General Administration Information
For storage information, see specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Intravenous (IV) Infusion
1.2 g Bulk Powder Vials for Injection
Reconstitution
-Reconstitute the vial with 30 mL of Sterile Water for Injection to provide a solution containing 40 mg/mL.
-The bulk vial should be penetrated 1 time with a suitable sterile dispensing set that allows measured distribution of the contents. The entire contents of the bulk vial should be used during reconstitution.
-Once penetration of the bulk vial has occurred, the contents should be used within 24 hours.
-FURTHER DILUTION IS REQUIRED.
-Storage: Reconstituted vials are stable under refrigeration (20 to 25 degrees C or 68 to 77 degrees F) for 96 hours or at room temperature for 24 hours.
Dilution
-Dilute in an appropriate volume corresponding with the dose in an appropriate solution. Final volume for administration depends on the patient's size and fluid status; the final volume must be sufficient to allow for accurate drug administration. Volumes as small as 25 mL have been used.
-A dilution concentration of 5 mg/mL has been suggested. For neonates, a dilution of 2 mg/mL has been recommended.
-Larger doses are commonly diluted in 50 to 100 mL.
Solution for Injection Vials
Dilution
-Dilute in an appropriate volume corresponding with the dose in an appropriate solution. Final volume for administration depends on the patient's size and fluid status; the final volume must be sufficient to allow for accurate drug administration. Volumes as small as 25 mL have been used.
-A dilution concentration of 5 mg/mL has been suggested. For neonates, a dilution of 2 mg/mL has been recommended.
-Larger doses are commonly diluted in 50 to 100 mL.
Solution for Injection Bulk Vials
Dilution
-The bulk vial should be penetrated 1 time with a suitable sterile dispensing set that allows measured distribution of the contents.
-The entire contents of the bulk vial should be used during reconstitution. Any unused portion must be discarded within 4 hours.
-Dilute in an appropriate volume corresponding with the dose in an appropriate solution. Final volume for administration depends on the patient's size and fluid status; the final volume must be sufficient to allow for accurate drug administration. Volumes as small as 25 mL have been used.
-A dilution concentration of 5 mg/mL has been suggested. For neonates, a dilution of 2 mg/mL has been recommended.
-Larger doses are commonly diluted in 50 to 100 mL.
Premixed IV Solution
Preparation
-Check for leaks by squeezing bag firmly. Do not add supplementary medication.
-Adjustments may be made to premixed containers to either add or remove contents to provide an appropriate dose.
-Do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
Intermittent IV Infusion
-Infuse over 20 to 60 minutes. An infusion time of 15 minutes has been recommended in neonates.
Intravenous (IV) Push*
NOTE: Tobramycin is not approved by the FDA for IV push administration.
Reconstitution / Dilution
-A report included 3652 doses of tobramycin administered by IV push in an outpatient parenteral antibiotic (OPAT) setting.
--Doses less than 800 mg were diluted in 0.9% Sodium Chloride Injection to a total volume of 20 mL.
-Doses 800 mg or larger were undiluted as the 40 mg/mL solution as supplied by the manufacturer.
-A study included 5 adults who received tobramycin via IV push.
--Doses of 2 mg/kg were prepared in 10 mL of 5% Dextrose Injection.
-Doses injected within 2 to 3 minutes of preparation.
-Stability: Plastic syringes reconstituted with Sterile Water for Injection from 1.2 g vials to a concentration of 40 mg/mL showed no significant change in concentrations after 2 months at 4 to 25 degrees C.
Intermittent IV Push
-An IV push rate of 3 to 5 minutes has been reported in pediatric patients. However, a range of 15 seconds to 5 minutes has been reported in adult patients.
Intramuscular Administration
-Do not use solutions prepared from commercially available bulk packages and premixed solution for IM administration.
-Withdraw appropriate dose directly from the vial of solution for injection. No dilution necessary. Inject deeply into a large muscle mass.
-In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
Inhalation Administration
Nebulized Solution for Inhalation
-The solution for nebulization is administered by inhalation only. Do not administer subcutaneously, intravenously, or intrathecally.
-Visually inspect the solution before use. The solution should be clear and without particles. The solution may darken with age; this color change does not mean there is any change in the quality of the medicine. Do not use if the solution is cloudy or has particles.
-Wash hands with soap and water before preparing each dose.
-Squeeze all the medicine from the ampule into the nebulizer cup, and firmly secure the nebulizer top. Do not dilute or mix with other medicines in the nebulizer.
-Turn on the compressor and check for a steady mist to be released from the mouthpiece. If there is no mist, check all tubing connections and make sure the compressor is working properly.
-If a patient misses a dose, administer the dose as soon as possible anytime up to 6 hours before the next scheduled dose. If less than 6 hours remain before the next dose, wait until the next scheduled dose.
Administration of Nebulized Solution for Inhalation
-Administer via inhalation while the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nose clips may help the patient breath through the mouth. Do not block the airflow with the tongue.
-Deliver the dose by inhalation over approximately 15 minutes, using a recommended hand-held nebulizer. Full treatment dose has been administered when the mouthpiece makes a spitting noise for at least 1 minute and the nebulizer cup is empty.
-If treatment is interrupted (i.e., need to cough or rest during treatment), turn off the compressor to save the medicine. Turn the compressor back on when ready to restart the treatment.
Powder for Inhalation
-Capsules are to be used with a Podhaler device and the contents of the capsules are for oral inhalation only. Do not swallow the capsules.
-Do not use the Podhaler capsules with any other device. Do not use the Podhaler to take any other medications
-Each Podhaler device is used for only 7 days. After 7 days, discard the used Podhaler device and its storage case. A new Podhaler device will be supplied for use with each weekly pack of capsules.
-A reserve Podhaler device is provided and should be used if the original device is wet, dirty, broken, has been dropped, or does not seem to be piercing the capsules properly.
-Administer after other inhaled medications and/or chest physiotherapy.
-Doses should be administered as close to 12 hours apart as possible and not less than 6 hours apart.
-Small pieces of the capsules can get into the mouth; these small pieces may be swallowed or inhaled.
-Storage: Store capsules in the blister cards until immediately before administration.
Administration of Powder for Inhalation
-Thoroughly wash and dry hands.
