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Tobramycin (systemic): Drug information

Tobramycin (systemic): Drug information
(For additional information see "Tobramycin (systemic): Patient drug information" and see "Tobramycin (systemic): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Nephrotoxicity:

Tobramycin can result in acute kidney injury, including acute renal failure. Risk factors that may contribute to nephrotoxicity include tobramycin accumulation (increasing serum trough levels), high peak concentrations (>12 mcg/mL), total cumulative dose, advanced age, volume depletion, and concurrent or sequential use of other nephrotoxic drugs. Avoid concurrent or sequential use of other potentially nephrotoxic drugs. Monitor serum tobramycin levels and renal function in all patients during drug treatment. Reduce the dose or discontinue tobramycin if renal impairment occurs.

Ototoxicity:

Tobramycin can cause irreversible auditory and vestibular toxicity that may continue to develop after the drug has been discontinued. Risk factors include high serum concentrations, prolonged therapy, renal impairment, concurrent and sequential use of other nephrotoxic or ototoxic drugs (eg, aminoglycosides), and extremes of age. Avoid concurrent or sequential use with other potentially ototoxic drugs. Monitor for signs and symptoms of auditory and vestibular toxicity. Reduce the dose or discontinue tobramycin if renal impairment occurs. Discontinue tobramycin if ototoxicity occurs.

Neuromuscular blockade:

Aminoglycosides have been associated with neuromuscular blockade. During therapy with tobramycin, monitor for adverse reactions associated with neuromuscular blockade, particularly in high-risk patients, such as patients with underlying neuromuscular disorders (including myasthenia gravis) or in patients concomitantly receiving neuromuscular-blocking agents.

Embryo-fetal toxicity:

Tobramycin and other aminoglycosides can cause fetal harm when administered to a pregnant woman. If tobramycin is used during pregnancy or if the patient becomes pregnant while taking tobramycin, apprise the patient of the potential hazard to the fetus.

Brand Names: Canada
  • JAMP-Tobramycin [DSC]
Pharmacologic Category
  • Antibiotic, Aminoglycoside
Dosing: Adult

Dosage guidance:

Dosing: For patients who are underweight (ie, total body weight [TBW] < ideal body weight [IBW]), calculate the dose based on TBW. For patients who are nonobese (ie, TBW 1 to 1.25 × IBW), calculate the dose based on TBW or IBW. TBW may be preferred in patients who are nonobese who may have increased Vd (eg, critically ill). For patients with obesity (ie, TBW >1.25 × IBW), use adjusted body weight ([0.4 × (TBW − IBW)] + IBW) for initial weight-based dosing and for estimating kidney function with Cockcroft-Gault (CrCl) (Ref).

Clinical considerations: Therapeutic drug monitoring is recommended to ensure efficacy and avoid toxicity, particularly in patients who are critically ill with serious infection or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, major surgery). Timing and frequency of concentration monitoring is individualized based on dosing and monitoring strategy (Ref).

Usual dosage range:

Gram negative infections:

Conventional/traditional dosing: IV, IM: 3 to 5 mg/kg/day in divided doses every 8 hours (Ref). Some experts favor an initial loading dose of 2.5 to 3 mg/kg (Ref). Target peak concentration depends on indication and site of infection; in general, adjust dose to achieve peak of 4 to 6 mg/L for urinary tract infections and 7 to 10 mg/L for serious infections (including life-threatening infections). Target trough concentrations should be <2 mg/L; ideal target <1 mg/L (Ref).

High-dose extended-interval dosing (once-daily dosing): IV: 5 to 7 mg/kg once daily; use with caution in patients with CrCl <40 mL/minute (Ref). Adjust tobramycin dose and interval to achieve an extrapolated peak concentration of ~15 to 20 mg/L and trough concentration <0.5 mg/L (Ref). Note: Published nomograms for dosage adjustment may not apply to patients with altered pharmacokinetics (eg, patients with ascites, burns covering >20% total BSA, end-stage renal disease requiring dialysis, pregnancy) (Ref); some experts prefer traditional intermittent dosing in such populations (Ref).

Indication-specific dosing:

Bloodstream infection

Bloodstream infection: Adjunctive empiric therapy for patients with concern for resistant gram-negative bacteria (eg, immunosuppression, prevalent local resistance, recent antibiotic exposure): IV: 5 to 7 mg/kg once daily in combination with a second gram-negative active agent; once culture and susceptibility results are available, can generally discontinue and use a single agent with documented activity. Tobramycin should not be used as monotherapy (Ref).

Cerebrospinal fluid shunt infection

Cerebrospinal fluid shunt infection (adjunct to systemic therapy): Note: Reserve for infections due to multidrug-resistant organisms, infections refractory to appropriate parenteral therapy, or when infected shunts cannot be removed (Ref).

Intraventricular (use a preservative-free preparation): 5 to 20 mg/day; some experts recommend adjusting dosage and administration interval based on cerebrospinal fluid (CSF) tobramycin concentrations (goal: 10 to 20 times minimum inhibitory concentration of causative organism), ventricle size, and daily output from ventricular drain (Ref). When intraventricular tobramycin is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF). Duration is individualized according to clinical and microbiological response (Ref).

Cystic fibrosis, acute pulmonary exacerbation

Cystic fibrosis, acute pulmonary exacerbation: For empiric or targeted therapy of P. aeruginosa or other gram-negative bacilli:

IV: 10 mg/kg once daily as part of an appropriate combination regimen (Ref). Duration is usually 10 to 14 days depending on clinical response (Ref).

Meningitis, bacterial

Meningitis, bacterial: P. aeruginosa: IV: 5 mg/kg/day in divided doses every 8 hours as part of an appropriate combination regimen (Ref).

Peritonitis, treatment

Peritonitis, treatment (peritoneal dialysis patients) (off-label use): As a component of empiric therapy or for pathogen-directed therapy.

Note: Intraperitoneal administration is preferred to IV administration. Once culture results are available, switch to another active antibiotic class, if possible, to decrease the risk of toxicity; otherwise, duration of therapy is ≥3 weeks for patients with adequate clinical response (Ref). Consider a 25% dose increase in patients with significant residual renal function (urine output >100 mL/day) (Ref).

Intermittent (strongly preferred): Intraperitoneal: 0.6 mg/kg added to one exchange of dialysis solution once daily (allow to dwell ≥6 hours) (Ref).

Continuous (with every exchange): Intraperitoneal: Loading dose: 3 mg/kg with first exchange of dialysate; maintenance dose: 0.3 mg/kg with each subsequent exchange of dialysate (Ref).

Plague, treatment

Plague (Yersinia pestis), treatment (alternative agent) (off-label use):

Note: Consult public health officials for event-specific recommendations.

IV, IM: 5 to 7 mg/kg once daily for 7 to 14 days and for at least a few days after clinical resolution (Ref).

Pneumonia, hospital-acquired or ventilator-associated

Pneumonia, hospital-acquired or ventilator-associated (alternative agent):

Note: Some experts reserve for patients with risk for multidrug-resistant pathogens (Ref).

IV: 5 to 7 mg/kg once daily in combination with a second gram-negative agent; once culture and susceptibility results are available, can generally discontinue tobramycin and use a single agent with documented activity (Ref). Note: Avoid use of tobramycin monotherapy (Ref).

Sepsis or septic shock, adjunctive empiric gram-negative coverage

Sepsis or septic shock, adjunctive empiric gram-negative coverage (eg, in the setting of intra-abdominal infection, pneumonia, gram-negative bacteremia, or severe burn): Note: Some experts reserve for patients with immunocompromising conditions or risk for resistant gram-negative pathogens, in particular P. aeruginosa (Ref).

IV: 5 to 7 mg/kg once daily in combination with a second gram-negative agent (Ref); once culture and susceptibility tests are available, can generally discontinue and use a single agent with documented activity. Tobramycin should not be used as monotherapy for severe infections outside of the urinary tract (Ref).

Urinary tract infection, complicated

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms) (alternative agent): Note: Some experts reserve for use when other long-acting parenteral antimicrobials (eg, ceftriaxone) or fluoroquinolones cannot be used due to allergy, intolerance, unmodifiable drug interactions, or resistance (Ref).

Inpatients: IV, IM: 5 mg/kg once daily. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Ref).

Outpatients: IV, IM: 5 mg/kg once, followed by 5 to 14 days of appropriate oral therapy (Ref). Note: For patients who are systemically ill or at risk for more severe illness, some experts continue daily parenteral therapy pending culture and susceptibility results (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

IM, IV:

Conventional dosing:

CrCl >60 mL/minute: Administer every 8 hours.

CrCl 40 to 60 mL/minute: Administer every 12 hours.

CrCl 20 to 39 mL/minute: Administer every 24 hours.

CrCl <20 mL/minute: Loading dose, then monitor levels.

IV:

High-dose extended-interval dosing (Ref): Interval may be extended (eg, every 36 to 48 hours) in patients with renal impairment and/or adjusted based on therapeutic drug monitoring.

CrCl ≥60 mL/minute: Administer every 24 hours.

CrCl 40 to 59 mL/minute: Administer every 36 hours.

CrCl 20 to 39 mL/minute: Administer every 48 hours.

CrCl <20 mL/minute: Monitor serum levels and redose when tobramycin level is <1 mg/L or use conventional dosing.

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days) (Ref): Dialyzable (25% to 70%; variable; dependent on filter, duration, and type of HD): IV:

Loading dose of 2 to 3 mg/kg, followed by:

Mild UTI: 1 mg/kg/dose every 48 to 72 hours; consider redosing for pre-HD or post-HD serum concentrations <1 mg/L.

Moderate to severe UTI: 1 to 1.5 mg/kg/dose every 48 to 72 hours; consider redosing for pre-HD serum concentrations <1.5 to 2 mg/L or post-HD concentrations <1 mg/L.

