Antimicrobial Agents in the Treatment of Infectious Disease
(This chapter has 6 pages)
© Kenneth Todar, PhD
Protein synthesis inhibitors
Many therapeutically useful antibiotics owe their action to inhibition of some step in the complex process of protein synthesis. Their attack is always at one of the events occurring on the ribosome and never at the stage of amino acid activation or attachment to a particular tRNA. Most have an affinity or specificity for 70S (as opposed to 80S) ribosomes, and they achieve their selective toxicity in this manner. The most important antibiotics with this mode of action are the tetracyclines, chloramphenicol, the macrolides (e.g. erythromycin) and the aminoglycosides (e.g. streptomycin).
The aminoglycosides are products of Streptomyces species and are represented by streptomycin, kanamycin, tobramycin and gentamicin. These antibiotics exert their activity by binding to bacterial ribosomes and preventing the initiation of protein synthesis.
Streptomycin binds to 30S subunit of the bacterial ribosome, specifically to the S12 protein which is involved in the initiation of protein synthesis. Experimentally, streptomycin has been shown to prevent the initiation of protein synthesis by blocking the binding of initiator N-formylmethionine tRNA to the ribosome. It also prevents the normal dissociation of ribosomes into their subunits, leaving them mainly in their 70S form and preventing the formation of polysomes. The overall effect of streptomycin seems to be one of distorting the ribosome so that it no longer can carry out its normal functions. This evidently accounts for its antibacterial activity but does not explain its bactericidal effects, which distinguishes streptomycin and other aminoglycosides from most other protein synthesis inhibitors.
Streptomycin is the first aminoglycoside antibiotic to be discovered, and was the first antibiotic to be used in treatment of tuberculosis. It was discovered in 1943, in the laboratory of Selman Waksman at Rutgers University. Waksman and his laboratory discovered several antibiotics, including actinomycin, streptomycin, and neomycin. Streptomycin is derived from the bacterium, Streptomyces griseus. Streptomycin stops bacterial growth by inhibiting protein synthesis. Specifically, it binds to the 16S rRNA of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit. This prevents initiation of protein synthesis.
Kanamycin and tobramycin have been reported to bind to the ribosomal 30S subunit and to prevent it from joining to the 50S subunit during protein synthesis. They may have a bactericidal effect because this leads to cytoplasmic accumulation of dissociated 30S subunits, which is apparently lethal to the cells.
Aminoglycosides have been used against a wide variety of bacterial infections caused by Gram-positive and Gram-negative bacteria. Streptomycin has been used extensively as a primary drug in the treatment of tuberculosis. Gentamicin is active against many strains of Gram-positive and Gram-negative bacteria, including some strains of Pseudomonas aeruginosa. Kanamycin is active at low concentrations against many Gram-positive bacteria, including penicillin-resistant staphylococci. Gentamicin and Tobramycin are mainstays for treatment of Pseudomonas infections. An unfortunate side effect of aminoglycosides has tended to restrict their usage: prolonged use is known to impair kidney function and cause damage to the auditory nerves leading to deafness.
Gentamicin is an aminoglycoside antibiotic, used mostly to treat Gram-negative infections. However, it is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila infections. It is synthesized by Micromonospora, a genus of Gram-positive bacteria widely distributed in water and soil. Like all aminoglycosides, when gentamicin is given orally, it is not systemically active because it is not absorbed to any appreciable extent from the small intestine. It is useful in treatment of infections caused by Pseudomonas aeruginosa.
The tetracyclines consist of eight related antibiotics which are all natural products of Streptomyces, although some can now be produced semisynthetically or synthetically. Tetracycline, chlortetracycline and doxycycline are the best known. The tetracyclines are broad-spectrum antibiotics with a wide range of activity against both Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa is less sensitive but is generally susceptible to tetracycline concentrations that are obtainable in the bladder. The tetracyclines act by blocking the binding of aminoacyl tRNA to the A site on the ribosome. Tetracyclines inhibit protein synthesis on isolated 70S or 80S (eucaryotic) ribosomes, and in both cases, their effect is on the small ribosomal subunit. However, most bacteria possess an active transport system for tetracycline that will allow intracellular accumulation of the antibiotic at concentrations 50 times as great as that in the medium. This greatly enhances its antibacterial effectiveness and accounts for its specificity of action, since an effective concentration cannot be accumulated in animal cells. Thus a blood level of tetracycline which is harmless to animal tissues can halt protein synthesis in invading bacteria.