-Hold the base of the Podhaler device and unscrew lid counter-clockwise. Stand the device upright.
-Unscrew the mouthpiece in a counter-clockwise direction while holding the body of the Podhaler.
-Tear the blister card in half lengthwise along the precut lines.
-Peel back the foil covering the first capsule. Only unfoil and remove 1 capsule at a time, immediately before use.
-Place 1 capsule in the capsule chamber at the top of the Podhaler device. Do not insert directly into the top of the mouthpiece.
-Reattach the mouthpiece and tighten in a clockwise direction; do not overtighten.
-While holding the Podhaler device with mouthpiece pointed downwards, press the blue button all the way down with your thumb. Release the blue button; do not press more than once.
-With mouth away from the mouthpiece, exhale completely.
-Place mouth over the mouthpiece, close lips tightly, and inhale deeply with a single breath. Hold breath for about 5 seconds, then exhale normally away from the Podhaler device.
-After a few normal breaths away from the device, repeat the exhale and inhale process using the same capsule.
-After the second inhalation from the Podhaler device, unscrew the mouthpiece and remove the capsule from the capsule chamber.
-Inspect the used capsule. It should be pierced and empty; if so, throw the capsule away. If the capsule is pierced but more than just a fine coating of powder remains, put the capsule back into the capsule chamber with pierced side pointed down. Reattach the mouthpiece and repeat the exhale and inhale process. If the capsule is not pierced, reinsert into the capsule chamber, reattach the mouthpiece, and repeat the exhale and inhale process. If the capsule is still not pierced, use the reserve Podhaler device.
-Once the contents of the first capsule have been successfully inhaled, repeat the process 3 more times until the total dose of 4 capsules has been inhaled.
-Once the full dose has been administered, reattach the mouthpiece onto the Podhaler device and wipe with a clean, dry cloth. Throw away all empty capsules; do not store capsules in the Podhaler device.
-Do not wash the Podhaler with water; it needs to stay dry at all times.
Ophthalmic Administration
Ointment or Solution
-Instruct patient on proper instillation of eye ointment and/or solution.
-Do not to touch the tip of the dropper to the eye, fingertips, or other surface.
Nephrotoxicity is a well-known adverse reaction to systemic tobramycin and other aminoglycoside antibiotics. Some studies suggest tobramycin is less nephrotoxic than gentamicin. Aminoglycoside antibiotics are taken up by lysosomes in cells lining the proximal tubule, which, in turn, leads to necrosis and/or fibrosis. With continued exposure, interstitial fibrosis, renal tubular necrosis, and renal tubular acidosis (RTA) occur. If aminoglycoside therapy is discontinued prior to this, renal dysfunction can be reversible. Although it is commonly believed that maintaining tobramycin serum concentrations within traditional ranges minimizes the risk of nephrotoxicity, some patients may still experience azotemia. Worsening of creatinine clearance, hyposthenuria (loss of concentrating ability), pyuria (increased WBCs), proteinuria, and cylindruria (cells or casts in the urine) are all manifestations of nephrotoxicity; oliguria occurs rarely. Various studies have identified risk factors for developing nephrotoxicity from aminoglycosides: excessive trough serum concentrations, other nephrotoxic agents, total dose or treatment duration, and preexisting renal disease. Finally, new approaches to clinical dosing of tobramycin can reduce the incidence of nephrotoxicity. Increases in serum creatinine have also been noted in patients receiving nebulized tobramycin.
Ototoxicity can occur during tobramycin therapy. This effect can be manifest as high-frequency hearing loss, tinnitus, vertigo, ataxia, or dizziness since either cochlear or vestibular toxicity is possible. These manifestations may be permanent. Hearing loss is usually manifested by diminishing high-tone acuity. The FDA-approved product labeling states factors that increase risk of ototoxicity include excessive dosage, dehydration, and previous exposure to other ototoxic drugs. The product labeling recommends audiograms be performed in patients who receive repeated or prolonged courses of therapy with tobramycin. Tinnitus (1.9% to 3.1%) and hearing loss (0.5% to 1%) have also been reported in trials or postmarketing reports with nebulized tobramycin.
Headache, lethargy, confusion, and disorientation have been reported with the use of systemic tobramycin. Additionally, headache (11-27%) has been reported commonly with the inhalational formulations.
Otalgia/ear pain was reported in 7.4% of patients receiving inhaled tobramycin solution.
Tobramycin solution and powder for inhalation are generally well tolerated. Voice alterations (dysphonia) were reported in 3.8% to 13.6% of patients in general clinical trials. During postmarketing use, cases of voice loss (aphonia) have been reported.
Neurotoxicity has been reported with tobramycin. Neuromuscular blockade or respiratory paralysis has occurred with aminoglycosides. Muscle weakness or a myasthenia gravis-like syndrome has been reported. Other neurotoxic effects may include numbness, skin tingling, muscle twitching, and convulsions (seizures).
Pain at the injection site has been noted with systemic tobramycin use. Irritation after IM injection of tobramycin has also been reported. Patients should be observed for a local injection site reaction after systemic administration of tobramycin.
Serious and sometimes fatal allergic and dermatologic reactions have been reported rarely with tobramycin therapy and include anaphylactoid reactions, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson syndrome. Other reported adverse events include rash, pruritus, and urticaria. Rash (2.3% to 5.4%), pruritus, and urticaria have also been reported with the use of inhalation products. Hypersensitivity for the ophthalmic products has also been described and has ranged from local effects to generalized reactions such as erythema, pruritus, urticaria, skin rash, anaphylaxis, anaphylactoid reactions, or bullous rash. Stevens-Johnson syndrome, erythema multiforme, and anaphylactic reactions have been reported with the ophthalmic products in postmarketing reports.
The most frequently reported adverse reactions associated with the use of ophthalmic tobramycin generally occur infrequently (less than 3% of patients in the general population) and include ocular irritation (i.e., lid/ocular pruritus and swelling) and conjunctival hyperemia. Ophthalmic ointments may cause impaired wound healing of corneal lesions or abrasions.
Anemia, granulocytopenia, thrombocytopenia, leukopenia, leukocytosis, and eosinophilia have been reported with the use of tobramycin. Eosinophilia (2%) and increased red blood cell sedimentation rate (8%) have been noted with the use of the inhalation solution.