Systemic gram-negative infection: 1.5 to 2 mg/kg/dose every 48 to 72 hours; consider redosing for pre-HD serum concentrations <3 to 5 mg/L or post-HD serum concentrations <2 mg/L.

Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.

CRRT (Ref): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as target drug concentrations (if appropriate). Note: The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment; therapeutic drug monitoring is recommended:

CVVH/CVVHD/CVVHDF: IV:

Mild UTI: Loading dose of 2 to 3 mg/kg, followed by 1 mg/kg/dose every 24 to 36 hours (redose when serum concentration <1 mg/L (Ref)).

Moderate-severe UTI: Loading dose of 2 to 3 mg/kg, followed by 1 to 1.5 mg/kg/dose every 24 to 36 hours (redose when serum concentration <1.5 to 2 mg/L (Ref)).

Systemic gram-negative infection: Loading dose of 2 to 3 mg/kg, followed by 1.5 to 2.5 mg/kg/dose every 24 to 48 hours (generally accepted to redose when serum concentration <2 mg/L; one reference suggests redosing when <3 mg/L (Ref)).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary; does not undergo hepatic metabolism.

Dosing: Obesity: Adult

The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):

IV: Use adjusted body weight for initial weight-based dosing when targeting Cmax/minimum inhibitory concentration (MIC) goals with either loading dose equation (based on target aminoglycoside concentration and estimated Vd) or mg/kg approach and when estimating kidney function with Cockcroft-Gault (CrCl) (Ref). Alternatively, use adjusted body weight to estimate CrCl and aminoglycoside dosing with the Bayesian approach when targeting AUC/MIC goals (Ref). Note: If aminoglycoside therapy is continued, use Cmax/MIC or AUC/MIC goals to optimize therapy, especially in the critically ill where weight and kidney function may be poor surrogates of Vd and clearance (Ref).

Rationale for recommendations: Aminoglycosides are hydrophilic medications with a low Vd and clearance that is proportional to GFR. Pharmacokinetic studies have observed adjusted body weight, using a correction factor of 0.4, is the most appropriate weight metric to correct Vd in the setting of obesity. However, there is wide variation in the correction factors reported, which could lead to under- or overdosing in clinical practice (Ref). Early use of therapeutic drug monitoring is recommended (Ref).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Tobramycin (systemic): Pediatric drug information")

Note: Initial dosing recommendations presented. Monitoring of serum concentrations is recommended to ensure efficacy and avoid toxicity, particularly in critically ill patients with serious infection or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, major surgery). Timing and frequency of concentration monitoring is individualized based on dosing and monitoring strategy (Ref). Routes of administration may vary (including IM, IV, intraperitoneal, intrathecal, and intraventricular); use caution. Some dosing is based on gentamicin studies.

Dosing consideration for obesity: In obese pediatric patients, use adjusted body weight (IBW + 0.4 [TBW – IBW]) to calculate initial dosage (Ref). Alternatively, adjusted body weight for obese pediatric patients may be calculated using the equation 0.7 x TBW (Ref), or fat-free mass can be used to calculate the initial dose in pediatric patients ≥2 years regardless of body habitus (Ref). Dosage should then be individualized based upon serum concentration monitoring.

General dosing, susceptible infection: Note: Optimal dose and frequency not established in patients receiving extracorporeal membrane oxygenation (ECMO); patient-specific considerations (eg, reason for ECMO) and variability with ECMO procedure itself make extrapolation of pharmacokinetic data and dosing to all patients receiving ECMO difficult; closely monitor serum concentrations and determine individual dosing needs in these patients.

Conventional dosing: Infants, Children, and Adolescents: IM, IV: 6 to 7.5 mg/kg/day divided every 6 to 8 hours (Ref).

Extended-interval dosing: Limited data available:

Weight-directed: Infants, Children, and Adolescents: IV: 5 to 7.5 mg/kg/dose every 24 hours (Ref).

Age-directed: Based on data from 114 pediatric patients receiving extended-interval dosing of gentamicin, the following has been suggested for tobramycin (Ref):

Infants ≥3 months and Children <2 years: IV: 9.5 mg/kg/dose every 24 hours.

Children 2 to <8 years: IV: 8.5 mg/kg/dose every 24 hours.

Children ≥8 years and Adolescents: IV: 7 mg/kg/dose every 24 hours.

Cystic fibrosis, pulmonary infection

Cystic fibrosis, pulmonary infection: Infants, Children, and Adolescents:

Conventional dosing: IM, IV: 3.3 mg/kg/dose every 8 hours (Ref).

Extended-interval dosing: IV: Initial: 10 to 12 mg/kg/dose every 24 hours (Ref); maximum reported dose from a survey of 28 Cystic Fibrosis (CF) Foundation-accredited centers ranged from 12 to 20 mg/kg/dose (Ref). Note: The CF Foundation recommends extended-interval dosing as preferred over conventional dosing.

Endocarditis, treatment

Endocarditis, treatment: Limited data available:

Synergy dosing (eg, gram-positive bacteria): Children and Adolescents: IV: 3 to 6 mg/kg/day divided every 8 hours; use in combination with other antibiotics dependent upon pathogen and source of infection (ie, valve-type) (Ref).

Treatment dosing (eg, gram-negative bacteria): Children and Adolescents: IV: 7.5 mg/kg/day divided every 8 hours; use in combination with other antibiotics (Ref).

Intra-abdominal infection, complicated

Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 3 to 7.5 mg/kg/day divided every 8 to 24 hours; use in combination with other antibiotics (Ref).

CNS infection

CNS infection:

Meningitis, including health care-associated meningitis: Limited data available: Infants, Children, and Adolescents: IV: Initial: 7.5 mg/kg/day divided every 8 hours in combination with additional antimicrobials; duration should be individualized based on patient characteristics, infecting organism, and response (Ref).

Ventriculitis (including health care-associated ventriculitis and cerebrospinal fluid [CSF] shunt infections): Limited data available: Infants, Children, and Adolescents: Intraventricular, intrathecal: Use a preservative-free preparation: 5 to 20 mg/day (Ref). Due to the smaller CSF volume in infants, some guidelines recommend decreasing the infant dose; dosage and administration interval can also be adjusted based on CSF tobramycin concentrations, ventricle size, and daily output from ventricular drain (Ref). Duration is individualized according to clinical and microbiological response (Ref).

Peritonitis

Peritonitis (peritoneal dialysis) (Ref): Limited data available: Infants, Children, and Adolescents: Intraperitoneal: Continuous: Loading dose: 8 mg per liter of dialysate; maintenance dose: 4 mg per liter.

Urinary tract infection

Urinary tract infection:

Note: Duration of therapy for multiple-dose regimens: For uncomplicated cystitis in patients ≥3 months of age, treat for 3 to 5 days; patients <2 years of age may require a longer course (eg, 7 days). For complicated urinary tract infection (UTI), including pyelonephritis, treat for a total of 6 to 10 days; while 7 to 14 days has been recommended for complicated UTI, this was not shown to improve outcomes compared to a shorter duration of 6 to 10 days (Ref).

Conventional dosing: Infants, Children, and Adolescents: IV: 5 mg/kg/day divided every 8 hours until clinical improvement and able to tolerate oral intake; complete course with oral antibiotics. Duration should be individualized based upon age, severity, and degree of urinary tract involvement.

Extended-interval dosing: Limited data available: Based on data from 90 patients (ages: 1 month to 12 years) receiving gentamicin, the following age-directed dosing has been suggested (Ref): Note: Patients were transitioned to oral therapy once afebrile for 24 hours.

Infants and Children <5 years: IV: 7.5 mg/kg/dose every 24 hours.

Children 5 to 10 years: IV: 6 mg/kg/dose every 24 hours.

Children 11 to 12 years: IV: 4.5 mg/kg/dose every 24 hours.

Single-dose regimen: Limited data available. Note: Recommended for treatment of uncomplicated cystitis caused by antimicrobial resistant gram-negative pathogens (Ref):

Infants, Children, and Adolescents: IM: 5 mg/kg as a single dose; dosing based on 2 prospective studies evaluating single-dose IM gentamicin in patients 1 month to 15 years and a systematic review evaluating studies of various single-dose aminoglycosides in pediatric and adult patients (Ref); one study limited doses to 300 mg (Ref). An overall pooled cure rate for single dose IM aminoglycoside for treatment of children and adults with mainly uncomplicated cystitis was reported as 94.5% ± 4.3% (Ref). Note: Guidelines do not address pediatric dosing; recommended aminoglycoside doses in adults include IV single doses (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Parenteral: Note: Tobramycin serum concentrations should be monitored in patients with kidney impairment; following the initial dose, subsequent doses may be determined based on therapeutic monitoring.

Infants, Children, and Adolescents: IM, IV:

The following adjustments have been recommended (Ref): Note: Renally adjusted dose recommendations are based on doses of 2.5 mg/kg/dose every 8 hours.

GFR >50 mL/minute/1.73 m2: No adjustment required.

GFR 30 to 50 mL/minute/1.73 m2: Administer every 12 to 18 hours.

GFR 10 to 29 mL/minute/1.73 m2: Administer every 18 to 24 hours.

GFR <10 mL/minute/1.73 m2: Administer every 48 to 72 hours.

Intermittent hemodialysis: Dialyzable (25% to 70%): 2 mg/kg/dose; redose as indicated by serum concentrations.

Peritoneal dialysis (PD): 2 mg/kg/dose; redose as indicated by serum concentrations.

