2012; 65(6):365-80.
• Article: [Antibacterial susceptibility surveillance of Haemophilus influenzae isolated from pediatric patients in Gifu and Aichi prefectures (2009-2010)].

  Mariko Takakura, Yoshiko Fukuda, Nobuhiko Nomura, Junichi Mitsuyama, Kazukiyo Yamaoka, Yuko Asano, Haruki Sawamura, Kouichi Katsuragawa, Hikonori Hashido, Yoko Matsukawa, Shigenori Matsubara, Hirotoshi Oota, Kunitomo Watanabe, Yuka Yamagishi, Hiroshige Mikamo
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  ABSTRACT: We investigated the susceptibility to antibacterial agents of 197 strains of Haemophilus influenzae isolated from pediatric patients at medical facilities in Gifu and Aichi prefectures between 2009 and 2010. Those strains were also examined for the mutations of ftsI coding for penicillin-binding protein 3, presence of bla TEM-1, serotype and beta-lactamase producing ability. Among the 197 strains, the most prevalent serotype was non-typeable (89.8%), followed by serotype b (8.1%), e (1.5%) and f (0.5%). Based on the susceptibility among the 197 strains to antibacterial agents, beta-lactamase nonproducing ampicillin-susceptible H. influenzae (BLNAS) accounted for 27.4%, beta-lactamase nonproducing ampicillin-resistant H. influenzae (BLNAR) for 62.4%, beta-lactamase producing ampicillin-resistant H. influenzae (BLPAR) for 6.1% and beta-lactamase producing amoxicillin/ clavulanic acid-resistant H. influenzae (BLPACR) for 4.1%. According to PCR-based genotyping, the strains were classified into 6 categories: gBLNAS, gLow-BLNAR, gBLNAR, gBLPAR, gBLPACR-I and gBLPACR-II. The incidences of each resistant class were 17.3% for gBLNAS, 6.6% for gLow-BLNAR, 66.0% for gBLNAR, 5.6% for gBLPAR and 4.6% for gBLPACR-II. The combined incidence of gLow-BLNAR and gBLNAR was 72.6%, which was higher than that of BLNAR (62.4%). The MIC90s of antibacterial agents against the 197 strains were as follows; 0.0156 microg/mL for tosufloxacin and garenoxacin, 0.0313 microg/mL for levofloxacin and pazufloxacin, 0.0625 microg/mL for norfloxacin, 0.25 microg/mL for tazobactam/piperacillin (TAZ/PIPC) and ceftriaxone, 0.5 microg/mL for TAZ/PIPC (1:8) and cefditoren, 1 microg/mL for piperacillin, cefteram, cefotaxime, meropenem, tebipenem and minocycline, 2 microg/mL for doripenem, 4 microg/mL for cefcapene, imipenem and azithromycin, 8 microg/mL for sulbactam/ampicillin, clavulanic acid/amoxicillin (1:2, CVA/AMPC) and cefdinir, 16 microg/mL for CVA/AMPC (1:14), flomoxef and clarithromycin, 32 microg/mL for ampicillin. Although there was no rapid increase in the antibacterial resistance, the prevalence of BLNAR was still over 50%. In order to ensure the appropriate chemotherapy, it is important to continue the surveillance of susceptibility among H. influenzae.
  The Japanese journal of antibiotics 10/2012; 65(5):305-21.
• Article: [Morphological changes in penicillin-resistant Streptococcus pneumoniae and beta-lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae after exposure to oral antibacterial agents].

