Disease relevance of Haberacin

• Pharmacokinetic-Pharmacodynamic Relationship of Arbekacin for Treatment of Patients Infected with Methicillin-Resistant Staphylococcus aureus [1].
• We adopted an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VAN), arbekacin (ABK), and gentamicin (GEN) alone or in combination [2].
• Arbekacin (ABK) was given at a dose of 2 mg/kg of body weight to 10 HD patients infected with methicillin-resistant Staphylococcus aureus (MRSA) for 2 weeks (six sessions in total), resulting in the complete disappearance of MRSA in 5 patients [3].
• Efficacy of ampicillin plus arbekacin in experimental rabbit endocarditis caused by an Enterococcus faecalis strain with high-level gentamicin resistance [4].
• Since arbekacin has broad-spectrum activity, these findings suggest that it may be a useful agent against MRSA infection, especially for polymicrobial MRSA infection with Gram-negative bacilli, such as Pseudomonas aeruginosa [5].

High impact information on Haberacin

• The population pharmacokinetics of arbekacin was investigated in the Japanese, using 353 patients infected with MRSA and 50 healthy or renally impaired volunteers [6].
• The C(max), C(min), and AUC of arbekacin were associated with the probability of clinical cure/improvement during monotherapy [1].
• Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA) [6].
• We encountered three clinical isolates of methicillin-resistant Staphylococcus aureus which were susceptible to netilmicin and arbekacin in the absence of beta-lactam antibiotics but which were resistant to them in the presence of beta-lactam antibiotics [7].
• A high rate of elimination of ABK was attained for each patient while the patient was on HD (range, 0.20 to 0.42 h-1; mean 0.28 +/- 0.08 h-1) by using high-performance dialyzers provided with membranes made of either polymethylmethacrylate, cellulose triacetate (CTA), or ethylene vinyl alcohol [3].

Chemical compound and disease context of Haberacin

• Only arbekacin and amikacin showed excellent therapeutic potential (minimum inhibitory concentrationis (MICs) < or =0.25-4 microg/ml) against 30 isolates of rapidly growing mycobacteria, including Mycobacterium fortuitum, M. chelonae and a related organism, Nocardia asteroides [8].
• Using a rat air pouch model, methicillin-resistant Staphylococcus aureus (MRSA) growing as a biofilm was treated with a combination of fosfomycin (FOM) and arbekacin (ABK) or by the agents alone [9].
• Comparison of the toxicity between 26 (and 27) and the arbekacin analogs (28-30) with change of the 1N-side-chain indicates that the observed decrease in toxicity was a function of the chain length rather than the introduction of fluorine [10].
• Among them, 2''-amino-2''-deoxyarbekacin and the 5-epiamino analog showed excellent antibacterial activities against not only MRSA but also Gram-negative bacteria including Pseudomonas, and lower toxicities than arbekacin [11].
• In addition, arbekacin had excellent antimicrobial activity against Pseudomonas aeruginosa, compared to other anti-pseudomonal agents such as piperacillin, ceftazidime and imipenem [12].

Biological context of Haberacin

• In Group C, nasopharyngeal decolonization of MRSA, which was achieved by the combination of intranasal mupirocin, arbekacin inhalation, and oral sulfamethoxazole/trimethoprim in all 24 patients, significantly reduced peristomal infections [13].
• The phosphorylation activity of the PRC104 enzyme was enhanced for arbekacin and reduced for gentamicin [14].
• Characterization of a bifunctional aminoglycoside-modifying enzyme with novel substrate specificity and its gene from a clinical isolate of methicillin-resistant Staphylococcus aureus with high arbekacin resistance [14].
• In this study, we found an integrated copy of pSK41 in the chromosome of an arbekacin-resistant MRSA strain, K-1, clinically isolated in Japan. This is the first report of the chromosomal integration of this large plasmid in MRSA [15].

Anatomical context of Haberacin

• Effects of arbekacin and vancomycin on release of lactate dehydrogenase and fragmentation of DNA in LLC-PK1 kidney epithelial cells [16].
• In the ileum, the ratios became smaller with increase in arbekacin concentration applied [17].
• This study was undertaken to examine the secretory transport of arbekacin, an aminoglycoside antibiotic, in the rat small intestine and to compare it with those in Caco-2 and LLC-PK1 cells [17].
• There was no directionality in arbekacin permeation across Caco-2 cell monolayers, suggesting the absence or very slight expression of the secretory system for arbekacin in this cell line [17].
• Serosal-to-mucosal (secretory)/mucosal-to-serosal (absorptive) permeation ratios of 0.5 mM arbekacin were 2.8 in the jejunum and 7.0 in the ileum, respectively, indicating that arbekacin permeation was highly secretory-oriented [17].

Associations of Haberacin with other chemical compounds

• The in vitro and in vivo antibacterial activities of SM-17466, a new 1 beta-methyl carbapenem, were evaluated against a wide range of clinical bacterial isoaltes and compared with the activities of meropenem, imipenem, vancomycin, and arbekacin [18].
• The combination of arbekacin plus vancomycin produced synergistic killing against 12 of 13 gentamicin-resistant MRSA isolates [19].
• METHODS: We evaluated the effects of panipenem (PAPM) combined with 3 aminoglycosides, arbekacin, amikacin, and netilmicin, and vancomicin (VCM) with an agar dilution checkerboard technique and the fractional inhibitory concentration index against 47 strains of MRSA and 56 strains of P. aeruginosa [20].
• The effect of TAK-599 against systemic infection caused by clinical isolates of MRSA in mice was comparable or superior to that of vancomycin, linezolid, teicoplanin, and arbekacin [21].

Gene context of Haberacin

• The results of this study strongly suggest that a specialized efflux system other than P-glycoprotein and multidrug resistance proteins was involved in the secretory transport of arbekacin in the rat intestine [17].
• The majority of isolates produced coagulase type II (75.5%) and beta-lactamase (72. 6%); there was high susceptibility to arbekacin (84.9%) but no resistance to vancomycin [22].
• About 90% of recent isolates belonged to type L21, indicating the spread of a specific type of MRSA in Japan. Of the type L21 strains, 41.9% included the aac(6')/aph(2") gene, which was one of the risk factors of arbekacin (ABK) resistance, but only 5.5% were resistant to ABK [23].
• Although arbekacin is inactivated by the enzyme APH (2")/AAC (6') which can modify both gentamicin and tobramycin, the rate of modification of arbekacin by this enzyme is only 17% or less of that of gentamicin [24].

Analytical, diagnostic and therapeutic context of Haberacin

• In total, 1,581 serum arbekacin concentrations were measured (primarily from routine patient care) and used to perform the present pharmacokinetic analysis [6].
• We suggest including arbekacin in future clinical trials of empirical treatment of late onset neonatal sepsis [25].
• PCR-restriction fragment length polymorphism typing of the coagulase gene was a more reliable method than coagulase serotyping from the viewpoint of arbekacin resistance [26].
• In this study, implantation of HABs loaded with the aminoglycoside antibiotic, arbekacin, were tested in established Staphylococcus aureus osteomyelitis in the proximal tibia of rats after debridement of the marrow cavity [27].
• The centrifugation method is simple, and dried ABK produced by heating loaded HA-b is particularly useful in clinical applications for osteomyelitis [28].

References