Continuous renal replacement therapy (CRRT): 2 to 2.5 mg/kg/dose every 12 to 24 hours, monitor serum concentrations.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment not likely to be necessary (does not undergo hepatic metabolism).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Central nervous system: Confusion, disorientation, dizziness, headache, lethargy, vertigo

Dermatologic: Exfoliative dermatitis, pruritus, skin rash, urticaria

Endocrine & metabolic: Decreased serum calcium, decreased serum magnesium, decreased serum potassium, decreased serum sodium, increased lactate dehydrogenase, increased nonprotein nitrogen

Gastrointestinal: Diarrhea, nausea, vomiting

Genitourinary: Casts in urine, oliguria, proteinuria

Hematologic & oncologic: Anemia, eosinophilia, granulocytopenia, leukocytosis, leukopenia, thrombocytopenia

Hepatic: Increased serum ALT, increased serum AST, increased serum bilirubin

Local: Pain at injection site

Otic: Auditory ototoxicity, hearing loss, tinnitus, vestibular ototoxicity

Renal: Increased blood urea nitrogen, increased serum creatinine

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Anaphylaxis, Clostridioides difficile-associated diarrhea, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

Contraindications

Hypersensitivity to tobramycin, other aminoglycosides, or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Severe allergic reactions (some fatal), including anaphylaxis, and dermatologic reactions (eg, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome) have been reported; discontinue therapy and initiate appropriate treatment if allergic reaction occurs.

• Nephrotoxicity: [US Boxed Warning]: May cause acute kidney injury, including acute renal failure. Risk factors include tobramycin accumulation (increasing serum trough levels), high peak concentrations (>12 mcg/mL), total cumulative dose, advanced age, volume depletion, and concurrent or sequential use of other nephrotoxic drugs. Avoid concurrent or sequential use of other potentially nephrotoxic drugs. Monitor serum tobramycin levels and renal function in all patients during drug treatment. Reduce the dose or discontinue the drug if renal impairment occurs. Kidney injury is usually reversible.

• Neuromuscular blockade: [US Boxed Warning]: Aminoglycosides have been associated with neuromuscular blockade. Monitor for adverse reactions associated with neuromuscular blockade during therapy, particularly in high-risk patients, such as patients with underlying neuromuscular disorders (including myasthenia gravis) or in patients concomitantly receiving neuromuscular-blocking agents. Neuromuscular blockade may lead to respiratory failure and prolonged respiratory paralysis; additional signs of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. Neuromuscular blockade is reversible but may require treatment (eg, administration of calcium salts).

• Ototoxicity: [US Boxed Warning]: May cause irreversible auditory and vestibular toxicity that may continue to develop after discontinuation. Risk factors include high serum concentrations, prolonged therapy, renal impairment, concurrent and sequential use of other nephrotoxic or ototoxic drugs (eg, aminoglycosides), and extremes of age. Avoid concurrent or sequential use with other potentially ototoxic drugs. Monitor for signs and symptoms of auditory and vestibular toxicity. Reduce the dose or discontinue therapy if renal impairment occurs. Discontinue use if ototoxicity occurs. Auditory changes are usually bilateral and may be partial or total. Ototoxicity symptoms may include dizziness, vertigo, tinnitus, roaring in the ears and hearing loss; consider serial audiograms in high-risk patients.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss.

• Hypocalcemia: Use with caution in patients with hypocalcemia.

• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis and Parkinson disease.

• Renal impairment: Use with caution in patients with preexisting renal insufficiency; dosage modification required during systemic therapy.

Special populations:

• Patients with genomic variants in MT-RNR1: Carriers of certain variants in the MT-RNR1 gene (eg, m.1555A>G) may be at increased risk for aminoglycoside-induced ototoxicity, including potentially significant hearing loss that may be irreversible, even when serum levels are within the normal range.

Dosage form specific issues:

• Sulfite: Solution for injection may contain sodium metabisulfate; use caution in patients with sulfite allergy.

Other warnings/precautions:

• Appropriate use: Not for intraocular and/or subconjunctival administration; macular necrosis has been reported following administration of aminoglycosides by these routes.

• Long-term use: Systemic therapy is not intended for long-term therapy due to toxic hazards associated with extended administration.

Warnings: Additional Pediatric Considerations

Use with caution in premature infants and neonates; immature renal function may increase risk of accumulation and related toxicity. Use with caution in pediatric patients on extracorporeal membrane oxygenation (ECMO); pharmacokinetics of aminoglycosides may be altered; dosage adjustment and close monitoring necessary.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Generic: 10 mg/mL (2 mL); 80 mg/2 mL (2 mL); 1.2 g/30 mL (30 mL)

Solution, Injection [preservative free]:

Generic: 80 mg/2 mL (2 mL); 2 g/50 mL (50 mL)

Solution Reconstituted, Injection:

Generic: 1.2 g (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 1.2 g (1 ea)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Tobramycin Sulfate Injection)

1.2 g/30 mL (per mL): $0.86 - $0.88

2 gm/50 mL (per mL): $1.26

10 mg/mL (per mL): $3.68

80 mg/2 mL (per mL): $0.93 - $2.03

Solution (reconstituted) (Tobramycin Sulfate Injection)

1.2 g (per each): $86.40 - $218.75

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Generic: 10 mg/mL (2 mL)

Solution, Injection, as sulfate:

Generic: 40 mg/mL (2 mL, 30 mL)

Solution Reconstituted, Injection:

Generic: 1.2 g (1 ea)

Administration: Adult

IM: May be administered IM by withdrawing the appropriate dose directly from a vial or by using a prefilled syringe. The pharmacy bulk package and tobramycin in sodium chloride 0.9% is not intended for IM administration.

IV: Administer by intermittent infusion over 20 to 60 minutes; higher doses are generally administered over 60 minutes (Ref). Flush line with saline before and after administration.

Intraventricular (off-label route): Use preservative-free preparations only. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow tobramycin solution to equilibrate in the CSF (Ref).

Administration: Pediatric

Parenteral:

IM: May be administered undiluted.

IV: Administer by intermittent infusion over 20 to 60 minutes; shorter infusion times (≤5 minutes) have been reported in pediatric patients, including preterm and term neonates, receiving ≤4 mg/kg/dose (Ref). Avoid infusing concomitantly with penicillins or cephalosporins if feasible; consult drug interactions database for more information.

Intrathecal/Intraventricular: Use preservative-free preparations only; must be diluted prior to administration. No specific administration information available; it has been suggested that instillation of small volumes (<3 mL) over 1 to 2 minutes is safe (Ref). When administered through a ventricular drain, clamp drain for 15 to 60 minutes to allow tobramycin solution to equilibrate in the cerebrospinal fluid (CSF) (Ref).

Use: Labeled Indications

Bloodstream infection: Treatment of bloodstream infection caused by Pseudomonas aeruginosa, Escherichia coli, and Klebsiella spp., in adult and pediatric patients.

Bone infections: Treatment of bone infections caused by P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus in adult and pediatric patients.

Intra-abdominal infections: Treatment of intra-abdominal infections, including peritonitis, caused by E. coli, Klebsiella spp., and Enterobacter spp. in adult and pediatric patients.

Meningitis, bacterial: Treatment of bacterial meningitis caused by susceptible bacteria in adult and pediatric patients.

Pneumonia: Treatment of pneumonia caused by P. aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., E. coli, and Staphylococcus aureus in adult and pediatric patients.

Skin and skin structure infections: Treatment of skin and skin structure infections caused by P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., and S. aureus in adult and pediatric patients.

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Treatment of complicated urinary tract infections caused by P. aeruginosa, Proteus spp., (indole-positive and indole-negative), E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., S. aureus, Providencia spp., and Citrobacter spp. in adult and pediatric patients.

Use: Off-Label: Adult

Peritonitis, treatment (peritoneal dialysis patients); Plague (Yersinia pestis), treatment

Medication Safety Issues
Sound-alike/look-alike issues:

Tobramycin may be confused with Trobicin, vancomycin

International issues:

Nebcin [Multiple international markets] may be confused with Naprosyn brand name for naproxen [US, Canada, and multiple international markets]; Nubain brand name for nalbuphine [Multiple international markets]

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Aminoglycosides: May enhance the nephrotoxic effect of other Aminoglycosides. Aminoglycosides may enhance the neurotoxic effect of other Aminoglycosides. Risk X: Avoid combination

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Ataluren: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, an increased risk of nephrotoxicity may occur with the concomitant use of ataluren and aminoglycosides. Risk X: Avoid combination

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

Bacitracin (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Bacitracin (Systemic) may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Aminoglycosides may enhance the nephrotoxic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy

Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Risk C: Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy

CARBOplatin: May enhance the nephrotoxic effect of Aminoglycosides. Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy

Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. CISplatin may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Management: Avoid coadministration of colistimethate and aminoglycosides whenever possible due to the risk of nephrotoxicity and neuromuscular blockade. If coadministration cannot be avoided, monitor renal and neuromuscular function. Risk D: Consider therapy modification

Cyclizine: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Risk C: Monitor therapy

Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination

Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination

Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination

Netilmicin (Ophthalmic): Aminoglycosides may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). Risk X: Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy

Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy

Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy

Polymyxin B: May enhance the nephrotoxic effect of Aminoglycosides. Polymyxin B may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Tacrolimus (Systemic): Aminoglycosides may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Vancomycin may enhance the neurotoxic effect of Aminoglycosides. Management: Consider avoiding coadministration of aminoglycosides and vancomycin unless clinically indicated. If coadministered, monitor closely for signs of nephrotoxicity and neurotoxicity. Risk D: Consider therapy modification

Pregnancy Considerations

Tobramycin crosses the placenta.

Tobramycin and other aminoglycosides can cause fetal harm when administered to a pregnant patient. If tobramycin is used during pregnancy or if the patient becomes pregnant while taking tobramycin, apprise the patient of the potential hazard to the fetus.

There are several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists.

Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of tobramycin may be altered (Bourget 1991).