  Naoko Chiba, Miyuki Morozumi, Kimiko Ubukata
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  ABSTRACT: Morphological changes in penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae (BLNAR) after exposure to oral antibacterial agents could be observed over time under a phase-contrast microscope. Morphological changes in BLNAR were also observed using a scanning electron microscope. The organisms used in this study were ME19F strain identified as genotypic(g) gPRSP (serotype: 19F) and JPH002 strain identified as gBLNAR (serotype: b). The antibacterial agents used were amoxicillin (AMPC), cefditoren (CDTR), tebipenem (TBPM), and tosufloxacin (TFLX). The concentration of each antibacterial agent to which the bacteria were exposed was set at the blood level one hour after Cmax when administered to children at the usual dose. Bacteriolysis of gPRSP cells started after exposure of only 20minutes to TBPM, and 90% of the cells were lysed within 2 hours. A high bactericidal action of TBPM on gPRSP was supported by these findings. When gBLNAR was exposed to AMPC and TBPM, lysis from spheroplasts and cells with vacuoles were sometimes observed. In contrast, after gBLNAR was exposed to CDTR, lysis occurred after marked filamentation in the cells, but after exposure to TFLX, cells deduced to be killed after mild filamentation without lysis. Time-dependent morphological changes that reflect the differences in bactericidal activity and PBP affinity among beta-lactams provide beneficial information to select antibacterial agents.
  The Japanese journal of antibiotics 10/2012; 65(5):323-34.
• Article: [Future outlook on the guidelines for the management of respiratory infections, centering on pneumonia: toward the development of a higher quality clinical guideline].

  Yoshinori Hasegawa
  The Japanese journal of antibiotics 10/2012; 65(5):291-304.
• Article: Comparison of four reading methods of broth microdilution based on the clinical and laboratory standards institute M27-A3 method for Candida spp.

  Hiromi Morishige, Yoko Mano, Toyoko Oguri, Nobuhiko Furuya
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  ABSTRACT: This study aimed to compare the susceptibilities of 5 reference strains and 28 isolates of Candida spp., to micafungin, amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and miconazole, obtained by visually determined minimum inhibitory concentration (MIC) using the agitation method (V-A), as described in the Clinical and Laboratory Standards Institute M27-A3 document; visual determinations without agitation (V-NA); and spectrophotometric determinations for the presence or absence of agitation (SP-A and SP-NA, respectively). Our results indicate that when the V-NA, SP-A, and SP-NA-the 3 alternative microdilution procedures for MIC endpoint determinations-were compared with the V-A, excellent agreements were observed between the V-NA and V-A rather than with the spectrophotometric methods (between the SP-A or SP-NA, and V-A). Furthermore, many errors occurred while using the SP-A method in the presence of agitation and some isolates showed major errors. Three of 5 isolates that showed very major errors between the spectrophotometric SP-A or SP-NA, and the reference V-A method were trailing isolates. Therefore, it was suggested that the MICs of Candida spp. obtained by the V-NA method were more precise than those by the conventional SP-A method.
  The Japanese journal of antibiotics 10/2012; 65(5):335-47.
• Article: [Clinical investigation of arbekacin sulfate based on Cmax/MIC].

  Masao Kimura, Yuka Yamagishi, Noriyo Kawasumi, Hiroshige Mikamo
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  ABSTRACT: We examined the peck concentration (Cmax)/minimal inhibitory concentration (MIC) and the clinical efficacy in methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and Gram-positive cocci bacteremia. We evaluated arbekacin (ABK) on 22 cases of pneumonia and 10 cases of bacteremia in Aichi Medical University Hospital between August 2008 and July 2011, retrospectively. In pneumonia cases, Cmax/MIC was 16.4 +/- 2.8 in the effective group, and was 17.6 +/- 4.5 in the not effective group, the significant differences were not accepted (p = 0.8). The dosage of ABK was 4.7 +/- 1.4 mg/kg/dose in the effective group and was 4.3 +/- 0.7 mg/kg/dose in the not effective group. In bacteremia cases, Cmax/MIC was 24.2 +/- 13.9 in the effective group and 12.9 +/- 3.9 in the not effective group about clinical efficacy, and the high tendency was accepted by the effective group (p < 0.05). The dosage of ABK was 3.4 +/- 1.1 mg/kg/dose in the effective group, and 3.0 +/- 0.6 mg/kg/dose in the not effective group. In this examination, the significant difference was not observed in clinical efficacy and Cmax/MIC in the pneumonia cases. Although it was reported that clinical efficacy of ABK was given Cmax/MIC at eight or more, in this examination, all cases was eight or more at Cmax/MIC, and the clinical effect was 40.9%. On Cmax/MIC of ABK, clinical effective group was higher than not effective group in bacteremia cases, it was suggested that the administration design should make that Cmax/MIC at least about 14 or more would be necessary.
  The Japanese journal of antibiotics 08/2012; 65(4):263-9.
• Article: Efficacy and safety of doripenem for sepsis with neutropenia in Japanese patients with hematologic diseases.