The tetracyclines have a remarkably low toxicity and minimal side effects when taken by animals. The combination of their broad spectrum and low toxicity has led to their overuse and misuse by the medical community and the wide-spread development of resistance has reduced their effectiveness. Nonetheless, tetracyclines still have some important uses, such as the use of doxycycline in the treatment of Lyme disease.
Some newly discovered members of the tetracycline family (e.g. chelocardin) have been shown to act by inserting into the bacterial membrane, not by inhibiting protein synthesis.
The tetracycline core structure. The tetracyclines are a large family of antibiotics that were discovered as natural products of Streptomyces bacteria beginning in the late 1940s. Tetracycline sparked the development of many chemically altered antibiotics and in doing so has proved to be one of the most important discoveries made in the field of antibiotics. It is a classic “broad-spectrum antibiotic” used to treat infections caused by Gram-positive and Gram-negative bacteria and some protozoa.
Doxycycline is a semisynthetic tetracycline developed in the 1960s. It is frequently used to treat chronic prostatitis, sinusitis, syphilis, chlamydia, pelvic inflammatory disease, acne and rosacea. In addition, it is used in the treatment and prophylaxis of anthrax and in prophylaxis against malaria. It is also effective against Yersinia pestis (the infectious agent of bubonic plague) and is prescribed for the treatment of Lyme disease, ehrlichiosis and Rocky Mountain spotted fever. Because doxycycline is one of the few medications that is effective in treating Rocky Mountain spotted fever (with the next best alternative being chloramphenicol), it is indicated even for use in children for this illness.
Chloramphenicol is a protein synthesis inhibitor that has a broad spectrum of activity but it exerts a bacteriostatic effect. It is effective against intracellular parasites such as the rickettsiae. Unfortunately, aplastic anemia develops in a small proportion (1/50,000) of patients. Chloramphenicol was originally discovered and purified from the fermentation of a Streptomyces species, but currently it is produced entirely by chemical synthesis. Chloramphenicol inhibits the bacterial enzyme peptidyl transferase, thereby preventing the growth of the polypeptide chain during protein synthesis.
Chemical structure of chloramphenicol
Chloramphenicol is entirely selective for 70S ribosomes and does not affect 80S ribosomes. Its unfortunate toxicity towards the small proportion of patients who receive it is in no way related to its effect on bacterial protein synthesis. However, since mitochondria originated from procaryotic cells and have 70S ribosomes, they are subject to inhibition by some of the protein synthesis inhibitors including chloramphenicol. This likely explains the toxicity of chloramphenicol. The eucaryotic cells most likely to be inhibited by chloramphenicol are those undergoing rapid multiplication, thereby rapidly synthesizing mitochondria. Such cells include the blood forming cells of the bone marrow, the inhibition of which could present as aplastic anemia. Chloramphenicol was once a highly prescribed antibiotic and a number of deaths from anemia occurred before its use was curtailed. Now it is seldom used in human medicine except in life-threatening situations (e.g. typhoid fever).
The macrolide family of antibiotics is characterized by structures that contain large lactone rings linked through glycoside bonds with amino sugars. The most important members of the group are erythromycin and oleandomycin. Erythromycin is active against most Gram-positive bacteria, Neisseria, Legionella and Haemophilus, but not against the Enterobacteriaceae. Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. Binding inhibits elongation of the protein by peptidyl transferase or prevents translocation of the ribosome or both. Macrolides are bacteriostatic for most bacteria but are cidal for a few Gram-positive bacteria.
Chemical structure of a macrolide antibiotic, erythromycin.
