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Annals of Laboratory Medicine Jul 2017
Topics: Adolescent; Anti-Bacterial Agents; DNA, Bacterial; Dibekacin; Female; Graft vs Host Disease; Humans; Immunocompromised Host; Mycoplasma Infections; Mycoplasma hominis; Polymerase Chain Reaction; Soft Tissue Infections; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tigecycline; Transplantation, Homologous
PubMed: 28445018
DOI: 10.3343/alm.2017.37.4.346 -
The Journal of Antimicrobial... Apr 2017Arbekacin is an aminoglycoside that shows strong antimicrobial activity against Gram-positive bacteria, including MRSA, as well as Pseudomonas aeruginosa . The... (Comparative Study)
Comparative Study
Efficacy and pharmacokinetics of ME1100, a novel optimized formulation of arbekacin for inhalation, compared with amikacin in a murine model of ventilator-associated pneumonia caused by Pseudomonas aeruginosa.
BACKGROUND
Arbekacin is an aminoglycoside that shows strong antimicrobial activity against Gram-positive bacteria, including MRSA, as well as Pseudomonas aeruginosa . The therapeutic effectiveness of arbekacin is directly related to C max at the infection site. To maximize drug delivery to the respiratory tract and minimize the systemic toxicity, arbekacin optimized for inhalation, ME1100, is under development. In this study, we investigated the efficacy and pharmacokinetics of ME1100 in a murine model of ventilator-associated pneumonia caused by P. aeruginosa by using a customized investigational nebulizer system.
METHODS
The mice were treated for 5 min, once daily, with placebo, 3, 10 or 30 mg/mL ME1100 or 30 mg/mL amikacin.
RESULTS
In the survival study, the survival rate was significantly improved in the 10 and 30 mg/mL ME1100 treatment groups compared with that in the placebo group. The number of bacteria in the lungs was significantly lower in the 30 mg/mL ME1100 treatment group at 6 h after the initial treatment, compared with all other groups. In the pharmacokinetic study, the C max in the 30 mg/mL ME1100 treatment group in the epithelial lining fluid (ELF) and plasma was 31.1 and 1.2 mg/L, respectively. Furthermore, we compared the efficacy of ME1100 with that of amikacin. Although there were no significant differences in ELF and plasma concentrations between 30 mg/mL of ME1100 and 30 mg/mL of amikacin, ME1100 significantly improved the survival rate compared with amikacin.
CONCLUSIONS
The results of our study demonstrated the in vivo effectiveness of ME1100 and its superiority to amikacin.
Topics: Administration, Inhalation; Amikacin; Animals; Anti-Bacterial Agents; Dibekacin; Disease Models, Animal; Drug Compounding; Lung; Mice; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 27999047
DOI: 10.1093/jac/dkw517 -
The Japanese Journal of Antibiotics Apr 2016We herein discovered a highly resistant clinical isolate of Pseudomonas aeruginosa with MICs to amikacin, gentamicin, and arbekacin of 128 μg/mL or higher in a drug...
We herein discovered a highly resistant clinical isolate of Pseudomonas aeruginosa with MICs to amikacin, gentamicin, and arbekacin of 128 μg/mL or higher in a drug sensitivity survey of 92 strains isolated from the specimens of Yoka hospital patients between January 2009 and October 2010, and Achromobacter xylosoxidans was separated from this P. aeruginosa isolate. The sensitivity of this bacterium to 29 antibiotics was investigated. The MICs of this A. xylosoxidans strain to 9 aminoglycoside antibiotics were: amikacin, gentamicin, arbekacin, streptomycin, kanamycin, neomycin, and spectinomycin, 1,024 μg/mL or ≥ 1,024 μg/mL; netilmicin, 512 μg/mL; and tobramycin, 256 μg/mL. This strain was also resistant to dibekacin. This aminoglycoside antibiotic resistant phenotype is very rare, and we are the first report the emergence of A. xylosoxidans with this characteristic.
