- Email: [email protected]
Perioperative Pharmacology: A Focus on Aminoglycosides
Perioperative Pharmacology: A Focus on Aminoglycosides KELLIE BRUCE, PhD, RN, FNP-BC; RODNEY W. HICKS, PhD, RN, FNP-BC, FAANP, FAAN
1.2
www.aorn.org/CE
ABSTRACT Aminoglycosides are used to treat aerobic gram-negative infections and can be administered with other antibiotics to treat resistant gram-positive infections. Aminoglycosides are most often administered topically or parenterally. During the surgical period, surgeons may use aminoglycosides to irrigate wounds or may apply them directly to surgical incisions. Because aminoglycosides are excreted almost exclusively via the renal system, health care providers must carefully consider the patient’s renal function before selecting these medications for treatment. Aminoglycosides can produce several significant adverse effects, including nephrotoxicity and ototoxicity. Perioperative nurses should familiarize themselves with aminoglycosides, particularly focusing on dosage, monitoring requirements, and effects in special populations. AORN J 93 (April 2011) 464-468. © AORN, Inc, 2011. doi: 10.1016/j.aorn.2010.09.030 Key words: pharmacology, aminoglycosides, aminoglycoside pharmacokinetics, medication safety
Editor’s note: This is the fourth in a series of articles on perioperative pharmacology. The first article was published in the January 2011 issue of the Journal.
A
minoglycosides continue to be a mainstay in IV and topical antibiotic treatment. Commonly used aminoglycosides include streptomycin, neomycin, gentamicin, indicates that continuing education contact hours are available for this activity. Earn the contact hours by reading this article, reviewing the purpose/goal and objectives, and completing the online Examination and Learner Evaluation at http://www.aorn.org/CE. The contact hours for this article expire April 30, 2014.
amikacin, and tobramycin. These antibiotics have a restricted scope and, therefore, have a very discrete treatment population. Typically, aminoglycosides are used to treat significant, organism-responsive illnesses and to treat aerobic gram-negative infections. Susceptible organisms include Acinetobacter, Enterobacter, Escherichia coli, Klebsiella, Proteus, Pseudomonas, and Serratia.1 Aminoglycosides can be administered concurrently with other antibiotics to treat certain gram-positive infections (eg, Staphylococcus aureus); however, this typically is reserved for infections that are resistant to other treatment regimens. Safe delivery of these powerful antibiotics results in fewer perioperative medication errors and improved patient outcomes. doi: 10.1016/j.aorn.2010.09.030
464
AORN Journal ●
April 2011
Vol 93
No 4
© AORN, Inc, 2011
AMINOGLYCOSIDES
www.aornjournal.org
METHOD OF ACTION Aminoglycosides exert their antibacterial effects by inhibiting protein synthesis within the bacterial cell. They interrupt protein synthesis by binding to the 30S ribosomal subunit, which results in impaired protein formation.2 Because of the narrow therapeutic window, aminoglycosides are more bactericidal at higher serum concentrations. These antibiotics also exhibit a postantibiotic effect, which means that the bactericidal effect continues even after serum levels have fallen below the level thought to be therapeutic (ie, the minimum inhibitory concentration).3 Aminoglycosides are almost exclusively excreted via the renal system. Glomerular filtration accounts for approximately 90% of the body’s metabolism and excretion of these antibiotics2; therefore, health care providers must carefully consider the patient’s renal function before selecting these medications for treatment.
are calculated at 3 mg/kg/day to 5 mg/kg/day in a patient with normal renal function, and doses of amikacin are calculated at 15 mg/kg/day.2 Peak concentrations occur approximately 30 to 60 minutes after IV infusion or intramuscular administration.4 Some health care providers, however, prescribe these medications in a single, daily dose because studies that evaluated the postantibiotic effect of aminoglycosides have shown single, daily dosing to be effective. For example, in 1999, Barclay et al5 reported that a review of meta-analyses showed that “5 of 9 meta-analyses found clinical efficacy to be significantly better with once daily administration.”5(p89) Bailey et al6 conducted a meta-analysis of 22 randomized, controlled trials and found similar results. They determined that single dosing yielded “reduced risk of clinical treatment failure.”6(p786) Desired peak and trough levels must be maintained regardless of dosing intervals.
