Dibekacin

Arbekacin sulfate (ABK), an aminoglycoside antibiotic, was discovered in 1972 and was derived from dibekacin to stabilize many common aminoglycoside modifying enzymes. ABK shows broad antimicrobial activities against not only Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) but also Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. ABK has been approved as an injectable formulation in Japan since 1990, under the trade name Habekacin, for the treatment of patients with pneumonia and sepsis caused by MRSA. The drug has been used in more than 250,000 patients, and its clinical benefit and safety have been proven over two decades. ABK currently shows promise for the application for the treatment of multidrug-resistant Gram-negative bacterial infections such as multidrug-resistant strains of P. aeruginosa and Acinetobacter baumannii because of its synergistic effect in combination with beta-lactams.

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.

Arbekacin (ABK) is one of aminoglycosides which has indications for septicemia and pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) in Japan. ABK shows good clinical and microbiological efficacies also against Gram-negative bacteria (GNB), including Pseudomonas aeruginosa. In addition, furthermore, ABK would be sometimes effective also against antimicrobial-resistant GNB. We investigated ABK inhalation, which showed good pulmonary drug delivery, for the treatment of pneumonia caused by multidrug-resistant Gram-negative organisms and MRSA. Six patients with pneumonia were treated with ABK inhalation therapy (50 mg x three times/day). We observed clinical effect for multidrug-resistant organisms in 6/6 patients. Although routine use of aerosolized antibiotics might not be able to be recommended for multidrug-resistant organisms, we might be able to adopt the ABK inhalation therapy for pneumonia especially caused by multidrug-resistant Gram-negative organisms in some situations where systemic therapy alone might be failure or inadequate, or where intravenous access is not available because of systemic toxicity.

Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States. We evaluated the occurrence of organisms isolated from pneumonias in U.S. hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and the in vitro activity of arbekacin. Organism frequency was evaluated from a collection of 2,203 bacterial isolates (339 from VAP) consecutively collected from 25 medical centers in 2012 through the SENTRY Antimicrobial Surveillance Program. Arbekacin activity was tested against 904 isolates from PHP collected in 2012 from 62 U.S. medical centers and 303 multidrug-resistant (MDR) organisms collected worldwide in 2009 and 2010 from various infection types. Susceptibility to arbekacin and comparator agents was evaluated by the reference broth microdilution method. The four most common organisms from PHP were Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella spp.