Azithromycin, shown above, is a subclass of macrolide antibiotics. Azithromycin is one of the world’s best-selling antibiotics. It is s derived from erythromycin, but it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring, thus making the lactone ring 15-membered. Azithromycin is used to treat certain bacterial infections, most often bacteria causing middle ear infections, tonsillitis, throat infections, laryngitis, bronchitis, pneumonia and sinusitis. It is also effective against certain sexually transmitted diseases, such as non-gonococcal urethritis and cervicitis.
Lincomycin and clindamycin are a miscellaneous group of protein synthesis inhibitors with activity similar to the macrolides. Lincomycin has activity against Gram-positive bacteria and some Gram-negative bacteria (Neisseria, H. influenzae). Clindamycin is a derivative of lincomycin with the same range of antimicrobial activity, but it is considered more effective. It is frequently used as a penicillin substitute and is effective against Gram-negative anaerobes (e.g. Bacteroides).
Clindamycin is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria. It is a common topical treatment for acne, and can be useful against some methicillin-resistant Staphylococcus aureus (MRSA) infections. The most severe common adverse effect of clindamycin is Clostridium difficile-associated diarrhea (the most frequent cause of pseudomembranous colitis). Although this side-effect occurs with almost all antibiotics, including beta-lactam antibiotics, it is classically linked to clindamycin use.
- What Are Aminoglycosides?
- Warnings and Precautions
- Common Side Effects
- Drug Interactions
- Aminoglycoside Antibiotics
- Adverse Effects from Gentamicin and Other Aminoglycosides
- Adverse Effects from Gentamicin and Other Aminoglycosides, Including Impact on Daily Living Activities
- AMINOGLYCOSIDES (Systemic)
- Further information
What Are Aminoglycosides?
These antibiotics are used mainly to treat serious infections in a clinical setting.
Aminoglycosides are a class of antibiotics used to treat serious infections caused by bacteria that either multiply very quickly or are difficult to treat.
Aminoglycosides are called bactericidal antibiotics because they kill bacteria directly. They accomplish this by stopping bacteria from producing proteins needed for their survival.
Because aminoglycosides are normally used to treat serious infections, they are typically administered into the veins of the body (intravenously, or IV).
However, some aminoglycosides can be taken orally, or as ear or eye drops.
Examples of aminoglycosides include:
- Gentamicin (generic version is IV only)
- Amikacin (IV only)
- Gentak and Genoptic (eye drops)
- Neo-Fradin (oral)
- Neomycin (generic version is IV only)
Warnings and Precautions
Avoid aminoglycosides if you’re allergic to them or any inactive ingredients these drugs may contain.
Also, you might want to ask your doctor about aminoglycosides if you:
- Are allergic to sulfites (often found in certain wines and dried fruits)
- Have kidney or hearing problems, including problems with balance and uncontrollable eye movements
- Have a disorder affecting the nerves and muscles, like multiple sclerosis or myasthenia gravis.
- Are 65 years of age or older
- You have a newborn or very young baby who might be treated for a serious infection using aminoglycosides
Common Side Effects
Aminoglycosides are very powerful antibiotics, and their side effects can be severe — especially when taken by mouth or IV.
The Food and Drug Administration (FDA) has issued black-box warnings for aminoglycosides taken orally or intravenously, noting the following possible side effects:
- Damage to the hearing structures in the ear, resulting in hearing loss
- Damage to the inner ear, resulting in trouble maintaining balance
- Kidney damage (noted by protein in the urine, dehydration, and low levels of magnesium)
- Paralysis of skeletal muscles
Although side effects and their severity may vary from person to person, the higher the dose of an aminoglycoside you receive, or the longer the duration of use, the greater your risk of side effects.
Don’t take aminoglycosides by mouth or intravenously if you’re already taking:
- Theracrys (BCG live intravesical)
- Vistide (cidofovir)
- Zanosar (streptozocin)
Ask your doctor about aminoglycosides if you’re already taking “water pills” known as loop diuretics, such as Lasix (furosemide) or Demadex (torsemide).
Talk to your doctor about aminoglycosides if you’re about to undergo surgery.
Certain drugs called neuromuscular blocking agents, often used to prevent patients from moving during surgery, enhance some of the side effects of aminoglycosides.
