Aminoglycosides


Article Author:
Megan Block


Article Editor:
Dana Blanchard


Editors In Chief:
Jon Parham
Abigail Frank
Jon Sivoravong


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
5/23/2019 7:49:40 AM

Indications

Although not a new class of antibiotics, aminoglycosides have continued to prove their clinical value in fighting infections. Aminoglycosides have a broad spectrum of activity covering aerobic organisms, including gram-negative bacteria and mycobacteria. Because there are several drugs within the aminoglycoside class including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin, FDA approved indications vary between the different individual aminoglycosides.  

In general, aminoglycosides are indicated for empirical or directed treatment. Since this drug class has been shown to be effective in multi-drug resistant Gram-negative pathogens, aminoglycosides are indicated for empiric therapy in patients with severe illness; this includes empiric treatment for patients with infective endocarditis, sepsis, complicated intraabdominal infections, and complicated genitourinary infections.  Typically, in these settings, aminoglycosides should not be used for more than 2 days, due to toxicity to the patient. 

For directed treatment, aminoglycosides may be used for longer than 48 hours. They are part of directed combination treatment for brucellosis, listeriosis, CNS nocardiosis, and Pseudomonas aeruginosa infection.  Aminoglycosides monotherapy is for tularemia, resistant mycobacteria, bacteremia caused by Campylobacter and Yersinia, and drug-resistant gram-negative pathogens. The Infectious Diseases Society of America Guidelines should be referenced to see if an aminoglycoside is a correct agent to use for a particular patient.[1][2]

Mechanism of Action

Aminoglycosides have bactericidal activity in which they bind to the bacteria ribosomal 30S subunit.  Specifically, they are believed to bind to the A-site on the 16S rRNA, a component of the ribosomal 30S subunit.  Through this binding, the genetic code gets misread, and the translation is disrupted, leading to the bacteria being unable to carry out protein synthesis.[3][4]

Administration

Depending on the aminoglycoside chosen, the administration can be oral, parenteral, inhalation, intraperitoneal, or intraventricular.  These agents are most commonly administered parenterally; gentamicin, amikacin, and tobramycin are the most frequently used aminoglycosides administered via the parenteral route.[1]  Tobramycin may be inhaled using a nebulizer for cystic fibrosis patients experiencing pulmonary exacerbation from infection.[5]  Aminoglycosides taken orally are paromomycin and neomycin because they are not able to be absorbed systemically; these two aminoglycosides demonstrate intraluminal activity in the bowel.  Furthermore, gentamicin is an aminoglycoside which can be administered intraperitoneally and intraventricularly.  Intraperitoneal administration of gentamicin is useful in peritoneal dialysis patients who develop peritonitis.[6]  Gentamicin administration intraventricularly has proved helpful in central nervous system infections.[7]

Adverse Effects

The main noted adverse effects of aminoglycosides are ototoxicity, nephrotoxicity, and neuromuscular blockade.  Therefore, patients should be educated to look out for warning signs of these adverse effects before the initiation of aminoglycoside therapy.[1]

Aminoglycoside-induced ototoxicity has been reported to occur in 2 to 45% of adults.  The ototoxicity can be vestibular and/or cochlear and is typically dose-dependent. Gentamicin, streptomycin, and tobramycin more commonly cause vestibular damage while amikacin and kanamycin result in more cochlear damage.[8]  Studies have found that aminoglycosides seem to create reactive oxygen species within the inner ear; this, in turn, causes damage to the vestibular and cochlear sensory cells along with cochlear neurons. Often the vestibular loss is salvageable while hearing loss is irreversible.[9][10]

Nephrotoxicity due to aminoglycosides may appear in up to 10 to 25% of patients.  In patients receiving aminoglycoside therapy, renal tubular toxicity, decreased blood flow to the kidneys, and reduced GFR most commonly causes the nephrotoxicity seen. Renal effects with aminoglycosides generally are reversible.  Furthermore, there are risk factors associated with the development of aminoglycoside-induced nephrotoxicity including dehydration, pregnancy, and hepatic dysfunction.  Taking other medications concurrently with aminoglycosides that can cause nephrotoxicity, such as NSAIDs, cyclosporine, and diuretics, also put a patient at risk for renal problems.  It is important to monitor patient renal function when taking aminoglycosides.[11][12]

Aminoglycosides have also demonstrated correlations with neuromuscular blockade. Although this is less common than ototoxicity and nephrotoxicity, patients with diseases affecting the neuromuscular junction and patients using medications prolonging neuromuscular blockade, most notably calcium channel blockers, should be cautious when using aminoglycosides.[13][14]

Contraindications

Aminoglycosides should be avoided in patients with myasthenia gravis because of the risk of prolonged neuromuscular blockade.