Nausea, vomiting, and diarrhea have been reported with the use of systemic tobramycin. Additionally, nausea (7.5% to 11.2%), vomiting (5.7% to 14%), diarrhea (1.9% to 6.2%), abdominal pain (12.8%), anorexia (18.6%), weight loss (10.1%), and taste perversion/dysgeusia (approximately 4% to 8%) have been reported commonly with the inhalational formulations. In clinical trials of tobramycin inhalational powder, dysgeusia was more common in patients younger than 20 years old (7.4%) than in patients older than 20 years (2.7%).
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with tobramycin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.
Fever occurs commonly (12.4% to 32.9%) in patients receiving tobramycin; however, it is often difficult to discern the incidence of drug-induced fever from fever caused by an underlying infection. In clinical trials of tobramycin inhalational products, asthenia (35.7% tobramycin vs. 39.3% placebo), back pain (7% tobramycin vs. 8% placebo), myalgia (4.7% vs. 2.7% placebo), unspecified pain (8.1% tobramycin vs. 12.6% placebo), and malaise (6.2% vs. 5.3% placebo) were noted. Chest pain (unspecified) has also been noted with inhalational products with a wide incidence range in clinical trials (2.9% to 26%). In one trial comparing the inhalational powder to the solution, chest discomfort occurred in 6.5% of patients in the dry powder group (n = 308) compared to 2.9% in the solution for inhalation group (n = 209).
General laboratory abnormalities reported with tobramycin use include hypocalcemia, hypomagnesemia, hyponatremia, and hypokalemia. Increased immunoglobulins (2%) and increased blood glucose (0.5% to 2.9%) were noted in patients receiving the inhalation formulations.
Elevated hepatic enzymes (AST, ALT), increased LDH, and hyperbilirubinemia have been reported with tobramycin use.
Bronchospasm (0.5% to 5%) may occur with the inhalation of tobramycin. Other respiratory adverse events associated with the use of inhaled tobramycin in pediatric and adult patients include increased cough (10% to 48.4%), pharyngitis (38%), increased sputum (37.6%), rhinitis (34.5%), dyspnea (12.4% to 33.7%), lung disorder (30.1% to 33.8%), sputum discoloration (21.3%), hemoptysis (12.4% to 19.4%), decreased lung function (16.3%), asthma (15.9%), sinusitis (8.1%), epistaxis (1.9% to 7%), upper and lower respiratory tract infection (5.8% to 8.6%), hyperventilation (5.4%), decreased FEV1 (1% to 31%), rales (6.2% to 19%), wheezing (5% to 6.8%), pharyngolaryngeal pain (3% to 14%), throat irritation (1.9% to 4.5%), nasal congestion (7.2% to 8.1%), laryngitis (4.3%), bronchitis (3%), and tonsillitis (2%). Because respiratory symptoms are common among patients with cystic fibrosis and often fluctuate with pulmonary status, it is difficult to identify the true drug-induced incidence of pulmonary adverse effects of the inhalational products. Sputum discoloration was noted in postmarketing reports with TOBI Podhaler.
Monitor patients receiving systemic aminoglycosides, such as tobramycin, closely for nephrotoxicity. Aminoglycosides are associated with major toxic effects on the renal tubules. In patients with preexisting renal impairment, renal failure, or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe nephrotoxic adverse reactions are sharply increased. Nephrotoxicity can manifest as decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine). When monitoring tobramycin serum concentrations using conventional dose regimens, avoid prolonged peak concentrations above 12 mcg/mL and trough concentrations above 2 mcg/mL. Single-daily dosing regimens that produce higher peak serum concentrations have been used without additional toxicity noted; however, it is important to allow the trough concentration to decrease appropriately before redosing. Evidence of nephrotoxicity requires dosage adjustment or discontinuance of therapy. Hemodialysis may aid in tobramycin removal in the event of overdose or toxic reactions, especially if renal function is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Avoid concurrent and/or sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic and/or neurotoxic because toxicity may be additive. Patients with dehydration or diabetes mellitus are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity.
Monitor patients receiving systemic and inhaled aminoglycosides, such as tobramycin, for neurotoxicity, including ototoxicity and hearing impairment. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. Consider serial audiograms for high-risk patients. The risk of hearing loss increases with the degree of exposure (high or prolonged therapy), pre-existing renal impairment, concomitant or sequential nephrotoxic or ototoxic agents, dehydration, and advanced age. Patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1), particularly the m.1555A>G variant, may develop ototoxicity even when aminoglycoside serum concentrations are within the recommended range. These variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity, including severe cases, is unknown. If there is a known maternal history of ototoxicity due to aminoglycosides or a known mitochondrial DNA variant, consider alternative treatments unless the severity of the infection and lack of alternatives outweighs the risk of permanent hearing loss. Discontinue therapy if there is evidence of auditory or vestibular toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. When monitoring tobramycin serum concentrations during use of conventional dose regimens, avoid prolonged tobramycin peak concentrations above 12 mcg/mL and trough concentrations above 2 mcg/mL. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Auditory changes are irreversible, usually bilateral, and may be partial or total. Symptoms of ototoxicity can include dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss and may manifest during therapy or after discontinuation. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions.
Tobramycin is contraindicated in patients with a history of tobramycin hypersensitivity or aminoglycoside hypersensitivity. Cross-sensitivity among aminoglycosides has been demonstrated. Serious and fatal allergic reactions, including anaphylaxis and serious rash, such as exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome, have been reported in patients receiving tobramycin.
Systemic aminoglycosides, such as tobramycin, are associated with neuromuscular blockade and may cause severe neuromuscular weakness lasting hours to days. Respiratory paralysis, respiratory insufficiency, or respiratory depression may occur when aminoglycosides are instilled after local irrigation and after topical application during surgical procedures. Neuromuscular blockade has also been reported with both oral and parenteral use of aminoglycosides. Clinicians should be aware of the possibility of neuromuscular blockade and respiratory paralysis if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular-blocking agents (e.g., tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood). Corrective therapy is required for any electrolyte imbalance, which may aggravate risk for neuromuscular/neurological symptoms. During or after aminoglycoside therapy, paresthesias, tetany, positive Chvostek and Trousseau signs, and mental confusion have been described in patients with hypomagnesemia, hypocalcemia, and hypokalemia. In infants, tetany and muscle weakness have been described. Aminoglycosides may aggravate muscle weakness in patients with neuromuscular disease such as myasthenia gravis, botulism, or parkinsonism.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including tobramycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Use of ophthalmic ointments, such as tobramycin ophthalmic ointment, may delay healing of corneal abrasion or lesions. Acute bronchospasm can occur with tobramycin inhalation products. Bronchospasm that occurs during the use of tobramycin inhalation solution should be treated as medically appropriate.