Pharmacokinetics The half-life of aminoglycosides is two hours, and the volume of distribution in a patient with normal renal function who is not obese is 0.26 L/kg. Health care providers must consider the patient’s hydration status carefully because the metabolism and distribution of these medications is so closely tied to renal function. In addition, providers must take into account the patient’s body weight. The volume of distribution is affected in patients who are 30% or more above ideal body weight, therefore, dose modifications may be necessary.3 The dose is calculated based on the patient’s total body weight (TBW) and the ideal body weight (IBW) by using the following formula: V (the medication dose) ⫽ 0.26 (IBW ⫹ 0.4 [TBW ⫺ IBW]).2 Generally, aminoglycosides are administered two to three times per day to maintain steadystate plasma levels. Precise patient-dose calculations are based on specific manufacturer recommendations and the patient’s renal function. Typically, doses of gentamicin and tobramycin
Resistance As with most classes of antibiotics, resistance to aminoglycosides can occur. Resistance is infrequent but when it does occur, it generally is a result of microbial mutation. Recently, clinicians have noticed with increasing frequency that Mycobacterium tuberculosis has become resistant to streptomycin as a result of organism mutation.1 Factors that interfere with medication uptake, such as volume overload or obesity, also can potentially lead to antibiotic resistance.1 CLINICAL INDICATIONS Aminoglycosides are most often administered topically or parenterally. Although aminoglycosides are rarely administered via the oral route because of their poor oral bioavailability, they can be used to retard oral bacterial flora when taken by mouth. Generally, aminoglycosides are the first-line therapy for infections such as tuberculosis, plague (eg, bubonic, pneumonic), and certain health care associated infections (eg, those AORN Journal
465
April 2011
Vol 93
No 4
BRUCE—HICKS
caused by Pseudomonas).4 In an effort to extend antimicrobial coverage to gram-positive organisms, aminoglycosides are often prescribed in combination with a beta lactam antibiotic (eg, penicillin derivatives, cephalosporins), which makes the bacterial cell wall more permeable to the aminoglycoside. The antibiotics should be administered separately (ie, not mixed in a single solution). When administered via the parenteral route, aminoglycosides treat peritonitis; central nervous system infections; and complicated urinary tract, respiratory, skin, and bone infections. Via topical administration, aminoglycosides are most commonly used to irrigate infected wounds.1 In addition, aminoglycosides may be used to treat infected burns, osteomyelitis, peritonitis, urosepsis, gastrointestinal bacterial destruction, and sepsis. Aminoglycosides, particularly gentamicin, also may be used to treat bacterial endocarditis. When treating these conditions, aminoglycosides can be used as the sole antimicrobial agent or may be administered with penicillins and other antibiotics.4
(ie, bacitracin plus neomycin and polymyxin). Combination antibiotic and cortisone-like medication preparations (ie, neomycin plus polymyxin B and hydrocortisone, tobramycin plus dexamethasone ophthalmic suspension) are available for ophthalmic instillation. Neomycin preparations can be used as an instillation solution to treat responsive bladder infections.
Topical Use During the surgical period, surgeons commonly use aminoglycosides to irrigate wounds or apply them directly on surgical incisions. Health care providers must take care to avoid overuse of irrigation solution because toxicity can occur from systemic absorption. Systemic absorption may be accelerated when aminoglycoside preparations are applied to excoriated skin surfaces or large gaping wounds. Health care providers should consider the patient’s renal function when prescribing topical preparations of aminoglycosides, as is the case with other antibiotic formulations. Occasionally, otic solutions are recommended; however, there must be a compelling reason to recommend these preparations because of the ototoxicity associated with aminoglycoside use. Common topical preparations include neomycin, gentamicin, and combination antibiotic preparations
ADVERSE EFFECTS Aminoglycoside use can place patients at an increased risk for nephrotoxicity and ototoxicity. These antibiotics can damage the auditory canal or vestibular system, and the damage may be permanent. Damage to the patient’s hearing is caused by accumulation of aminoglycosides in lymph fluid in the inner ear that results in sensory cellular damage.2 Hearing loss is initially experienced at high frequencies and, if left unattended, can progress to lower frequency loss, and finally, permanent hearing loss.2 Health care providers should closely monitor patients who are receiving aminoglycosides for signs of tinnitus. If the patient experiences tinnitus, the medication should be discontinued immediately. Aminoglycoside use also can result in nephrotoxicity by causing damage to the cells in the proximal tubule, which adversely affects the
466
AORN Journal
Parenteral Use Typically, aminoglycosides are reserved to treat serious gram-negative bacterial infections and frequently are administered with other types of antibiotics to increase their spectrum of activity. Generally, aminoglycosides are recommended for short-term use; most are given for no more than 14 consecutive days. Penicillin-type antibiotics potentially can inactivate some aminoglycosides; therefore, penicillin-type antibiotics and aminoglycosides should never be mixed in the same solution.2 Serum peak and trough concentrations must be monitored closely, and therapeutic levels should be maintained according to specific medication recommendations.
AMINOGLYCOSIDES
www.aornjournal.org
kidneys’ ability to function. Generally, true kidney damage as a result of aminoglycoside administration occurs after three to five days of treatment. The patient’s kidney function may return to normal when treatment is stopped.2 Other common adverse reactions include skin rash, ataxia, nausea, vomiting, hypotension, fever, hypocalcemia, hyponatremia, hypomagnesemia, and hypokalemia.1 Generally, adverse effects are linked to toxic levels of the aminoglycoside being used. Rarely, neuromuscular blockade that results in respiratory muscle paralysis has been seen in patients with aminoglycoside toxicity. Patients with a history of myasthenia gravis are more likely to experience an acute neuromuscular blockade related to aminoglycosides.4 PERIOPERATIVE MEDICATION ERRORS INVOLVING AMINOGLYCOSIDES Findings from the USP MEDMARX Data Report that summarizes perioperative medication errors indicate that aminoglycoside products have been implicated in errors.7 Errors were noted in each of the four perioperative settings: outpatient surgery; preoperative holding area; OR; and postanesthesia care unit, specifically for gentamicin administration (Table 1). The
majority of errors involved adult and geriatric patients, and there was a mixture of omission errors (eg, medication not administered) and errors that involved the incorrect quantity of medication being administered.7
DOSAGE CONSIDERATIONS Generally, IV aminoglycosides are administered during a 30-minute time frame. Occasionally, if clinical considerations necessitate (eg, chronic renal insufficiency, large surface area burns), aminoglycosides can be infused during a 60-minute interval. Health care providers must cautiously monitor the patient’s serum peak and trough levels to avoid patient injury and to maintain therapeutic levels. Therapeutic peak levels are based on a specific medication’s chemical structure. For example, the peak concentrations for gentamicin and tobramycin are 5 mcg/mL to 10 mcg/mL, and amikacin peak levels should reach 15 mcg/mL to 20 mcg/mL.2 Tissue and organ penetration requirements must be considered and necessary peak levels should be adjusted accordingly. When recommended peak levels are exceeded, the potential for adverse effects increases. Toxicity usually occurs when serum trough levels are greater than 2 mcg/mL to 3 mcg/mL for
TABLE 1. Summary of Gentamicin-related Medication Errors in Perioperative Settings Products
N
%
Comments
Outpatient surgery1 Preoperative holding area2 Operating room3 Postanesthesia care unit4
61 10 64 10
1.8 1.4 1.7 0.8
Based on 2,979 records, 3,323 selections, and 384 unique products reported Based on 631 records, 719 selections, and 139 unique products reported Based on 3,298 records, 3,703 selections, and 343 unique products reported Based on 1,063 records, 1,189 selections, and 185 unique products reported*
* The medication errors in the postanesthesia care unit encompassed only the adult population. Gentamicin was not one of the leading products when records for all populations were considered. 1. Table 1-12. Most commonly reported products involved in medication errors by population in outpatient surgery. In: MEDMARX® Data Report: A Chartbook of Medication Error Findings from Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006:36. 2. Table 2-8. Most commonly reported products in preoperative holding area medication errors by population. In: MEDMARX® Data Report: A Chartbook of Medication Error Findings from Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006:56. 3. Table 3-8. Most commonly reported products involved in operating room medication errors by population. In: MEDMARX® Data Report: A Chartbook of Medication Error Findings from Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006:79. 4. Table 4-8. Most commonly reported products involved in postanesthesia care unit medication errors by population. In: MEDMARX® Data Report: A Chartbook of Medication Error Findings from Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006:103.
