What Factors Affect a Sufficient Tobramycin Dose?

Tobramycin, also known as Anxin or Topromycin, is a white to off-white hygroscopic powder chemical. The molecular formula is C ₁₈ H ₃₇ N ₅ O ₉ and the molecular weight is 467.51400. Soluble in water, very slightly soluble in ethanol, almost insoluble in chloroform and ether, pH value of 10% aqueous solution is 9.0 ~ 11.0. Clinically, it is mainly applicable to the treatment of neonatal sepsis, sepsis, central nervous system infections (including meningitis), urogenital infections, and lung infections caused by gram-negative bacilli.

Chinese name: Tobramycin
English name: Tobramycin
nickname: Anxin, Anti-Prammycin, Niramycin Factor 6, Tromycin, Toxin
Chemical formula: C18H37N5O9
Molecular weight: 467.51400
CAS Registry Number: 32986-56-4

Melting point: 178
Boiling point: 775.4 at 760mmHg
Water soluble: Easily soluble in water (1 part of product is soluble in 1.5 parts of water)
Density: 1.52 g / cm3
Exterior: White solid
Flash point: 422.8 ° C
Application: Neonatal sepsis, sepsis, central nervous system infection, etc.

Introduction of tobramycin compounds

Tobramycin, also known as tobramycin, is an aminoglycoside antibiotic that can be used to treat a variety of bacterial infections, especially those caused by Gram-negative bacteria ^[1] .

Basic information of tobramycin

Tobramycin: Tobramycin (Obracin)

Alias: Napaxin, Topromycin, Tobramycin

CAS number: 32986-56-4

Molecular formula: C ₁₈ H ₃₇ N ₅ O ₉

Chemical structure:

Molecular weight: 467.51400

Exact mass: 467.25900

PSA: 268.17000 ^[1]

Physicochemical properties of tobramycin

Appearance: white solid

Melting point: 178 ° C

Boiling point: 775.4 ° C at 760 mmHg ^[1]

Refractive index: 143 ° (C = 4, H ₂ O)

Flash point: 422.8 ° C

Density: 1.52 g / cm ³

Solubility: H ₂ O: 50 mg / ml, clear, faintly yellow

Water soluble: Very soluble in water ^[1]

Solubility: easily soluble in water (1 part of the product is dissolved in 1.5 parts of water), very slightly soluble in ethanol (1 part of the product is dissolved in 2000 parts of ethanol), insoluble in chloroform and ether ^[2]

Specific rotation:

+ 129 ° (c = 1.0, H ₂ O) ^[3] .

Overview of Tobramycin Drug Related Information

Tobramycin Pharmacology and Toxicology

Tobramycin can be linked at the junctions of 30S and 50S, hinder the formation of 70S complexes, prevent mRNA from being translated into proteins, and cause cell death. Mainly effective against Gram-negative bacteria such as Pseudomonas aeruginosa, E. coli, Klebsiella, Enterobacter, Proteus, Citrobacter. Clinically, it is mainly used for severe infections caused by sensitive bacteria, such as burn infections caused by gram-negative bacteria, especially Pseudomonas aeruginosa, E. coli, and pneumoniae, sepsis, respiratory infections, urinary system infections, gallbladder and biliary infections, and severe soft tissue infection Etc. ^[4] .

Tobramycin pharmacokinetics

Hemodialysis can clear this drug Absorption is rapid and complete after intramuscular injection. After local rinsing or topical application, a certain amount can also be absorbed through the body surface. After absorption, it is mainly distributed in extracellular fluid; 5 to 15% of it is redistributed into tissues and accumulated in renal cortical cells. The product can pass through the placenta. The distribution volume is 0, 26L / kg. The drug concentration in urine is high, and the concentration in urine can reach 75-100 g / ml after intramuscular injection of 1 mg / kg. After intramuscular injection of 1 mg / kg, the blood drug concentration can reach 4 g / ml; intravenous drip of the above dose for 1 hour, the blood drug concentration is similar to intramuscular injection. T _1/2 is 1.9 to 2.2 hours, and the protein binding rate is very low. The product is not metabolized in the body and is excreted by glomerular filtration. 85 to 93% of the dose is discharged within 24 hours. This product can be removed by hemodialysis or peritoneal dialysis ^[5] .