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- Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, Williams-Warren J, Vasiljev-K M, Borowitz D, Bowman CM, Marshall BC, et al. 1999. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med 340: 23–30.
- Rather PN, Orosz E, Shaw KJ, Hare R, Miller G. 1993. Characterization and transcriptional regulation of the 2′-N-acetyltransferase gene from Providencia stuartii. J Bacteriol 175: 6492–6498.
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- Roos D, Dijksman LM, Tijssen JG, Gouma DJ, Gerhards MF, Oudemans-van Straaten HM. 2013. Systematic review of perioperative selective decontamination of the digestive tract in elective gastrointestinal surgery. Br J Surg 100: 1579–1588.
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- Skeggs PA, Thompson J, Cundliffe E. 1985. Methylation of 16S ribosomal RNA and resistance to aminoglycoside antibiotics in clones of Streptomyces lividans carrying DNA from Streptomyces tenjimariensis. Mol Gen Genet 200: 415–421.
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- Taber HW, Mueller JP, Miller PF, Arrow AS. 1987. Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev 51: 439–457.
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- Thompson J, Skeggs PA, Cundliffe E. 1985. Methylation of 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Micromonospora purpurea. Mol Gen Genet 201: 168–173.
- Vakulenko SB, Mobashery S. 2003. Versatility of aminoglycosides and prospects for their future. Clin Microbiol Rev 16: 430–450.
- Wachino J, Arakawa Y. 2012. Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: An update. Drug Resist Updat 15: 133–148.
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- Project Information
- Historical Perspectives
- The Pre-Antibacterial Era
- The Golden Age of Antibacterials
- What Lies Beyond?
- Antimicrobials: An Introduction
- Spectrum of Activity
- Effect on Bacteria
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- Antibiotics of Veterinary Importance
- Beta Lactam Antibiotics
- Diaminopyrimidines (Trimethoprim)
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- Antimicrobial Resistance
- Bacterial Resistance Strategies
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- Strategy 1: Preventing Access
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- Molecular Basis for Antimicrobial Resistance
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- I. Introduction
- Examples of Antimicrobials Important in Human Medicine Being Used for Animal Treatment, Metaphylaxis or Growth Promotion
- Figure 2. Possible Spread of Antibiotic-Resistant Bacteria from Animals to Humans.
- II. The Human Health Impact Of Antimicrobial Resistance In Animal Populations
- A. Increased human morbidity
- B. Increased human mortality
- C. Reduced efficacy to related antibiotics used in human medicine
- D. Increased human healthcare costs
- E. Increased carriage and dissemination
- F. Facilitated emergence of resistance in human pathogens
- III. The environmental impact of imprudent antimicrobial use in animals
- A. Veterinary antibiotics in soil
- B. Veterinary antibiotics in water
- C. Effects on other ecosystems
- IV. The Global Health Impact Of Antimicrobial Resistance In Animal Populations
- Veterinary-related Factors Influencing the Global Spread of AMR
- National and International AMR Programs
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- Integrated Principals
- 1. Purpose and Goals
- 2. Introduction
- 3. Mechanisms of resistance
- 4. The public health officer
- 5. Salmonella epidemiology
- 6. Food History
- 7. Small Animal Clinic
- 8. The physical exam
- 9. Simon the cat
- 10. Horse exposure
- 11. Farm biosecurity
- 12. Use of antibiotics
- 13. At the micro lab
- 14. Selecting an antibiotic
- 15. Empiric Therapy
- 16. Pharmacology
- 17. Using MIC values
- 18. Case Wrap-up
- 19. Antimicrobials and agriculture
- 20. Salmonella resistance
- Resistance: Animal to Human (2 of 2)
- 21. Conclusion
- 22. Epilog
- The Hunt for Ella Salmonella
- The Hunt for Ella Salmonella Book II
- Global Perspectives – The Danish Experiment:
- Integrated Principals
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- Dairy Cattle
- Medicated Milk Replacer
- 1. Farm Background
- 2. Farm Tour
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- 4. Calf Management
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- 6. MMR Frequency of Use
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- Neonatal Scours, Antibiotics and Dairy Calves
- 1. Intro to Neonatal Scours, Antibiotics and Dairy Calves
- 2. Farm Background
- 3. Calf Management
- 4. What next?