AORN Journal
467
April 2011
Vol 93
BRUCE—HICKS
No 4
gentamicin and tobramycin and greater than 10 mcg/mL for amikacin.2 Serum peak levels should be measured 30 minutes after infusion, and serum trough levels should be measured after the second or third IV infusion. Subsequent trough levels depend on the length of therapy.1 MONITORING CONSIDERATIONS Health care practitioners should routinely monitor the metabolic panel in patients receiving aminoglycoside therapy and pay particular attention to magnesium, calcium, potassium, and sodium levels because of the potential for electrolyte imbalances. Practitioners also should carefully evaluate the patient’s blood urea nitrogen and creatinine levels and white blood cell count to evaluate treatment response.2
patient outcomes. Perioperative nurses have an important role to ensure that the medications are administered as ordered and to participate in appropriate laboratory monitoring to reduce the opportunity for a medication error. References 1.
2.
3.
4.
5.
SPECIAL POPULATIONS Depending on the specific type, aminoglycosides are designated as pregnancy category C (ie, risk to the fetus cannot be excluded based on the lack of human/animal studies that show no or little risk) or D (ie, there is a definite risk to the fetus based on human trials). Gentamicin, tobramycin, and amikacin are considered pregnancy category C; whereas, neomycin and streptomycin are designated pregnancy category D. Renal function and glomerular filtration rates often decline in the aging individual, so health care providers must pay special attention to the older adult patient’s blood urea nitrogen and creatinine levels. Likewise, providers should carefully monitor pediatric patients with respect to renal function.1 SUMMARY Aminoglycosides are potent antibiotics. These medications can have serious adverse effects; therefore, serum peak and trough levels must be monitored strictly to avoid patient injury and to maintain therapeutic levels. When prescribed and monitored correctly, these medications can have significant clinical benefit and result in positive
468
AORN Journal
6.
7.
Edmunds MW, Mayhew MS. Pharmacology for the Primary Care Provider. 3rd ed. St Louis, MO: Mosby Elsevier; 2009. Bauer LA. The aminoglycoside antibiotics. In: Bauer LA, ed. Applied Clinical Pharmacokinetics. 2nd ed. New York, NY: McGraw-Hill Companies, Inc; 2008:97-206. Bauer LA. Clinical pharmacokinetics and pharmacodynamics. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York, NY: McGraw-Hill Companies, Inc; 2008:9-30. Chambers HF. Aminoglycosides. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Companies, Inc; 2006:1155-1172. Barclay ML, Kirkpatrick CM, Begg EJ. Once-daily aminoglycoside therapy. Is it less toxic than multiple daily doses and how should it be monitored? Clin Pharmacokinet. 1999;36(2):89-98. 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. Hicks R, Becker SC, Cousins DD. MEDMARX Data Report: A Chartbook of Medication Error Findings from the Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006.
Kellie Bruce, PhD, RN, FNP-BC, is an assistant professor and family nurse practitioner track coordinator for the Graduate Program, Nurse Practitioner Studies at Texas Tech University Health Sciences Center, Lubbock, TX. Dr Bruce has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article. Rodney W. Hicks, PhD, RN, FNP-BC, FAANP, FAAN, is a nurse researcher and consultant, Lubbock, TX. Dr Hicks has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article.
EXAMINATION CONTINUING EDUCATION PROGRAM
1.2
Perioperative Pharmacology: A Focus on Aminoglycosides
www.aorn.org/CE
PURPOSE/GOAL To educate perioperative nurses about perioperative use of aminoglycosides.
OBJECTIVES 1. 2. 3. 4. 5.
Explain the purpose of administering aminoglycosides. Identify commonly used aminoglycosides. Describe the method of action of aminoglycosides. Discuss risks associated with aminoglycoside use. Explain how appropriate monitoring of aminoglycosides helps ensure patient safety.
The Examination and Learner Evaluation are printed here for your convenience. To receive continuing education credit, you must complete the Examination and Learner Evaluation online at http://www.aorn.org/CE.