Tobramycin injection may be used for the management of cystic fibrosis in pregnant patients with P. aeruginosa (inhalation is preferred unless risk of infection is great) (Edenborough 2008) and as an alternative antibiotic for prophylactic use prior to cesarean delivery (Bratzler 2013).

Tobramycin is used in the management of plague (Yersinia pestis). Untreated infections in pregnant patients may result in hemorrhage (including postpartum hemorrhage), maternal and fetal death, preterm birth, and stillbirth. Limited data suggest maternal-fetal transmission of Y. pestis can occur if not treated. Pregnant patients should be treated for Y. pestis; parenteral antibiotics are preferred for initial treatment when otherwise appropriate. Tobramycin is an alternative aminoglycoside recommended for use (in combination with a fluroquinolone) for treating pregnant patients with bubonic, pharyngeal, pneumonic, or septicemic plague (CDC [Nelson 2021]).

Breastfeeding Considerations

Tobramycin is present in breast milk following injection (Festini 2006; Uwaydah 1975).

In general, modification of bowel flora may occur with any antibiotic exposure (Chung 2002). Breastfed infants should be monitored for loose or bloody stools, thrush, and diaper rash.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Aminoglycosides have poor oral bioavailability and therefore use may be considered in patients who are breastfeeding (Panchaud 2016).

Dietary Considerations

May require supplementation of calcium, magnesium, potassium.

Monitoring Parameters

Urinalysis, urine output, BUN, serum creatinine, plasma tobramycin levels (as appropriate to dosing method). Test hearing before, during, and after treatment, particularly in those at risk for ototoxicity or who will be receiving prolonged therapy (>2 weeks).

Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.

Reference Range

Conventional/traditional dosing:

Timing of serum samples: Draw peak 30 minutes after 30-minute infusion has been completed or 1 hour following IM injection or beginning of infusion; draw trough within 30 minutes before next dose. Obtain drug levels after the third dose unless renal dysfunction/toxicity expected.

Therapeutic levels:

Peak:

Sepsis, pneumonia, and other serious infections: 7 to 10 mg/L (Drew 2023; Matzke 1983).

Urinary tract infections, including pyelonephritis: 4 to 6 mg/L.

Cystic fibrosis (P. aeruginosa): 20 to 30 mg/L (Simon 2021).

Trough:

Gram negative infections: <2 mg/L; ideal target <1 mg/L (Bertino 1994; Drew 2023; Matzke 1983).

High-dose extended-interval dosing (once-daily dosing): Obtain a random tobramycin level between 6 and 14 hours after the start of the tobramycin infusion. Refer to institution-specific nomogram/policies to determine appropriate dosing interval (Bailey 1997; Nicolau 1995). Alternatively, obtain 2 random tobramycin levels with the first level ≥1 to 2 hours after the end of the infusion and the second level 6 to 12 hours later (≥1 to 2 half-lives apart); adjust dose and interval to achieve an extrapolated peak concentration of ~15 to 20 mcg/mL and trough concentration ≤0.5 mcg/mL (Buijk 2002; Leggett 2015; Mueller 2009; Nicolau 1995; Pagkalis 2011; Prescott 2010). When therapy is continued for 5 days or more, monitor the tobramycin levels once or twice weekly (Bailey 1997; Nicolau 1995).

Intraventricular therapeutic drug monitoring: Limited data available (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]): Prior to administration of the next intraventricular dose, withdraw a sample of cerebrospinal fluid (CSF). This trough cerebrospinal fluid concentration divided by the tobramycin minimum inhibitory concentration of the isolated bacterial pathogen (inhibitory quotient) should exceed 10 to 20.

Mechanism of Action

Interferes with bacterial protein synthesis by binding to 30S ribosomal subunit, resulting in a defective bacterial cell membrane

Pharmacokinetics (Adult Data Unless Noted)

Absorption:

Oral: Poorly absorbed.

IM: Rapid and complete.

Distribution: Distributes to extracellular fluid, including serum, abscesses, ascitic, pericardial, pleural, synovial, lymphatic, and peritoneal fluids; poor penetration into CSF, eye, bone, prostate.

Vd: Varies with age; increased in patients with edema, ascites, fluid overload; decreased in patients with dehydration:

Neonates: 0.45 ± 0.1 L/kg.

Infants: 0.4 ± 0.1 L/kg.

Children: 0.35 ± 0.15 L/kg.

Adolescents: 0.3 ± 0.1 L/kg.

Adults: 0.2 to 0.3 L/kg.

CSF:blood level ratio: Normal meninges: <10%; Inflamed meninges: ≤25% (MacDougall 2011).

Lung: Epithelial lining fluid Cmax (peak):serum Cmax (peak) ratio: ~12% to 30%, varies with time (Boselli 2007; Carcas 1999; Heffernan 2019; Rodvold 2011).

Protein binding: <30%.

Half-life elimination:

Neonates: ≤1,200 g: 11 hours; >1,200 g: 2 to 9 hours.

Infants: 4 ± 1 hour.

Children: 2 ± 1 hour.

Adolescents: 1.5 ± 1 hour.

Adults: IV: 2 to 3 hours; directly dependent upon glomerular filtration rate.

Adults with impaired renal function: 5 to 70 hours.

Time to peak, serum: IM: 30 to 60 minutes; IV: ~30 minutes.

Note: Distribution is prolonged after larger doses (≥60 minutes after 60-minute infusion of 10 mg/kg [Aminimanizani 2002]; ≥90 minutes after 60-minute infusion of a high-dose aminoglycoside [gentamicin 7 mg/kg] [Demczar 1997]).

Excretion: Normal renal function: Urine (~90% to 95%) within 24 hours.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Clearance is decreased in renal impairment.

Anti-infective considerations:

Parameters associated with efficacy:

Gram-negative bacilli: Concentration-dependent, associated with Cmax (peak)/minimum inhibitory concentration (MIC), goal: ≥8 to 10 (Craig 2011; Kashuba 1999; Moore 1987; Zelenitsky 2003) or AUC24/MIC, goal: 30 to 50 (mild/moderate infection) or 80 to 100 (severe infection) (Bland 2018; Craig 2011; Drusano 2007; Smith 2001).

P. aeruginosa in patients with cystic fibrosis: Cmax (peak)/MIC ≥10, AUC/MIC ≥50 (Burkhardt 2006).

Expected drug exposure in adults with normal renal function:

Cmax (peak), postdistributional: 7 mg/kg: ~20 to 22 mg/mL (Craig 2011; Finnell 1998).

AUC24:

Cystic fibrosis:

10 mg/kg: ~108 mg•hour/L (Aminimanizani 2002).

7 mg/kg: 70 to 110 mg•hour/L (Barclay 1995; Craig 2011; Finnell 1998).

Critically ill: 5 mg/kg: ~86 mg•hour/L (Conil 2011).

Parameters associated with toxicity: Nephrotoxicity is associated with more frequent administration and elevated Cmin (trough) concentrations leading to renal accumulation (Bertino 1993; Rybak 1999).