Monitoring

Therapeutic drug monitoring is necessary with aminoglycosides to optimize patient outcome and limit toxicity.  However, there is no universal agreement on the method of monitoring.  Therapeutic drug monitoring has shown to reduce hospital stay duration and toxicities.  Studies also suggest that therapeutic drug monitoring reduces mortality. It is important to note that monitoring clearance should be considered in critically ill, burn, and obese patients due to their abnormal distribution volume.[15]

For toxicity purposes, renal function and cochlear function require monitoring. Serial audiometry may be considered to prevent irreversible hearing loss.  Additionally, monitoring serum creatinine must be done to assess for nephrotoxicity in patients requiring aminoglycoside therapy.[9][11]

Toxicity

There is no antidote for toxicities of aminoglycosides.  However, agents with protective effects on the ear and kidney may help prevent aminoglycoside-induced toxicity.  In particular, N-acetylcysteine demonstrates promising protective effects on patients using aminoglycosides.[16]

Enhancing Healthcare Team Outcomes

Evaluating the need for aminoglycoside therapy requires a holistic approach by a team of professional individuals, including but not limited to physicians, specialists, nurses, pharmacists, laboratory technologists, audiometric technicians, and social workers, to achieve optimal outcomes. [Level V] Physicians and pharmacists have a critical role in determining the need for empiric treatment or directed treatment with an aminoglycoside.  Both healthcare professionals need to utilize communication and their expertise to determine if and which aminoglycoside is necessary, what is the correct dosing, and what is the optimal duration of therapy.  Therapeutic dose monitoring should also be done for the patient to achieve the best results with aminoglycoside treatment. When in the hospital, it is imperative for nurses to assess for any toxicities developing in a patient.  Because toxicity outcome typically depends on early detection, healthcare professionals need to monitor patients for any adverse signs and communicate with the team for the next step in therapy.  Laboratory technologists and audiometric technicians are essential for checking serum creatinine in all patients and performing audiometry. Lastly, the role of a social worker is significant in preparing a patient for discharge while still on aminoglycoside therapy.  All professionals have their roles to play in the team, making communication and collaboration key in providing patients with the best outcome possible.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Aminoglycosides - Questions

Take a quiz of the questions on this article.

Take Quiz
Aminoglycosides are indicated for the empirical treatment of any diseases such as infectious endocarditis and sepsis. They are often utilized in combination therapy as well. However, when used alone they are effective in treating infections caused by Yersinia pestis, Francisella tularensis, and Campylobacter. Based on infections aminoglycosides can be used for with monotherapy, what the major therapeutic target of aminoglycoside antibiotics?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 17-year-old patient presents with tularemia and is put on the first-line antibiotic. Which of the following is an adverse effect the patient could experience due to this antibiotic?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with third-degree burns to 20% of his body is started on cephalosporin. The provider does not recommend starting an aminoglycoside at the same time as it will increase the risk for which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 45-year-old male presents to the floor with confusion and fatigue. Physical examination demonstrates a flapping tremor of the hands. Upon further investigation, the patient is found to have elevated ammonia levels. Which of the following medications can be used orally for the treatment of this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
An 8-year-old girl was doing well in school until recently. Seven months ago, the patient had a urinary tract infection with associated hydronephrosis treated gentamicin for 3 weeks. What is the most likely cause of her decline in functioning at school?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 37-year-old female is admitted to the floor for severe sepsis. After much discussion about treatment options, the provider decides to treat her empirically with amikacin. Where does amikacin initially act against bacteria?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 12-month-old baby has an audiogram is done and shows a hearing loss of more than 60 dB compared to 2 months ago. The parents want to know what may be the cause of this since he has been meeting his milestones at all his well child checks thus far. What is the most likely cause for the hearing loss in this infant?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 33-year-old female with a past medical history of cystic fibrosis presents with a respiratory infection due to Pseudomonas aeruginosa. She is prescribed tobramycin and her infection eventually resolves. Which is the mechanism of action of tobramycin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Obtaining aminoglycoside levels in patients is very important due to toxicities that may be experienced by a patient. Levels need to be monitored especially in those who may have increased or decreased clearance rates. When should peak aminoglycoside levels be obtained?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 20-year-old male comes into the clinic complaining of decreased urine output and lower extremity edema. He has been treated for a week with streptomycin for an infection. Physical examination shows mild bilateral edema of the feet and ankles. Vital signs are within normal limits. A complete blood count and basic metabolic panel are drawn. Lab results are significant for elevated BUN and creatinine, demonstrating likely nephrotoxicity due to streptomycin use. Other than nephrotoxicity, which of the following is a major adverse effect associated with aminoglycoside use?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 17-year-old female admitted to the hospital is found to have an infection caused by Yersinia enterocolitica. Yersinia enterocolitica is commonly treated with a combination of doxycycline with another particular class of antibiotics. The patient tolerates the doxycycline well but demonstrates a common adverse effect due to the other class of antibiotics she was given. What is the most likely adverse effect she is experiencing?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient is treated with gentamicin for an infection, but levels become toxic despite standard dosing. Which patients typically require an extended interval of more than 8 hours when dosing aminoglycosides?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Most protein synthesis-inhibiting drugs are bacteriostatic. However, one of the drug classes of drugs in this list inhibits protein synthesis and is bacteriocidal against certain types of bacteria. Which one of the following is bactericidal and not merely an inhibitor of bacterial replication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
An otherwise healthy 25-year-old male has severe hearing loss, resulting in the use of hearing aids in both ears. On further questioning, the man reveals that he suffered a sudden hearing loss from an antibiotic he received for a severe infection while in high school. What drug or drug class was most likely the causative agent?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Aminoglycosides - References