QUESTIONS 1. Commonly used aminoglycosides include 1. amikacin. 2. cephazolin. 3. gentamicin. 4. neomycin. 5. streptomycin. 6. tobramycin. a. 1, 3, and 5 b. 2, 4, and 6 c. 1, 3, 4, 5, and 6 d. 1, 2, 3, 4, 5, and 6
2. Typically, aminoglycosides are administered a. for routine preoperative antibiotic coverage. b. to treat aerobic gram-negative infections. c. for patients who are allergic to penicillin. d. to treat renal infections in pediatric and older adult patients. © AORN, Inc, 2011
3. The administration of aminoglycosides with other antibiotics typically is reserved for infections that a. are caused by atypical organisms. b. affect the central nervous system. c. require long-term treatment (ie, longer than 14 days). d. are resistant to other treatment regimens. 4. Aminoglycosides exert their antibacterial effects by ______________________________ within the bacterial cell. a. blocking synthesis of amino acids b. inhibiting protein synthesis c. interfering with DNA and RNA synthesis d. prohibiting production of antibodies 5. Aminoglycosides continue to have a bactericidal effect even after serum levels have fallen below the minimum inhibitory concentration. April 2011
Vol 93
No 4 ● AORN Journal
469
April 2011
Vol 93
a. true
CE EXAMINATION
No 4
b. false
6. Aminoglycosides are almost exclusively excreted via the ________________ system. a. gastrointestinal b. immune c. renal d. respiratory 7. Resistance to aminoglycosides can occur as a result of 1. microbial mutation. 2. factors that interfere with medication uptake. 3. volume overload. 4. obesity. a. 1 and 3 b. 2 and 4 c. 1, 2, and 4 d. 1, 2, 3, and 4 8. Health care providers must take care to avoid overuse of irrigation solution because toxicity can occur from systemic absorption.
a. true
b. false
9. Hearing loss related to aminoglycoside use 1. can be permanent. 2. is caused by accumulation of aminoglycosides in lymph fluid in the inner ear. 3. is initially experienced at low frequencies. 4. is more prevalent in patients with a history of myasthenia gravis. a. 1 and 2 b. 3 and 4 c. 1, 2, and 3 d. 1, 2, 3, and 4 10. The patient’s serum peak and trough levels of the administered aminoglycoside are monitored to 1. avoid patient injury. 2. determine when the course of treatment is completed. 3. exclude patient allergies to the medication. 4. maintain therapeutic levels. a. 1 and 4 b. 2 and 3 c. 1, 3, and 4 d. 1, 2, 3, and 4
The behavioral objectives and examination for this program were prepared by Rebecca Holm, MSN, RN, CNOR, clinical editor, with consultation from Susan Bakewell, MS, RN-BC, director, Center for Perioperative Education. Ms Holm and Ms Bakewell have no declared affiliations that could be perceived as posing potential conflicts of interest in the publication of this article.
470
AORN Journal
LEARNER EVALUATION CONTINUING EDUCATION PROGRAM
1.2
Perioperative Pharmacology: A Focus on Aminoglycosides
T
his evaluation is used to determine the extent to which this continuing education program met your learning needs. Rate the items as described
below.
OBJECTIVES To what extent were the following objectives of this continuing education program achieved? 1. Explain the purpose of administering aminoglycosides. Low 1. 2. 3. 4. 5. High 2. Identify commonly used aminoglycosides. Low 1. 2. 3. 4. 5. High 3. Describe the method of action of aminoglycosides. Low 1. 2. 3. 4. 5. High 4. Discuss risks associated with aminoglycoside use. Low 1. 2. 3. 4. 5. High 5. Explain how appropriate monitoring of aminoglycosides helps ensure patient safety. Low 1. 2. 3. 4. 5. High
CONTENT 6. To what extent did this article increase your knowledge of the subject matter? Low 1. 2. 3. 4. 5. High 7. To what extent were your individual objectives met? Low 1. 2. 3. 4. 5. High 8. Will you be able to use the information from this article in your work setting? 1. Yes 2. No
www.aorn.org/CE
9. Will you change your practice as a result of reading this article? (If yes, answer question #9A. If no, answer question #9B.) 9A. How will you change your practice? (Select all that apply) 1. I will provide education to my team regarding why change is needed. 2. I will work with management to change/implement a policy and procedure. 3. I will plan an informational meeting with physicians to seek their input and acceptance of the need for change. 4. I will implement change and evaluate the effect of the change at regular intervals until the change is incorporated as best practice. 5. Other: 9B. If you will not change your practice as a result of reading this article, why? (Select all that apply) 1. The content of the article is not relevant to my practice. 2. I do not have enough time to teach others about the purpose of the needed change. 3. I do not have management support to make a change. 4. Other: 10. Our accrediting body requires that we verify the time you needed to complete the 1.2 continuing education contact hour (72-minute) program:
This program meets criteria for CNOR and CRNFA recertification, as well as other continuing education requirements. AORN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. AORN recognizes these activities as continuing education for registered nurses. This recognition does not imply that AORN or the American Nurses Credentialing Center approves or endorses products mentioned in the activity. AORN is provider-approved by the California Board of Registered Nursing, Provider Number CEP 13019. Check with your state board of nursing for acceptance of this activity for relicensure.
Event: #11010; Session: #4063 Fee: Members $6, Nonmembers $12 The deadline for this program is April 30, 2014. A score of 70% correct on the examination is required for credit. Participants receive feedback on incorrect answers. Each applicant who successfully completes this program can immediately print a certificate of completion.
