Tobramycin inhaled

Tobramycin Inhalation solution For chronic pulmonary infection cystic fibrosis. 

To prevent development of resistance and promote synergy, inhaled tobramycin or colistin is usually added to an oral fluoroquinolone for P. aeruginosa coverage.1,3 Methicillin-sensitive S. aureus (MSSA) may be treated with oral amoxiciUin-clavulanic acid, dicloxacillin, first- or second-generation cephalosporins, trimethoprim-sulfamethoxazole, or clindamycin, depending on sensitivity. Likewise, methiciUin-resistant S. aureus (MRSA) may be treated with oral trimethoprim-sulfamethoxazole, clindamycin, minocycline, or linezolid. H. influenzae often produces... 

Inhaled tobramycin (TOBI ) is typically administered to patients 6 years of age and older in alternating 28-day cycles of 300 mg nebulized twice daily, followed by a 28-day washout or off period to minimize development of resistance. Longterm intermittent administration improves pulmonary function, decreases microbial burden, and reduces the need for hospitalization for IV therapy.24,25 Due to minimal systemic absorption, pharmacokinetic monitoring is not necessary with normal renal function. Lower doses of nebulized tobramycin solution for injection have been used in younger children, and studies are underway using 300 mg twice daily in children under age 6. 

Nebulized colistin using the IV formulation may be an option in patients with tobramycin-resistant strains or intolerance to inhaled tobramycin. Due to an increased risk of bronchoconstriction after colistin inhalation, patients should pre-treat with albuterol and administer the first doses under medical observation.1,5... 

Newer examples of aminoglycoside antibiotics include amikacin, neomycin (Neosporin, Cortisporin), and tobramycin (TOBI, TobraDex). Injectable tobramycin is used in the treatment of serious infections at many body sites. It has also been formulated in an inhalable dosage form that has a very specific use to treat cystic fibrosis patients having Pseudomonas aeruginosa lung infections. In the form suitable for inhalation by the patient, it delivers the antibiotic directly to the site of infection. 

P. aeruginosa is commonly found in the bronchial secretions of patients with cystic fibrosis. In one study, daily inhalation of large doses of tobramycin decreased the colonization by this organism 100-fold and significantly improved pulmonary function. 

Cheer SM, Waugh J, Noble S Inhaled tobramycin (TOBI) A review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Drugs 2003 63 2501. [PMID 14609360]... 

Bums, J.L., Van Dalfsen, J.M., Shawar, R.M., Otto, K.L., Garber, R.L., Quan, J.M., Montgomery, A.B., Albers, G.M., Ramsey, B.W., Smith, A.L. Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. J Infect Dis 179 (1999) 1190-1196. 

Ramsey, B. W., Pepe, M. S., Quan, J. M., et al. (1999), Intermittent administration of inhaled tobramycin in patients with cystic fibrosis, cystic fibrosis inhaled tobramycin study group, N. Engl. J. Med.., 340,23-30. 

Topical uses. Neomycin and framycetin, whilst too toxic for systemic use, are effective for topical treatment of infections of the conjunctiva or external ear. They are sometimes used in antimicrobial combinations selectively to decontaminate the bowel of patients who are to receive intense immunosuppressive therapy. Tobramycin is given by inhalation for therapy of infective exacerbations of cystic fibrosis. 

Nikolaizik WH, Trociewicz K, Ratjen F. Bronchial reactions to the inhalation of high-dose tobramycin in cystic fibrosis. Eur Respir J 2002 20(l) 122-6. 

In a randomized comparison of nebulized tobramycin and nebulized colistin in patients with cystic fibrosis, 26 of 53 patients treated with tobramycin had at least one respiratory adverse event, most commonly pharyngitis (3). In 520 patients, inhaled tobramycin (300 mg bd for three 28-day cycles, each cycle being separated by a 28-day period of no treatment) was compared with placebo. Respiratory function was significantly improved as early as the second week and remained so for the rest of the study, even dnring periods withont aerosol treatment. There was also a parallel rednetion in the relative risk of hospitalization, the number of days of hospitalization, and the number of days of intravenous antibiotic treatment (4). 

Inhalation of the intravenous formulation of tobramycin can cause bronchoconstriction, as has been confirmed in 26 children with mild to moderate cystic fibrosis (11). Nevertheless, while bronchoconstriction did occur, many patients did not have bronchoconstriction in response to the standard intravenous formulation. The risk of bronchoconstriction may further be reduced by pretreatment with salbutamol. 

