Tobramycin dosing

Sjolin J, Goscinski G, Lundholm M, Bring J, Odenholt I. Endotoxin release from Escherichia coli after exposure to tobramycin dose-dependency and reduction in cefuroxime-induced endotoxin release Clin Microbiol Infect 2000 6(2) 74-81. 

A prospective, single-centre study assessing once daily intravenous tobramycin dosing to treat pulmonary exacerbations of CF noted two cases (8%) of transient vestibular disturbance, without any significant nephrotoxicity. Vestibular disturbance appeared to be an early indicator of tobramycin toxicity [18 ]. Cessation of therapy or dose reduction with careful monitoring should be considered in patients experiencing vestibular symptoms. 

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... 

Gram-negative rods Tobramycin 3-14 mg/mL or Gentamicin 3-14 mg/mL or Ceftazidime SO mg/mL or Fluoroquinolones 3 mg/mL Less severe keratitis may use less frequent dosing Antibiotics may be alternated each hour for ulcers and contact lens... 

Empirical therapy for postoperative infections in neurosurgical patients (including patients with CSF shunts) should include vancomycin in combination with either cefepime, ceftazidime, or meropenem. Linezolid has been reported to reach adequate CSF concentrations and resolve cases of meningitis refractory to vancomycin.35 However, data with linezolid are limited. The addition of rifampin should be considered for treatment of shunt infections. When culture and sensitivity data are available, pathogen-directed antibiotic therapy should be administered. Removal of infected devices is desirable aggressive antibiotic therapy (including high-dose intravenous antibiotic therapy plus intraventricular vancomycin and/or tobramycin) may be effective for patients in whom hardware removal is not possible.36... 

Dual therapy with Cefepime, ceftazidime, imipenem, meropenem, Gentamicin or tobramycin 2 mg/kg loading dose... 

For penicillin-allergic adults, use a fluoroquinolone (ciprofloxacin 0.5-0.75 g orally every 12 hours or 0.4 g IV every 12 hours levofloxacin 0.5-0.75 g orally or IV every 24 hours or moxifloxacin 0.4 g orally or IV every 24 hours). eGentamicin or tobramycin, 2 mg/kg loading dose, then maintenance dose as determined by serum concentrations, fluoroquinolone or aztreonam 1 g IV every 6 hours may be used in place of the aminoglycoside in patients with severe renal dysfunction or other relative contraindications to aminoglycoside use. 

The steady-state maximum plasma concentration, Cmaxss, of gentamycin and tobramycin are 6 to 10 mcg/mL. The Cmax ss of amikacin is 25 to 30 mcg/mL. The Cmin ss of both gentamycin and tobramycin is 0.5 to 1.5 mcg/mL, while that of amikacin is 5 to 8 mcg/mL. In order for these drugs to be effective, it is important to closely monitor their therapeutic concentrations. An important observation of these antibiotics is that with prolonged therapy, the Cminsl, values increase. This increase is due to the renal impairment. In the case where Cmin ss is less than the desired Cmin ss, the dose may be insufficient. 

Monitoring In patients with normal renal function, serum tobramycin concentrations are approximately 1 mcg/mL 1 hour after dose administration. Monitoring of serum concentrations in patients with renal dysfunction or patients treated with concomitant parenteral tobramycin may reduce the risk of toxicity. 

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. 

The pharmacokinetic properties of tobramycin are virtually identical with those of gentamicin. The daily dose of tobramycin is 5-6 mg/kg intramuscularly or intravenously, traditionally divided into three equal amounts and given every 8 hours. Monitoring blood levels in renal insufficiency is an essential guide to proper dosing. 

Amikacin Intravenous resistant to many enzymes that inactivate gentamicin and tobramycin higher doses and target peaks and troughs than gentamicin and tobramycin... 

Olsen KM et al Effect of once-daily dosing vs. multiple daily dosing of tobramycin on enzyme markers of nephrotoxicity. Crit Care Med 2004 32 1678. [PMID 15286543]... 

Tobramycin Dexamethasone Ophthalmic (TobraDex) [Antibiotic/Anti-inflammatory] Uses Ocular bacterial Infxns associated w/ significant inflammation Action Antibiotic w/ anti-inflammatory Dose Oint soln Caution [C, M] Contra Aminoglycoside sensitivity Disp Oint susp 2.5, 5, 10 mL tobramycin 0.3% dexamethasone 0.1% SE Local irrita-tion/edema see Tobramycin EMS See Tobramycin OD Unlikely w/ ophthalmic form... 

In ophthalmology, both trans-scleral and transcomeal dmg delivery has been studied. Drags investigated include fluorescein, tobramycin, gentamicin, ticarcillin, cefazolin, dexamethasone and ketoconazole. Iontophoresis has been found to be both safe and effective in delivering the required doses locally, at the intended site of action. Excepting for lidocaine, which has been tested in human volunteers, all the other drags have been tested in rabbits. 

Serum concentrations of tobramycin following administration of the same dose of drug to normal and azotemic patients. 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

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