The Japanese journal of antibiotics最新文献

In vitro activities of sitafloxacin (STFX) along with fluoroquinolones (levofloxacin (LVFX), moxifloxacin (MFLX), garenoxacin (GRNX)) and macrolides (azithromycin, clarithromycin) against atypical bacteria (Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae) recovered from clinical specimens from 2009 to 2014 at different healthcare facilities in Japan were investigated. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC₉₀) against M pneumoniae (n= 14) was 0.03μg/mL which was comparable to GRNX, 4- and 16-fold more active than MFLX and LVFX, respectively. Reduced susceptibilities of M pneumoniae (9/14 isolates) to macrolides were observed. MIC₉₀ of STFX against L. pneumophila (n =15) was 0.004μg/mL which was 2- and 4-fold more active than GRNX/LVFX and MFLX, respectively. The minimum inhibitory concentration range of STFX against C. trachomatis (n=5) and C. pneumoniae (n=5) were from 0.015 to 0.03 and from 0.03 to 0.06μg/mL, respectively. Furthermore, differences between the activities of STFX against various clinical isolates in 2009 and those in 2012, which were already published in two articles (Jpn. J. Antibiotics 63:411- 430, 2010, 66:311-330, 2013), were also evaluated. The MIC90s of STFX against methicillin- susceptible Staphylococcus aureus (MSSA), Streptococcus spp. and Enterococcus faecalis isolated in 2012 were 4 or 8 times higher than those in 2009, however there was no difference between STFX activities against other species in 2009 and those in 2012. In conclusion, STFX showed potent activity against atypical bacteria (M pneumoniae, L. pneumophila, C. trachomatis, C. pneumoniae) and no tendency for emergence resistance to Gram- positive cocci, Gram-negative bacteria and anaerobes except MSSA, Streptococcus spp. andt. faecalis.

Visual disturbance or central symptom like hallucination is well known to be one of the common drug adverse events in response to voriconazole (VRCZ). We observed 123 patients treated VRCZ from April 2012 to January 2016. Two of these cases experienced visual disturbance and 4 of these cases experienced central symptom. Six patients appeared visual disturbance or central symptom within 1 week after administration of VRCZ (visual disturbance; 3 days [2-42 days], central symptom; 6 days [3-9 days]) and disappeared visual disturbance or central symptom at an early date after discontinuation of administration or decreasing dose of VRCZ. The trough concentration of VRCZ in patients who experienced central symptom was similar with that in-patients who did not experience adverse events by VRCZ (case 3; 3.79μg/ mL, case 4; 1.28μg/mL vs 3.73μg/mL [0.09-13.27 μg/mL]). On the other hand, the trough concentration of VRCZ in patients who experienced visual disturbance was higher than that in patients who did not experience adverse events by VRCZ (case 5; 7.49μg/mL, case 6; 4.45μg/ mL vs 3.73μg/mL [0.09-13.27μg/mL]). In conclusion, we thought that the risk factor of visual disturbance was the increasing concentration of VRCZ. Therefore, we should monitor the onset of visual disturbance or central symptom in patients treated with VRCZ, especially central symptom that the concentration is unconcerned.

A 4mg/kg dose of tebipenem pivoxil (TBPM-PI) was administered twice daily for 3 days to 34 pediatric patients with pneumonia who had chest X-ray findings indicative of pneumonia and CRP values of at least 3.0 mg/dL. The clinical effects of this regimen were evaluated by retrospectively examining medical charts for the period from April 2012 to March 2015. The patients were 6 months to 8 years old, with serum CRP values ranging from 3.06 to 14.25 mg/dL. Fever resolved within 24 hours and respiratory symptoms improved within 3 to 5 days after the start of treatment in all 34 patients. Although CRP was positive in 28 of 30 patients at the end of the treatment period, none of these children showed worsening of pneumonia. Eight patients (23.5%) experienced adverse drug reactions including diarrhea. These results indicate that a 3-day course of TBPM-PI is useful for treating pediatric pneumonia.