Topics: Achromobacter denitrificans; Aminoglycosides; Anti-Bacterial Agents; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 27544979
DOI: No ID Found -
The Journal of Antibiotics Aug 2016Two new compounds, designated paraphaeosphaeride D (1) and berkleasmin F (2) together with a previously known compound, berkleasmin A (3), isolated from a culture broth...
Two new compounds, designated paraphaeosphaeride D (1) and berkleasmin F (2) together with a previously known compound, berkleasmin A (3), isolated from a culture broth of the fungus Paraphaeosphaeria sp. TR-022, proved to be new circumventors of arbekacin (ABK) resistance in methicillin-resistant Staphylococcus aureus (MRSA). The structures of 1 and 2 were elucidated by spectroscopic analyses, including various NMR experiments. All compounds showed 10-100 times ABK circumvention activities using the paper disc method and reduced the MIC values of ABK against MRSA from 16 μg ml(-1) to 4 μg ml(-1) (fourfold) using the agar dilution method. These new compounds might be promising lead compounds for developing circumventors of ABK resistance in MRSA.
Topics: Anti-Bacterial Agents; Ascomycota; Dibekacin; Drug Resistance, Bacterial; Lactams; Magnetic Resonance Spectroscopy; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Pyrones; Sesquiterpenes
PubMed: 27328869
DOI: 10.1038/ja.2016.70 -
Journal of Infection and Chemotherapy :... Jul 2016The efficacy of arbekacin in patients with MRSA infections is influenced by the peak concentration (Cpeak)/MIC ratio (≧8). A daily arbekacin dose of 4-6 mg/kg is...
The efficacy of arbekacin in patients with MRSA infections is influenced by the peak concentration (Cpeak)/MIC ratio (≧8). A daily arbekacin dose of 4-6 mg/kg is primarily used for the treatment of MRSA infection. However, clinical pharmacokinetic studies of arbekacin that evaluate changes in patients with different infectious diseases have been limited. This study was to evaluate the pharmacokinetics of arbekacin in different infectious diseases and to evaluate its dosing regimens. This work describes a single-centre, retrospective study. The pharmacokinetic parameters of arbekacin were calculated from individual serum-concentration data using WinNonlin ver. 6.3. A total of 331 serum samples were obtained from 170 patients. Our drug concentration-time data were well described by a two-compartment open model. The final model showed that drug clearance was related to creatinine clearance and that the total distribution volume (Vd) was related to actual body weight and the presence of bacteremia. The individual Vd in bacteremia patients was significantly higher than those of other patients (bacteremia: 29.7 ± 0.5 L, pneumonia: 20.8 ± 0.4 L, other infections: 21.4 ± 0.4 L; p < 0.05). Additionally, Monte Carlo simulation showed that target (Cpeak/MIC ≧ 8) attainment was only 10.1%, even at a dose of 6 mg/kg, especially for MRSA bacteremia patients with an arbekacin MIC = 2 μg/mL. In conclusion, our study revealed that the Vd may be higher in bacteremia patients than in patients with other infectious diseases. Therefore, an increase in the daily dose of arbekacin should be considered for bacteremia patients.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Dibekacin; Dose-Response Relationship, Drug; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Models, Biological; Retrospective Studies; Staphylococcal Infections; Young Adult
PubMed: 27260679
DOI: 10.1016/j.jiac.2016.03.008 -
Rinsho Byori. the Japanese Journal of... Oct 2015Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting, ultimately resulting in the... (Review)
Review
Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting, ultimately resulting in the death of patients in their twenties or thirties. DMD is characterized by a deficiency of the muscle dystrophin as a result of mutations in the dystrophin gene. Currently, no effective treatment for DMD is available. Promising molecular therapies which are mutation-specific have been developed. Transformation of an out-of-frame mRNA into an in-frame dystrophin message by inducing exon skipping is considered one of the approaches most likely to lead to success. We demonstrated that the intravenous administration of the antisense oligonucleotide against the splicing enhancer sequence results in exon skipping and production of the dystrophin protein in DMD case for the first time. After extensive studies, anti-sense oligonucleotides comprising different monomers have undergone clinical trials and provided favorable results, enabling improvements in ambulation of DMD patients. Induction of the read-through of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations, which are detected in 19% of DMD cases. The clinical effectiveness of gentamicin and PTC124 has been reported. We have demonstrated that arbekacin-mediated read-through can markedly ameliorate muscular dystrophy in vitro. We have already begun a clinical trial of nonsense mutation read-through therapy using arbekacin. Some of these drug candidates are planned to undergo submission for approval to regulatory agencies in the US and EU. We hope that these molecular therapies will contribute towards DMD treatment.