Tobramycin indications

Pseudomonas aeruginosa This product is suitable for Pseudomonas aeruginosa, Proteus (indole positive and negative), Escherichia coli, Klebsiella, Enterobacter, Serratia and Staphylococcus (including penicillin-resistant G and methicillin-resistant strains) Neonatal sepsis, sepsis, central nervous system infections (including meningitis), urogenital infections, lung infections, biliary tract infections, abdominal infections (and peritonitis), bone infections, skin and soft tissue infections (including burns) ), Acute and chronic otitis media, sinusitis, etc. The product can be administered by intrathecal injection at the same time when used for Pseudomonas aeruginosa meningitis or ventriculitis; when used for bronchial and pulmonary infections, it can be inhaled as an adjuvant therapy at the same time. Tobramycin is not effective against most group D streptococcal infections. It is used for bacterial infections of the eye such as conjunctivitis and keratitis, especially for Gram-negative stalk infections resistant to gentamicin, such as severe Pseudomonas aeruginosa infection.

Tobramycin dosage and usage

Serum creatinine 1. Adults usually use intramuscular injection or intravenous drip, once according to the weight of 1-1.7mg / kg, once every 8 hours, the course of treatment is 7 to 10 days. Severely infected patients can increase to 8 mg / kg daily, intravenously in divided doses, but should be reduced as soon as possible after the condition improves ^[4] .

2. For children, intramuscular injection or intravenous drip is usually used. According to body weight, 2mg / kg at 0-7 days of birth, once every 12 hours; infants and children 2mg / kg, every 8 hours. See Gentamicin sulfate.

If the creatinine clearance is below 70ml / min, the maintenance dose should be adjusted based on the measured creatinine clearance.

Tobramycin injection must be fully diluted after intravenous infusion. 50-200ml of 5% glucose injection or sodium chloride injection can be added for each dosage to dilute to a concentration of 1mg / ml (0.1%). Drop within 60 minutes (instillation time should not be less than 20 minutes), the amount of diluted fluid should be reduced accordingly when the medication is used in children.

This product should not be injected subcutaneously, because it can cause pain. It is generally believed that when the peak drug concentration of the product exceeds 12 g / ml and the trough concentration exceeds 2 g / ml, toxic reactions are likely to occur. A course of treatment does not exceed 7-10 days. Eye drops, 1 to 2 drops each time, once every 2h. Apply to the eyes, apply the appropriate amount to the conjunctival sac, twice a day, or once before bedtime.

Tobramycin is prohibited with caution

For renal insufficiency, blood drug monitoring should be performed.

Instructions for tobramycin administration

See Gentamicin sulfate.

Tobramycin adverse reactions

See Gentamicin sulfate.

This product is toxic to the auditory nerve and kidney, and can cause kidney damage. This product is less toxic to the kidney than gentamicin. Only about 1% of patients have symptoms of renal dysfunction, such as cast urine, oliguria. , Proteinuria or elevated serum creatinine concentration. Patients with renal insufficiency should be monitored for blood concentration, which can cause gastrointestinal reactions: nausea, vomiting, loss of appetite, bloating, diarrhea, liver damage, elevated transaminase, decreased platelets, decreased white blood cells, decreased granulocytes, rash , Phlebitis, etc. A small number of patients may have changes in their hemogram, and may have neurotoxicity, double infection, and toxic psychosis at high doses. High-dose, anesthesia, intrathoracic, and intraperitoneal applications all have the risk of neuromuscular blockade. The incidence of allergic reactions is low, similar to gentamicin. The most common are urticaria, eosinophilia, and pimples. .

Tobramycin interaction

Furosemide See Gentamicin sulfate.

1. Combined with strong diuretics (such as furosemide, itanilic acid, etc.) can strengthen ototoxicity. 2. Combined with other ototoxic drugs (such as erythromycin), the possibility of ear poisoning may be strengthened.

3. Combined application with cephalosporins can cause enhanced renal toxicity. Dextran can enhance the renal toxicity of this class of drugs.

4, combined with muscle relaxants or drugs with such effects (such as diazepam, etc.) can cause the strengthening of nerve-muscle block effect. Neostigmine or other anticholinesterase drugs can antagonize neuro-muscular blockade.