Use tobramycin with caution in neonates and premature neonates due to renal immaturity and the prolongation of serum half-life of the drug, which increases the risk of aminoglycoside-induced toxicity. When tobramycin is used in the neonatal population, careful monitoring is warranted for signs and symptoms of toxicity including auditory, vestibular, and renal toxicity and neuromuscular blockade.
Description: Tobramycin is an aminoglycoside antibiotic that is active against aerobic gram-negative rods, but is not active against any anaerobic bacteria. Systemic and orally inhaled/nebulized tobramycin is used as part of combination therapy for management of cystic fibrosis. Systemic tobramycin is used for the treatment of gram-negative urinary tract, respiratory tract, abdominal, and CNS infections. Tobramycin is considered to be a narrow therapeutic index drug, and therefore, serum concentration monitoring is recommended for most regimens. The major toxicities include nephrotoxicity, ototoxicity, and neurotoxicity. Systemic tobramycin is FDA-approved for use in pediatric patients as young as neonates; the oral inhalation/nebulized products are FDA-approved in patients as young as 6 years; the ophthalmic products are FDA-approved in patients as young as 2 months.
General Dosing Information:
-While initial tobramycin doses can be recommended, individualize maintenance dosing (except for low-dose regimens used for synergy) based on pathogen, site of infection, and serum concentrations.
-Monitor renal function closely in all patients receiving tobramycin. Measure tobramycin serum concentrations if there is a decrease in urine output or a laboratory value that suggests a change in renal function.
-In overweight patients, use a modified dosing body weight to calculate the dosage. The equation used in adult patients is: Dosing Body Weight = [(total body weight - ideal body weight) x 0.4] + ideal body weight.
-Enterococcus species are generally resistant to therapeutic concentrations of aminoglycosides. Aminoglycosides are only effective in clinical cure of Enterococcus infections when used to provide synergistic bactericidal activity to penicillins or vancomycin. The degree of synergy is related to the level of aminoglycoside resistance of the specific Enterococcus strain.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Acinetobacter calcoaceticus, Citrobacter sp., Enterobacter sp., Enterococcus sp., Escherichia coli, Haemophilus aegyptius, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella aerogenes, Klebsiella pneumoniae, Klebsiella sp., Moraxella lacunata, Morganella morganii, Neisseria sp., Proteus mirabilis, Proteus vulgaris, Providencia sp., Pseudomonas aeruginosa, Serratia sp., Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Staphylococcus sp., Streptococcus pneumoniae, Streptococcus sp.
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Acinetobacter sp., Aeromonas sp., Bacillus anthracis, Salmonella sp., Shigella sp.
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of meningitis and ventriculitis*:
Intravenous or Intramuscular dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 48 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 36 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 30 to 34 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 36 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 30 to 34 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Infants, Children, and Adolescents: 5 to 7.5 mg/kg/dose IV or IM every 24 hours. The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.
Intravenous or Intramuscular dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 12 to 18 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 8 to 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Premature infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
Infants, Children, and Adolescents: 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.
Intrathecal* or Intraventricular dosage* (preservative-free formulations only):
Infants, Children, and Adolescents: 5 to 20 mg intraventricularly once daily in combination with systemic therapy has been recommended in general without specific pediatric qualifications. Doses of 1.5 to 5 mg intraventricularly once daily and 2.5 mg intraventricularly every 8 hours have been used in pediatric case reports. Doses should be adjusted to maintain adequate CSF concentrations depending on the susceptibility of the infecting organism.
For the treatment of pulmonary exacerbation or improvement of respiratory symptoms in persons with cystic fibrosis:
-for the treatment of pulmonary exacerbation in persons with cystic fibrosis:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 10 mg/kg/dose IV every 24 hours. Doses as high as 12 to 15 mg/kg/dose IV every 24 hours have been used. The FDA-approved dosage is 10 mg/kg/day IV or IM in 4 divided doses.
Respiratory (Inhalation) dosage (solution for inhalation):
Children and Adolescents 6 to 17 years: 300 mg inhaled by nebulizer twice daily for 28 days.
Respiratory (Inhalation) dosage (powder for inhalation):
Children and Adolescents 6 to 17 years: 112 mg inhaled by mouth twice daily for 28 days.
-for the improvement of respiratory symptoms in persons with cystic fibrosis with chronic P. aeruginosa:
Respiratory (Inhalation) dosage (solution for inhalation):
Children and Adolescents 6 to 17 years: 300 mg inhaled by nebulizer twice daily for 28 days in alternating 28-day periods. Tobramycin inhalation solution is FDA-approved for persons with FEV1 of 25% to 75% predicted for TOBI or FEV1 of 40% to 80% predicted for Bethkis.
Respiratory (Inhalation) dosage (powder for inhalation):
Children and Adolescents 6 to 17 years: 112 mg inhaled by mouth twice daily for 28 days in alternating 28-day periods. Tobramycin inhalation powder is FDA-approved for persons with FEV1 of 25% to 80% predicted.
For the treatment external infections of the eye including, of blepharitis, blepharoconjunctivitis, bacterial conjunctivitis, dacryocystitis, keratitis, keratoconjunctivitis, and acute meibomianitis:
Ophthalmic dosage (0.3% ophthalmic ointment):
Infants, Children, and Adolescents 2 months to 17 years: 0.5 inch ribbon in the affected eye(s) 2 or 3 times daily; up to 0.5 inch ribbon in the affected eye(s) every 3 to 4 hours until improvement for severe infections.
Ophthalmic dosage (0.3% ophthalmic solution):
Infants, Children, and Adolescents 2 months to 17 years: 1 to 2 drops in the affected eye(s) every 4 hours; up to 2 drops in the affected eye(s) every hour until improvement for severe infections.