© AORN, Inc, 2011
April 2011
Vol 93
No 4 ● AORN Journal
471
1.2
www.aorn.org/CE
ABSTRACT Aminoglycosides are used to treat aerobic gram-negative infections and can be administered with other antibiotics to treat resistant gram-positive infections. Aminoglycosides are most often administered topically or parenterally. During the surgical period, surgeons may use aminoglycosides to irrigate wounds or may apply them directly to surgical incisions. Because aminoglycosides are excreted almost exclusively via the renal system, health care providers must carefully consider the patient’s renal function before selecting these medications for treatment. Aminoglycosides can produce several significant adverse effects, including nephrotoxicity and ototoxicity. Perioperative nurses should familiarize themselves with aminoglycosides, particularly focusing on dosage, monitoring requirements, and effects in special populations. AORN J 93 (April 2011) 464-468. © AORN, Inc, 2011. doi: 10.1016/j.aorn.2010.09.030 Key words: pharmacology, aminoglycosides, aminoglycoside pharmacokinetics, medication safety
Editor’s note: This is the fourth in a series of articles on perioperative pharmacology. The first article was published in the January 2011 issue of the Journal.
A
minoglycosides continue to be a mainstay in IV and topical antibiotic treatment. Commonly used aminoglycosides include streptomycin, neomycin, gentamicin, indicates that continuing education contact hours are available for this activity. Earn the contact hours by reading this article, reviewing the purpose/goal and objectives, and completing the online Examination and Learner Evaluation at http://www.aorn.org/CE. The contact hours for this article expire April 30, 2014.
amikacin, and tobramycin. These antibiotics have a restricted scope and, therefore, have a very discrete treatment population. Typically, aminoglycosides are used to treat significant, organism-responsive illnesses and to treat aerobic gram-negative infections. Susceptible organisms include Acinetobacter, Enterobacter, Escherichia coli, Klebsiella, Proteus, Pseudomonas, and Serratia.1 Aminoglycosides can be administered concurrently with other antibiotics to treat certain gram-positive infections (eg, Staphylococcus aureus); however, this typically is reserved for infections that are resistant to other treatment regimens. Safe delivery of these powerful antibiotics results in fewer perioperative medication errors and improved patient outcomes. doi: 10.1016/j.aorn.2010.09.030
464
AORN Journal ●
April 2011
Vol 93
No 4
© AORN, Inc, 2011
AMINOGLYCOSIDES
www.aornjournal.org
METHOD OF ACTION Aminoglycosides exert their antibacterial effects by inhibiting protein synthesis within the bacterial cell. They interrupt protein synthesis by binding to the 30S ribosomal subunit, which results in impaired protein formation.2 Because of the narrow therapeutic window, aminoglycosides are more bactericidal at higher serum concentrations. These antibiotics also exhibit a postantibiotic effect, which means that the bactericidal effect continues even after serum levels have fallen below the level thought to be therapeutic (ie, the minimum inhibitory concentration).3 Aminoglycosides are almost exclusively excreted via the renal system. Glomerular filtration accounts for approximately 90% of the body’s metabolism and excretion of these antibiotics2; therefore, health care providers must carefully consider the patient’s renal function before selecting these medications for treatment.
are calculated at 3 mg/kg/day to 5 mg/kg/day in a patient with normal renal function, and doses of amikacin are calculated at 15 mg/kg/day.2 Peak concentrations occur approximately 30 to 60 minutes after IV infusion or intramuscular administration.4 Some health care providers, however, prescribe these medications in a single, daily dose because studies that evaluated the postantibiotic effect of aminoglycosides have shown single, daily dosing to be effective. For example, in 1999, Barclay et al5 reported that a review of meta-analyses showed that “5 of 9 meta-analyses found clinical efficacy to be significantly better with once daily administration.”5(p89) Bailey et al6 conducted a meta-analysis of 22 randomized, controlled trials and found similar results. They determined that single dosing yielded “reduced risk of clinical treatment failure.”6(p786) Desired peak and trough levels must be maintained regardless of dosing intervals.
Pharmacokinetics The half-life of aminoglycosides is two hours, and the volume of distribution in a patient with normal renal function who is not obese is 0.26 L/kg. Health care providers must consider the patient’s hydration status carefully because the metabolism and distribution of these medications is so closely tied to renal function. In addition, providers must take into account the patient’s body weight. The volume of distribution is affected in patients who are 30% or more above ideal body weight, therefore, dose modifications may be necessary.3 The dose is calculated based on the patient’s total body weight (TBW) and the ideal body weight (IBW) by using the following formula: V (the medication dose) ⫽ 0.26 (IBW ⫹ 0.4 [TBW ⫺ IBW]).2 Generally, aminoglycosides are administered two to three times per day to maintain steadystate plasma levels. Precise patient-dose calculations are based on specific manufacturer recommendations and the patient’s renal function. Typically, doses of gentamicin and tobramycin
Resistance As with most classes of antibiotics, resistance to aminoglycosides can occur. Resistance is infrequent but when it does occur, it generally is a result of microbial mutation. Recently, clinicians have noticed with increasing frequency that Mycobacterium tuberculosis has become resistant to streptomycin as a result of organism mutation.1 Factors that interfere with medication uptake, such as volume overload or obesity, also can potentially lead to antibiotic resistance.1 CLINICAL INDICATIONS Aminoglycosides are most often administered topically or parenterally. Although aminoglycosides are rarely administered via the oral route because of their poor oral bioavailability, they can be used to retard oral bacterial flora when taken by mouth. Generally, aminoglycosides are the first-line therapy for infections such as tuberculosis, plague (eg, bubonic, pneumonic), and certain health care associated infections (eg, those AORN Journal
465
April 2011
Vol 93
No 4
BRUCE—HICKS
caused by Pseudomonas).4 In an effort to extend antimicrobial coverage to gram-positive organisms, aminoglycosides are often prescribed in combination with a beta lactam antibiotic (eg, penicillin derivatives, cephalosporins), which makes the bacterial cell wall more permeable to the aminoglycoside. The antibiotics should be administered separately (ie, not mixed in a single solution). When administered via the parenteral route, aminoglycosides treat peritonitis; central nervous system infections; and complicated urinary tract, respiratory, skin, and bone infections. Via topical administration, aminoglycosides are most commonly used to irrigate infected wounds.1 In addition, aminoglycosides may be used to treat infected burns, osteomyelitis, peritonitis, urosepsis, gastrointestinal bacterial destruction, and sepsis. Aminoglycosides, particularly gentamicin, also may be used to treat bacterial endocarditis. When treating these conditions, aminoglycosides can be used as the sole antimicrobial agent or may be administered with penicillins and other antibiotics.4
(ie, bacitracin plus neomycin and polymyxin). Combination antibiotic and cortisone-like medication preparations (ie, neomycin plus polymyxin B and hydrocortisone, tobramycin plus dexamethasone ophthalmic suspension) are available for ophthalmic instillation. Neomycin preparations can be used as an instillation solution to treat responsive bladder infections.