Postantibiotic effect: Bacterial killing continues after tobramycin concentration drops below the MIC of targeted pathogen; generally 0.5 to 7.5 hours, though the actual time of postantibiotic effect varies based on multiple factors including organism, tobramycin Cmax (peak), and concomitant antimicrobial therapy (Craig 2011; Gudmundsson 1993; Lacy 1998).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Nebcin;
  • (AR) Argentina: Tobral | Tobramicina gen med;
  • (AT) Austria: Tobramycin b.braun | Tobrasix;
  • (AU) Australia: Nebcin | Tobra Day | Tobramycin | Tobramycin mylan | Tobramycin wockhardt;
  • (BD) Bangladesh: Brulamycin;
  • (BE) Belgium: Obracin | Tobramycine B. Braun | Tobramycine mayne pharma (ben);
  • (BG) Bulgaria: Tobramycin;
  • (BR) Brazil: Tobramina;
  • (CH) Switzerland: Obracin;
  • (CN) China: Nuo neng | Tai xing | Tobramycin | Tobramycin sulfate | Tuo xin | Yu er ning;
  • (CO) Colombia: Tobra;
  • (CZ) Czech Republic: Brulamycin | Nebcin;
  • (DE) Germany: Gernebcin | Tobra | Tobra cell | Tobramycin b.braun | Tobramycin MP | Tobrazid;
  • (DO) Dominican Republic: Nebcina | Tobra gobens;
  • (EE) Estonia: Brulamycin | Gernebcin | Nebcin | Obracin | Tobramicin | Tobramycin MP | Tobrazid | Tocin;
  • (EG) Egypt: Nebcin | Tobra alex;
  • (ES) Spain: Tobra gobens | Tobramicina normon;
  • (FI) Finland: Nebcina | Tobramycin B Braun | Tomycin;
  • (FR) France: Nebcine | Tobramycine b braun | Tobramycine merck;
  • (GB) United Kingdom: Nebcin | Tobramycin | Tobramycin cox;
  • (GR) Greece: Medphatobra | Nebcin | Tobramycin | Tobramycin Actavis | Tobramycin MP;
  • (HK) Hong Kong: Nebcin;
  • (HU) Hungary: Brulamycin | Nebcin | Tobramycine cf;
  • (ID) Indonesia: Dartobcin | Tobramycin | Tobryne;
  • (IE) Ireland: Nebcin | Tobramycin;
  • (IL) Israel: Nebcin;
  • (IN) India: Nebracin | Tobacin | Tobex | Tobraneg | Tocin | Toracin;
  • (IT) Italy: Bramicil | Nebicina | Tobramicina | Tobramicina B. Braun;
  • (JO) Jordan: Nebcin;
  • (JP) Japan: Tobracin eli lilly | Tobracin jdolph;
  • (KR) Korea, Republic of: Binex tobramycin | Korus tobramycin | Mytob | Nebcin | Pharmedix tobramycin | Samjin tobramycin | Tenebra | Toberan | Tobicyran | Tobra | Tobramycin | Tobramycin huons | Tobramycin pre-mix | Tobramycin sulfate huons | Tobroxine | Tobucin | Tronamycin;
  • (LB) Lebanon: Nebcin;
  • (LT) Lithuania: Brulamycin | Nebcin;
  • (LU) Luxembourg: Obracin | Tobramycin;
  • (LV) Latvia: Brulamycin | Nebcin;
  • (MA) Morocco: Nebcine;
  • (MX) Mexico: Tobra;
  • (NL) Netherlands: Obracin | Tobramycine;
  • (NO) Norway: Nebcin | Nebcina | Tobramycin B. Braun | Tobramycin x gen;
  • (NZ) New Zealand: Nebcin | Tobra Day | Tobramycin | Tobramycin mylan | Tobramycin viatris;
  • (PH) Philippines: Nebcin;
  • (PK) Pakistan: Abbocin | Brulamycin | Magracin | Nebcin | Obramycin | Tobcin | Tobracil | Tobracin | Tobramed | Tobrin | Tocin;
  • (PL) Poland: Brulamycin | Nebcine | Obracin | Tobramycin MP;
  • (PR) Puerto Rico: Nebcin | Tobramycin;
  • (PT) Portugal: Distobram | Tobra gobens | Tobramicina B. Braun | Tobramicina labesfal;
  • (PY) Paraguay: Tobramicina quimfa;
  • (RO) Romania: Tobramicina sun;
  • (RU) Russian Federation: Brulamycin | Nebcin;
  • (SA) Saudi Arabia: Nebcin;
  • (SE) Sweden: Nebcina;
  • (SG) Singapore: Tobramycin;
  • (SI) Slovenia: Bramitob | Gernebicin | Nebcin | Tobramicina normon;
  • (SK) Slovakia: Brulamycin | Tobramycin b.braun;
  • (TH) Thailand: Nebcin;
  • (TN) Tunisia: Nebcine;
  • (TR) Turkey: Nebcin | Tobel;
  • (TW) Taiwan: Biomicin | Nebcin | Tobcin | Tobra | Tobucin | Topramycin | Topsin | Zerodiar;
  • (UA) Ukraine: Braxon | Brulamycin | Tobramycin;
  • (VE) Venezuela, Bolivarian Republic of: Tobra | Tobramicina;
  • (VN) Viet Nam: Intolacin | Union tobracin;
  • (ZA) South Africa: Micro tobramycin | Nebcin | Q-med tobramycin | Tobramycin-fresenius
  1. American Academy of Pediatrics, Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595-610. [PubMed 21873693]
  2. American Academy of Pediatrics (AAP). In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd ed. American Academy of Pediatrics; 2021.
  3. Aminimanizani A, Beringer PM, Kang J, Tsang L, Jelliffe RW, Shapiro BJ. Distribution and elimination of tobramycin administered in single or multiple daily doses in adult patients with cystic fibrosis. J Antimicrob Chemother. 2002;50(4):553-559. doi:10.1093/jac/dkf168 [PubMed 12356801]
  4. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007.
  5. Autore G, Bernardi L, La Scola C, et al. Management of pediatric urinary tract infections: a Delphi study. Antibiotics (Basel). 2022;11(8):1122. doi:10.3390/antibiotics11081122 [PubMed 36009990]
  6. Baddour L, Flynn PM, Fekete T. Infections of cerebrospinal fluid shunts and other devices. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 12, 2020.
  7. Bailey TC, Little JR, Littenberg B, Reichley RM, Dunagan WC. A meta-analysis of extended-interval dosing versus multiple daily dosing of aminoglycosides. Clin Infect Dis. 1997;24(5):786-795. doi:10.1093/clinids/24.5.786 [PubMed 9142771]
  8. Balighian E, Burke M. Urinary tract infections in children. Pediatr Rev. 2018;39(1):3-12. [PubMed 29292282]
  9. Baltimore RS, Gewitz M, Baddour LM, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young and the Council on Cardiovascular and Stroke Nursing. Infective endocarditis in childhood: 2015 update: a scientific statement from the American Heart Association. Circulation. 2015;132(15):1487-1515. doi:10.1161/CIR.0000000000000298 [PubMed 26373317]
  10. Barclay ML, Duffull SB, Begg EJ, Buttimore RC. Experience of once-daily aminoglycoside dosing using a target area under the concentration-time curve. Aust N Z J Med. 1995;25(3):230-235. doi:10.1111/j.1445-5994.1995.tb01529.x [PubMed 7487691]
  11. Bartel K, Habash T, Lugauer S, et al. Optimal Tobramycin Dosage in Patients With Cystic Fibrosis − Evidence for Predictability Based on Previous Drug Monitoring. Infection. 1999;27(4-5):268-271. [PubMed 10885841]
  12. Bauer LA, Blouin RA. Influence of Age on Tobramycin. Pharmacokinetics in Patients With Normal Renal Function. Antimicrob Agents Chemother. 1981;20(5):587-589. doi:10.1128/aac.20.5.587 [PubMed 7325627]
  13. Begg EJ, Barclay ML, Kirkpatrick CJ. The therapeutic monitoring of antimicrobial agents. Br J Clin Pharmacol. 1999;47(1):23-30. [PubMed 10073735]
  14. Bergenwall M, Walker SAN, Elligsen M, et al. Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation - a retrospective study. BMC Pediatr. 2019;19(1):318. [PubMed 31492162]
  15. Bertino JS Jr, Booker LA, Franck PA, Jenkins PL, Franck KR, Nafziger AN. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring. J Infect Dis. 1993;167(1):173-179. doi:10.1093/infdis/167.1.173 [PubMed 8418164]
  16. Bertino JS Jr, Rodvold KA, Destache CJ. Cost considerations in therapeutic drug monitoring of aminoglycosides. Clin Pharmacokinet. 1994;26(1):71-81. doi:10.2165/00003088-199426010-00006 [PubMed 8137600]
  17. Blackburn LM, Tverdek FP, Hernandez M, Bruno JJ. First-dose pharmacokinetics of aminoglycosides in critically ill haematological malignancy patients. Int J Antimicrob Agents. 2015;45(1):46-53. doi:10.1016/j.ijantimicag.2014.09.006 [PubMed 25455848]
  18. Bland CM, Pai MP, Lodise TP. Reappraisal of contemporary pharmacokinetic and pharmacodynamic principles for informing aminoglycoside dosing. Pharmacotherapy. 2018;38(12):1229-1238. doi:10.1002/phar.2193 [PubMed 30403305]
  19. Boselli E, Breilh D, Djabarouti S, et al. Reliability of mini-bronchoalveolar lavage for the measurement of epithelial lining fluid concentrations of tobramycin in critically ill patients. Intensive Care Med. 2007;33(9):1519-1523. doi:10.1007/s00134-007-0688-x [PubMed 17530217]
  20. Bourget P, Fernandez H, Delouis C, et al. Pharmacokinetics of Tobramycin in Pregnant Women. Safety and Efficacy of a Once-Daily Dose Regimen. J Clin Pharm Ther. 1991;16(3):167-176. [PubMed 1869596]
  21. Bradley JS, Nelson JD, Barnett ED, et al, eds. Nelson's Pediatric Microbial Therapy. 27th ed. American Academy of Pediatrics; 2021.
  22. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery. Am J Health Syst Pharm. 2013;70(3):195-283. [PubMed 23327981]
  23. Buck ML. Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet. 2003;42(5):403-417. [PubMed 12739981]
  24. Buijk SE, Mouton JW, Gyssens IC, Verbrugh HA, Bruining HA. Experience with a once-daily dosing program of aminoglycosides in critically ill patients. Intensive Care Med. 2002;28(7):936-942. doi:10.1007/s00134-002-1313-7 [PubMed 12122533]
  25. Burkart JM. Microbiology and therapy of peritonitis in peritoneal dialysis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 21, 2022.
