dibekacin and Pneumonia

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., and Enterobacter spp. The highest arbekacin MIC among S. aureus isolates from PHP (43% methicillin-resistant S. aureus [MRSA]) was 4 μg/ml. Among P. aeruginosa isolates from PHP, only one had an arbekacin MIC of >16 μg/ml (MIC50 and MIC90, 1 and 4 μg/ml), and susceptibility rates for gentamicin, tobramycin, and amikacin were 88.0, 90.0, and 98.0%, respectively. Arbekacin (MIC50, 2 μg/ml) and tobramycin (MIC50, 4 μg/ml) were the most potent aminoglycosides tested against Acinetobacter baumannii. Against Enterobacteriaceae from PHP, arbekacin and gentamicin (MIC50 and MIC90, 0.25 to 1 and 1 to 8 μg/ml for both compounds) were generally more potent than tobramycin (MIC50 and MIC90, 0.25 to 2 and 1 to 32 μg/ml) and amikacin (MIC50 and MIC90, 1 to 2 and 2 to 32 μg/ml). Arbekacin also demonstrated potent in vitro activity against a worldwide collection of well-characterized MDR Gram-negative and MRSA strains.

Topics: Amikacin; Anti-Bacterial Agents; Dibekacin; Enterobacter; Humans; Klebsiella; Microbial Sensitivity Tests; Pneumonia; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Staphylococcus aureus; Tobramycin

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. Further studies would be needed for ABK inhalation therapy for pneumonia.

Topics: Adult; Aged; Anti-Bacterial Agents; Child; Dibekacin; Female; Humans; Infant; Male; Pneumonia

Aiming at measuring the antimicrobial activities of arbekacin (ABK) against the strains of methicillin-resistant Staphylococcus aureus (MRSA), isolated from pediatrics patients in 1992, the minimum inhibitory concentration (MIC) of 8 antibiotics including ABK was determined and the coagulase types of those strains were also examined. The obtained results are summarized as follows. 1. Among coagulase types of a total of 78 strains, Type II, Type IV and Type VII were 84.6%, 12.8% and 2.6%, respectively. No clear difference in coagulase types were observed among their origins of isolation. 2. MIC90 of ABK against 42 strains isolated from the air passage of suspected pneumoniae patients and 36 strains isolated from the blood of suspected septicemia patients were 1.56 micrograms/ml and 3.13 micrograms/ml, respectively, and MIC90 of ABK against the 78 strains was 1.56 micrograms/ml, which was equal to that of vancomycin (VCM). 3. Most of these strains exhibited resistance against multiple antibiotic agents including cefmetazole (CMZ), imipenem (IPM), fosfomycin (FOM) and minocycline. Strains isolated from the blood were mostly resistant to multiple agents, and most of them were especially highly resistant to CMZ and IPM. ABK, however, showed potent antimicrobial activities even to those strains. These results were similar to the results obtained several years ago. 4. Considering the fact that ABK demonstrates not only potent antimicrobial activities against MRSAs isolated from the pediatric patients, but also shows remarkable clinical effects with concomitant use with beta-lactams or FOM, the prospect of ABK use in MRSA infectious diseases of children is excellent.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Child; Dibekacin; Humans; Kanamycin Resistance; Methicillin Resistance; Pneumonia; Respiratory System; Staphylococcal Infections; Staphylococcus aureus

Dibekacin (DKB), an antibiotic of aminoglycoside group, was administered at 4 different dosages of 0.5, 1.0, 1.5 and 2.0 mg/kg as intravenous drip infusion taking 30 minutes or 1 hour. For each dose level, 3 cases each were used out of 24 boys from 1 year and 1 month to 14 years and 7 months of age, and serum concentrations as well as urinary concentrations and recovery rate were determined. After removed of 4 cases unassessable of therapeutic efficacy, 7 cases consisting of 1 case of chronic bronchitis, 1 case of lung abscess and 5 cases of urinary tract infections were treated with DKB at a mean daily dosage of 3.3 mg/kg in 2 or 3 divided doses as intravenous drip infusion taking 30 minutes or 1 hour. The mean treatment period was 7 days. The clinical and bacteriological results were analyzed in these cases and for analysis of side effects drop out cases were also included. The following results were obtained. Following 30 minutes intravenous drip infusion of DKB at 0.5, 1.0, 1.5 and 2.0 mg/kg, the serum concentration peaked at the end of infusion for all dose levels. The highest peak concentration of 9.17 mcg/ml was obtained for the dose level of 2.0 mg/kg. The highest dosage with which serum concentration does not exceed concentrations of 10 to 12 mcg/ml was found to be 2.0 mg/kg. The mean highest serum concentrations obtained were 1.65, 3.49, 5.40 and 8.67 mcg/ml for the dosages of 0.5, 1.0, 1.5 and 2.0 mg/kg, respectively, and the mean AUCs determined by the two-compartment model were 2.99, 6.04, 10.5 and 14.2 mcg X hr/ml, respectively, showing dose response relation in terms of peak concentration and AUC among groups. The mean T1/2 values for each dosage were 1.55, 1.54, 1.77 and 2.03 hours, respectively, with a longer tendency in T1/2 for the dose level of 2.0 mg/kg with unknown cause. When 0.5, 1.0, 1.5 and 2.0 mg/kg of DKB were infused taking 1 hour, the peak of serum concentration appeared also at the end of the infusion. The highest concentration was obtained with 2.0 mg/kg and it was 7.02 mcg/ml. Considering from the concentrations obtained for 0.5 mg/kg and 1.0 mg/kg groups the highest dosage at which the serum concentration does not exceed 10 to 12 mcg/ml was estimated to be 2.5 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Bronchitis; Child; Child, Preschool; Dibekacin; Drug Administration Schedule; Female; Humans; Infant; Infusions, Parenteral; Kanamycin; Kinetics; Lung Abscess; Male; Pneumonia; Urinary Tract Infections

The serum concentration of dibekacin (DKB) were determined in 4 healthy adult volunteers after intramuscular injection, intravenous injection and 1-hour or 2-hour intravenous drip infusion of 100 mg of DKB, and 1-hour drip infusion of 50 mg. The mean peak concentration after the 2-hour drip infusion of 100 mg of DKB was a rather low level. While the 1-hour drip infusion of 50 mg of DKB produced a peak concentration of 7.9 micrograms/ml, which is comparable to that after intramuscular injection of 100 mg. In the cases of the 1-hour drip infusion of 100 mg, the peak serum level reached 13.3 micrograms/ml, which is a relatively higher level than that after intramuscular injection of the same dose. Based on the above findings, it is suggested that the 1-hour intravenous drip infusion of DKB in doses of 50 mg to 100 mg be practically applied for therapeutic use.

Topics: Adult; Animals; Anti-Bacterial Agents; Dibekacin; Humans; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Kanamycin; Klebsiella Infections; Lung; Male; Mice; Pneumonia