Topical Use During the surgical period, surgeons commonly use aminoglycosides to irrigate wounds or apply them directly on surgical incisions. Health care providers must take care to avoid overuse of irrigation solution because toxicity can occur from systemic absorption. Systemic absorption may be accelerated when aminoglycoside preparations are applied to excoriated skin surfaces or large gaping wounds. Health care providers should consider the patient’s renal function when prescribing topical preparations of aminoglycosides, as is the case with other antibiotic formulations. Occasionally, otic solutions are recommended; however, there must be a compelling reason to recommend these preparations because of the ototoxicity associated with aminoglycoside use. Common topical preparations include neomycin, gentamicin, and combination antibiotic preparations
ADVERSE EFFECTS Aminoglycoside use can place patients at an increased risk for nephrotoxicity and ototoxicity. These antibiotics can damage the auditory canal or vestibular system, and the damage may be permanent. Damage to the patient’s hearing is caused by accumulation of aminoglycosides in lymph fluid in the inner ear that results in sensory cellular damage.2 Hearing loss is initially experienced at high frequencies and, if left unattended, can progress to lower frequency loss, and finally, permanent hearing loss.2 Health care providers should closely monitor patients who are receiving aminoglycosides for signs of tinnitus. If the patient experiences tinnitus, the medication should be discontinued immediately. Aminoglycoside use also can result in nephrotoxicity by causing damage to the cells in the proximal tubule, which adversely affects the
466
AORN Journal
Parenteral Use Typically, aminoglycosides are reserved to treat serious gram-negative bacterial infections and frequently are administered with other types of antibiotics to increase their spectrum of activity. Generally, aminoglycosides are recommended for short-term use; most are given for no more than 14 consecutive days. Penicillin-type antibiotics potentially can inactivate some aminoglycosides; therefore, penicillin-type antibiotics and aminoglycosides should never be mixed in the same solution.2 Serum peak and trough concentrations must be monitored closely, and therapeutic levels should be maintained according to specific medication recommendations.
AMINOGLYCOSIDES
www.aornjournal.org
kidneys’ ability to function. Generally, true kidney damage as a result of aminoglycoside administration occurs after three to five days of treatment. The patient’s kidney function may return to normal when treatment is stopped.2 Other common adverse reactions include skin rash, ataxia, nausea, vomiting, hypotension, fever, hypocalcemia, hyponatremia, hypomagnesemia, and hypokalemia.1 Generally, adverse effects are linked to toxic levels of the aminoglycoside being used. Rarely, neuromuscular blockade that results in respiratory muscle paralysis has been seen in patients with aminoglycoside toxicity. Patients with a history of myasthenia gravis are more likely to experience an acute neuromuscular blockade related to aminoglycosides.4 PERIOPERATIVE MEDICATION ERRORS INVOLVING AMINOGLYCOSIDES Findings from the USP MEDMARX Data Report that summarizes perioperative medication errors indicate that aminoglycoside products have been implicated in errors.7 Errors were noted in each of the four perioperative settings: outpatient surgery; preoperative holding area; OR; and postanesthesia care unit, specifically for gentamicin administration (Table 1). The
majority of errors involved adult and geriatric patients, and there was a mixture of omission errors (eg, medication not administered) and errors that involved the incorrect quantity of medication being administered.7
DOSAGE CONSIDERATIONS Generally, IV aminoglycosides are administered during a 30-minute time frame. Occasionally, if clinical considerations necessitate (eg, chronic renal insufficiency, large surface area burns), aminoglycosides can be infused during a 60-minute interval. Health care providers must cautiously monitor the patient’s serum peak and trough levels to avoid patient injury and to maintain therapeutic levels. Therapeutic peak levels are based on a specific medication’s chemical structure. For example, the peak concentrations for gentamicin and tobramycin are 5 mcg/mL to 10 mcg/mL, and amikacin peak levels should reach 15 mcg/mL to 20 mcg/mL.2 Tissue and organ penetration requirements must be considered and necessary peak levels should be adjusted accordingly. When recommended peak levels are exceeded, the potential for adverse effects increases. Toxicity usually occurs when serum trough levels are greater than 2 mcg/mL to 3 mcg/mL for
TABLE 1. Summary of Gentamicin-related Medication Errors in Perioperative Settings Products
N
%
Comments
Outpatient surgery1 Preoperative holding area2 Operating room3 Postanesthesia care unit4
61 10 64 10
1.8 1.4 1.7 0.8
Based on 2,979 records, 3,323 selections, and 384 unique products reported Based on 631 records, 719 selections, and 139 unique products reported Based on 3,298 records, 3,703 selections, and 343 unique products reported Based on 1,063 records, 1,189 selections, and 185 unique products reported*
* The medication errors in the postanesthesia care unit encompassed only the adult population. Gentamicin was not one of the leading products when records for all populations were considered. 1. Table 1-12. Most commonly reported products involved in medication errors by population in outpatient surgery. In: MEDMARX® Data Report: A Chartbook of Medication Error Findings from Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006:36. 2. Table 2-8. Most commonly reported products in preoperative holding area medication errors by population. In: MEDMARX® Data Report: A Chartbook of Medication Error Findings from Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006:56. 3. Table 3-8. Most commonly reported products involved in operating room medication errors by population. In: MEDMARX® Data Report: A Chartbook of Medication Error Findings from Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006:79. 4. Table 4-8. Most commonly reported products involved in postanesthesia care unit medication errors by population. In: MEDMARX® Data Report: A Chartbook of Medication Error Findings from Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006:103.