Nephrotoxic manifestations 5. The combined use of this class of drugs and alkaline drugs (such as sodium bicarbonate, aminophylline, etc.) can enhance the antibacterial efficacy, but at the same time, the toxicity also increases accordingly, so you must be cautious.

6. The antibacterial effect of penicillins on certain streptococci can be strengthened by the combination of aminoglycosides. For example, it is recognized that Streptococcus grass green endocarditis and enterococcal infections can be added with penicillin at the same time (Or other aminoglycosides). However, it is not certain whether other bacteria have synergistic effects. There are even reports of treatment failure caused by the combination of two drugs. Therefore, the combination of these two drugs must follow its indications and not be used at will.

Tobramycin preparation type

Tobramycin is an antibiotic obtained from Streptomyces in 1967. It can also be deoxygenated from kanamycin B. Its clinical preparation is its sulfate.

Based on tobramycin. Tobramycin sulfate injection1ml: 10mg1ml: 40mg 2m1: 80mg Tobramycin sulfate for injection 1, 2g intramuscularly or intravenously, 3-5mg per kilogram of body weight per day, divided into 2-3 times, newborns, 4 mg per kilogram of body weight per day, divided into 2 doses, 7-10 days for general use, eye drops: 0, 3%. Eye ointment: 0, 3%.

Tobramycin Tobramycin Sulfate Injection

Pharmacological action

Tobramycin sulfate injection This product is an aminoglycoside antibiotic. The antibacterial spectrum is similar to gentamicin, and it is effective against Escherichia coli, Aeromonas, Klebsiella, Proteus mirabilis, some indole-positive Proteus, Pseudomonas aeruginosa, some Neisseria, some Gram-negative bacteria, such as Serratia acnes and Shigella, have antibacterial effect; the product has 3 to 5 times stronger antibacterial effect against Pseudomonas aeruginosa and is moderately sensitive to Pseudomonas aeruginosa. Monascus is highly sensitive to this product. Among Gram-positive bacteria, Staphylococcus aureus (including lactamase-producing strains) is sensitive to this product; Streptococcus (including Streptococcus pyogenes, Pneumococcus, Streptococcus faecalis, etc.) are resistant to this product. Anaerobic Bacteria (Bacteroides), Mycobacterium tuberculosis, Rickettsia, viruses and fungi are also resistant to this product. The mechanism of action of this product is to bind to the bacterial ribosome 30S subunit and inhibit the synthesis of bacterial proteins. Color or slightly yellow clear solution ^[6] .

dynamics

The product is absorbed quickly and completely after intramuscular injection. It is mainly distributed in extracellular fluid, of which 5% to 15% is redistributed into tissues and accumulated in renal cortical cells. The product can pass through the placenta. The distribution volume (Vd) is 0, 26L / kg. The concentration of the drug in urine is high, and the concentration in urine can reach 75-100mg / L after intramuscular injection of 1mg / kg. The synovial fluid can reach an effective concentration, and the concentration is low in bronchial secretions, cerebrospinal fluid, bile, feces, milk, and aqueous humor. After intramuscular injection of 1mg / kg of the product, the blood concentration is about 4mg / L; intravenous drip of 1mg / kg of the product within 1 hour, the blood concentration obtained is similar to that of intramuscular injection. Blood elimination life (t1 / 2 () is 1, 9 ~ 2, 2 hours, the protein binding rate is very low. The product is not metabolized in the body, and is excreted by glomerular filtration. 85% of the administered dose is excreted in 24 hours ~ 93%. This product can be cleared by hemodialysis or peritoneal dialysis ^[6] .

Indication

septicemia This product is suitable for neonatal sepsis, sepsis, and central nervous system infections caused by Pseudomonas aeruginosa, Proteus, Escherichia coli, Klebsiella, Enterobacter, Serratia (including Meningitis), urogenital infections, lung infections, biliary tract infections, celiac infections and peritonitis, bone infections, burns, skin and soft tissue infections, acute and chronic otitis media, sinusitis, etc., or combined with other antibacterial drugs for staphylococcal infections (Methicillin-resistant strains are not effective). The product can be administered by intrathecal injection when used for Pseudomonas aeruginosa meningitis or ventriculitis; when used for bronchial and lung infections, it can be inhaled as an adjuvant therapy by air inhalation at the same time. This product is not effective against most group D streptococcal infections ^[6] .