References

Avent ML,Rogers BA,Cheng AC,Paterson DL, Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity. Internal medicine journal. 2011 Jun;     [PubMed]
Pagkalis S,Mantadakis E,Mavros MN,Ammari C,Falagas ME, Pharmacological considerations for the proper clinical use of aminoglycosides. Drugs. 2011 Dec 3;     [PubMed]
Kotra LP,Haddad J,Mobashery S, Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrobial agents and chemotherapy. 2000 Dec;     [PubMed]
Krause KM,Serio AW,Kane TR,Connolly LE, Aminoglycosides: An Overview. Cold Spring Harbor perspectives in medicine. 2016 Jun 1;     [PubMed]
Smith S,Rowbotham NJ,Charbek E, Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. The Cochrane database of systematic reviews. 2018 Oct 30;     [PubMed]
Ranganathan D,Varghese JM,Fassett RG,Lipman J,D'Intini V,Healy H,Roberts JA, Optimising intraperitoneal gentamicin dosing in peritoneal dialysis patients with peritonitis (GIPD) study. BMC nephrology. 2009 Dec 16;     [PubMed]
LeBras M,Chow I,Mabasa VH,Ensom MH, Systematic Review of Efficacy, Pharmacokinetics, and Administration of Intraventricular Aminoglycosides in Adults. Neurocritical care. 2016 Dec;     [PubMed]
Selimoglu E, Aminoglycoside-induced ototoxicity. Current pharmaceutical design. 2007;     [PubMed]
Guthrie OW, Aminoglycoside induced ototoxicity. Toxicology. 2008 Jul 30;     [PubMed]
Leis JA,Rutka JA,Gold WL, Aminoglycoside-induced ototoxicity. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2015 Jan 6;     [PubMed]
Wargo KA,Edwards JD, Aminoglycoside-induced nephrotoxicity. Journal of pharmacy practice. 2014 Dec;     [PubMed]
Lopez-Novoa JM,Quiros Y,Vicente L,Morales AI,Lopez-Hernandez FJ, New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney international. 2011 Jan;     [PubMed]
Del Pozo E,Baeyens JM, Effects of calcium channel blockers on neuromuscular blockade induced by aminoglycoside antibiotics. European journal of pharmacology. 1986 Aug 22;     [PubMed]
Barrons RW, Drug-induced neuromuscular blockade and myasthenia gravis. Pharmacotherapy. 1997 Nov-Dec;     [PubMed]
Roberts JA,Norris R,Paterson DL,Martin JH, Therapeutic drug monitoring of antimicrobials. British journal of clinical pharmacology. 2012 Jan;     [PubMed]
Vural A,Koçyiğit İ,Şan F,Eroğlu E,Ketenci İ,Ünal A,Tokgöz B,Ünlü Y, Long-Term Protective Effect of N-Acetylcysteine against Amikacin-Induced Ototoxicity in End-Stage Renal Disease: A Randomized Trial. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 2018 Jan-Feb;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Family Medicine. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Family Medicine, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Family Medicine, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Family Medicine. When it is time for the Family Medicine board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Family Medicine.