For the empiric treatment of febrile neutropenia*:
Intravenous dosage (conventional dosing):
Infants, Children, and Adolescents: 2 to 2.5 mg/kg/dose IV every 8 hours. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.
Intravenous dosage (extended-interval dosing):
Infants, Children, and Adolescents: 6 to 9 mg/kg/dose IV every 24 hours. In a pharmacokinetic analysis of a randomized controlled trial in pediatric patients with febrile neutropenia, age-specific initial doses of 10 mg/kg/dose IV (6 months to younger than 9 years), 8 mg/kg/dose IV (9 to 11 years), and 6 mg/kg/dose IV (12 years and older) given every 24 hours were recommended to achieve target serum tobramycin concentrations. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.
For surgical infection prophylaxis*:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 2.5 mg/kg IV or IM as a single dose administered within 60 minutes prior to surgical incision. Intraoperative redosing of tobramycin is not typically needed. Generally, surgical prophylaxis should be discontinued within 24 hours after the end of surgery. Tobramycin, in combination with another appropriate antimicrobial (vancomycin or clindamycin/metronidazole depending on procedure), is recommended as an alternate therapy for penicillin-allergic patients prior to surgical procedures such as vascular, colorectal, gastroduodenal, biliary tract, or urologic.
For the treatment of intraabdominal infections, including peritonitis:
Intravenous or Intramuscular dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 48 hours.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 36 hours.
Neonates 30 to 34 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 36 hours.
Neonates 30 to 34 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 24 hours.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV or IM every 24 hours.
Infants, Children, and Adolescents: 5 to 7.5 mg/kg/dose IV or IM every 24 hours. Treatment is recommended for 4 to 7 days.
Intravenous or Intramuscular dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Premature infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
Infants, Children, and Adolescents: 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Treatment is recommended for 4 to 7 days.
-for the treatment of peritonitis in patients receiving peritoneal dialysis:
Intraperitoneal dosage*:
Infants, Children, and Adolescents: 8 mg/L IP loading dose then 4 mg/L IP as continuous therapy in each dialysate exchange bag. For intermittent therapy, 0.6 mg/kg IP in anuric patients and 0.75 mg/kg IP in non-anuric patients administered during the longest daily dialysate dwell period.
For the treatment of complicated urinary tract infection (UTI) and pyelonephritis:
Intravenous or Intramuscular dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 48 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 36 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 30 to 34 weeks gestation and 0 to 10 days: 5 mg/kg/dose IV or IM every 36 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 30 to 34 weeks gestation and 11 days and older: 5 mg/kg/dose IV or IM every 24 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV or IM every 24 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants younger than 2 months: 5 to 7.5 mg/kg/dose IV or IM every 24 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants, Children, and Adolescents 2 months to 17 years: 5 to 7.5 mg/kg/dose IV or IM every 24 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
Intravenous or Intramuscular dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Premature infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants younger than 2 months: 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants, Children, and Adolescents 2 months to 17 years: 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
NOTE: Use lean body mass to calculate the tobramycin dose. Adjust dose based on serum tobramycin concentrations.
-for the treatment of nonspecific lower respiratory tract infections (LRTIs):
Intravenous or Intramuscular dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 24 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours. This dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 24 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. This dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Premature Infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. This dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
Infants, Children, and Adolescents: 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Intravenous or Intramuscular dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 48 hours.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 36 hours.
Neonates 30 to 34 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 36 hours.
Neonates 30 to 34 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 24 hours.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV or IM every 24 hours.
Infants, Children, and Adolescents: 5 to 8 mg/kg/dose IV or IM every 24 hours.
-for the treatment of community-acquired pneumonia (CAP):
Intravenous dosage (conventional dosing):
HIV-Infected Adolescents: 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours for 5 to 7 days as an alternative in combination therapy for hospitalized patients at risk for P. aeruginosa.
Intravenous dosage (extended-interval dosing)*:
HIV-Infected Adolescents: 5 to 8 mg/kg/dose IV every 24 hours for 5 to 7 days as an alternative in combination therapy for hospitalized patients at risk for P. aeruginosa.
For the treatment of infective endocarditis*:
Intravenous dosage:
Children and Adolescents: 3 to 6 mg/kg/day IV divided every 8 hours in combination with an appropriate antimicrobial agent is recommended by guidelines. An aminoglycoside (specific agent depends on susceptibility), in combination with a third or fourth generation cephalosporin (i.e., ceftazidime, cefotaxime, cefepime), is a preferred treatment option for endocarditis due to gram-negative microorganisms. An aminoglycoside, in combination with ampicillin, is recommended as an alternative therapy for endocarditis due to HACEK organisms. Treat for 4 weeks for HACEK endocarditis and at least 6 weeks for endocarditis due to other gram-negative microorganisms.
For the treatment of bacteremia and sepsis:
Intravenous or Intramuscular dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 48 hours.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 36 hours.
Neonates 30 to 34 weeks gestation and 0 to 10 days: 5 mg/kg/dose IV or IM every 36 hours.
Neonates 30 to 34 weeks gestation and 11 days and older: 5 mg/kg/dose IV or IM every 24 hours.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV or IM every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Infants, Children, and Adolescents: 5 to 7.5 mg/kg/dose IV or IM every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Intravenous or Intramuscular dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Premature infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Infants, Children, and Adolescents: 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
For the treatment of bone and joint infections, including osteomyelitis and infectious arthritis:
NOTE: Use lean body mass to calculate the tobramycin dose. Adjust dose based on serum tobramycin concentrations.
-for the treatment of osteomyelitis:
Intravenous dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV every 48 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV every 36 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 30 to 34 weeks gestation and 0 to 10 days: 5 mg/kg/dose IV every 36 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 30 to 34 weeks gestation and 11 days and older: 5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 5 to 7.5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 5 to 7.5 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Intravenous dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV every 18 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV every 18 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV every 18 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours.
Premature infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV every 18 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Infants 1 to 2 months: 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis:
Intravenous dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV every 48 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV every 36 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 30 to 34 weeks gestation and 0 to 10 days: 5 mg/kg/dose IV every 36 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 30 to 34 weeks gestation and 11 days and older: 5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 5 to 7.5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 5 to 7.5 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Intravenous dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV every 18 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV every 18 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV every 18 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours.