Dosage

Intramuscular injection or intravenous drip. 1. Adults should weigh 1 to 1, 7 mg / kg once every 8 hours for 7 to 14 days. 2. According to the weight of children, premature infants or children born 0 to 7 days: once 2mg / kg once every 12 to 24 hours; other children: once 2mg / kg once every 8 hours.

Adverse reactions

1. Systemic administration combined with intrathecal injection may cause leg convulsions, rashes, fever, and systemic spasms.

This drug is an ototoxic drug

2. Those who have a higher incidence have hearing loss, tinnitus or fullness in the ears (ototoxicity), hematuria, a significant decrease in the number of urinations or decreased urine output, decreased appetite, extreme thirst (nephrotoxicity), instability, dizziness ( Ototoxicity, affecting vestibular, renal toxicity). Those with lower incidences have difficulty breathing, drowsiness, and extreme weakness (neuromuscular block or renal toxicity). The incidence of renal failure caused by this product is lower than that of gentamicin.

3. If hearing loss, tinnitus or ear fullness occur after stopping the drug, pay attention to ototoxicity.

Taboo

1. Those who are allergic to the product or other aminoglycosides, or someone in the family or someone who is deaf due to the use of streptomycin, are prohibited.

2. Renal failure is disabled ^[6] .

Precautions

1. Patients with renal insufficiency, abnormal liver function, vestibular function or hearing loss, dehydration, myasthenia gravis or Parkinson's disease and elderly patients should be used with caution.

2. The course of treatment of this product does not exceed 7 to 14 days.

3. Cross-allergy: Patients who are allergic to an aminoglycoside antibiotic such as streptomycin and gentamicin may be allergic to this product.

4. Patients (especially those with impaired renal function, premature babies, newborns, infants or elderly patients, patients with shock, heart failure, ascites or severe dehydration) should be monitored:

Audiogram: Elderly patients must be used to detect high-frequency hearing impairment before, during and after regular and long-term medication;

Temperature stimulation test: used to detect vestibular toxicity before, during and after long-term administration;

(3) Routine urine test and renal function measurement. The renal function should be measured regularly before and during the medication to prevent serious renal toxicity.

The serum concentration of this product should be monitored during the medication. Generally, the peak serum concentration is measured from 30 minutes to 1 hour after intravenous drip, and the serum trough concentration is measured before the next medication. When it exceeds 2g / ml, toxic reaction is easy to occur.

5. For creatinine clearance below 70ml / min, the maintenance dose must be adjusted based on the measured creatinine clearance.

6, the product must be fully diluted during intravenous infusion. Add 50 200ml of 5% glucose injection or sodium chloride injection for each dosage to dilute it into a solution with a concentration of 1mg / ml (0, 1%), and complete the drip within 30 to 60 minutes (the drip time should not be less than 20 minutes), the amount of diluted fluid should be reduced accordingly.

7. This product cannot be injected intravenously to avoid neuromuscular block and respiratory depression. It should not be injected subcutaneously, as it can cause pain.

8. Long-term application of this product may lead to excessive growth of drug-resistant bacteria.

9. Patients should be given enough water to reduce renal tubular damage.

10. Interference with laboratory inspection indicators: This product can increase the measured values of alanine aminotransferase, aspartate aminotransferase, serum bilirubin concentration and serum lactate dehydrogenase concentration; blood calcium, magnesium The measured values of potassium, potassium, and sodium may decrease. Age has a significant effect on the blood concentration of the product. At the same dose, the average peak plasma concentration of children under 5 years old is about half that of adults, and children between 5 and 10 years old are about 2/3 of adults. Calculating the dose based on body surface area eliminates differences due to age.

11, children should use this product with caution. During the use in children, pay attention to monitoring hearing and kidney function to prevent the nephrotoxicity and ototoxicity produced by the product.

The product can pass through the placenta, and the concentration in umbilical cord blood is about the same as that in maternal blood. It has been reported that aminoglycosides have caused hearing loss in human fetuses, so pregnant women are contraindicated.

This product can also be secreted in small amounts in human milk, so breastfeeding women should use it with caution or suspend breastfeeding during medication. Elderly patients can produce various toxic reactions after applying this product, so it is extremely important to monitor renal function during the course of treatment. Hearing loss may also occur in patients with normal renal function. In addition, elderly patients should use smaller doses or longer dosing intervals to suit their age, renal function, and function of the 8th pair of brain nerves.