- 5. Scours History
- 6. Calf Records
- 7. Farm Tour
- 8. Physical Exam
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- 13. Fluid Administration
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- 15. Colostrum Management
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- 18. Laboratory Results
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- Model Mastitis Control Program
- Contagious Mastitis Control in Dairy Cows
- 1. Contagious Mastitis
- 2. Contagious Mastitis
- 3. Contagious Mastitis
- 4. Contagious Mastitis
- Contagious Mastitis 5
- 6. Contagious Mastitis
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- 12. Contagious Mastitis
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- Cows to Culture
- Cows to Culture
- 14. Contagious Mastitis
- 15. Mastitis Treatment and Prevention
- 16. Summary
- 17. References
- Medicated Milk Replacer
- Beef Cattle
- Regression to the Mean and Antibiotic Efficacy
- Antibiotics and Bovine Respiratory Disease:
- 1. Introduction to Bovine Respiratory Disease (BRD)
- 2. Cow-calf BRD
- 3. Bovine Respiratory Disease Prevention
- 4. Opportunistic Agents
- 5. Preconditioning
- 6. Preventing BRD
- 7. Feedlot
- 8. Diagnosis
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- 10. Management Summary
- 11. Study questions
- Pet Animals
- Antimicrobial Use and Resistance In Companion Animal Medicine
- 1. Introduction to Antimicrobial Use In Small Animals
- 2. Scenario
- 3. Antimicrobial use in small animal practice.
- 4. Classes and types of antimicrobials used in small animal practice.
- 5. Antimicrobial use and antimicrobial resistance.
- 6. Improving antimicrobial use
- 7. Wrap up
- 8. Reference List
- Rodent Multiple-Drug Resistant Salmonella Outbreak
- 1. Index Case
- 2. Initial Questions
- 3. Interview
- 4. Necropsy
- 5. Rodent Salmonella Outbreak
- 6. PFGE
- 7. Control Questions
- 8. Source Identification
- 9. Control Measures
- 10. Additional Cases
- 11. Pocket Pet Industry
- 12. Rodent Antibiotics
- 13. Salmonella & Antibiotics
- 14. Public Awareness
- 15. Antibiotic Summary
- 16. Traceback Diagram
- 17. Conclusions
- Canine Pyoderma Teaching Module
- 2. Introduction
- 3. Differential Diagnoses
- 4. Physical Examination
- 5. Diagnostic Tests
- 6. More Diagnostic Testing
- 7. Laboratory Findings
- 8. Initial Treatment
- 9. Choosing an Antibiotic
- 10. Clinical Response to Treatment
- 11. Culture and Susceptibility Testing
- 12. Sensitivity Results and Summary
- Antibiotic Use in Feline Urinary Tract Disease
- 01 Introduction
- 02 Questions to ask
- 03 Physical examination
- 04 Narrowing your differentials
- 05 Diagnostic Tests
- 06 Sample Collection
- 07 Cystocentesis
- 08 Sample problems
- 09 Getting a sample
- 10 Results
- 11 Diagnosis
- 12 What to do next?
- 13 Culture
- 14 Initial Treatment
- 15 Culture Results
- 16 Diagnosis
- 17 How to proceed?
- 18 Treatment Plan
- 19 Update
- 20 References
- Antimicrobial Use and Resistance In Companion Animal Medicine
- Equine Upper Respiratory Infections
- 1. Talking with the Owner
- 2. Physical Exam
- 3. Treatment Record for Cowboy
- 4. Rounds
- Equine Upper Respiratory Infections
- Post-Weaning Scours in Pigs
- 01 Setup
- 02 Clinical Signs-Post Mortem Exam Results
- 03 Clinical Diagnosis
- 04 Immediate Therapy implemented
- 05 VCPR-PQA
- 06 Diagnostic submission
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- 08 Optional Reading and Resources
- 09 Follow-up check on the farm’s clinical picture.