Premature infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV every 18 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Infants 1 to 2 months: 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
For the treatment of skin and skin structure infections, including burn wound infection and necrotizing infections:
NOTE: Serum concentrations should be used to guide dosage adjustments. A 'dosing' weight should be used to calculate initial dosages in patients weighing more than their ideal body weight.
-for the treatment of unspecified skin and skin structure infections:
Intravenous or Intramuscular dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 48 hours.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 36 hours.
Neonates 30 to 34 weeks gestation and 0 to 10 days: 5 mg/kg/dose IV or IM every 36 hours.
Neonates 30 to 34 weeks gestation and 11 days and older: 5 mg/kg/dose IV or IM every 24 hours.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV or IM every 24 hours.
Infants, Children, and Adolescents: 5 to 7.5 mg/kg/dose IV or IM every 24 hours.
Intravenous or Intramuscular dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Premature Infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Infants, Children, and Adolescents: 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Intravenous or Intramuscular dosage (extended-interval dosing)*:
Neonates younger than 30 weeks gestation and 0 to 14 days: 5 mg/kg/dose IV or IM every 48 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
Neonates younger than 30 weeks gestation and 15 days and older: 5 mg/kg/dose IV or IM every 36 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
Neonates 30 to 34 weeks gestation and 0 to 10 days: 5 mg/kg/dose IV or IM every 36 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
Neonates 30 to 34 weeks gestation and 11 days and older: 5 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
Neonates 35 weeks gestation and older and 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
Neonates 35 weeks gestation and older and 8 days and older: 5 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
Infants, Children, and Adolescents: 5 to 7.5 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
Intravenous or Intramuscular dosage (conventional dosing):
Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 18 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours.
Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours.
Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 to 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV or IM every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV or IM every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
Premature Infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV or IM every 18 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
Infants, Children, and Adolescents: 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
For the treatment of plague* infection:
-for the treatment of bubonic or pharyngeal plague*:
Intravenous or Intramuscular dosage:
Neonates 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
Neonates 8 days and older: 5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
Infants, Children, and Adolescents: 4.5 to 7.5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
-for the treatment of pneumonic or septicemic plague*:
Intravenous or Intramuscular dosage:
Neonates 0 to 7 days: 4 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
Neonates 8 days and older: 5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
Infants, Children, and Adolescents: 4.5 to 7.5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
For the treatment of bronchiectasis*:
-for the treatment of acute exacerbations of bronchiectasis*:
Intravenous dosage (extended-interval dosing):
Infants, Children, and Adolescents: 5 to 7.5 mg/kg/dose IV every 24 hours for 14 days as part of combination therapy.
-for the eradication of first or new isolates of Pseudomonas aeruginosa in patients with bronchiectasis*:
Intravenous dosage (extended-interval dosing):
Infants, Children, and Adolescents: 5 to 7.5 mg/kg/dose IV every 24 hours for 14 days as part of combination therapy, followed by inhaled antibiotics for 4 to 12 weeks.
Respiratory (Inhalation) dosage (solution for inhalation):
Children and Adolescents 6 to 17 years: 300 mg inhaled by nebulizer every 12 hours; may be used in combination with initial systemic therapy for 14 days; treat for 4 to 12 weeks following systemic therapy.
-for the treatment of bronchiectasis* to reduce exacerbations in patients with high exacerbation rates:
Respiratory (Inhalation) dosage (solution for inhalation):
Children and Adolescents 6 to 17 years: 300 mg inhaled by nebulizer every 12 hours based on limited data.
Therapeutic Drug Monitoring:
Conventional Dosing
Usual target peak concentration: 5 to 10 mcg/mL depending on site of infection and pathogen
Usual target trough concentration: less than 2 mcg/mL; some experts recommend less than 1 mcg/mL for mild-moderate infections and patients at risk for renal toxicity
Extended-Interval Dosing
Neonates:
Usual target peak concentration: 5 to 12 mcg/mL depending on site of infection and pathogen
Usual target trough concentration: less than 2 mcg/mL
Infants, Children, and Adolescents:
Usual target peak concentrations: 10 to 20 mcg/mL depending on site of infection and pathogen; some experts would suggest targets of 20 to 40 mcg/mL in patients with cystic fibrosis.
Usual target trough concentration: less than 1 mcg/mL
Optimal serum concentration monitoring has not been determined in pediatric patients; various methods have been developed and are often institution-specific. In general, the goal is to obtain a significant peak concentration, often in the range of 20 to 35 mcg/mL, and then allow sufficient time for the serum concentration to become undetectable. One method that has been used is to obtain 2 serum concentrations at least one half-life apart (e.g., 2 and 6 hours after the dose) and use those concentrations to calculate a peak and trough and ensure that the serum concentration is not undetectable for significantly longer than the estimated post-antibiotic effect (e.g., 4 to 7 hours). Once an extended interval dose has been determined to be appropriate by measuring serum concentrations, follow-up concentrations are often trough-only to ensure no accumulation is occurring.
General Therapeutic Drug Monitoring Information
-The importance of achieving peak concentrations in several-fold excess of the organism's MIC has been established. Both time-kill studies as well as studies in humans have shown that a peak:MIC of more than 8 to 12:1 is associated with successful regimens for systemic infections. Consideration must also be given to the site of infection as antimicrobial tissue penetration is also a factor. These data have lead to the development of extended-interval aminoglycoside therapy (often referred to as 'single-daily dosing' or 'once-daily dosing'), with a high dose of tobramycin given to achieve the peak:MIC goals. In adults, with 7 mg/kg/day dosing, peak concentrations often reach 20 mcg/mL to maintain a serum peak:MIC of 10 for organisms with MICs of 2 mcg/mL.
-Because elevated serum trough concentrations are associated with an increased risk of toxicity, trough values for conventional dosing should fall below 2 mcg/mL and trough values for extended-interval dosing regimens are designed to fall below the MIC for an extended period of time and are often undetectable. The post-antibiotic effect (PAE) of aminoglycosides against gram-negative organisms is also used to justify the low trough concentrations.
-Most urinary tract infections may be adequately treated with lower peak serum concentrations as aminoglycosides are mainly renally eliminated; therefore, drug accumulation in the urine is higher than in the serum.