In a comparison of different dosage regimens, inhaled tobramycin caused bronchial obstruction (12). However, after 10 minutes of inhalation, lung function returned to baseline the effect was independent of dose. 

In two placebo-controlled, randomized studies, inhaled tobramycin significantly reduced sputum density of P. aeruginosa however, more patients in the treatment group reported increased dyspnea and wheezing, although the symptoms did not limit therapy (13,14). 

Nephrotoxicity due to inhaled tobramycin has recently been described in a 20-year-old patient with cystic fibrosis who developed acute non-oliguric renal insufficiency after taking inhaled tobramycin 300 mg bd for 1 week the clinical and renal biopsy findings were consistent with aminoglycoside-induced changes (36). 

Hypersensitivity to inhaled tobramycin has been reported in a 9-year-old boy who developed a rash after a course of gentamicin (38). The rash resolved after withdrawal, but returned all over his body when inhaled tobramycin was restarted. He was desensitized using escalating doses of inhaled tobramycin, tolerated the procedure well, and was still using once-a-day tobramycin 9 months after desensitization. 

Intermittent administration of inhaled tobramycin has been recommended in patients with cystic fibrosis, as it improves pulmonary function, reduces the density of P. aeruginosa in sputum, and reduces the risk of hospitalization. The proportion of patients with isolates of P. aeruginosa with higher minimal inhibitory concentrations of tobramycin may increase (39). Treatment with inhaled tobramycin does not increase isolation of Burkholderia cepacia, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans however, isolation of Candida albicans and Aspergillus species may increase (40). 

With combined inhalational and intravenous tobramycin, toxic serum drug concentrations can occur (48). 

Barker AF, Couch L, Fiel SB, Gotfried MH, Ilowite J, Meyer KC, O Donnell A, Sahn SA, Smith LJ, Stewart JO, Abuan T, Tully H, Van Dalfsen J, Wells CD, Ouan J. Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis Am J Respir Crit Care Med 2000 162(2 Pt l) 481-5. 

Ramagopal M, Lands LC. Inhaled tobramycin and bronchial hyperactivity in cystic fibrosis. Pediatr Pulmonol 2000 29(5) 366-70. 

Hoffmann IM, Rubin BK, Iskandar SS, Schechter MS, Nagaraj SK, Bitzan MM. Acute renal failure in cystic fibrosis association with inhaled tobramycin therapy. Pediatr Pulmonol 2002 34(5) 375-7. 

Elidemir O, Maciejewski SR, Oermann CM. Falsely elevated serum tobramycin concentrations in cystic fibrosis patients treated with concurrent intravenous and inhaled tobramycin. Pediatr Pulmonol 2000 29(l) 43-5. 

Cannella CA, and Wilkinson ST. 2006. Acute renal failure associated with Inhaled tobramycin. Am J Health Syst Pharm 63 1858-1861. 

Izquierdo MJ, Gomez-Alamlllo C, Ortiz F, Calabia ER, Ruiz JC, de Francisco AL, and Arias M. 2006. Acute renal failure associated with use of inhaled tobramycin for treatment of chronic airway colonization with Pseudomonas aeruginosa. Clin Nephrol66 464-467. 

Clinically important, potentially hazardous interactions with aminoglycosides, betamethasone, cyclosporine, gentamicin, halothane, inhalational anesthetics, kanamycin, magnesium salts, neomycin, quinidine, streptomycin, succinylcholine, tazobactum, tobramycin... 

A number of antibiotics have been used as aerosol therapies. Examples include beta lactam agents, polymycin antimicrobials, neomycin, gentamicin, and tobramycin. Many of the early efforts were reported as case studies, and observations and data regarding safety and efficacy were lacking. Controlled clinical trials were not conducted until the middle of the 1980s. More recent evaluations have focused on the role of inhaled tobramycin used as suppressive therapy for cystic fibrosis patients colonized with Pseudomonas aeruginosa. 

Although a potential advantage of inhaled antibiotic therapy is the achievement of high concentrations in the sputum, there is substantial variability reported, which may reflect differences in collection and bioassay techniques. There is no clear relationship between systemic and inhaled doses of individual agents. Currently, the decisions about inhaled doses should be made on data specific for an individual agent. In trials with the commercially available inhaled tobramycin product, sputum concentrations of 1200 pg per mL were measured 10 minutes after the dose. Measured concentrations exceeded 25 times the minimum inhibitory concentration (MIC) for the most resistant isolate in 95% of subjects evaluated [7]. 

---