Supplies of high quality antibiotic products to clinics contributed greatly to the health maintenance of the citizens of Japan. In this report, we describe the results of our investigation and analyses on the establishment and amendments of 'he quality standards for individual antibiotic products, which were regarded as the guidelines for quality control in the production processes. "The minimum requirements of penicillin" enacted in May of 1947 was at a relatively moderate standard level, due to considerations for domestic technical levels. However, after several amendments, in response to the rapid development of manufacturing technologies and new penicillin preparations, standards became increasingly stricter. "The minimum requirements of streptomycin" enacted in December of 1949 was prepared by the use of streptomycin preparations imported from the USA. The 3rd and 4th standards, "the minimum requirements of dihydrostreptomycin" and "the minimum requirements of chloramphenicol", were prepared by applying provisions described in the rules for certification of the U.S. Food and Drug Administration. In accordance with an increase in the varieties of antibiotic products, "the minimum requirements of antibacterial products" was enacted by the integration of previously existing standards and newly enacted ones. Thereafter, in response to the innovation of scientific technologies and the globalization of antibiotic products, "the minimum requirements for antibiotic products in Japan" was further developed and became the basis for supplying high quality antibiotic preparations.

We conducted the post-marketing surveillance of tebipenem pivoxil (Orapeneme fine granules 10% for pediatric), an oral carbapenem antibacterial agent, to investigate changes in bacterial susceptibility against tebipenem (TBPM). Bacterial strains used in this surveillance were methicillin-susceptible Staphylococcus aureus (MSSA: 303 strains), Streptococcus pneumoniae (554 strains), other Streptococcus spp. (242 strains: including Streptococcus pyogenes 133 strains), Moraxella catarrhalis (306 strains) and Haemophilus influenzae (506 strains) isolated from pediatric patients in 15 medical facilities in Japan between April 2010 and March 2015. Investigation was conducted three times (April 2010-March 2011, April 2012-March 2013 and April 2014-March 2015), and in any of these investigation periods, there were a large number of isolates from infants in terms of the frequency of isolates by age. The MIC90s of TBPM against MSSA, S. pneumoniae, other Streptococcus spp., M. catarrhalis and H. influenzae in these investigations were 0.015-0.03, 0.06, 0.008-0.015 (0.002 for S. pyogenes), 0.03 and 0.5-1 μg/mL, respectively, which were less than 2-fold, and a remarkable increase in MIC90 was not shown. On the other hand, the MIC50s of carbapenems including TBPM and penicillins against S. pneumoniae decreased to 1/4-1/8 during the investigation periods, and decreased gPRSP*¹ (48.7% - 26.1%) and increased gPISP (2x)*² (24.1% -+ 46.8%) were suggested to be involved in these changes in susceptibility. In S. pneumoniae, a decrease of macrolides-resistant strains due to mefA*³ (38.5% - 18.8%) and an increase of macrolides-resistant strains due to ermB*⁴ (41.7% - 62.4%) were noted. In H. influenzae, the frequencies of gBLNAR*⁵ and β-lactamase-producing strains were about 60-70% and 7-9%, respectively, and a remarkable change in susceptibility was not shown. As a result of investigations in the susceptibility of clinical isolates collected from pediatric patients as post-marketing surveillance, there was no decrease in TBPM susceptibility noted.

In order to investigate the roles of quality requirements for antibiotics products in Japan, from historical and hygienic aspects, we examined how technology and knowledge in the production and quality control of streptomycin were introduced from the United States of America. In this study, through detailed investigations and analyses, it was confirmed that the introduction of technology and knowledge on streptomycin was strongly supported by Brigadier General CRAWFORD SAms, the chief of the Public Health and Welfare Section (PHW) of the Supreme Commander for Allied Powers/General Headquarters, via the Ministry of Welfare in Japan. Dr. SELMAN WAKSMAN, the discoverer of streptomycin, along with scientists of Merck & Co., also helped Japanese industries extensively, via PHW, by providing the original streptomycin-producing strains and transferring expertise in streptomycin production. With the technology and knowledge being introduced from the USA, domestic production of streptomycin preparations increased very rapidly. As noted in our previous report, domestic production reached amounts enough to satisfy national demand within three years. Japanese people have a racial tendency to be highly susceptible to tuberculosis known as an incurable national disease. Thanks to streptomycin therapy, the tuberculosis mortality rate (per 100,000 population) had fallen dramatically within only five years from 187.2 in 1947 to 82.2 in 1952.