- 10 Prevention plan created
- 11 What will we do going forward and what would the result likely be?
- 12 Additional Resources
- Post-Weaning Scours in Pigs
- Dairy Cattle
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Adverse Effects from Gentamicin and Other Aminoglycosides
Aminoglycosides are known to cause ototoxic damage, vestibulo-toxic impairments, nephrotoxicity (kidney damage), and encephalopathy. If you have been adversely affected by aminoglycosides you may want to participate in this survey.
Adverse Effects from Gentamicin and Other Aminoglycosides, Including Impact on Daily Living Activities
Aminoglycosides are a class of drugs that are particularly potent against gram-negative bacteria, but are known to have toxic effects on some patients. This class of drugs includes gentamicin, tobramycin, neomycin, streptomycin, amikacin, kanamycin, netilmicin, and paromomycin. The medication may be given orally, as eardrops, topically, and perhaps most effectively intravenously or intramuscularly. This class of medications are effective against other types of bacteria, but because of the potential toxic effects of these drugs, they are usually reserved for specific types of infections.
People who have been damaged by aminoglycosides, particularly gentamicin, often experience a multitude of symptoms, have difficulty being diagnosed, and must learn to adapt to permanent damage and resultant limitations. It is well known that these drugs have the potential to cause hearing loss, vestibular damage, vision problems, kidney damage (nephrotoxicity), and some research exists documenting problems with thinking (cognitive impairment) when the vestibular system is damaged. Of course, a person suffering from any health problem may also experience emotional struggles as they learn to adapt to permanent limitations.
The purpose of this study is to explore the day to day limitations reported by people who have had an adverse effect from gentamicin and other drugs in the aminoglycoside family. It incorporates questions from the World Health Organization’s Disability Schedule, along with a list of general impairments and limitations that have been developed by an online group of patients who reported their day to day struggles living without a sense of balance. Many vestibular researchers focus on dizziness or vertigo which is not always present with patients damaged by aminoglycosides. When the vestibular system is damaged, people can lose a sense of where their body is in space, which is known as proprioception. When other senses are impaired, such as in the dark, a person without a fully functioning vestibular system may fall. This study also explores other symptoms drawn from adverse-reporting sites for these drugs and also explores health conditions that arose after the administration of aminoglycosides in order to look for other common health issues in these patients.
If you have been adversely affected by aminoglycosides and would like to participate in this survey, please
Aminoglycosides are known to cause ototoxic damage, vestibulo-toxic impairments, nephrotoxicity (kidney damage), and encephalopathy. These four categories are discussed below.
Ototoxicity refers to damage usually caused by medications that damage the inner ear, including the cochlea, vestibule, semicircular canals and otoliths (1). The results of this toxic damage include hearing loss, tinnitus, dizziness, and balance impairment. Although the ototoxic results of aminoglycosides have been demonstrated, the exact mechanism of the damage they cause is still a subject of research. Sensory hair cells within the ear canal die, but the exact reason why this occurs and how it might be prevented are current topics of interest to researchers. (2)
The vestibular system itself is composed of the both peripheral and central vestibular components. The ear canals and the otolithic organs within the ear are constantly picking up sensory information and relaying it to the central vestibular system, which also receives information from our vision and proprioceptive input to let us retain balance as we walk and move (3). Damage can occur both to the peripheral vestibular system and the central vestibular system. The central vestibular system includes parts of the brain and brainstem that process information obtained from the peripheral vestibular system regarding balance and spatial orientation. Those with damage to the central vestibular system may not experience vertigo, but instead have more difficulty with balance and exhibit ataxia, which is the medical term for an abnormal gait when walking (3).
Aminoglycosides are also well known to cause nephrotoxicity (kidney damage) although this can usually be reversed. Methods of preventing such damage, which usually occurs when the medication is given intravenously, have not been completely successful in medical care (4). Currently, while giving gentamicin and/or a combination of aminoglycosides intravenously the patient’s creatinine levels are monitored to protect the kidneys. But this does not eliminate potential damage to susceptible patients. Exactly why certain patients are more susceptible to kidney damage is unclear. No dose of gentamycin is safe (5).
