Tobramycin

Tobramycin

The effect of tobramycin incorporated with bismuth-ethanedithiol loaded on niosomes on the quorum sensing and biofilm formation of Pseudomonas aeruginosa.[Pubmed:28323149]

Microb Pathog. 2017 Jun;107:129-135.

Pseudomonas aeruginosa is an opportunistic pathogen, enable of causing infections especially in immunocompromised patients. Recently many isolates developed multiple drug resistance, resulting in treatment failure in serious infections. In this study, the effect of Tobramycin incorporated with bismuth-ethanedithiol loaded on niosomes on the quorum sensing and biofilm production by P. aeruginosa was evaluated. Thin layer hydration method with cholesterol (30%), Span 40 and Tween 40 were used to make niosomes. The physical properties and particle size of the niosomes were investigated. Micro dilution method was used to determine the Minimum Inhibitory Concentration (MIC) for Tobramycin, niosomal Tobramycin, bismuth ethanedithiol, niosomal bismuth ethanedithiol, Tobramycin incorporated with bismuth-ethanedithiol and niosomal Tobramycin incorporated with bismuth-ethanedithiol. Biofilm formation was evaluated using microtiter plate. The effect of different combination on N-acyl homoserine lactone (AHL) production was evaluated in presence of Agrobacterium tumefaciens strain (GV3101). The best combination inhibiting the growth of various strains of P. aeruginosa were niosomal Tobramycin and niosomal Tobramycin incorporated with bismuth-ethanedithiol which reduced the MIC of Tobramycin significantly. Sub-MIC concentration of these compounds reduced the rate of biofilm formation 80% lower than the untreated bacteria, and effectively inhibited the production of AHL molecule. The prepared formulations containing non-ionic surfactants, can kept the drug and gradually release it. Encapsulation of Tobramycin in combination with bismuth-ethanedithiol in niosome had the ability to reduce the MIC of Tobramycin and effectively inhibiting the biofilm formation. These combinations can be used as an excellent combination for further evaluation for treatment of infections caused by MDR isolates of P. aeruginosa.

Nebulized Gentamicin as an Alternative to Nebulized Tobramycin for Tracheitis in Pediatric Patients.[Pubmed:28337076]

J Pediatr Pharmacol Ther. 2017 Jan-Feb;22(1):9-14.

OBJECTIVES: Tracheitis is an infection of the lower respiratory tract and is defined by the US Centers for Disease Control and Prevention (CDC) based on signs and symptoms with no radiographic evidence of pneumonia. One method of treatment involves the use of Tobramycin given by nebulizer. The purpose of this study was to compare the safety and efficacy of nebulized gentamicin with nebulized Tobramycin. METHODS: This study was conducted in patients under 21 years of age who received greater than or equal to 1 day of gentamicin, 80 mg, or Tobramycin, 300 mg, given twice a day by nebulization within the 14-month study period. The primary endpoint was amount of time until the patient no longer met the CDC definition of tracheitis. RESULTS: There were 19 patients who presented with 60 separate encounters. The average age of the patients within the gentamicin group was 7.2 and 5 years old within the Tobramycin group. The average duration of time for the gentamicin treatment encounters to be free of the CDC definition of tracheitis was 3.36 days compared to 3.17 days with Tobramycin. No adverse effects were observed that were attributable to aminoglycoside nebulization. CONCLUSIONS: No differences were detected between the safety and efficacy of intravenous gentamicin administered twice a day by nebulizer and that of Tobramycin inhalation solution given twice daily in children without cystic fibrosis.

Once daily aerosolised tobramycin in adult patients with cystic fibrosis in the management of Pseudomonas aeruginosa chronic infection.[Pubmed:28184305]

Multidiscip Respir Med. 2017 Feb 7;12:2.

It is estimated that about 60-70% of Cystic Fibrosis patients develop Pseudomonas aeruginosa chronic infection, with progressive loss of lung function, as well as increased antibiotic resistance and mortality. The current strategy is to maintain lung function by chronic suppressive antipseudomonas antibiotic therapy. Tobramycin inhalation solution was the first approved aerosolised antibiotic to be used against P. aeruginosa; inhalatory Tobramycin frequency of administration is twice daily and inhalation time is estimated to be 15 to 20 min. From the pharmacokinetic point of view, aminoglycosides are dose-dependent antibiotics and therefore once-daily dosing intravenous regimens have shown to be superior to the conventional multiple daily dosing. Therefore, there is no pharmacological reason to prefer the b.i.d administration as it is usually performed in current clinical practice. Should this be confirmed also for inhalatory route, the use of once-daily dosed aerosolized Tobramycin could be an important step in making treatment burden easier in CF patients. The aim of this proof of concept study was to explore the effectiveness of treatment with once daily inhaled Tobramycin in reducing P. aeruginos a density in sputum of chronically infected patients.