Maximum Dosage Limits:
-Neonates
0 to 7 days: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 4 mg/kg/day IV/IM; however, this dose could be excessive in some patients. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.
8 to 29 days: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 7.5 mg/kg/day IV/IM; however, this dose could be excessive in some patients. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.
-Infants
1 month: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.
2 to 12 months: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution. Maximum dosage of ophthalmic ointment not established. The safety and efficacy of the nebulized or oral inhalation products have not been established.
-Children
1 to 5 years: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution. Maximum dosage of ophthalmic ointment not established. The safety and efficacy of the nebulized or oral inhalation products have not been established.
6 to 12 years: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day powder for oral inhalation. Maximum dosage of ophthalmic ointment not established.
-Adolescents
Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day powder for oral inhalation. Maximum dosage of ophthalmic ointment not established.
Patients with Hepatic Impairment Dosing
Tobramycin does not undergo hepatic metabolism. Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Conventional Dosing
Dosage adjustments are recommendations based on a usual dose of 2.5 mg/kg/dose IV/IM every 8 hours.
GFR more than 50 mL/minute/1.73 m2: No initial adjustment; monitor serum concentrations.
GFR 30 to 50 mL/minute/1.73 m2: 2.5 mg/kg/dose IV/IM every 12 to 18 hours; monitor serum concentrations.
GFR 10 to 29 mL/minute/1.73 m2: 2.5 mg/kg/dose IV/IM every 18 to 24 hours; monitor serum concentrations.
GFR less than 10 mL/minute/1.73 m2: 2.5 mg/kg/dose IV/IM every 48 to 72 hours; monitor serum concentrations.
Extended-Interval Dosing
Give a single dose and monitor serum concentrations. If significant impairment is present, consider reducing the initial dose and then evaluate serum concentrations.
Intermittent hemodialysis
A dose of 2 mg/kg IV/IM after the initial hemodialysis session. Subsequent doses should be guided by serum tobramycin concentrations. Factors such as patient size, site of infection, and organism susceptibility should also be considered.
Continuous ambulatory peritoneal dialysis (CAPD)
2 mg/kg/dose IV/IM as indicated by serum concentrations.
Continuous renal replacement therapy (CRRT)
2 to 2.5 mg/kg dose IV/IM every 12 to 24 hours; monitor serum concentrations.
*non-FDA-approved indication
Monograph content under development
Mechanism of Action: Tobramycin is bactericidal in action. Similar to other aminoglycosides, it works by inhibiting bacterial protein synthesis through irreversible binding to the 30 S ribosomal subunit of susceptible bacteria. Tobramycin is actively transported into the bacterial cell where it binds to receptors present on the 30 S ribosomal subunit. This binding interferes with messenger RNA (mRNA). As a result, abnormal, nonfunctional proteins are formed due to misreading of the bacterial DNA. Eventually, susceptible bacteria die because of the lack of functional proteins. One aspect essential to aminoglycoside lethality is the need to achieve intracellular concentrations in excess of extracellular. Anaerobic bacteria are not susceptible to aminoglycosides due, at least in part, to a lack of an active transport mechanism for aminoglycoside uptake. The uptake of aminoglycosides may be facilitated by the presence of inhibitors of the bacterial cell wall (i.e. beta-lactams, vancomycin).
Against gram-negative aerobic rods, aminoglycosides exhibit 'concentration-dependent killing' and a 'post-antibiotic effect' (PAE). 'Concentration-dependent killing' describes the principle that bactericidal effects increase as the concentration increases. PAE is where suppression of bacterial growth continues after the antibiotic concentration falls below the bacterial MIC. The PAE can be bacteria specific, as well as drug specific. The PAE of aminoglycosides is short for most gram-positive organisms (less than 2 hours) and longer for gram-negative organisms (2 to 8 hours), such as E. coli, K. pneumoniae, and P. aeruginosa. Both of these phenomena are being exploited in designing dosage regimens that employ higher doses administered at longer intervals. The major pharmacodynamic parameter that determines efficacy of aminoglycosides is the serum peak concentration to MIC ratio (peak to MIC ratio). Both time-kill studies as well as studies in humans have shown that a peak to MIC ratio of more than 8 to 12:1 is associated with successful regimens.
The mechanism of renal toxicity with aminoglycosides is associated with accumulation of aminoglycosides in the renal tubule, which is a saturable process. Elevated serum trough concentrations are associated with an increased risk of toxicity.
The mechanism of ototoxicity relates to the aminoglycoside-induced destruction of sensory hair cells of the inner ear. The cochlear sensory cells that are most vulnerable are in the basal end, thereby leading to high-frequency hearing loss first. As ototoxicity ascends toward the apex of the cochlea, the lower frequencies are affected. Sensory cells that deal with vestibular function may also be affected. Aminoglycosides may cause free-radical damage to sensory cells and neurons. Biochemically, aminoglycosides may bind to polyphosphoinositides, which are part of the transmembrane signaling system mediating physiological effects of hormones, neurotransmitters, and neuromodulators which may interfere with essential mechanisms of cell physiology. Neural destruction without any cochlear hair cell damage has also been described. There may also be a genetic mitochondrial RNA mutation that may predispose some patients to aminoglycoside ototoxicity. Aminoglycosides enter the inner ear rapidly, but it is suggested that aminoglycoside concentrations do not correlate with the development of ototoxicity. Likely, the aminoglycoside concentrations in the inner ear dissipate slowly, which is consistent with the possibility of developing ototoxicity days to weeks after drug discontinuation.
The susceptibility interpretive criteria for tobramycin are delineated by pathogen. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterobacterales and P. aeruginosa. The MICs are defined for Enterobacterales by FDA as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more; however, the MICs are defined for Enterobacterales by the CLSI as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more (based on a dosage regimen of 7 mg/kg every 24 hours). The MICs are defined for P. aeruginosa by the FDA as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more; however, the MICs are defined for P. aeruginosa by the CLSI as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more (based on a dosage regimen of 7 mg/kg every 24 hours). The MICs are defined for S. aureus, non-Enterobacterales, and Acinetobacter sp. as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more. Interpretive criteria for inhaled tobramycin are not defined. The in vitro susceptibility test methods used for parenteral therapy can be used to monitor the susceptibility of P. aeruginosa isolated from persons with cystic fibrosis; however, breakpoints established for parenteral administration of tobramycin do not apply to aerosolized administration of tobramycin as the relationship between in vitro susceptibility test results and clinical outcome is not clear. A single sputum sample from a person with cystic fibrosis may contain multiple morphotypes of P. aeruginosa which may each have a different level of in vitro susceptibility to tobramycin.
