Antimicrobial Drugs-Aminoglycosides

Antimicrobial Drugs—Aminoglycosides: Amikacin, Gentamicin, Tobramycin; Tricyclic Glycopeptide: Vancomycin

Synonym/acronym: Amikacin (Amikin); gentamicin (Garamycin, Genoptic, Gentacidin, Gentafair, Gentak, Gentamar, Gentrasul, G-myticin, Oco-Mycin, Spectro-Genta); tobramycin (Nebcin, Tobrex); vancomycin (Lyphocin, Vancocin, Vancoled).

Common use

To evaluate specific drugs for subtherapeutic, therapeutic, or toxic levels in treatment of infection.

Specimen

Serum (1 mL) collected in a red-top tube.

Drug	Route of Administration	Recommended Collection Time*
Amikacin	IV, IM	Trough: immediately before next dose
		Peak: 30 min after the end of a 30-min IV infusion
Gentamicin	IV, IM	Trough: immediately before next dose
		Peak: 30 min after the end of a 30-min IV infusion
Tobramycin	IV, IM	Trough: immediately before next dose
		Peak: 30 min after the end of a 30-min IV infusion
Tricyclic glycopeptide and vancomycin	IV, PO	Trough: immediately before next dose Peak: 30–60 min after the end of a 60-min IV infusion

*Usually after fifth dose if given every 8 hr or third dose if given every 12 hr. IM = intramuscular; IV = intravenous; PO = by mouth.

Normal findings

(Method: Immunoassay)

Drug	Therapeutic Range Conventional Units	Conversion to SI units	SI Units	Half-Life (hr)	Distribution (L/kg)	Volume of Binding (%)	Excretion
Amikacin
Peak	15–30 mcg/mL	SI units = Conventional Units × 1.71	26–51 micromol/L	4–8	0.4–1.3	50	1° renal
Trough	4–8 mcg/mL	SI units = Conventional Units × 1.71	7–14 micromol/L				1° renal
Gentamicin (Standard dosing)
Peak	5–10 mcg/mL	SI units = Conventional Units × 2.09	10–21 micromol/L	4–8	0.4–1.3	50	1° renal
Trough	Less than 2 mcg/mL	SI units = Conventional Units × 2.09	Less than 4 micromol/L				1° renal
Tobramycin (Standard dosing)
Peak	4–8 mcg/mL	SI units = Conventional Units × 2.09	8.4–16.7 micromol/L	4–8	0.4–1.3	50	1° renal
Trough	Less than 1 mcg/mL	SI units = Conventional Units × 2.09	Less than 2.1 micromol/L				1° renal
Tobramycin (Once daily dosing)
Peak	8–12 mcg/mL	SI units = Conventional Units × 2.09	16.7–25.1 micromol/L	4–8	0.4–1.3	50	1° renal
Trough	Less than 0.5 mcg/mL	SI units = Conventional Units × 2.09	Less than 1 micromol/L				1° renal
Vancomycin
Trough (General) Values vary with indication	5–15 mcg/mL	SI units = Conventional Units × 0.69	3.4–10.4 micromol/L	6–12	0.4–1	10–15	1° renal

Description

The aminoglycoside antibiotics amikacin, gentamicin, and tobramycin are used against many gram-negative (Acinetobacter, Citrobacter,Enterobacter, Escherichia coli,Klebsiella,Proteus,Providencia,Pseudomonas,Raoultella,Salmonella,Serratia,Shigella, and Stenotrophomonas) and some gram-positive (Staphylococcus aureus) pathogenic microorganisms. Aminoglycosides are poorly absorbed through the gastrointestinal tract and are most frequently administered IV.

Vancomycin is a tricyclic glycopeptide antibiotic used against many gram-positive microorganisms, such as staphylococci, Streptococcus pneumoniae, group A β-hemolytic streptococci, enterococci, Corynebacterium, and Clostridium. Vancomycin has also been used in an oral form for the treatment of pseudomembranous colitis resulting from Clostridium difficile infection. This approach is less frequently used because of the emergence of vancomycin-resistant enterococci (VRE).

Many factors must be considered in effective dosing and monitoring of therapeutic drugs, including patient age, patient weight, interacting medications, electrolyte balance, protein levels, water balance, conditions that affect absorption and excretion, and ingestion of substances (e.g., foods, herbals, vitamins, and minerals) that can either potentiate or inhibit the intended target concentration. The most serious side effects of the aminoglycosides and vancomycin are nephrotoxicity and irreversible ototoxicity (uncommon). Peak and trough collection times should be documented carefully in relation to the time of medication administration. Creatinine levels should be monitored every 2 to 3 days to detect renal impairment due to toxic drug levels.

Important note: These medications are metabolized and excreted by the kidneys and are therefore contraindicated in patients with renal disease and cautiously advised in patients with renal impairment. Information regarding medications must be clearly and accurately communicated to avoid misunderstanding of the dose time in relation to the collection time. Miscommunication between the individual administering the medication and the individual collecting the specimen is the most frequent cause of subtherapeutic levels, toxic levels, and misleading information used in the calculation of future doses. Some pharmacies use a computerized pharmacokinetics approach to dosing that eliminates the need to be concerned about peak and trough collections; random specimens are adequate. If administration of the drug is delayed, notify the appropriate department(s) to reschedule the blood draw and notify the requesting health-care provider (HCP) if the delay has caused any real or perceived therapeutic harm.