Overdose

The severity of the overdose is related to the dose size, the patient's renal function, dehydration status, age, and whether or not drugs with similar toxic effects are used at the same time. The daily dosage for adults exceeds 5mg / kg, the daily dosage for children exceeds 7,5mg / kg, or the medication duration is too long, and the dosage of the medication is not adjusted for patients with renal insufficiency can cause toxicity of the product. Toxic episodes can occur 10 days after administration. Toxic effects are mainly manifested as renal impairment and vestibular and auditory nerve damage. Neuromuscular blockade and respiratory paralysis can also occur. This product has no specific antidote, and when it is excessive or causes a toxic reaction, symptomatic therapy and supportive therapy are mainly used. Hemodialysis or peritoneal dialysis helps to clear the product from the blood. Newborns can also consider transfusion therapy ^[6] .

medicine interactions

1. This product can be combined with other aminoglycosides or applied continuously or locally or systemically to increase ototoxicity, renal toxicity, and neuromuscular blockade. Hearing loss may occur, and deafness may still develop after stopping the medication; hearing damage may recover or be permanent. Neuromuscular blockade can lead to skeletal muscle weakness, respiratory depression, or paralysis (apnea). Anticholinergic drugs or calcium salts can help block recovery.

Dextran increases ototoxicity and nephrotoxicity

2. This product is used in combination with neuromuscular blocking drugs, which can aggravate the neuromuscular blocking effect, leading to muscle weakness, respiratory depression or paralysis (apnea). Combined with plasma-based drugs such as dextran, sodium alginate, diuretics such as itanilic acid, furosemide and capreomycin, cisplatin, vancomycin, etc., or continuous local or systemic application can increase ototoxicity and kidney Toxicity, hearing damage may occur, and deafness may still develop after stopping the drug. Hearing damage may recover or be permanent.

3. Local or systemic combination of this product with ceftiophen may increase renal toxicity.

4. This product is used in combination with polymyxins, or successively applied locally or systemically, because it can increase renal toxicity and neuromuscular blockade, which can cause skeletal muscle weakness, respiratory depression or paralysis (apnea) .

5. This product should not be used in combination with other nephrotoxicity or ototoxicity or applied in order to avoid aggravating nephrotoxicity or ototoxicity.

6. This product is often used in combination with -lactams (cephalosporins or penicillins) to obtain synergistic effects.

7. Mixing this product with -lactams (cephalosporins or penicillins) can cause mutual inactivation. When combined application is required, it must be instilled in separate bottles. This product is not suitable for infusion with other drugs.

preparation

2ml: 80mg (80,000 units)

Tobramycin Tobramycin Eye Drops

Drug Name

Common name: Tobramycin Eye Drops

Tobramycin eye drops ^[4]

English name: Tobramycin Eye Drops

Phonetic script (Hanyu Pinyin): Tuobumeisu Diyanye

Dosage form: eye drops

[Ingredients] tobramycin.

Chemical name: O-3-amino-3-deoxy--O-glucopyranosyl- (1 6) -O- [2,6-diamino-2,3,6-trideoxy-- D-nucleo-hexylpyranosyl- (1 4)]-2-deoxy-D-streptamine.

Chemical Structure:

Molecular formula: C18H37N5O9

Molecular weight: 467.52

[Properties] This product is a clear solution with little or no color.

[Pharmacology and toxicology] Glucocorticoids can inhibit inflammatory reactions caused by various factors, and may also delay healing. Glucocorticoids can inhibit the body's defense function against infection. If this inhibition ability is clinically significant, antibiotics should be considered in combination. The antibacterial activity of tobramycin is similar to that of gentamicin, and it has a good effect on most Gram-negative and Pseudomonas aeruginosa. Strains are less effective. This product has a stronger effect on Pseudomonas aeruginosa than gentamicin. Enterococcus and Streptococcus are resistant to this product.

[Pharmacokinetics] A small amount of this product is absorbed into the systemic blood circulation after eye drops.

Tobramycin products (15 photos)

[Indications] This product is suitable for local infection of external eyes and appendages caused by sensitive bacteria.

[Usage and Dosage] Drop in the eyelid. Mild to moderate infection: 1-2 drops at a time, once every 4 hours; Severe infection: 2 drops at a time, once per hour.