  Nobu Akiyama, Akihisa Kanamaru, Kazuo Tamura, Mitsune Tanimoto, Kazuma Ohyashiki, Yasunori Nakagawa, Akio Urabe, Toru Masaoka
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  ABSTRACT: Doripenem (DRPM) is one of the carbapenems which has a broad-spectrum and strong activity against Pseudomonas aeruginosa. This observational study was conducted between April 2006 and March 2007 in Japan to evaluate the efficacy and safety of DRPM 0.5 g three times a day for sepsis with neutropenia in patients with hematologic diseases. One hundred-nineteen patients were enrolled from 34 medical institutes, comprising 117 patients for safety evaluation and 104 for efficacy evaluation. Monotherapy of DRPM 0.5 g three times a day (DRPM monotherapy) was evaluated in 73 patients. The response rates of DRPM monotherapy at 72 hours and at Day 7 were 31.5% (23/73) and 67.1% (49/73), respectively. The incidence of adverse reactions including abnormal changes in laboratory values was 23.1%, and hepatic toxicity was most common. All of these adverse events were judged by the investigators as non-serious and tolerable. These results suggest that DRPM is useful for sepsis with neutropenia, though further study may be warranted.
  The Japanese journal of antibiotics 08/2012; 65(4):251-62.
• Article: Evaluation of arbekacin anti-MRSA agents for adult in Japan.

  Yukihiro Hamada, Kazuyoshi Tamura, Ikumi Koyama, Megumi Seki, Kazuo Yago, Keisuke Sunakawa, Masakazu Kuroyama
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  ABSTRACT: There are a limited number of reports that compare the clinical efficacy of anti-MRSA agents such as arbekacin (ABK), vancomycin (VCM), teicoplanin (TEIC) and linezolid (LZD). There is a tendency for these four agents to show variation in the inflammatory response parameters, in C-reactive protein (CRP) and in white blood cell count (WBC), depending on the administration period. There was no significant difference among the agents in analysis of variance (ANOVA) in the group of days 1-3 (p = 0.0536) but there was some significant difference in the group of days 4-7, as well as days 8-14 (p < 0.001, p < 0.01) in relative variation rate of CRP. Furthermore, we compared in more detail the groups of LZD, VCM and ABK, with a significant decrease of CRP, each of which showed more decrease in comparison with the group of TEIC in the period days 4-7 (p < 0.01). We took 1-hr serum level after days 3-4, with the ABK treatment as the peak concentration (C(peak)). Having made nonlinear logistic regression analysis of CRP and C(peak)/MIC, we concluded that the decrease rate estimable by early inflammatory effect could be decreased to some 40%, assuming that C(peak)/MIC shows the high value within 4 days after ABK treatment.
  The Japanese journal of antibiotics 08/2012; 65(4):221-34.
• Article: Compatibility of carbapenem antibiotics with nafamostat mesilate in arterial infusion therapy for severe acute pancreatitis: stabilities of carbapenem antibiotics.

