Disease relevance of NEBRAMYCIN

• BACKGROUND AND METHODS: We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection [1].
• Aerosolized tobramycin in patients with cystic fibrosis [2].
• Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin [3].
• Two hundred fifty-eight patients with suspected sepsis were treated with tobramycin or gentamicin in a prospective, randomized, double-blind trial [3].
• Gentamicin and tobramycin are important antibiotics in the treatment of hospital infections because of their activity against a wide range of bacterial genera [4].

Psychiatry related information on NEBRAMYCIN

• These data suggest that a short period of food deprivation modulates the temporal variations of tobramycin nephrotoxicity [5].

High impact information on NEBRAMYCIN

• CONCLUSIONS: In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization [1].
• RESULTS: The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001) [1].
• Pulmonary function, the density of P. aeruginosa in sputum, ototoxicity, nephrotoxicity, and the emergence of tobramycin-resistant P. aeruginosa were monitored [6].
• The pharmacokinetics of tobramycin were studied in 11 of the 20 patients and in eight normal subjects receiving continuous intravenous infusions of the drug [7].
• Increased glomerular filtration rate in patients with major burns and its effect on the pharmacokinetics of tobramycin [7].

Chemical compound and disease context of NEBRAMYCIN

• A single intravenous dose of tobramycin and lincomycin, given at the start of gastrointestinal operations, significantly reduced the incidence of postoperative wound infection from 34% to 5% [8].
• Resistance to gentamicin and tobramycin during the period of amikacin use showed a statistically significant decrease (p greater than 0.001) due to decreased resistance to gentamicin of Providencia, Serratia, indole-positive Proteus, and decreased resistance to tobramycin of Pseudomonas aeruginosa [9].
• Microbial causes of proven pelvic inflammatory disease and efficacy of clindamycin and tobramycin [10].
• Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment [11].
• CONCLUSIONS: Selected patients with S. aureus endocarditis can be treated safely and effectively with a 2-week course of nafcillin plus tobramycin [12].

Biological context of NEBRAMYCIN

• Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity [6].
• Plasmid studies on isolates from 20 hospital and nursing home patients revealed that 17 had a common 54-kilobase plasmid, which conferred ceftazidime resistance via the ESBL TEM-10, and mediated resistance to trimethoprim-sulfamethoxazole, gentamicin, and tobramycin; all 20 isolates harbored this ESBL [13].
• Phagocytosis of P. aeruginosa killed by tobramycin or Formalin was glucose dependent, suggesting that the glucose exerted its effects on the M phi rather than the bacteria [14].
• Steady-state aminoacylation kinetics of unmodified yeast tRNA(Asp) transcript indicate that the complex between tRNA(Asp) and tobramycin is a competitive inhibitor of the aspartylation reaction with an inhibition constant (K(I)) of 36 nM [15].
• Binding of tobramycin leads to conformational changes in yeast tRNA(Asp) and inhibition of aminoacylation [15].

Anatomical context of NEBRAMYCIN

• A decrease in the density of P. aeruginosa in sputum by a factor of 100 (P < 0.001) was found during all periods of tobramycin administration [6].
• In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from week 0 to week 20, as compared with an increase of 0.3 log10 CFU per gram in the placebo group (P<0.001) [1].
• All patients admitted to the ICU who were thought likely to stay in the unit for at least 5 days and to need intubation for longer than 48 h were enrolled and randomly allocated to groups receiving placebo or SDD (amphotericin, colistin, and tobramycin applied to the oropharynx and enterally); all patients received intravenous cefotaxime for 72 h [16].
• Consistent with this, treatment of SMA patient fibroblasts with tobramycin and amikacin resulted in a quantitative increase in SMN-positive gems and an overall increase in detectable SMN protein [17].
• CONCLUSION: The therapeutic strategy of ciprofloxacin and rifampin followed by once-daily vancomycin and tobramycin markedly reduced the incidence of infection and virtually eliminated bacteremia in both purged and nonpurged bone marrow recipients [18].

Associations of NEBRAMYCIN with other chemical compounds

• Cost effectiveness of gentamicin and tobramycin [19].
• All three antibiotics induce biofilm formation; tobramycin increases bacterial motility, and tetracycline triggers expression of P. aeruginosa type III secretion system and consequently bacterial cytotoxicity [20].
• At therapeutic doses, gentamicin, tobramycin, netilmicin, and amikacin induce an early lysosomal phospholipidosis in the human kidney cortex comparable to that observed in animals treated with low doses of these drugs [21].
• The nucleotide sequence of the aadB gene which confers resistance to kanamycin, gentamicin, and tobramycin has been determined [22].
• We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections [23].

Gene context of NEBRAMYCIN

• We then investigated whether the daily administration of the aminoglycoside antibiotics gentamicin or tobramycin could restore the expression of a detectable level of CFTR protein [24].
• Regarding aminoglycoside-modifying enzymes, 7 strains (12%) appeared to be producing aminoglycoside 4',4"-adenyltransferase AAD(4',4") encoded by aadD without coproduction of bifunctional aminoglycoside 6'-acetyltransferase/2"-phosphotransferase AAC(6')/APH(2") encoded by aacA-aphD (referred to as tobramycin-resistant type, TOBr) [25].
• IL-6 levels in rats treated with cefuroxime were lower than in rats treated with tobramycin or vancomycin and the control group [26].
• Are recombinant human bone morphogenetic protein-7 and tobramycin compatible? An experiment in rats [27].
• Other aminoglycosides such as tobramycin, streptomycin, and neomycin also inhibited PTH-stimulated Mg2+ entry and cAMP formation [28].

Analytical, diagnostic and therapeutic context of NEBRAMYCIN

• We conducted a randomized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections [6].
• Removal of tobramycin during plasma exchange therapy [29].
• Risk factors for nephrotoxicity in patients treated with aminoglycosides were determined from the case records of 214 patients in two prospective, randomized clinical trials of gentamicin and tobramycin [30].
• Here, we show that suppression of S. aureus respiration by a P. aeruginosa exoproduct, 4-hydroxy-2-heptylquinoline-N-oxide (HQNO), protects S. aureus during coculture from killing by commonly used aminoglycoside antibiotics such as tobramycin [31].
• Peritonitis caused by Staphylococcus aureus in four patients undergoing continuous ambulatory peritoneal dialysis failed to respond to, or relapsed immediately after cessation of, intraperitoneal antibiotic therapy with vancomycin or cephalothin and tobramycin [32].

References