[Adverse reactions] Occasionally local irritation symptoms, such as: eyelid burning or swelling, conjunctival erythema, etc .; rare allergic reactions.

[Contraindication] Those who are allergic to this product and other aminoglycoside antibiotics are contraindicated.

Precautions

Patients with renal insufficiency, abnormal liver function, vestibular function or hearing loss, dehydration, myasthenia gravis or Parkinson's disease and elderly patients.

Cross-sensitivity: If an allergic reaction occurs, the drug should be discontinued immediately.

Long-term application of this product may lead to excessive growth of resistant bacteria and even cause fungal infection.

If the patient is receiving systemic administration of aminoglycoside antibiotics at the same time, the blood concentration of this product and aminoglycoside antibiotics should be monitored.

Keep the area around the bottle mouth clean to prevent contamination.

Interference to diagnosis: This product may increase the measured values of alanine aminotransferase, aspartate aminotransferase, serum bilirubin concentration, and serum lactate dehydrogenase concentration; blood calcium, magnesium, potassium, sodium The measured value of the concentration may decrease.

[Medication for pregnant women and lactating women] A small amount of this product is absorbed into the systemic blood circulation after eye drops. Because a small amount of the absorbed part can pass through the placenta and can be secreted into milk, it should be used with caution by pregnant women. Breastfeeding should be suspended.

[Children's medication] Due to its potential nephrotoxicity and ototoxicity, it should be used with caution in children.

[Medication for elderly patients] Due to its potential nephrotoxicity and ototoxicity, it should be used with caution in elderly patients.

[Drug interaction] 1. This product is used in combination with other aminoglycosides. 2. The product is used in combination with neuromuscular blocking drugs7, or successively applied locally or systemically, which can increase ototoxicity and renal toxicity, hearing loss may occur, and it may still develop to deafness after stopping the drug, hearing damage may recover or present Permanent. 3. The combination of this product with ceftiophen may increase renal toxicity. 4. This product combined with polymyxins can increase nephrotoxicity and neuromuscular blockade. Neuromuscular blockade can cause skeletal muscle weakness, respiratory depression or paralysis (apnea). 5. This product should not be used in combination with other nephrotoxic or ototoxic drugs or applied in order to avoid nephrotoxicity or ototoxicity.

[Drug overdose] The symptoms of drug overdose are similar to the symptoms of adverse reactions.

[Specifications] 5ml: 15mg (15,000 units).

Cases of Tobramycin Drug Allergy

Introduction of Tobramycin

Patient, male, 20 years old. Due to cough and sputum for 5 days, diagnosis based on examination: acute bronchitis. The patient was treated with 250ml of 10% glucose and 80mg of tobramycin sulfate in an outpatient clinic. The patient was given an intravenous drip. About 10 minutes later, he had a pale complexion, dyspnea, loss of consciousness, and cold limbs. The intravenous drip of tobramycin was stopped immediately, and 1 mg of epinephrine was given subcutaneously, and 10 mg of dexamethasone was given intravenously. Examination: 25 breaths / min, blood pressure 80 / 50mmHg, heart rate 138 beats / min, diagnosis of anaphylactic shock caused by tobramycin sulfate. Following intravenous injection of 10 mg of dexamethasone, intravenous drip of 100 mg of hydrocortisone, 10 ml of 10% calcium gluconate was added to the liquid intravenous drip, and the patient's symptoms and signs gradually returned to normal after 1 hour.

Tobramycin expert discussion

In this case, other causes of shock can be ruled out, so the diagnosis of anaphylactic shock with tobramycin sulfate can be established. Tobramycin sulfate is an aminoglycoside antibiotic, which is widely used in diseases such as lung infection, biliary tract infection, and bone infection caused by sensitive bacteria, and has a good effect. In the course of clinical medication, rash, fever, hearing loss, tinnitus, hematuria and other adverse reactions may occasionally occur. However, no anaphylactic shock has been reported for this drug. The author believes that in the clinical work, patients should be asked about their allergic history. An aminoglycoside antibiotic such as streptomycin or gentamicin may be allergic to this product, so it should be used with caution. During clinical application, the patient's performance should be closely observed, and if there is an allergic reaction, rescue should be actively carried out.