dibekacin and Disease-Models--Animal

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.. The mice were treated for 5 min, once daily, with placebo, 3, 10 or 30 mg/mL ME1100 or 30 mg/mL amikacin.. 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.. 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 aeruginosa; Pseudomonas Infections

Biofilms are a major concern for clinicians in the treatment of infectious disease because of the resistance to a wide range of antibiotics. 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. This model has the advantage of permitting frequent sampling of exudates for bacterial counts and anti-bacterial activity, and morphological examination of the biofilm structure and inflammatory process in the pouch tissues. A clear synergistic effect was observed in the rats treated with a combination of fosfomycin and arbekacin. Morphological studies using scanning electron microscopy and histological staining showed dramatic changes of the biofilm structure as well as the inflammatory response in the rats. These results suggested an enhancement of bactericidal activity of arbekacin penetrating through the biofilm layer by virtue of fosfomycin. A possible mechanism of the synergistic effect is discussed.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Biofilms; Dibekacin; Disease Models, Animal; Drug Synergism; Fosfomycin; Granuloma; Male; Methicillin Resistance; Microbial Sensitivity Tests; Rats; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus

Combined effects of arbekacin (ABK) with biapenem (BIPM) were examined on both in vitro and in vivo model of a mixture of MRSA and Pseudomonas aeruginosa. As a result, significant effect in vitro was observed in combined use of ABK (1/2 MIC) with BIPM (1/4 and 1/2 MIC) against MRSA as compared with ABK or BIPM alone. Against P. aeruginosa combined effect was also observed, showing reduction of viable cells to the limitation of detection within 2 hours. Moreover, with respect to the protective effect on mixed systemic infection of MRSA and P. aeruginosa, the combined treatment with ABK and BIPM showed more excellent efficacy as compared with the single use of each drug.

Topics: Aminoglycosides; Animals; Anti-Infective Agents; Dibekacin; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Drug Therapy, Combination; Male; Methicillin Resistance; Mice; Mice, Inbred ICR; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Thienamycins

Biofilms are a major concern for clinicians in the treatment of infectious disease because of their resistance to a wide range of antibiotics. Arbekacin, an aminoglycoside antibiotic, is the drug of choice for the treatment of infection caused by methicillin-resistant Staphylococcus aureus (MRSA). However, it has not yet been defined whether arbekacin tends to penetrate into the biofilm structure induced by MRSA infection. In this study, we treated a biofilm mode of MRSA growth with arbekacin, using a rat air-pouch model. The model has the advantage of permitting frequent sampling of exudates for bacterial counts and antibacterial activity. A clear dose-dependent bactericidal effect was detected in rats treated with arbekacin at concentrations between 0.3 and 10 mg/kg, but 0.1 mg/kg of arbekacin was ineffective against the experimental MRSA infection in rats. Morphological studies using scanning electron microscopy and histochemical staining demonstrated that an effective dosage of arbekacin induced dramatic changes in the biofilm membranous structure as well as in the inflammatory response, resulting in eradication of the biofilm structure and resolution of inflammation.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Biofilms; Dibekacin; Disease Models, Animal; Granuloma; Humans; Male; Methicillin Resistance; Microscopy, Electron, Scanning; Necrosis; Rats; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

We developed a calcium phosphate cement containing arbekacin sulfate and polylactic acid (CPC95AP) and examined its effects on bone strength by injecting the CPC95AP into the femoral medullary cavity in model rats with osteoporosis. Favorable cortical bone strength was maintained for more than 6 months when CPC95AP was injected into the femoral cavities. This phenomenon was more significant in the weakened femur of osteoporotic rats. The reasons for the increased bone strength are thought to be that the CPC95AP filling increased the geometric moment of inertia and that the binding of CPC95AP with the bones increased Young's modulus. The most important factor is believed to be the increased Young's modulus. The binding of CPC95AP with the bones after filling the femur cavities compensates for the weak extensional strength of CPC95AP, and provides an opportunity to utilize the compressive strength, which is the advantage of CPC95. CPC95AP has antibiotic properties and biocompatibility, and it increases the mechanical strength of the weakened bone; therefore, it is considered useful in bone filling and stiffening.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Biocompatible Materials; Bone Cements; Calcium Phosphates; Dibekacin; Disease Models, Animal; Drug Delivery Systems; Female; Femur; Lactic Acid; Osteoporosis; Polyesters; Polymers; Rats; Rats, Sprague-Dawley; Stress, Mechanical

Enterococcus faecalis LC40 is an ampicillin-susceptible clinical isolate with high-level gentamicin resistance due to the aac(6')-Ie-aph(2")-Ia aminoglycoside resistance gene. The combination of ampicillin plus arbekacin reduced mean bacterial vegetation counts significantly more than ampicillin alone or ampicillin plus gentamicin in a rabbit model of aortic-valve endocarditis caused by E. faecalis LC40.

Topics: Aminoglycosides; Ampicillin; Animals; Anti-Bacterial Agents; Dibekacin; Disease Models, Animal; Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecalis; Gentamicins; Gram-Positive Bacterial Infections; Microbial Sensitivity Tests; Rabbits; Treatment Outcome

The relationship between the degree of chronic middle ear inflammation and pneumatization was investigated in the pig as an animal model, since its tympanic bulla closely resembles the human mastoid air cell system. Ten piglets (sire: Landrace-Hampshire crossbreed; dam: Duroc) were used for this experiment. Four ears of two animals served as the normal control group and 16 ears of eight animals were the experimental group. In this latter group, otitis media was induced by injecting glycerin into the middle ear clefts 1 months after birth, and the degree of inflammation was varied by administering or withholding antibiotics (cefamandole and dibekacin) and adjusting the dosage regimen. The animals were sacrificed 6 months after birth and examined for the relationship between the degree of chronic middle ear inflammation present and tympanic bulla pneumatization. Various degrees of inflammation were successfully induced by injecting the antibiotics: the more severe the inflammation found, the greater was the inhibition of pneumatization. Findings demonstrated that the degree of inhibition of pneumatization produced was directly proportional to the severity of chronic middle ear inflammation.

Topics: Animals; Bone Resorption; Cefamandole; Chronic Disease; Dibekacin; Disease Models, Animal; Ear, Middle; Epithelium; Glycerol; Image Processing, Computer-Assisted; Injections, Intramuscular; Osteoblasts; Osteoclasts; Osteosclerosis; Otitis Media; Swine; Temporal Bone

Topics: Animals; Anti-Bacterial Agents; Body Weight; Dibekacin; Disease Models, Animal; Ear, Inner; Gentamicins; Hypertension; Injections, Intramuscular; Kanamycin; Male; Rats; Ribostamycin; Tissue Distribution