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Journal of Infection and Chemotherapy :... Jan 2021Arbekacin is the first aminoglycoside antibacterial agent approved for treating methicillin-resistant Staphylococcus aureus infection in Japan. Although therapeutic drug... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Arbekacin is the first aminoglycoside antibacterial agent approved for treating methicillin-resistant Staphylococcus aureus infection in Japan. Although therapeutic drug monitoring (TDM) is recommended during arbekacin treatment, little evidence for the target exposure and once-daily dosing has been reported. This study aimed to clarify the target peak/trough concentrations and the effectiveness of once-daily dosing of arbekacin against nephrotoxicity or treatment failure via meta-analysis.
METHODS
A literature search was performed using MEDLINE, Cochrane Library, and Ichushi-Web.
RESULTS
Nine observational cohort studies met the inclusion criteria. A peak arbekacin concentration of ≥15-16 μg/mL did not exhibit a statistically significant lower risk of treatment failure (risk ratio [RR] = 0.61, 95% confidence interval [CI] = 0.30-1.24). A trough arbekacin concentration of <2 μg/mL resulted in a significantly lower risk of nephrotoxicity (RR = 0.30, 95% CI = 0.15-0.61). Once-daily dosing significantly reduced the risk of treatment failure (RR = 0.61, 95% CI = 0.39-0.97) but not nephrotoxicity (RR = 0.54, 95% CI = 0.16-1.75).
CONCLUSIONS
Once-daily dosing can improve the therapeutic efficacy of arbekacin, and a trough arbekacin concentration of <2 μg/mL can reduce the risk of nephrotoxicity. A peak arbekacin concentration of ≥15-16 μg/mL did not exhibit the significant lower risk of treatment failure. Additional clinical trials are required to confirm these findings.
Topics: Anti-Bacterial Agents; Dibekacin; Drug Monitoring; Humans; Japan; Methicillin-Resistant Staphylococcus aureus
PubMed: 32828677
DOI: 10.1016/j.jiac.2020.08.002 -
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 -
Antimicrobial Agents and Chemotherapy Oct 2014Stenotrophomonas maltophilia IOMTU250 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Iak. The encoded protein, AAC(6')-Iak, consists of 153...
Stenotrophomonas maltophilia IOMTU250 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Iak. The encoded protein, AAC(6')-Iak, consists of 153 amino acids and has 86.3% identity to AAC(6')-Iz. Escherichia coli transformed with a plasmid containing aac(6')-Iak exhibited decreased susceptibility to arbekacin, dibekacin, neomycin, netilmicin, sisomicin, and tobramycin. Thin-layer chromatography showed that AAC(6')-Iak acetylated amikacin, arbekacin, dibekacin, isepamicin, kanamycin, neomycin, netilmicin, sisomicin, and tobramycin but not apramycin, gentamicin, or lividomycin.
Topics: Acetyltransferases; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Neomycin; Netilmicin; Sisomicin; Stenotrophomonas maltophilia; Tobramycin
PubMed: 25092711
DOI: 10.1128/AAC.03354-14 -
Microbiology Spectrum Aug 2022Seven drug-resistant strains of Stenotrophomonas maltophilia were isolated from patients at two university hospitals in Nepal. S. maltophilia JUNP497 was found to encode...
Stenotrophomonas maltophilia from Nepal Producing Two Novel Antibiotic Inactivating Enzymes, a Class A β-Lactamase KBL-1 and an Aminoglycoside 6'--Acetyltransferase AAC(6')-Iap.
Seven drug-resistant strains of Stenotrophomonas maltophilia were isolated from patients at two university hospitals in Nepal. S. maltophilia JUNP497 was found to encode a novel class A β-lactamase, KBL-1 (Kathmandu β-lactamase), consisting of 286 amino acids with 52.98% identity to PSV-1. Escherichia coli transformants expressing were less susceptible to penicillins. The recombinant KBL-1 protein efficiently hydrolyzed penicillins. The genomic environment surrounding was a unique structure, with the upstream region derived from strains in China and the downstream region from strains in India. S. maltophilia JUNP350 was found to encode a novel 6'-N-aminoglycoside acetyltransferase, AAC(6')-Iap, consisting of 155 amino acids with 85.0% identity to AAC(6')-Iz. E. coli transformants expressing were less susceptible to arbekacin, amikacin, dibekacin, isepamicin, neomycin, netilmicin, sisomicin and tobramycin. The recombinant AAC(6')-Iap protein acetylated all aminoglycosides tested, except for apramycin and paromomycin. The genomic environment surrounding was 90.99% identical to that of S. maltophilia JV3 obtained from a rhizosphere in Brazil. Phylogenetic analysis based on whole genome sequences showed that most S. maltophilia isolates in Nepal were similar to those isolates in European countries, including Germany and Spain. The emergence of drug-resistant S. maltophilia has become a serious problem in medical settings worldwide. The present study demonstrated that drug-resistant S. maltophilia strains in Nepal harbored novel genes encoding a class A β-lactamase, KBL-1, or a 6'-N-aminoglycoside acetyltransferase, AAC(6')-Iap. Genetic backgrounds of most S. maltophilia strains in Nepal were similar to those in European countries. Surveillance of drug-resistant S. maltophilia in medical settings in Nepal is necessary.