Encephalopathy is a term used to describe a malfunction in the brain caused by some other agent, such as a neurotoxin, infection, impaired liver function, or other condition. Several studies have indicated that gentamicin may be involved in its development. Post-mortem findings in a patient who was given intrathecal (through the spinal cord) administration of gentamicin included brain lesions in multiple areas and damage to myelin sheaths. The authors of that study were able to reproduce those findings using rabbits (6). In a more recent report, a woman was given an overdose of gentamicin and developed myoclonus (involuntary muscle jerks or spasms), which abated when the intravenous administration of gentamicin was discontinued (7). Many patients with vestibular disorders from gentamicin report problems with memory and cognitive functions, such as the inability to multi-task and concentrate (8). A case study on a 9 year old boy reported encephalopathy after treatment with gentamicin (9). Aminoglycosides are toxic not only to hair cells in the inner ear, but also to the ganglia around the eighth cranial nerve. This damage is not instantaneous but understood to be an ongoing process of cell damage (10). Medical staff often do not notice the symptoms that develop as a result of gentamicin dosing, especially if the patient is confined to the bed. Because many medical practitioners are unaware of the signs of ototoxic or vestibular damage, checking patients for hearing loss or balance disorders often does not occur. In an Australian retrospective study, 103 patients were interviewed. Of those, twenty-one patients first noted symptoms while still receiving treatment with gentamicin, and only one reported that treatment was halted after their complaints (11).
On eHealthMe, over 8000 reports of side effects from the administration of gentamicin were listed. Encephalopathy was not identified, but conditions such as multi-organ failure, hypoesthesia (partial loss of sensation), and death were reported (12). A similar variety of symptoms were reported for other aminoglycosides. The purpose of this study is to have patients with aminoglycoside-induced impairments to complete the World Health Organization Disability Assessment Schedule 2.0 along with a list of symptoms they experienced and health conditions that arose after administration of this class of drugs. It is hoped that a compilation of the severity of impairments and daily living limitations might be helpful information for those who are seeking care from medical providers and dealing with insurance companies. If you have been adversely affected by aminoglycosides and would like to participate, please click on the link below.
To participate in the research survey, .
Name: Ann M. Kerlin, PhD
Assistant Professor of Counseling
Address: 3038 Evans Mill Road, Lithonia, GA 30038
Phone: 770-484-1204 ext. 5688
Some commonly used brand names are:
In the U.S.—
- Amikin 1
- Garamycin 2
- G-Mycin 2
- Jenamicin 2
- Kantrex 3
- Nebcin 7
- Netromycin 5
- Amikin 1
- Garamycin 2
- Nebcin 7
- Netromycin 5
For quick reference, the following aminoglycosides are numbered to match the corresponding brand names.
- Antibacterial, antimycobacterial—Streptomycin
- Antibacterial, systemic—Amikacin; Gentamicin; Kanamycin; Netilmicin; Streptomycin; Tobramycin
Aminoglycosides (a-mee-noe-GLYE-koe-sides) are used to treat serious bacterial infections. They work by killing bacteria or preventing their growth.
Aminoglycosides are given by injection to treat serious bacterial infections in many different parts of the body. In addition, some aminoglycosides may be given by irrigation (applying a solution of the medicine to the skin or mucous membranes or washing out a body cavity) or by inhalation into the lungs. Streptomycin may also be given for tuberculosis (TB). These medicines may be given with 1 or more other medicines for bacterial infections, or they may be given alone. Aminoglycosides may also be used for other conditions as determined by your doctor. However, aminoglycosides will not work for colds, flu, or other virus infections.
Aminoglycosides given by injection are usually used for serious bacterial infections for which other medicines may not work. However, aminoglycosides may also cause some serious side effects, including damage to your hearing, sense of balance, and kidneys. These side effects may be more likely to occur in elderly patients and newborn infants. You and your doctor should talk about the good these medicines may do as well as the risks of receiving them .