Pilot trial of tobramycin inhalation powder in cystic fibrosis patients with chronic Burkholderia cepacia complex infection.[Pubmed:28262569]

J Cyst Fibros. 2017 Jul;16(4):492-495.

There is no effective chronic suppressive therapy Burkholderia cepacia complex infection in cystic fibrosis (CF) patients. This was a pilot, open-label clinical trial of Tobramycin inhalation powder (TIP) delivered via Podhaler twice daily for 28days in adults and children with CF and chronic B. cepacia complex infection in Toronto, Canada. A total of 10 subjects (4 pediatric, 6 adult patients) were treated. There was a mean drop of 1.4 log (CFU/ml) in sputum bacterial density (p=0.01) and sputum IL-8 levels decreased significantly after 28days of TIP (p=0.04). The mean relative change in FEV1 (L) from Day 0 to Day 28 of TIP administration was a 4.6% increase but this was not statistically significant. The majority of patients (70%) had no or mild adverse events.

Protection by antibiotics against myeloperoxidase-dependent cytotoxicity to lung epithelial cells in vitro.[Pubmed:8380814]

J Clin Invest. 1993 Jan;91(1):38-45.

Myeloperoxidase, in the presence of noncytotoxic concentrations of H2O2, was used to induce cytotoxicity to the lung epithelial cell line, AKD. When the cationic aminoglycosides, Tobramycin and gentamicin were added to the cells in the presence of myeloperoxidase and H2O2, cytotoxicity was completely inhibited. In addition, Tobramycin prevented cytotoxicity induced by cystic fibrosis sputum and H2O2. Protection against myeloperoxidase and H2O2 was also observed with the thioether-containing antibiotics, ticarcillin and ceftazidime, but at higher concentrations than with the aminoglycosides. Analysis of spectral properties, dimethylsulfoxide-mediated reduction, and ethyl acetate/NaCl partitioning, demonstrated that aminoglycosides converted HOCl to hydrophilic noncytotoxic chloramines, but were unable to prevent the oxidation of sulfhydryls and methionine by HOCl. In contrast, ticarcillin and ceftazidime were highly effective inhibitors of HOCl-mediated sulfhydryl and methionine oxidation. These results suggest that aminoglycosides protect lung epithelial cells against myeloperoxidase-dependent oxidant injury by binding to anionic cell surfaces and converting HOCl to hydrophilic noncytotoxic chloramines, whereas penicillins and cephalosporins are potent HOCl scavengers capable of protecting critical extracellular molecules against oxidation.

In vitro studies of tobramycin, an aminoglycoside antibiotic.[Pubmed:4670427]

Antimicrob Agents Chemother. 1972 Jan;1(1):41-5.

Tobramycin is an aminoglycoside antibiotic which has excellent antibacterial activity against Pseudomonas, Staphylococcus aureus, and many members of the Enterobacteriaceae. Most strains of Serratia, Providence, Streptococcus, and Diplococcus pneumoniae were resistant to concentrations of Tobramycin which could be achieved in man. Tobramycin was effective against certain Pseudomonas strains resistant to gentamicin. The growth medium used to determine the inhibitory level of Tobramycin had a significant effect upon the minimal inhibitory concentration. Calcium and magnesium ions inhibited the bactericidal effect of Tobramycin. Tobramycin and carbenicillin acted in a synergistic manner. Ethylenediaminetetraacetic acid did not act in a synergistic manner with Tobramycin. Broth-dilution susceptibility tests and disc-diffusion tests in agar (10-mug discs) showed excellent correlation except with Proteus strains.

Tobramycin (Nebramycin Factor 6) is a parenterally administered, broad spectrum aminoglycoside antibiotic that is widely used in the treatment of moderate to severe bacterial infections due to sensitive organisms.

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