This procedure is contraindicated for

N/A

Indications

Assist in the diagnosis and prevention of toxicity
Monitor renal dialysis patients or patients with rapidly changing renal function
Monitor therapeutic regimen

Potential diagnosis

Level	Response
Normal levels	Therapeutic effect
Subtherapeutic levels	Adjust dose as indicated
Toxic levels	Adjust dose as indicated
Amikacin	Renal, hearing impairment
Gentamicin	Renal, hearing impairment
Tobramycin	Renal, hearing impairment
Vancomycin	Renal, hearing impairment

Critical findings

The adverse effects of subtherapeutic levels are important. Care should be taken to investigate signs and symptoms of too little and too much medication. Note and immediately report to the health-care provider (HCP) any critically increased or subtherapeutic values and related symptoms.
Timely notification of a critical finding for lab or diagnostic studies is a role expectation of the professional nurse. The notification processes will vary among facilities. Upon receipt of the critical finding the information should be read back to the caller to verify accuracy. Most policies require immediate notification of the primary HCP, hospitalist, or on-call HCP. Reported information includes the patient’s name, unique identifiers, critical finding, name of the person giving the report, and name of the person receiving the report. Documentation of notification should be made in the medical record with the name of the HCP notified, time and date of notification, and any orders received. Any delay in a timely report of a critical finding may require completion of a notification form with review by Risk Management.
Signs and symptoms of toxic levels of these antibiotics are similar and include loss of hearing and decreased renal function. Suspected hearing loss can be evaluated by audiometry testing. Impaired renal function may be identified by monitoring BUN and creatinine levels as well as intake and output. The most important intervention is accurate therapeutic drug monitoring so the medication can be discontinued before irreversible damage is done.

Drug Name	Toxic Levels Conventional Units	Toxic Levels SI Units
Amikacin	Greater than 10 mcg/mL	Greater than 17.1 micromol/L
Gentamicin	Peak greater than 12 mcg/mL, trough greater than 2 mcg/mL	Peak greater than 25.1 micromol/L, trough greater than 4.2 micromol/L
Tobramycin	Peak greater than 12 mcg/mL, trough greater than 2 mcg/mL	Peak greater than 25.1 micromol/L, trough greater than 4.2 micromol/L
Vancomycin	Trough greater than 30 mcg/mL	Trough greater than 20.7 micromol/L

Interfering factors

Blood drawn in serum separator tubes (gel tubes).
Drugs that may decrease aminoglycoside efficacy include penicillins (e.g., carbenicillin, piperacillin).
Obtain a culture before and after the first dose of aminoglycosides.
The risks of ototoxicity and nephrotoxicity are increased by the concomitant administration of aminoglycosides.

Nursing Implications and Procedure

Pretest

Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
Patient Teaching: Inform the patient this test can assist in monitoring for subtherapeutic, therapeutic, or toxic drug levels used in treatment of infection.
Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
Obtain a history of the patient’s immune system, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
Nephrotoxicity is a risk associated with administration of aminoglycosides. Obtain a history of the patient’s genitourinary system, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
Ototoxicity is a risk associated with administration of aminoglycosides. Obtain a history of the patient’s known or suspected hearing loss, including type and cause; ear conditions with treatment regimens; ear surgery; and other tests and procedures to assess and diagnose auditory deficit.
Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus). Note the last time and dose of medication taken.
Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
Obtain a culture, if ordered, before the first dose of aminoglycosides.
Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
Note that there are no food, fluid, or medication restrictions unless by medical direction.

Intratest

Potential complications: N/A
Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Consider recommended collection time in relation to the dosing schedule. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection, noting the last dose of medication taken. Perform a venipuncture.
Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
Promptly transport the specimen to the laboratory for processing and analysis.

Post-Test

Inform the patient that a report of the results will be made available to the requesting HCP, who will discuss the results with the patient.
Instruct the patient receiving aminoglycosides to immediately report any unusual symptoms (e.g., hearing loss, decreased urinary output) to his or her HCP.
Nutritional Considerations: Include avoidance of alcohol consumption.
Administer antibiotic therapy if ordered. Remind the patient of the importance of completing the entire course of antibiotic therapy, even if signs and symptoms disappear before completion of therapy.
Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Explain to the patient the importance of following the medication regimen and instructions regarding food and drug interactions. Answer any questions or address any concerns voiced by the patient or family.
Instruct the patient to be prepared to provide the pharmacist with a list of other medications he or she is already taking in the event that the requesting HCP prescribes a medication.
Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.

Related Monographs

Related tests include albumin, audiometry hearing loss, BUN, CBC WBC and differential, creatinine, creatinine clearance, cultures bacterial (ear, eye, skin, wound, blood, stool, sputum, urine), otoscopy, potassium, spondee speech recognition test, tuning fork tests, and UA.
See the Auditory, Genitourinary, and Immune systems tables at the end of the book for related tests by body system.