Topics: Animals; Codon, Nonsense; Dibekacin; Dystrophin; Exons; Gentamicins; Humans; Mice; Molecular Targeted Therapy; Muscular Dystrophy, Duchenne; Oligonucleotides, Antisense; Pathology, Molecular; Prostaglandin D2
PubMed: 26897856
DOI: No ID Found -
International Journal of Dermatology Apr 2016Periodic investigations into patterns of antimicrobial resistance can help to optimize the efficacy of treatment and limit the development of resistance.
BACKGROUND
Periodic investigations into patterns of antimicrobial resistance can help to optimize the efficacy of treatment and limit the development of resistance.
OBJECTIVES
The aim of this study was to update information on patterns of antimicrobial resistance in Staphylococcus aureus isolated from skin infections in South Korea.
METHODS
We retrospectively analyzed clinical information and in vitro antimicrobial resistance data for 965 clinical S. aureus isolates obtained from skin infections during 2010-2013 in a university hospital in South Korea.
RESULTS
The rate of resistance to oxacillin (methicillin-resistant S. aureus [MRSA]) was 47.4%. Similar rates of resistance to erythromycin (45.6%), fusidic acid (44.0%), and clindamycin (42.3%) were noted. The rate of resistance to mupirocin was 8.4%. Overall, 4.9% of isolates were resistant to both fusidic acid and mupirocin. None of the isolates showed resistance to habekacin, synercid, teicoplanin, or vancomycin. Generally, antimicrobial resistance rates did not increase from 2010 to 2013 except with reference to a few agents such as mupirocin and rifampin. Isolates from surgical patients, inpatients, non-dermatology outpatients, and adult patients showed relatively high rates of resistance to multiple antimicrobials. Resistance to mupirocin was not only lower than that to fusidic acid but was consistent across clinical contexts.
CONCLUSIONS
The prevalence of MRSA in skin infections in South Korea did not increase during 2010-2013. Isolates from dermatology outpatients showed relatively lower rates of resistance to multiple antimicrobials than isolates from non-dermatology outpatients. Among topical antimicrobials, resistance to mupirocin was relatively low regardless of clinical condition.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Ciprofloxacin; Clindamycin; Dibekacin; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Fusidic Acid; Gentamicins; Humans; Infant; Infant, Newborn; Ketolides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Mupirocin; Oxacillin; Republic of Korea; Retrospective Studies; Rifampin; Staphylococcal Skin Infections; Staphylococcus aureus; Teicoplanin; Tetracycline; Vancomycin; Virginiamycin; Young Adult
PubMed: 26892888
DOI: 10.1111/ijd.13046 -
International Journal of Hematology Mar 2016We performed a clinical trial to investigate the efficacy and safety of arbekacin (ABK), a unique aminoglycoside with activity against methicillin-resistant... (Clinical Trial)
Clinical Trial
We performed a clinical trial to investigate the efficacy and safety of arbekacin (ABK), a unique aminoglycoside with activity against methicillin-resistant Staphylococcus aureus (MRSA), in patients with hematological malignancies complicated by high-risk infections. ABK was administered intravenously at a dose of approximately 5 mg/kg with various broad-spectrum β-lactams, followed by therapeutic drug monitoring (TDM). A total of 54 febrile or infectious episodes were registered, and TDM was performed in 44 (81%) cases. The absolute neutrophil count was below 500/μl in 49 (91%) cases, and cytotoxic chemotherapy was being administered in 47 (87%) cases. Before initiation of ABK, 52 (96%) patients had received fluoroquinolones (n = 37) and/or broad-spectrum β-lactams (n = 34). There were 10 cases of documented infections including one of MRSA pneumonia, and 44 cases of febrile neutropenia. The efficacy at the end of treatment was 80% for all patients, and efficacy was significantly higher in patients attaining maximum concentrations ≥ 16 µg/ml or receiving TDM-guided dose-adjustment of ABK (n = 19, 95 vs. 71%, P = 0.039). Renal toxicity was observed in six cases (11%) but was generally acceptable. This study demonstrated that TDM-guided ABK administration may be applicable under limited conditions for patients with hematological malignancies.