Aminoglycoside resistance is well documented. There are a variety of resistance mechanisms employed by different pathogens. Enzymatic inhibition by gram-negative pathogens and Enterococcus sp. via aminoglycoside-modifying enzymes is achieved by modification of the aminoglycoside as it is transported across the cytoplasmic membrane. Alterations in the inner membrane porin channels by P. aeruginosa decrease antimicrobial penetration to the site of activity within the bacterial cell. Some gram-negative organisms and Enterococcus sp. can alter the ribosomal target sites of the aminoglycosides to decrease binding, thereby decreasing antimicrobial activity. Treatment for 6 months with inhaled tobramycin in clinical trials did not affect the susceptibility of the majority of P. aeruginosa isolates tested; however increased MICs were noted in some. The clinical significance of this has not been established in the treatment of P. aeruginosa in persons with cystic fibrosis.
Pharmacokinetics: Tobramycin is administered intravenously, intramuscularly, by oral inhalation, and by ophthalmic administration. Tobramycin is not absorbed orally. It distributes into extracellular fluid; therefore, peak serum concentrations may be lower in patients with a large volume of extracellular fluid. The volume of distribution may be higher in patients with sepsis, fever, severe burns, congestive cardiac failure, and peritonitis which may result in lower peak concentrations. Protein binding of tobramycin is negligible. After administration, tobramycin can be detected in sputum, peritoneal fluid, synovial fluid, and abscess fluid. Tobramycin appears in low concentrations in the CSF, and concentrations are dependent on dose, rate of penetration, and degree of meningeal inflammation.
Tobramycin is not metabolized. Elimination is almost exclusively via glomerular filtration. Thus, elimination half-life varies according to renal function. Reabsorption of a small amount of the drug by the proximal tubule results in accumulation in the renal cortex, which may be responsible for nephrotoxicity. Animal models suggest that tobramycin has a diminished affinity for the proximal tubule. In patients with normal renal function, 93% of the dose is recovered in the urine within 24 hours. The plasma elimination half-life is about 2 to 3 hours in adults with normal renal function. In children with normal renal function, the serum half-life is approximately 1 to 2 hours; however, there is considerable interpatient variation. Biliary excretion is minimal. Elimination half-lives for the inhaled formulations are approximately 3 hours for TOBI Podhaler and 4.4 hours for Bethkis.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
When tobramycin is administered by intravenous infusion over 1 hour, the serum concentrations are similar to those obtained by intramuscular administration. After an infusion of 1 mg/kg, maximum serum concentrations reach about 4 mcg/mL, and measurable concentrations persist for as long as 8 hours.
Intramuscular Route
Tobramycin is rapidly absorbed after intramuscular administration with peak concentrations occurring between 30 to 90 minutes after administration. After an intramuscular dose of 1 mg/kg, maximum serum concentrations reach about 4 mcg/mL, and measurable concentrations persist for as long as 8 hours.
Inhalation Route
Tobramycin administered via inhalation concentrates primarily in the airways, with bioavailability varying based on airway pathology and nebulizer performance.
Solution for inhalation: The average tobramycin concentration in sputum is 1,237 mcg/g (range: 35 to 7,414 mcg/g) after 10 minutes and 814 mcg/g (range: 23 to 2,843 mcg/g) after 30 minutes. Tobramycin does not accumulate in sputum with repeated dosing. The mean serum tobramycin concentration at 1 hour after inhalation of a single 300 mg dose by cystic fibrosis patients is 0.95 mcg/mL (range: 0.06 to 1.89 mcg/mL); after repeated dosing for 20 weeks, the average serum concentration is 1.05 mcg/mL.
Powder for inhalation: After a single 112 mg dose in cystic fibrosis patients, the mean sputum tobramycin concentration is 1,048 +/- 1,080 mcg/g. A mean peak serum concentration of 1.02 +/- 0.53 mcg/mL is achieved approximately 1 hour post-dose, which is comparable to concentrations observed with a 300 mg dose of TOBI. Systemic exposure is also comparable to the 300 mg TOBI dose (4.6 +/- 2 mcg x hour/mL vs. 4.8 +/- 2.5 mcg x hour/mL). After a 28-day dosing cycle, peak serum concentrations range from 1.48 +/- 0.69 mcg/mL to 1.99 +/- 0.59 mcg/mL.
-Special Populations
Pediatrics
Neonates
Pharmacokinetics are highly variable in neonates, with factors such as renal maturation and postmenstrual age playing a significant role. Neonates have a larger volume of distribution (Vd) and a reduced clearance compared with children and adults. In an analysis of pharmacokinetic studies of tobramycin in neonates with varying gestational ages and postnatal days, the Vd ranged from 0.49 to 0.94 L/kg, clearance ranged from 0.69 to 1.19 mL/kg/minute, and elimination half-life ranged from approximately 4.4 to 9.9 hours. Clearance increases with increasing gestational age. In a study (n = 20), the half-life decreased from 6.9 to 15.8 hours in neonates with a gestational age of 28 to 30 weeks to 3.5 to 6.7 hours in neonates with a gestational age of older than 34 weeks. In another study (n = 120), the half-life decreased from 10 to 10.3 hours in neonates with a postmenstrual age of younger than 30 weeks to 4.7 to 5.9 hours in neonates with a postmenstrual age of 34 weeks or older.
Infants, Children, and Adolescents
Volume of distribution (Vd) is approximately 0.25 L/kg in children and adolescents. In children and adolescents with normal renal function, the serum half-life is approximately 1 to 2 hours, which is similar to adults. Infants may have a slightly longer half-life. However, there is considerable interpatient variation.
Renal Impairment
In patients with impaired renal function, the tobramycin plasma elimination half-life can be 24 hours or more. Aminoglycosides are removed efficiently by hemodialysis with 25% to 70% of the dose removed.
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