  Yukihiro Hamada, Hiroshi Imaizumi, Shirou Miyazawa, Mitsuhiro Kida, Kazui Souma, Wasaburou Koizumi, Keisuke Sunakawa, Masakazu Kuroyama
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  ABSTRACT: The effectiveness of continuous regional arterial infusion therapy using protease inhibitors and antibiotics for severe acute pancreatitis has been previously reported. Carbapenem antibiotics, which have a broad antibacterial spectrum, and nafamostat mesilate are often used for this therapeutic approach. We investigated the compatibility of various carbapenem antibiotics with nafamostat mesilate. Carbapenem antibiotics were dissolved in 30 mL of saline or 5% glucose and the appearance, pH, and stability of the solutions were determined. The changes in each carbapenem antibiotic solution after mixing with nafamostat mesilate were then investigated. Biapenem and doripenem showed a residual rate of > or = 90% at 8 hours after dissolution in saline or 5% glucose and exhibited an appropriate appearance and residual rate (> or = 90%). After mixing with nafamostat mesilate, biapenem maintained a residual rate of > or = 90% for the longest time period (8 hours) and exhibited a slight coloration, followed by doripenem (6 hours) and meropenem dissolved in saline. The other carbapenem antibiotics that were tested exhibited changes in appearance or their residual rate. Biapenem and doripenem, which exert their effects in a time-dependent manner, can be infused for prolonged periods for the treatment of not only severe acute pancreatitis, but also other severe infections.
  The Japanese journal of antibiotics 08/2012; 65(4):235-49.
• Article: [A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia].

  Kenji Imajo, Yasunori Ueda, Fumio Kawano, Hiroshi Sao, Tomohiko Kamimura, Yoshikazu Ito, Atuko Mugitani, Kenshi Suzuki, Naokuni Uike, Koichi Miyamura, [......], Yoshitaka Morimatsu, Nobu Akiyama, Hirokazu Nagai, Akira Ohara, Mitsune Tanimoto, Kazutaka Takaki, Kosuke Chayama, Masao Urabe, Yoshihisa Nagatoshi, Kazuo Tamura
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  ABSTRACT: Efficacy, safety and pharmacokinetics of meropenem (MEPM) were assessed when 1 g (40 mg/kg for some of the pediatric patients) t.i.d. was administered every 8hours to 101 adult and 6 pediatric patients with febrile neutropenia (FN) as diagnosed based on the Japanese guideline for FN treatment. The efficacy rate evaluated as antifebrile effect up to Day 4 of treatment was 40.0% (40/100) in adult and 66.7% (4/6) in pediatric patients. The antifebrile effect in adult patients was analyzed after stratifying them according to their neutrophil counts up to Day 4. Treatment with MEPM produced an antifebrile effect not only in patients with higher neutrophil counts (> or = 500/mm3) but also in those with lower counts (< 100/mm3), and the efficacy rate was comparable between the two groups: 38.2% in the < 100/mm3 group and 29.4 to 55.6% in the > or = 500/mm3 group. The bacteriological efficacy of MEPM evaluated as disappearance rate on Days 3 to 5 and Day 7 was both 100% (8/8 and 4/4, respectively). The time above minimal inhibitory concentration (% T > MIC) in the treatment interval was greater than 90% in 9 out of 10 patients for whom likely causative organism was isolated and identified after MEPM treatment or for whom causative organism emerging after treatment was isolated and identified. The incidence of adverse events was 93.1% in adult and 83.3% in pediatric patients. There were three deaths and one serious adverse event reported among the adult patients; however, all these cases were assessed as not related to the study medication. The incidence of adverse drug reactions was 45.5% and 66.7%, respectively. All the observed adverse drug reactions were mild or moderate in severity and none of them was severe. Adverse drug reactions which were unknown from the previous MEPM clinical studies and investigation of the results of clinical experience include 'chest discomfort', 'blood uric acid decreased', 'lymphocyte deformation', 'blood uric acid increased', 'abnormal funduscopy', 'hypesthesia' and 'hemorrhagic cystitis'. All these events were mild or moderate in severity and resolved without requiring any action or after providing symptomatic treatment. There was no unknown adverse drug reaction that resulted in treatment discontinuation. No nervous system disorders such as convulsion and impaired consciousness were reported. The results show that monotherapy of MEPM 1 g (or 40 mg/kg for some of the pediatric patients) t.i.d. every 8 hours was effective, and was also safe and well tolerated in adult and pediatric patients with FN. Therefore, MEPM monotherapy is expected to be useful as the initial treatment for Japanese patients with FN.
  The Japanese journal of antibiotics 08/2012; 65(4):271-87.
• Article: [Clinical efficacy of tosufloxacin in children with pneumonia due to Mycoplasma pneumoniae].