Topics: Acetyltransferases; Amino Acids; Anti-Bacterial Agents; Escherichia coli; Humans; Microbial Sensitivity Tests; Nepal; Penicillins; Phylogeny; Stenotrophomonas maltophilia; beta-Lactamases
PubMed: 35862995
DOI: 10.1128/spectrum.01143-22 -
The Journal of the Association of... Jul 2019Antibiotic resistance is one of the biggest menace to global health. Deaths from Drug-resistant infections is set to escalate exponentially. Pipeline for new...
Antibiotic resistance is one of the biggest menace to global health. Deaths from Drug-resistant infections is set to escalate exponentially. Pipeline for new antibacterials is almost empty. The World Health Organization has reinforced its warning that to tackle growing threat of antimicrobial resistance, development of a new antibiotics is seriously lacking. Arbekacin is a novel aminoglycoside primarily used in the treatment of infections caused by resistant Staphylococcus Aureus i.e. Methicillin Resistant Staphylococcus Aureus (MRSA). Besides MRSA it also demonstrates activity against Enterococci and several Gram negative pathogens such as Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii including resistant strain. Arbekacin which has been used in Japan and Korea since more than two and half decades has been recently approved in India. This review will examine how Arbekacin evades the common mechanisms of antibiotic resistance, the pharmacokinetics of Arbekacin, and the various pharmacological properties and its spectrum of in vitro activity. The results of clinical trials on Arbekacin are also described, as is the patient safety and tolerability observed during these studies.
Topics: Anti-Bacterial Agents; Dibekacin; Drug Resistance, Bacterial; Humans; India; Japan; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections
PubMed: 31559785
DOI: No ID Found -
Antibiotics (Basel, Switzerland) May 2015Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify...
Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify drugs that eliminate uropathogenic E. coli persisters, we screened a clinical drug library consisting of 1524 compounds using high throughput drug exposure assay in 96-well plates. Bacterial survival was assessed by growth on LB plates. We identified 14 drug candidates (tosufloxacin, colistin, sparfloxacin, moxifloxacin and gatifloxacin, enrofloxacin and sarafloxacin, octodrine, clofoctol, dibekacin, cephalosporin C, pazufloxacin, streptomycin and neomycin), which had high anti-persister activity. Among them, tosufloxacin and colistin had the highest anti-persister activity and could completely eradicate E. coli persisters in 3 days in vitro while the current UTI antibiotics failed to do so. Our findings may have implications for the development of a more effective treatment for UTIs.
PubMed: 27025620
DOI: 10.3390/antibiotics4020179 -
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 -
European Journal of Orthopaedic Surgery... May 2018Antibiotic-loaded acrylic cement (ALAC) spacers are useful for treatment of infected prostheses in the course of a two-stage revision. Spacers are handmade or are made...
PURPOSE
Antibiotic-loaded acrylic cement (ALAC) spacers are useful for treatment of infected prostheses in the course of a two-stage revision. Spacers are handmade or are made using a commercial template, with reportedly good treatment outcomes. This study aimed to confirm the usefulness of custom-made ALAC spacers shaped like bipolar hip prostheses using a dental silicone template for treatment of infected hip prostheses, and described their manufacture.
METHODS
This study evaluated 10 patients who underwent two-stage revision for treatment of infected hip prostheses. Custom-made ALAC spacers were used in all patients. Templates were made with dental silicone. We investigated the following in treatment of the infected hip prostheses: bacterial pathogens; antibiotic-cement mixtures; waiting time to revision; dislocation, breakage, and migration of custom-made ALAC spacers; current hip status; progress during follow-up; presence or absence of recurrence; and walking ability.
RESULTS
Dislocation, breakage, and migration were not observed in custom-made ALAC spacers. All patients recovered after two-stage revision without additional surgery and showed no recurrence during the follow-up period.
CONCLUSION
Custom-made ALAC spacers shaped like bipolar hip prostheses using a template made of dental silicone may be useful for treatment of infected hip prostheses.
Topics: Adult; Aged; Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Bone Cements; Dibekacin; Equipment Design; Female; Hip Prosthesis; Humans; Male; Methicillin Resistance; Middle Aged; Polymethyl Methacrylate; Prosthesis-Related Infections; Reoperation; Silicone Elastomers; Staphylococcal Infections; Surgical Instruments; Time-to-Treatment; Treatment Outcome; Vancomycin
PubMed: 29332203
DOI: 10.1007/s00590-017-2117-3 -
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 -
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