  26. Burkhardt O, Lehmann C, Madabushi R, Kumar V, Derendorf H, Welte T. Once-daily tobramycin in cystic fibrosis: better for clinical outcome than thrice-daily tobramycin but more resistance development? J Antimicrob Chemother. 2006;58(4):822-829. doi:10.1093/jac/dkl328 [PubMed 16885180]
  27. Butterfield JM, Lodise TP, Beegle S, Rosen J, Farkas J, Pai MP. Pharmacokinetics and pharmacodynamics of once-daily administration of intravenous tobramycin in adult patients with cystic fibrosis hospitalized for an acute pulmonary exacerbation. Antimicrob Agents Chemother. 2013;57(10):5175-5177. doi:10.1128/AAC.00539-13 [PubMed 23896470]
  28. Carapetis JR, Jaquiery AL, Buttery JP, et al. Randomized, Controlled Trial Comparing Once Daily and Three Times Daily Gentamicin in Children With Urinary Tract Infections. Pediatr Infect Dis J. 2001;20(3):240-246. [PubMed 11303823]
  29. Carcas AJ, García-Satué JL, Zapater P, Frías-Iniesta J. Tobramycin penetration into epithelial lining fluid of patients with pneumonia. Clin Pharmacol Ther. 1999;65(3):245-250. doi:10.1016/S0009-9236(99)70103-7 [PubMed 10096256]
  30. Chow MS, Quintiliani, Nightingale CH. In Vivo Inactivation of Tobramycin by Ticarcillin. A Case Report. JAMA. 1982;247(5):658-659. [PubMed 6798229]
  31. Chung AM, Reed MD, Blumer JL. Antibiotics and breast-feeding: a critical review of the literature. Paediatr Drugs. 2002;4(12):817-837. [PubMed 12431134]
  32. Conil JM, Georges B, Ruiz S, et al. Tobramycin disposition in ICU patients receiving a once daily regimen: population approach and dosage simulations. Br J Clin Pharmacol. 2011;71(1):61-71. doi:10.1111/j.1365-2125.2010.03793.x [PubMed 21143502]
  33. Cook AM, Mieure KD, Owen RD, Pesaturo AB, Hatton J. Intracerebroventricular administration of drugs. Pharmacotherapy. 2009;29(7):832-845. doi: 10.1592/phco.29.7.832 [PubMed 19558257]
  34. Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV, et al. Extended-Interval Aminoglycoside Administration for Children: A Meta-Analysis. Pediatrics. 2004;114(1):e111-e118. [PubMed 15231982]
  35. Craig WA. Optimizing aminoglycoside use. Crit Care Clin. 2011;27(1):107-121. doi:10.1016/j.ccc.2010.11.006 [PubMed 21144989]
  36. Daly JS, Dodge RA, Glew RH, et al. Effect of Time and Temperature on Inactivation of Aminoglycosides by Ampicillin at Neonatal Dosages. J Perinatol. 1997;17(1):42-45. [PubMed 9069064]
  37. de Hoog M, Mouton JW, Schoemaker RC, et al. Extended-Interval Dosing of Tobramycin in Neonates: Implications for Therapeutic Drug Monitoring. Clin Pharmacol Ther. 2002;71(5):349-358. [PubMed 12011820]
  38. Demczar DJ, Nafziger AN, Bertino JS Jr. Pharmacokinetics of Gentamicin at Traditional Versus High Doses: Implications for Once-Daily Aminoglycoside Dosing. Antimicrob Agents Chemother. 1997;41(5):1115-1119. [PubMed 9145878]
  39. DiCenzo R, Forrest A, Slish JC, et al. A Gentamicin Pharmacokinetic Population Model and Once-Daily Dosing Algorithm for Neonates. Pharmacotherapy. 2003;23(5):585-591. [PubMed 12741432]
  40. Dowell JA, Korth-Bradley J, Milisci M, et al. Evaluating Possible Pharmacokinetic Interactions Between Tobramycin, Piperacillin, and a Combination of Piperacillin and Tazobactam in Patients With Various Degrees of Renal Impairment. J Clin Pharmacol. 2001;41:979-986. [PubMed 11549103]
  41. Drew RH. Dosing and administration of parenteral aminoglycosides. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 8, 2023.
  42. Drusano GL, Ambrose PG, Bhavnani SM, Bertino JS, Nafziger AN, Louie A. Back to the future: using aminoglycosides again and how to dose them optimally. Clin Infect Dis. 2007;45(6):753-760. doi:10.1086/520991 [PubMed 17712761]
  43. Edenborough FP, Borgo G, Knoop C, et al. Guidelines for the management of pregnancy in women with cystic fibrosis. J Cyst Fibros. 2008;7(suppl 1):S2-32. [PubMed 18024241]
  44. El-Chaar GM, Supaswud-Franks T, Venugopalan L, Kohn N, Castro-Alcaraz S. Extended-interval gentamicin administration in neonates: a simplified approach. J Perinatol. 2016;36(8):660-665. [PubMed 26986995]
  45. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-1247. doi:10.1007/s00134-021-06506-y [PubMed 34599691]
  46. Festini F, Ciuti R, Taccetti G, et al. Breast-Feeding in a Woman With Cystic Fibrosis Undergoing Antibiotic Intravenous Treatment. J Matern Fetal Neonatal Med. 2006;19(6):375-376. [PubMed 16801316]
  47. Finnell DL, Davis GA, Cropp CD, Ensom MH. Validation of the Hartford nomogram in trauma surgery patients. Ann Pharmacother. 1998;32(4):417-421. doi:10.1345/aph.17243 [PubMed 9562135]
  48. Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic Fibrosis Pulmonary Guidelines: Treatment of Pulmonary Exacerbations. Am J Respir Crit Care Med. 2009;180(9):802-808. [PubMed 19729669]
  49. Fox MT, Amoah J, Hsu AJ, Herzke CA, Gerber JS, Tamma PD. Comparative effectiveness of antibiotic treatment duration in children with pyelonephritis. JAMA Netw Open. 2020;3(5):e203951. doi:10.1001/jamanetworkopen.2020.3951 [PubMed 32364593]
  50. Friedman ND, Sexton DJ. Gram-negative bacillary meningitis: Treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 12, 2020.
  51. Gilbert DN and Leggett JE. Aminoglycosides. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Churchill Livingstone Elsevier; 2009.
  52. Gilbert DN. Once-Daily Aminoglycoside Therapy. Antimicrob Agents Chemother. 1991;35(3):399-405. [PubMed 2039189]
  53. Goodlet KJ, Benhalima FZ, Nailor MD. A systematic review of single-dose aminoglycoside therapy for urinary tract infection: is it time to resurrect an old strategy?. Antimicrob Agents Chemother. 2018;63(1):e02165-18. [PubMed 30397061]
  54. Goss CH, Heltshe SL, West NE, et al; STOP2 Investigators. A randomized clinical trial of antimicrobial duration for cystic fibrosis pulmonary exacerbation treatment. Am J Respir Crit Care Med. 2021;204(11):1295-1305. doi:10.1164/rccm.202102-0461OC [PubMed 34469706]
  55. Green TP, Mirkin BL, Peterson PK, et al. Tobramycin Serum Level Monitoring in Young Patients With Normal Renal Function. Clin Pharmacokinet. 1984;9(5):457-468. [PubMed 6499344]
  56. Gudmundsson S, Einarsson S, Erlendsdottir H, Moffat J, Bayer W, Craig WA. The post-antibiotic effect of antimicrobial combinations in a neutropenic murine thigh infection model. J Antimicrob Chemother. 1993;31(suppl D):177-191. doi:10.1093/jac/31.suppl_d.177 [PubMed 8335520]
  57. Gupta K. Acute complicated urinary tract infection (including pyelonephritis) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 20, 2021.
  58. Gupta K, Hooton TM, Naber KG, et al; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. doi:10.1093/cid/ciq257 [PubMed 21292654]
  59. Hagen I, Øymar K. Pharmacological Differences Between Once Daily and Twice Daily Gentamicin Dosage in Newborns With Suspected Sepsis. Pharm World Sci. 2009;31(1):18-23. [PubMed 18982422]
  60. Hammett-Stabler CA, Johns T. Laboratory guidelines for monitoring of antimicrobial drugs. National Academy of Clinical Biochemistry. Clin Chem. 1998;44(5):1129-1140. [PubMed 9590397]
  61. Hansen A, Forbes P, Arnold A, et al. Once-Daily Gentamicin Dosing for the Preterm and Term Newborn: Proposal for a Simple Regimen That Achieves Target Levels. J Perinatol. 2003;23(8):635-639. [PubMed 14647159]
  62. Hari P, Meena J, Kumar M, et al. Evidence-based clinical practice guideline for management of urinary tract infection and primary vesicoureteric reflux. Pediatr Nephrol. Published online October 28, 2023. doi:10.1007/s00467-023-06173-9 [PubMed 37897526]
  63. Hartman SJF, Orriëns LB, Zwaag SM, Poel T, de Hoop M, de Wildt SN. External validation of model-based dosing guidelines for vancomycin, gentamicin, and tobramycin in critically ill neonates and children: a pragmatic two-center study. Paediatr Drugs. 2020;22(4):433-444. [PubMed 32507958]
  64. Hassan E, Ober JD. Predicted and measured aminoglycoside pharmacokinetic parameters in critically ill patients. Antimicrob Agents Chemother. 1987;31(11):1855-1858. doi:10.1128/aac.31.11.1855 [PubMed 3435131]
  65. Heffernan AJ, Sime FB, Lipman J, et al. Intrapulmonary pharmacokinetics of antibiotics used to treat nosocomial pneumonia caused by Gram-negative bacilli: a systematic review. Int J Antimicrob Agents. 2019;53(3):234-245. doi:10.1016/j.ijantimicag.2018.11.011 [PubMed 30472292]
  66. Heintz BH, Matzke GR, Dager WE. Antimicrobial Dosing Concepts and Recommendations for Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis. Pharmacotherapy. 2009;29(5):562-577. [PubMed 19397464]
  67. Hitt CM, Patel KB, Nicolau DP, et al. Influence of Piperacillin-Tazobactam on Pharmacokinetics of Gentamicin Given Once Daily. Am J Health Syst Pharm. 1997;54(23):2704-2708. [PubMed 9408514]
  68. Hustinx WN, Hoepelman IM. Aminoglycoside Dosage Regimens. Is Once a Day Enough? Clin Pharmacokinet. 1993;25(6):427-432. [PubMed 8119044]
  69. Jaffe G, Meyers BR, Hirschman SZ. Pharmacokinetics of Tobramycin in Patients With Stable Renal Impairment, Patients Undergoing Peritoneal Dialysis, and Patients on Chronic Hemodialysis. Antimicro Agents Chemother. 1974;5(6):611-616. [PubMed 15825414]