  Hiroshi Sakata
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  ABSTRACT: We retrospectively examined pediatric 83 patients with pneumonia due to Mycoplasma pneumoniae, ranging in age from 6 months to 14 years, treated with tosufloxacin (TFLX) for more than 3 days between October 2010 and December 2011. The TFLX dose was 12 mg/kg/day (maximum 360 mg/day). Seventy-eight of the 83 children treated with this drug showed symptom amelioration, and the response rate to the drug was 94.0%. The remaining 5 patients showed no improvement despite drug administration for 3 to 6 days, and TFLX was switched to minocycline, which relieved symptoms. Forty-six of the 83 were given TFLX as initial treatment, and the remaining 37 not responding to clarithromycin (CAM) and azithromycin (AZM) were also treated with TFLX. This drug was effective in 41 (89.1%) of the 46 patients initially treated with TFLX and TFLX was effective in all 37 (100%) patients not responding to CAM and AZM. Side effects of TFLX included mild diarrhea, observed in 3 patients, but no patients had joint symptoms or convulsions.
  The Japanese journal of antibiotics 06/2012; 65(3):173-9.
• Article: [Febrile neutropenia in lung cancer patients].

  Masaki Fujita
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  ABSTRACT: A malignant tumor and infection have a close relation which is hard to separate. The differential diagnosis of the infection is necessary even at the time of the diagnosis of the malignant tumor. Controlling infection is another difficulty at the anti-cancer treatment as next step. In this report, the issues concerning the infection with lung cancer, especially febrile neutropenia, was argued.
  The Japanese journal of antibiotics 06/2012; 65(3):155-61.
• Article: [Current status adult pertussis in Japan].

  Hiroshige Mikamo, Yuka Yamagishi
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  ABSTRACT: Pertussis has been prevalent among the infants in summer, however, in recent years, it is increasing also in the adult. The epidemiology in 2010 showed pertussis in the adults dominated over 50%. Although the cough in the adults persists for a long time comparing with the infants, the adult pertussis is easy to be overlooked since the symptom is not typical especially in the adults. Therefore, it might be lead to the outbreak in the community. Pertussis is mainly treated by macrolides, such as erythromycin (EM) or clarithromycin (CAM) at present.
  The Japanese journal of antibiotics 06/2012; 65(3):163-71.
• Article: [In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,866 clinical isolates obtained from 72 centers in 2010].

