TAUBRIGENE

Aminoglycosides, many of which are derived directly from Streptomyces spp., are concentration-dependent bactericidal antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative organisms.

Inhaled tobramycin is notable for its use in treating chronic Pseudomonas aeruginosa infections in cystic fibrosis patients, as P. aeruginosa is notoriously inherently resistant to many antibiotics. 1, 2, 13 However, tobramycin can also be administered Intravenous and topically to treat a variety of infections caused by susceptible bacteria. 14, 15 Its use is limited in some cases by characteristic toxicities such as nephrotoxicity and ototoxicity, yet it remains a valuable option in the face of growing resistance to front-line antibiotics such as β-lactams and cephalosporins. 1, 12, 13, 15 Tobramycin was approved by the FDA in and is currently available in a variety of forms for administration by inhalation, injection, and external application to the eye (ophthalmic). 13, 14, 15.

Inhaled tobramycin is indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa, but is not recommended in patients under six years of age, those with forced expiratory volume in 1 second (FEV 1 ) 80% predicted, or in those with Burkholderia cepacia. 13, 18 Tobramycin applied topically to the eyes is indicated for the treatment of external eye (and adjoining structure) infections by susceptible bacteria.

Tobramycin injection is indicated in adult and pediatric patients for the treatment of serious bacterial infections, including septicemia (caused by P. aeruginosa, Escherichia coli, and Klebsiella spp)., lower respiratory tract infections (caused by P. aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., E. coli, and Staphylococcus aureus, both penicillinase and non-penicillinase-producing strains), serious central-nervous-system infections (meningitis, caused by susceptible organisms), intra-abdominal infections including peritonitis (caused by E. coli, Klebsiella spp., and Enterobacter spp)., skin, bone, and skin structure infections (caused by P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., Serratia spp. and S. aureus ), and complicated and recurrent urinary tract infections (caused by P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., S. aureus, Providencia spp., and Citrobacter spp).

Aminoglycosides, including tobramycin, should generally not be used in uncomplicated urinary tract infections or staphylococcal infections unless less toxic antibiotics cannot be used and the bacteria in question are known to be sensitive to aminoglycosides. 15, 17 As with all antibiotics, tobramycin use should be limited to cases where bacterial infections are known or strongly suspected to be caused by sensitive organisms, and the possible emergence of resistance should be monitored closely. 13, 14,

Tobramycin is an aminoglycoside antibiotic derived from the actinomycete Streptomyces tenebrarius.

It has a broad spectrum of activity against Gram-negative bacteria, including Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Moraxella lacunata, Proteus spp., Haemophilus spp., Acinetobacter spp., Neisseria spp., and, importantly, Pseudomonas aeruginosa.

Aminoglycosides also generally retain activity against the biothreat agents Yersinia pestis and Francisella tularensis.

In addition, aminoglycosides are active against some Gram-positive bacteria such as Staphylococcus spp., including methicillin-resistant (MRSA) and vancomycin-resistant strains, Streptococcus spp., and Mycobacterium spp. 1, 14 Like other aminoglycosides, tobramycin is taken up and retained by proximal tubule and cochlear cells in the kidney and ear, respectively, and hence carries a risk of nephrotoxicity and ototoxicity. 1, 15 There is also a risk of neuromuscular block, which may be more pronounced in patients with preexisting neuromuscular disorders such as myasthenia gravis or Parkinson's disease. 1, 13, 15 Aminoglycosides can cross the placenta, resulting in total, irreversible, bilateral congenital deafness in babies born to mothers who were administered an aminoglycoside during pregnancy. 13, 15 Due to the low systemic absorption of inhaled and topical tobramycin formulations, these effects are more pronounced with injected tobramycin than with other formulations. 13, 14, 15 However, all formulations carry a risk of hypersensitivity reactions, including potentially fatal cutaneous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. 13, 14, 15.

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Tobramycin administered by inhalation in cystic fibrosis patients showed greater variability in sputum as compared to serum.

After a single 112 mg dose, the serum C max was 1.02 ± 0.53 μg/mL, which was reached in one hour (T max ), while the sputum C max was 1048 ± 1080 μg/g.

Comparatively, for a 300 mg dose, the serum C max was 1.04 ± 0.58 μg/mL, which was also reached within one hour, while the sputum C max was 737 ± 1028 μg/g.

The systemic exposure (AUC 0-12 ) was also similar between the two doses, at 4.6 ± 2.0 μg∙h/mL for the 112 mg dose and 4.8 ± 2.5 μg∙h/mL for the 300 mg dose.

When tobramycin was administered over a four-week cycle at 112 mg twice daily, the C max measured one hour after dosing ranged from 1.48 ± 0.69 μg/mL to 1.99 ± 0.59 μg/mL.

Inhalation tobramycin had an apparent volume of distribution in the central compartment of 85.1 L for a typical cystic fibrosis patient.

Tobramycin is primarily excreted unchanged in the urine.

Tobramycin has an apparent serum terminal half-life of ~3 hours following a single 112 mg inhaled dose in cystic fibrosis patients.

Inhaled tobramycin has an apparent serum clearance of 14.5 L/h in cystic fibrosis patients aged 6-58 years.

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information regarding tobramycin is not readily available.

Patients experiencing an overdose are at an increased risk of severe adverse effects such as nephrotoxicity, ototoxicity, neuromuscular blockade, and respiratory failure/paralysis.

Symptomatic and supportive measures are recommended; hemodialysis may help clear excess tobramycin.

Accidental ingestion of tobramycin is unlikely to result in an overdose, as aminoglycosides are poorly absorbed in the gastrointestinal tract. 13, 15 Poor gastrointestinal absorption is reflected in animal studies.

When administered by the intraperitoneal or subcutaneous route, the LD50 for mice and rats ranges from 367-1030 mg/kg while the oral LD50 values are more than 7500 mg/kg.