AORN Journal
467
April 2011
Vol 93
BRUCE—HICKS
No 4
gentamicin and tobramycin and greater than 10 mcg/mL for amikacin.2 Serum peak levels should be measured 30 minutes after infusion, and serum trough levels should be measured after the second or third IV infusion. Subsequent trough levels depend on the length of therapy.1 MONITORING CONSIDERATIONS Health care practitioners should routinely monitor the metabolic panel in patients receiving aminoglycoside therapy and pay particular attention to magnesium, calcium, potassium, and sodium levels because of the potential for electrolyte imbalances. Practitioners also should carefully evaluate the patient’s blood urea nitrogen and creatinine levels and white blood cell count to evaluate treatment response.2
patient outcomes. Perioperative nurses have an important role to ensure that the medications are administered as ordered and to participate in appropriate laboratory monitoring to reduce the opportunity for a medication error. References 1.
2.
3.
4.
5.
SPECIAL POPULATIONS Depending on the specific type, aminoglycosides are designated as pregnancy category C (ie, risk to the fetus cannot be excluded based on the lack of human/animal studies that show no or little risk) or D (ie, there is a definite risk to the fetus based on human trials). Gentamicin, tobramycin, and amikacin are considered pregnancy category C; whereas, neomycin and streptomycin are designated pregnancy category D. Renal function and glomerular filtration rates often decline in the aging individual, so health care providers must pay special attention to the older adult patient’s blood urea nitrogen and creatinine levels. Likewise, providers should carefully monitor pediatric patients with respect to renal function.1 SUMMARY Aminoglycosides are potent antibiotics. These medications can have serious adverse effects; therefore, serum peak and trough levels must be monitored strictly to avoid patient injury and to maintain therapeutic levels. When prescribed and monitored correctly, these medications can have significant clinical benefit and result in positive
468
AORN Journal
6.
7.
Edmunds MW, Mayhew MS. Pharmacology for the Primary Care Provider. 3rd ed. St Louis, MO: Mosby Elsevier; 2009. Bauer LA. The aminoglycoside antibiotics. In: Bauer LA, ed. Applied Clinical Pharmacokinetics. 2nd ed. New York, NY: McGraw-Hill Companies, Inc; 2008:97-206. Bauer LA. Clinical pharmacokinetics and pharmacodynamics. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York, NY: McGraw-Hill Companies, Inc; 2008:9-30. Chambers HF. Aminoglycosides. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Companies, Inc; 2006:1155-1172. Barclay ML, Kirkpatrick CM, Begg EJ. Once-daily aminoglycoside therapy. Is it less toxic than multiple daily doses and how should it be monitored? Clin Pharmacokinet. 1999;36(2):89-98. 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. Hicks R, Becker SC, Cousins DD. MEDMARX Data Report: A Chartbook of Medication Error Findings from the Perioperative Settings from 1998-2005. Rockville, MD: USP Center for the Advancement of Patient Safety; 2006.
Kellie Bruce, PhD, RN, FNP-BC, is an assistant professor and family nurse practitioner track coordinator for the Graduate Program, Nurse Practitioner Studies at Texas Tech University Health Sciences Center, Lubbock, TX. Dr Bruce has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article. Rodney W. Hicks, PhD, RN, FNP-BC, FAANP, FAAN, is a nurse researcher and consultant, Lubbock, TX. Dr Hicks has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article.
EXAMINATION CONTINUING EDUCATION PROGRAM
1.2
Perioperative Pharmacology: A Focus on Aminoglycosides
www.aorn.org/CE
PURPOSE/GOAL To educate perioperative nurses about perioperative use of aminoglycosides.
OBJECTIVES 1. 2. 3. 4. 5.
Explain the purpose of administering aminoglycosides. Identify commonly used aminoglycosides. Describe the method of action of aminoglycosides. Discuss risks associated with aminoglycoside use. Explain how appropriate monitoring of aminoglycosides helps ensure patient safety.
The Examination and Learner Evaluation are printed here for your convenience. To receive continuing education credit, you must complete the Examination and Learner Evaluation online at http://www.aorn.org/CE.