Topics: Adult; Aged; Anti-Infective Agents; Dibekacin; Drug Monitoring; Drug Therapy, Combination; Febrile Neutropenia; Female; Fluoroquinolones; Hematologic Neoplasms; Humans; Infusions, Intravenous; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Bacterial; Staphylococcal Infections; Treatment Outcome; beta-Lactams
PubMed: 26715149
DOI: 10.1007/s12185-015-1926-6 -
Journal of Infection and Chemotherapy :... Jan 2016Methicillin-resistant Staphylococcus aureus (MRSA) is prevalent in Japan, and the Staphylococcus cassette chromosome mec (SCCmec) type II is common among...
Methicillin-resistant Staphylococcus aureus (MRSA) is prevalent in Japan, and the Staphylococcus cassette chromosome mec (SCCmec) type II is common among hospital-acquired MRSA isolates. Information pertaining to MRSA characteristics is limited, including SCCmec types, in primary or secondary care facilities. A total of 128 MRSA isolates (90 skin and soft tissue isolates and 38 blood isolates) were collected at a secondary care facility, Kawatana Medical Center, from 2005 to 2011. Antimicrobial susceptibility testing for anti-MRSA antibiotics and molecular testing for SCCmec and virulence genes (tst, sec, etb, lukS/F-PV) were performed. Strains positive for lukS/F-PV were analyzed by multilocus sequence typing and phage open-reading frame typing. SCCmec typing in skin and soft tissue isolates revealed that 65.6% had type IV, 22.2% had type II, 8.9% had type I, and 3.3% had type III. In blood isolates, 50.0% had type IV, 47.4% had type II, and 2.6% had type III. Minimum inhibitory concentrations, MIC(50)/MIC(90), against vancomycin, teicoplanin, linezolid, and arbekacin increased slightly in SCCmec II isolates from skin and soft tissue. MICs against daptomycin were similar between sites of isolation. SCCmec type II isolates possess tst and sec genes at a greater frequently than SCCmec type IV isolates. Four lukS/F-PV-positive isolates were divided into two clonal patterns and USA300 was not included. In conclusion, SCCmec type IV was dominant in blood, skin, and soft tissue isolates in a secondary care facility in Japan. Because antimicrobial susceptibility varies with the SCCmec type, SCCmec typing of clinical isolates should be monitored in primary or secondary care facilities.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Toxins; Cross Infection; Daptomycin; Dibekacin; Exotoxins; Humans; Japan; Leukocidins; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Multilocus Sequence Typing; Open Reading Frames; Recombinases; Secondary Care Centers; Skin; Soft Tissue Infections; Staphylococcus aureus; Teicoplanin; Vancomycin; Virulence Factors
PubMed: 26617349
DOI: 10.1016/j.jiac.2015.08.011 -
Journal of Clinical Microbiology Jan 201616S rRNA methyltransferases confer resistance to most aminoglycosides, but discriminating their activity from that of aminoglycoside-modifying enzymes (AMEs) is...
16S rRNA methyltransferases confer resistance to most aminoglycosides, but discriminating their activity from that of aminoglycoside-modifying enzymes (AMEs) is challenging using phenotypic methods. We demonstrate that arbekacin, an aminoglycoside refractory to most AMEs, can rapidly detect 16S methyltransferase activity in Enterobacteriaceae with high specificity using the standard disk susceptibility test.
Topics: Anti-Infective Agents; Dibekacin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Enterobacteriaceae; Genotype; Humans; Phenotype; RNA, Ribosomal, 16S; tRNA Methyltransferases
PubMed: 26537447
DOI: 10.1128/JCM.02642-15