  70. Jenh AM, Tamma PD, Milstone AM. Extended-interval aminoglycoside dosing in pediatrics. Pediatr Infect Dis J. 2011;30(4):338-339. [PubMed 21407038]
  71. Kaiser AB, McGee ZA. Aminoglycoside therapy of gram-negative bacillary meningitis. N Engl J Med. 1975;293(24):1215-1220. doi:10.1056/NEJM197512112932401 [PubMed 1102982]
  72. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111. doi:10.1093/cid/ciw353 [PubMed 27418577]
  73. Kanj SS, Sexton DJ. Principles of antimicrobial therapy of Pseudomonas aeruginosa infections. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 13, 2020.
  74. Kashuba AD, Nafziger AN, Drusano GL, Bertino JS Jr. Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram-negative bacteria. Antimicrob Agents Chemother. 1999;43(3):623-629. [PubMed 10049277]
  75. Khan AJ, Kumar K, Evans HE. Single-dose gentamicin therapy of recurrent urinary tract infection in patients with normal urinary tracts. J Pediatr. 1987;110(1):131-135. [PubMed 3794874]
  76. Klompas M. Treatment of hospital-acquired and ventilator-associated pneumonia in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 20, 2022.
  77. Knoderer CA, Everett JA, Buss WF. Clinical Issues Surrounding Once-Daily Aminoglycoside Dosing in Children. Pharmacotherapy. 2003;23(1):44-56. [PubMed 12523459]
  78. König K, Lim A, Miller A, Saker S, Guy KJ, Barfield CP. Gentamicin trough levels using a simplified extended-interval dosing regimen in preterm and term newborns. Eur J Pediatr. 2015;174(5):669-673. [PubMed 25388408]
  79. Koshida R, Nakashima E, Taniguchi N, Tsuji A, Benet LZ, Ichimura F. Prediction of the distribution volumes of cefazolin and tobramycin in obese children based on physiological pharmacokinetic concepts. Pharm Res. 1989;6(6):486-491. [PubMed 2762224]
  80. Kraus DM, Pai MP, Rodvold KA. Efficacy and Tolerability of Extended-Interval Aminoglycoside Administration in Pediatric Patients. Paediatr Drugs. 2002;4(7):469-484. [PubMed 12083974]
  81. Lacy MK, Nicolau DP, Nightingale CH, Quintiliani R. The pharmacodynamics of aminoglycosides. Clin Infect Dis. 1998;27(1):23-27. doi:10.1086/514620 [PubMed 9675444]
  82. LeBras M, Chow I, Mabasa VH, Ensom MH. Systematic review of efficacy, pharmacokinetics, and administration of intraventricular aminoglycosides in adults. Neurocrit Care. 2016;25(3):492-507. doi:10.1007/s12028-016-0269-3 [PubMed 27043949]
  83. Leggett JE. Aminoglycosides. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Elsevier Saunders; 2015.
  84. Li PK, Szeto CC, Piraino B, et al; International Society for Peritoneal Dialysis. Peritoneal dialysis-related infections recommendations: 2010 update. Perit Dial Int. 2010;30(4):393-423. doi:10.3747/pdi.2010.00049 [PubMed 20628102]
  85. Li PK, Szeto CC, Piraino B, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment. Perit Dial Int. 2016;36(5):481-508. doi:10.3747/pdi.2016.00078 [PubMed 27282851]
  86. Louie A, Liu W, Fikes S, Brown D, Drusano GL. Impact of meropenem in combination with tobramycin in a murine model of Pseudomonas aeruginosa pneumonia. Antimicrob Agents Chemother. 2013;57(6):2788-2792. doi:10.1128/AAC.02624-12 [PubMed 23571540]
  87. MacDougall C, Chambers HF, eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 12th ed. McGraw-Hill Global Education Holding; 2011.
  88. Mancini A, Todd L. Inconsistencies in ISPD peritonitis recommendations: 2016 update on prevention and treatment and the ISPD catheter-related infection recommendations: 2017 update. Perit Dial Int. 2018;38(4):309-310. doi:10.3747/pdi.2018.00026 [PubMed 29987068]
  89. Massie J, Cranswick N. Pharmacokinetic Profile of Once Daily Intravenous Tobramycin in Children With Cystic Fibrosis. J Paediatr Child Health. 2006;42(10):601-605. [PubMed 16972966]
  90. Masvosva P, Buckingham SC, Einhaus S, Phelps SJ. Intraventricular and Intravenous Tobramycin with Ceftazidime for Ventriculitis Secondary to Pseudomonas aeruginosa. J Pediatr Pharmacol Ther. 2003;8(2):138-143. doi:10.5863/1551-6776-8.2.138 [PubMed 23300401]
  91. Matzke GR, Burkle WS, Lucarotti RL. Gentamicin and tobramycin dosing guidelines: an evaluation. Drug Intell Clin Pharm. 1983;17(6):425-432. doi:10.1177/106002808301700604 [PubMed 6861633]
  92. Matzke GR, Jameson JJ, Halstenson CE. Gentamicin Disposition in Young and Elderly Patients With Various Degrees of Renal Function. J Clin Pharmacol. 1987;27(3):216-220. [PubMed 3680577]
  93. Mayer PR, Brown CH, Carter RA, et al. Intramuscular Tobramycin Pharmacokinetics in Geriatric Patients. Drug Intell Clin Pharm. 1986;20:611-615. [PubMed 3743420]
  94. Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg Infect (Larchmt). 2017;18(1):1-76. [PubMed 28085573]
  95. Mazzei T, Novelli A, De Lalla F, Mini E, Periti P. Tissue penetration and pulmonary disposition of tobramycin. J Chemother. 1995;7(4):363-370. doi:10.1179/joc.1995.7.4.363 [PubMed 8568547]
  96. McCormack JP and Jewesson PJ. A Critical Re-evaluation of the “Therapeutic Range” of Aminoglycosides. Clin Infect Dis. 1992;14(1):320-339.
  97. McDade EJ, Wagner JL, Moffett BS, et al. Once-Daily Gentamicin Dosing in Pediatric Patients Without Cystic Fibrosis. Pharmacotherapy. 2010;30(3):248-253. [PubMed 20180608]
  98. McWilliam SJ, Antoine DJ, Smyth RL, Pirmohamed M. Aminoglycoside-induced nephrotoxicity in children. Pediatr Nephrol. 2017;32(11):2015-2025. [PubMed 27848094]
  99. Miller MM, Burton ME, Johnson PN, Miller JL. "Once-daily" versus "extended-interval" administration of aminoglycosides in neonates: need for standard terminology. Am J Health Syst Pharm. 2014;71(24):2108-2109. [PubMed 25465576]
  100. Moehring R, Anderson DJ. Gram-negative bacillary bacteremia in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 13, 2020.
  101. Moffett BS, Kam C, Galati M, et al. The "ideal" body weight for pediatric gentamicin dosing in the era of obesity: a population pharmacokinetic analysis. Ther Drug Monit. 2018;40(3):322-329. [PubMed 29521784]
  102. Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013;187(7):680-689. [PubMed 23540878]
  103. Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987;155(1):93-99. doi:10.1093/infdis/155.1.93 [PubMed 3540140]
  104. Mouton JW, Jacobs N, Tiddens H, Horrevorts AM. Pharmacodynamics of tobramycin in patients with cystic fibrosis. Diagn Microbiol Infect Dis. 2005;52(2):123-127. doi:10.1016/j.diagmicrobio.2005.02.011 [PubMed 15964500]
  105. Mueller EW, Boucher BA. The use of extended-interval aminoglycoside dosing strategies for the treatment of moderate-to-severe infections encountered in critically ill surgical patients. Surg Infect (Larchmt). 2009;10(6):563-570. doi:10.1089/sur.2007.080 [PubMed 20035611]
  106. Murray KL, Wright D, Laxton B, Miller KM, Meyers J, Englebright J. Implementation of standardized pediatric i.v. medication concentrations. Am J Health Syst Pharm. 2014;71(17):1500-1508. [PubMed 25147175]
  107. Nahata MC, Powell DA, Durrell DE, et al. Effect of Gestational Age and Birth Weight on Tobramycin Kinetics in Newborn Infants. J Antimicrob Chemother. 1984;14(1):59-65.
  108. Nelson CA, Meaney-Delman D, Fleck-Derderian S, et al; Contributors. Antimicrobial treatment and prophylaxis of plague: recommendations for naturally acquired infections and bioterrorism response. MMWR Recomm Rep. 2021;70(3):1-27. doi:10.15585/mmwr.rr7003a1 [PubMed 34264565]
  109. Nezic L, Derungs A, Bruggisser M, Tschudin-Sutter S, Krähenbühl S, Haschke M. Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy. Eur J Clin Pharmacol. 2014;70(7):829-837. doi:10.1007/s00228-014-1680-3 [PubMed 24756148]
  110. Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2184 adult patients. Antimicrob Agents Chemother. 1995;39(3):650-655. doi: 10.1128/aac.39.3.650 [PubMed 7793867]
  111. Norris AH, Shrestha NK, Allison GM, et al. 2018 Infectious Diseases Society of America clinical practice guideline for the management of outpatient parenteral antimicrobial therapy. Clin Infect Dis. 2019;68(1):e1-e35. [PubMed 30423035]
  112. Ohler KH, Menke JA, Fuller L. Use of Higher Dose Extended Interval Aminoglycosides in a Neonatal Intensive Care Unit. Am J Perinatol. 2000;17(6):285-290. [PubMed 11144309]
  113. Pagkalis S, Mantadakis E, Mavros MN, Ammari C, Falagas ME. Pharmacological considerations for the proper clinical use of aminoglycosides. Drugs. 2011;71(17):2277-2294. doi:10.2165/11597020-000000000-00000 [PubMed 22085385]
  114. Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy. 2007;27(8):1081-1091. doi:10.1592/phco.27.8.1081 [PubMed 17655508]
  115. Pai MP, Rodvold KA. Aminoglycoside dosing in patients by kidney function and area under the curve: the Sawchuk-Zaske dosing method revisited in the era of obesity. Diagn Microbiol Infect Dis. 2014;78(2):178-187. doi:10.1016/j.diagmicrobio.2013.10.011 [PubMed 24268292]