Human metapneumovirus (hMPV) is known as one of popular agents of acute respiratory infection in children. We reviewed the patients' background, result of initial blood test, bacterial culture, chest X-ray and clinical features of hospitalized children with lower respiratory tract infections caused by hMPV from March 2014 to February 2015 and compared them with the infections due to respiratory syncytial virus (RSV) and other causative agents. Of 419 patients tested by rapid virus antigen tests, 35 were positive for hMPV, 145 were positive for RSV, and 239 were negative for both viruses. Most of hMPV infections occurred between March and June, and 72% of households of hMPV-positive children got sick. hMPV-positive children did not have any specific symptoms such as wheezing in RSV- positive children. However, many of them were admitted due to prolonged high fever and/or ill appearance despite of no respiratory distress. Although it is said that hMPV-positive children admitted to hospitals tend to have pneumonia, the ratio of children'with pneumonia in this study was less than 60%.

Nucleic acid amplification tests (NAATs) are considered as one of critical diagnostic methods on Chlamydia trachomatis and Neisseria gonorrhoeae infections due to their high sensitivity and accuracy. However, conventional NAATs required 2-6 hours to complete the measurements including extraction, amplification, and detection of the target nucleic acids. To reduce the time, we evaluated the clinical significance of the rapid NAAT using GENECUBE (TOYOBO CO., LTD.) which can complete the measurement within 1 hour. We compared the performance of GENECUBE with those of TMA method (APTIMA" Combo2 chlamydia/ gonorrhoeae, Hologic Japan, Inc.) and lateral flow immunochromatographic assay (Clearview Chlamydia, Clearview gonorrhoeae, Alere Medical Co., Ltd.) by detecting specimens from 96 cervical swabs. The overall agreement results between GENECUBE and TMA were 95.8% and 100% for C. trachomatis and N. gonorrhoeae, respectively. The results suggested that GENECUBE showed equivalent sensitivity and specificity of TMA. Indeed, more than half of the positive samples in NAATs were measured as negative in the lateral flow. The lateral flow is known as a rapid assay, however the results revealed its poor sensitivity. We think rapid NAATs using GENECUBE on C. trachomatis and N. gonorrhoeae can be one of the methods, which realize rapid tests with high sensitivity and accuracy.

A study was conducted of the 1,225 Pseudomonas aeruginosa strains that were isolated at 20 medical institutions in the Kinki district between 2011 and 2013 to determine their antimicrobial susceptibility and to characterize the strains of multidrug-resistant Pseudomonas aeruginosa (MDRP) and the metallo-β-lactamase (MBL) -producing strains. The MIC50/MIC90 values (μg/mL) of the various antimicrobial agents were as follows: imipenem, 2/>8; meropenem, 1/>8; doripenem, 0.5/8; biapenem, 1/>8; tazobactam/piperacillin, 8/>64; piperacillin, 8/>64; sulbactam/cefoperazone, 8/64; cefepime, 4/16; cefozopran, 2/>16; aztreonam, 8/>16; amikacin, 4/16; levofloxacin, 1/>4; and ciprofloxacin, 0.25/>2. From the viewpoint of the annual changes in the susceptibility rates (according to the CLSI guidelines [M100-S22]), the susceptibility to tazobactam/piperacillin, piperacillin, cefepime, cefozopran and aztreonam decreased in 2013. On the other hand, two antimicrobial agents showed high susceptibility rates each year; amikacin (94.0-95.6%) showed the highest rate, followed by doripenem (80.3-82.6%). With the exception of amikacin, there were substantial inter-institutional differences in antimicrobial susceptibility. In comparison to the previous CLSI guidelines (M100-S21), the new CLSI guidelines (M100-S22) on the use of carbapenems and penicillins show that the MIC80 has been affected. The MDRP detection rates in 2011, 2012 and 2013 were 1.8% (8 strains), 1.8% (8 strains), and 2.8% (10 strains), respectively. The MBL detection rates were as follows: bla(VIM-2), 0.2% (1 strain) in 2011; bla(IMP-1), 0.9% (4 strains) in 2012, and 1.7% (6 strains, including bla(IMP-1) [3 strains], bla(IMP-2) [2 strains] and bla(VIM-2) [1 strain]) in 2013.