  Keizo Yamaguchi, Akira Ohno, Yoshikazu Ishii, Kazuhiro Tateda, Morihiro Iwata
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  ABSTRACT: Postmarketing surveillance of levofloxacin (LVFX) has been conducted continuously since 1992. The present survey was performed to investigate in vitro susceptibility of recent clinical isolates in Japan to 30 selected antibacterial agents, focusing on fluoroquinolones (FQs). The common respiratory pathogens Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae continue to show a high susceptibility to FQs. In contrast, widely-prevailing resistance to macrolides was markedly noted among S pneumoniae and S. pyogenes. Regarding H. influenzae, the prevalence of beta-lactamase-negative ampicillin-resistant isolates has been increasing year by year (25.8% in 2002, 40.0% in 2004, 50.1% in 2007, and 57.9% in 2010). Enterobacteriaceae showed high susceptibility to FQs, however, prevalence of LVFX-resistant Escherichia coli, including intermediate resistance, was 29.3%, showing an increase over time. Nevertheless, the increase in the prevalence of LVFX-resistant E. coli isolates has slowed since 2007 (8.2% in 2000, 11.8% in 2002, 18.8% in 2004, 26.2% in 2007, and 29.3% in 2010), suggesting the influence of LVFX 500 mg tablets since its approval in 2009. Another Enterobacteriaceae member, Klebsiella pneumoniae, showed low resistance to FQs, in contrast with E. coli. In methicillin-resistant Staphylococcus aureus (MRSA), the percentage of FQ-susceptible isolates was low, at 51.6% for susceptibility to sitafloxacin, and at only around 10% for susceptibility to other FQs. However, methicillin-susceptible S. aureus (MSSA) isolates were highly susceptible to FQs, with the percentage ranging from 88.5% to 99.1%. The prevalence of FQs-resistant isolates in methicillin-resistant coagulase-negative staphylococci was higher than that in methicillin-susceptible coagulase-negative staphylococci, although it was lower than the prevalence of FQ-resistance in MRSA. The prevalence of FQs-resistant Pseudomonas aeruginosa isolates derived from urinary tract infections (UTIs) was 15.4-21.3%, higher than the prevalence of 6.1-12.3% in P. aeruginosa isolates from respiratory tract infections (RTIs). While this trend was consistent with the results of previous surveillance, gradual decreases were noted in the prevalence of FQ-resistant P. aeruginosa isolates derived from UTIs. The prevalence of multidrug-resistant P. aeruginosa was 2.3% among isolates derived from UTIs and 0.3% among isolates from RTIs, a decrease from the results of 2007. Acinetobacter spp. showed high susceptibility to FQs. Imipenem-resistant Acinetobacter baumannii, which is currently an emerging issue, was detected at a prevalence of 2.4% (13 isolates). Neisseria gonorrhoeae showed a high resistance of 81.3-82.5%, to FQs. Ceftriaxone (CTRX) continued to show 100% susceptibility until 2007, but the present survey revealed the advent of resistance to CTRX in some clinical isolates. The result of the present survey indicated that although methicillin-resistant staphylococci, Enterococcus faecium, P. aeruginosa from UTIs, N. gonorrhoeae, and E. coli showed resistance of about 20% or more (19.5-89.2%) against the FQs which have been used clinically for over 17 years, the trends observed were similar to the results of previous surveillance. While FQ resistance has been prevailing in E. coli, E. coli still shows more than 70% susceptibility to FQs. The other bacterial species maintained high susceptibility rates of greater than 80%, against FQs.
  The Japanese journal of antibiotics 06/2012; 65(3):181-206.
• Article: [Arbekacin sulfate concentrations in peripheral lymph and in serum after intravenous injection: report of four cases].

  Masahiko Hayashi, Kazuya Ooi, Satoko Yamada, Hiromi Wakabayashi, Takao Imanishi, Makoto Kondo, Masami Nishii, Kazuro Ikawa, Norifumi Morikawa
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  ABSTRACT: Antibiotic levels in serum are commonly used to guide antibiotic therapy. The antibiotic levels in peripheral lymph are a more accurate reflection of the efficacy of antibiotic penetration into the tissues of patients with complicated skin and soft-tissue infections. The pharmacokinetics of arbekacin sulfate (ABK) in peripheral lymph after systemic administration has not been studied. Four patients (cases 1-4) with skin and soft-tissue infections (average age 74.3 years, range 54 to 85) received 200 mg of ABK intravenously once a day either by slow bolus (5min.) or by slow infusion (60 min.). The serum concentrations collected 60min. after the start ofABK infusion (C60) and the peripheral lymph concentrations of ABK were measured. 55 min. after initiation of slow 5-min. bolus (case 1), C60 was 32.5l microg/mL. The daily average concentration of ABK in peripheral lymph after slow bolus (case 1) was 14.84 microg/mL. The ratio peripheral lymph on daily average/C60 was 0.46. Patients (cases 2, 3 and 4) had been intravenously administered ABK at an infusion time of 60 min. C60 (cases 2, 3 and 4) were 14.10, 11.48 and 8.26 microg/mL, respectively. The daily average concentration of ABK in peripheral lymph after slow infusion (case 2) was 7.80 microg/mL. The average concentrations of ABK in peripheral lymph during the third eight hours since slow infusion (cases 3 and 4) were 0.72 and 2.23 microg/mL. The ratio peripheral lymph/C60 was 0.55, 0.06 and 0.27, respectively. An increase in the serum peak concentration of ABK may lead to considerable elevation of the concentration of ABK in peripheral lymph.
  The Japanese journal of antibiotics 06/2012; 65(3):207-15.
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  Mitsuo Kaku
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  Masaki Sotoshima
  The Japanese journal of antibiotics 04/2012; 65(2):129-34.