QUESTIONS 1. Commonly used aminoglycosides include 1. amikacin. 2. cephazolin. 3. gentamicin. 4. neomycin. 5. streptomycin. 6. tobramycin. a. 1, 3, and 5 b. 2, 4, and 6 c. 1, 3, 4, 5, and 6 d. 1, 2, 3, 4, 5, and 6
2. Typically, aminoglycosides are administered a. for routine preoperative antibiotic coverage. b. to treat aerobic gram-negative infections. c. for patients who are allergic to penicillin. d. to treat renal infections in pediatric and older adult patients. © AORN, Inc, 2011
3. The administration of aminoglycosides with other antibiotics typically is reserved for infections that a. are caused by atypical organisms. b. affect the central nervous system. c. require long-term treatment (ie, longer than 14 days). d. are resistant to other treatment regimens. 4. Aminoglycosides exert their antibacterial effects by ______________________________ within the bacterial cell. a. blocking synthesis of amino acids b. inhibiting protein synthesis c. interfering with DNA and RNA synthesis d. prohibiting production of antibodies 5. Aminoglycosides continue to have a bactericidal effect even after serum levels have fallen below the minimum inhibitory concentration. April 2011
Vol 93
No 4 ● AORN Journal
469
April 2011
Vol 93
a. true
CE EXAMINATION
No 4
b. false
6. Aminoglycosides are almost exclusively excreted via the ________________ system. a. gastrointestinal b. immune c. renal d. respiratory 7. Resistance to aminoglycosides can occur as a result of 1. microbial mutation. 2. factors that interfere with medication uptake. 3. volume overload. 4. obesity. a. 1 and 3 b. 2 and 4 c. 1, 2, and 4 d. 1, 2, 3, and 4 8. Health care providers must take care to avoid overuse of irrigation solution because toxicity can occur from systemic absorption.
a. true
b. false
9. Hearing loss related to aminoglycoside use 1. can be permanent. 2. is caused by accumulation of aminoglycosides in lymph fluid in the inner ear. 3. is initially experienced at low frequencies. 4. is more prevalent in patients with a history of myasthenia gravis. a. 1 and 2 b. 3 and 4 c. 1, 2, and 3 d. 1, 2, 3, and 4 10. The patient’s serum peak and trough levels of the administered aminoglycoside are monitored to 1. avoid patient injury. 2. determine when the course of treatment is completed. 3. exclude patient allergies to the medication. 4. maintain therapeutic levels. a. 1 and 4 b. 2 and 3 c. 1, 3, and 4 d. 1, 2, 3, and 4
The behavioral objectives and examination for this program were prepared by Rebecca Holm, MSN, RN, CNOR, clinical editor, with consultation from Susan Bakewell, MS, RN-BC, director, Center for Perioperative Education. Ms Holm and Ms Bakewell have no declared affiliations that could be perceived as posing potential conflicts of interest in the publication of this article.
470
AORN Journal
LEARNER EVALUATION CONTINUING EDUCATION PROGRAM
1.2
Perioperative Pharmacology: A Focus on Aminoglycosides
T
his evaluation is used to determine the extent to which this continuing education program met your learning needs. Rate the items as described
below.
OBJECTIVES To what extent were the following objectives of this continuing education program achieved? 1. Explain the purpose of administering aminoglycosides. Low 1. 2. 3. 4. 5. High 2. Identify commonly used aminoglycosides. Low 1. 2. 3. 4. 5. High 3. Describe the method of action of aminoglycosides. Low 1. 2. 3. 4. 5. High 4. Discuss risks associated with aminoglycoside use. Low 1. 2. 3. 4. 5. High 5. Explain how appropriate monitoring of aminoglycosides helps ensure patient safety. Low 1. 2. 3. 4. 5. High
CONTENT 6. To what extent did this article increase your knowledge of the subject matter? Low 1. 2. 3. 4. 5. High 7. To what extent were your individual objectives met? Low 1. 2. 3. 4. 5. High 8. Will you be able to use the information from this article in your work setting? 1. Yes 2. No
www.aorn.org/CE
9. Will you change your practice as a result of reading this article? (If yes, answer question #9A. If no, answer question #9B.) 9A. How will you change your practice? (Select all that apply) 1. I will provide education to my team regarding why change is needed. 2. I will work with management to change/implement a policy and procedure. 3. I will plan an informational meeting with physicians to seek their input and acceptance of the need for change. 4. I will implement change and evaluate the effect of the change at regular intervals until the change is incorporated as best practice. 5. Other: 9B. If you will not change your practice as a result of reading this article, why? (Select all that apply) 1. The content of the article is not relevant to my practice. 2. I do not have enough time to teach others about the purpose of the needed change. 3. I do not have management support to make a change. 4. Other: 10. Our accrediting body requires that we verify the time you needed to complete the 1.2 continuing education contact hour (72-minute) program:
This program meets criteria for CNOR and CRNFA recertification, as well as other continuing education requirements. AORN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. AORN recognizes these activities as continuing education for registered nurses. This recognition does not imply that AORN or the American Nurses Credentialing Center approves or endorses products mentioned in the activity. AORN is provider-approved by the California Board of Registered Nursing, Provider Number CEP 13019. Check with your state board of nursing for acceptance of this activity for relicensure.
Event: #11010; Session: #4063 Fee: Members $6, Nonmembers $12 The deadline for this program is April 30, 2014. A score of 70% correct on the examination is required for credit. Participants receive feedback on incorrect answers. Each applicant who successfully completes this program can immediately print a certificate of completion.
© AORN, Inc, 2011
April 2011
Vol 93
No 4 ● AORN Journal
471