  116. Panchaud A, Di Paolo ER, Koutsokera A, et al. Safety of drugs during pregnancy and breastfeeding in cystic fibrosis patients. Respiration. 2016;91(4):333-348. [PubMed 26942733]
  117. Prescott WA Jr. National survey of extended-interval aminoglycoside dosing in pediatric cystic fibrosis pulmonary exacerbations. J Pediatr Pharmacol Ther. 2011;16(4):262-269. [PubMed 22768010]
  118. Prescott WA Jr, Nagel JL. Extended-interval once-daily dosing of aminoglycosides in adult and pediatric patients with cystic fibrosis. Pharmacotherapy. 2010;30(1):95-108. doi:10.1592/phco.30.1.95 [PubMed 20030477]
  119. Preston SL, Briceland LL. Single Daily Dosing of Aminoglycosides. Pharmacotherapy. 1995;15(3):297-316. [PubMed 7667165]
  120. Ramsey BW, Pepe MS, Quan JM, et al; Cystic Fibrosis Inhaled Tobramycin Study Group. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med. 1999;340(1):23-30. doi:10.1056/NEJM199901073400104 [PubMed 9878641]
  121. Ratjen F, Munck A, Kho P, Angyalosi G; ELITE Study Group. Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax. 2010;65(4):286-291. [PubMed 19996339]
  122. Rea RS, Capitano B, Bies R, Bigos KL, Smith R, Lee H. Suboptimal aminoglycoside dosing in critically ill patients. Ther Drug Monit. 2008;30(6):674-681. doi:10.1097/FTD.0b013e31818b6b2f [PubMed 19057371]
  123. Redmann S, Wainwright C, Stacey S, et al. Misleading High Tobramycin Plasma Concentrations Can Be Caused by Skin Contamination of Fingerprick Blood Following Inhalation of Nebulized Tobramycin (TOBI): A Short Report. Ther Drug Monit. 2005;27(2):205-207. [PubMed 15795653]
  124. Refer to manufacturer's labeling.
  125. Robinson RF, Nahata MC. Safety of intravenous bolus administration of gentamicin in pediatric patients. Ann Pharmacother. 2001;35(11):1327-1331. [PubMed 11724077]
  126. Rodvold KA, George JM, Yoo L. Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents. Clin Pharmacokinet. 2011;50(10):637-664. doi:10.2165/11594090-000000000-00000 [PubMed 21895037]
  127. Roy C, Gray C, Ruda L, Bell A, Bolt J. High-dose, extended-interval gentamicin and tobramycin for pediatric inpatients: a survey of Canadian hospital pharmacists. Can J Hosp Pharm. 2016;69(5):367-375. [PubMed 27826154]
  128. Rughoo L, Bourguignon L, Maire P, Ducher M. Study of relationship between volume of distribution and body weight application to amikacin. Eur J Drug Metab Pharmacokinet. 2014;39(2):87-91. doi:10.1007/s13318-013-0160-y [PubMed 24599705]
  129. Rybak MJ, Abate BJ, Kang SL, Ruffing MJ, Lerner SA, Drusano GL. Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity. Antimicrob Agents Chemother. 1999;43(7):1549-1555. [PubMed 10390201]
  130. Rybak MJ, Boike SC, Levine DP, Erickson SR. Clinical use and toxicity of high-dose tobramycin in patients with pseudomonal endocarditis. J Antimicrob Chemother. 1986;17(1):115-120. [PubMed 3949634]
  131. Safi KH, Damiani JM, Sturza J, Nasr SZ. Extended-interval aminoglycoside use in cystic fibrosis exacerbation in children and young adults: a prospective quality improvement project. Glob Pediatr Health. 2016;3:2333794X16635464. [PubMed 27336007]
  132. Schmidt GA, Mandel J. Evaluation and management of suspected sepsis and septic shock in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 13, 2020.
  133. Serane TV, Zengeya S, Penford G, et al. Once Daily Dose Gentamicin in Neonates - Is Our Dosing Correct? Acta Paediatr. 2009;98(7):1100-1105. [PubMed 19397541]
  134. Simon RH. Cystic fibrosis: Management of pulmonary exacerbations. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 20, 2022.
  135. Smith PF, Ballow CH, Booker BM, Forrest A, Schentag JJ. Pharmacokinetics and pharmacodynamics of aztreonam and tobramycin in hospitalized patients. Clin Ther. 2001;23(8):1231-1244. doi:10.1016/s0149-2918(01)80103-x [PubMed 11558860]
  136. Smyth A, Tan KH, Hyman-Taylor P, et al. Once Versus Three-Times Daily Regimens of Tobramycin Treatment for Pulmonary Exacerbations of Cystic Fibrosis − The TOPIC Study: A Randomised Controlled Trial. Lancet. 2005;365(9459):573-578. [PubMed 15708100]
  137. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164. [PubMed 20034345]
  138. Southgate WM, DiPiro JT, Robertson AF. Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 1989;33(6):817-819. [PubMed 2764529]
  139. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59(2):e10-52. doi:10.1093/cid/ciu296 [PubMed 24947530]
  140. Stout J. Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 17, 2022.
  141. Szeto CC, Li PK. Concerns regarding inconsistencies within and between ISPD recommendations for peritonitis and catheter-related infections-in reply. Perit Dial Int. 2018;38(4):311-312. doi:10.3747/pdi.2018.00046 [PubMed 29987069]
  142. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America Antimicrobial Resistant Treatment Guidance: Gram-Negative Bacterial Infections. Clin Infect Dis. Published online October 27, 2020. [PubMed 33106864]
  143. Tobramycin 40 mg/mL and 10 mg/mL multiple-dose vial (tobramycin sulfate injection solution) [prescribing information]. Lake Forest, IL: Hospira; October 2022.
  144. Tobramycin 40 mg/mL multiple-dose vial (tobramycin sulfate injection solution) [prescribing information]. Lake Zurich, IL: Deerfield, IL: Baxter Healthcare Corporation; October 2022.
  145. Tobramycin 1.2 g vial (tobramycin sulfate injection solution) [prescribing information]. Lake Zurich, IL: Fresenius Kabi USA LLC; February 2023.
  146. Touw DJ, Westerman EM, Sprij AJ. Therapeutic drug monitoring of aminoglycosides in neonates. Clin Pharmacokinet. 2009;48(2):71-88. [PubMed 19271781]
  147. Traynor AM, Nafziger AN, Bertino JS Jr. Aminoglycoside dosing weight correction factors for patients of various body sizes. Antimicrob Agents Chemother. 1995;39(2):545-548. doi: 10.1128/aac.39.2.545 [PubMed 7726530]
  148. Trotman RL, Williamson JC, Shoemaker DM, et al. Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy. Clin Infect Dis. 2005;41(8):1159-1166. [PubMed 16163635]
  149. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis. 2004;39(9):1267-1284. [PubMed 15494903]
  150. Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventriculitis and meningitis [published online February 14, 2017]. Clin Infect Dis. 2017;64(6):e34-e65. doi:10.1093/cid/ciw861 [PubMed 28203777]
  151. UK Cystic Fibrosis Trust Antibiotic Working Group. Antibiotic treatment for cystic fibrosis – 3rd edition. May 2009. Available at https://www.cysticfibrosis.org.uk/~/media/documents/the-work-we-do/care/consensus-docs-with-new-address/anitbiotic-treatment.ashx?la=en
  152. Uwaydah M, Bibi S, Salman S. Therapeutic Efficacy of Tobramycin - A Clinical and Laboratory Evaluation. J Antimicrob Chemother. 1975;1(4):429-437. [PubMed 1107297]
  153. Valitalo PA, van den Anker JN, Allegaert K, et al. Novel model-based dosing guidelines for gentamicin and tobramycin in preterm and term neonates. J Antimicrob Chemother. 2015;70(7):2074-2077. [PubMed 25766737]
  154. van Donge T, Pfister M, Bielicki J, et al. Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into Question Its Current Dosing Recommendations. Antimicrob Agents Chemother. 2018;62(4):e02004-17. [PubMed 29358294]
  155. van Maarseveen EM, Sprij A, Touw DJ. Extended-interval dosing of gentamicin aiming for a drug-free period in neonates: a prospective cohort study. Ther Drug Monit. 2016;38(3):402-406. [PubMed 26836810]
  156. Van Meter DJ, Corriveau M, Ahern JW, et al. A Survey of Once-Daily Dosage Tobramycin Therapy in Patients With Cystic Fibrosis. Pediatr Pulmonol. 2009;44(4):325-329. [PubMed 19330772]
  157. Varese LA, Grazioli F, Viretto A, Antoniola P. Single-dose (bolus) therapy with gentamicin in management of urinary tract infection. International Journal of Pediatric Nephrology. 1980;1(2):104-105.
  158. Warady BA, Bakkaloglu S, Newland J, et al. Consensus Guidelines for the Prevention and Treatment of Catheter-Related Infections and Peritonitis in Pediatric Patients Receiving Peritoneal Dialysis: 2012 Update. Perit Dial Int. 2012;(32)(suppl 2):S32-S86. [PubMed 22851742]
  159. Wassil SK, Fox KM, White JW. Once daily dosing of aminoglycosides in pediatric cystic fibrosis patients: a review of the literature. J Pediatr Pharmacol Ther. 2008;13(2):68-75. [PubMed 23055867]
  160. Zelenitsky SA, Harding GK, Sun S, Ubhi K, Ariano RE. Treatment and outcome of Pseudomonas aeruginosa bacteraemia: an antibiotic pharmacodynamic analysis. J Antimicrob Chemother. 2003;52(4):668-674. doi:10.1093/jac/dkg403 [PubMed 12951354]
  161. Zobell JT, Epps K, Kittell F, et al. Tobramycin and beta-lactam antibiotic use in cystic fibrosis exacerbations: a pharmacist approach. J Pediatr Pharmacol Ther. 2016;21(3):239-246. [PubMed 27453702]
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