Aminoglycosides are to be administered only by or under the immediate supervision of your doctor. They are available in the following dosage forms:
- Irrigation solution (U.S.)
Before Receiving This Medicine
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For aminoglycosides, the following should be considered:
Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to any of the aminoglycosides. Also tell your health care professional if you are allergic to any other substances, such as foods, sulfites, or other preservatives.
Pregnancy—Studies on most of the aminoglycosides have not been done in pregnant women. Some reports have shown that aminoglycosides, especially streptomycin and tobramycin, may cause damage to the infant’s hearing, sense of balance, and kidneys if the mother was receiving the medicine during pregnancy. However, this medicine may be needed in serious diseases or other situations that threaten the mother’s life. Be sure you have discussed this with your doctor.
Breast-feeding—Aminoglycosides pass into breast milk in small amounts. However, they are not absorbed very much when taken by mouth. To date, aminoglycosides have not been reported to cause problems in nursing babies.
Children—Children are especially sensitive to the effects of aminoglycosides. Damage to hearing, sense of balance, and kidneys is more likely to occur in premature infants and neonates.
Older adults—Elderly people are especially sensitive to the effects of aminoglycosides. Serious side effects, such as damage to hearing, sense of balance, and kidneys may occur in elderly patients.
Other medicines—Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving aminoglycosides it is especially important that your health care professional knows if you are taking any of the following:
Other medical problems—The presence of other medical problems may affect the use of the aminoglycosides. Make sure you tell your doctor if you have any other medical problems, especially:
- Kidney disease—Patients with kidney disease may have increased aminoglycoside blood levels and increased chance of side effects
- Loss of hearing and/or balance (eighth-cranial-nerve disease)—High aminoglycoside blood levels may cause hearing loss or balance disturbances
- Myasthenia gravis or
- Parkinson’s disease—Aminoglycosides may cause muscular problems, resulting in further muscle weakness
Proper Use of This Medicine
To help clear up your infection completely, aminoglycosides must be given for the full time of treatment , even if you begin to feel better after a few days. Also, this medicine works best when there is a certain amount in the blood or urine. To help keep the correct level, aminoglycosides must be given on a regular schedule.
Dosing—The dose of aminoglycosides will be different for different patients. Follow your doctor’s orders or the directions on the label . The following information includes only the average doses of aminoglycosides. Your dose may be different if you have kidney disease. If your dose is different, do not change it unless your doctor tells you to do so.
The dose of most aminoglycosides is based on body weight and must be determined by your doctor. The medicine is injected into a muscle or vein. Depending on the aminoglycoside prescribed, doses are given at different times and for different lengths of time. These times are as follows:
- For amikacin
- For all dosage forms:
- Adults and children: The dose is given every eight or twelve hours for seven to ten days.
- Newborn babies: The dose is given every twelve hours for seven to ten days.
- Premature babies: The dose is given every eighteen to twenty-four hours for seven to ten days.
- For gentamicin
- For all dosage forms:
- Adults and children: The dose is given every eight hours for seven to ten days or more.
- Infants: The dose is given every eight to sixteen hours for seven to ten days or more.
- Premature and full-term newborn babies: The dose is given every twelve to twenty-four hours for seven to ten days or more.
- For kanamicin
- For all dosage forms:
- Adults and children: The dose is given every eight or twelve hours for seven to ten days.
- For netilmicin
- For all dosage forms:
- Adults and children: The dose is given every eight or twelve hours for seven to fourteen days.
- For streptomycin
- For all dosage forms—The dose of streptomycin is often not based on body weight and the amount given depends on the disease being treated.
- Treatment of tuberculosis (TB) :
- Adults: Dose is based on body weight and must be determined by your doctor. This dose is injected into a muscle. The dosing schedule will also be determined by your doctor, usually once daily or twice weekly or three times-a-week. This medicine must be given with other medicines for tuberculosis (TB).
- Children and adolescents: Dose is based on body weight and must be determined by your doctor. This dose is injected into a muscle. The dosing schedule will also be determined by your doctor, usually once daily or twice weekly or three times-a-week. This medicine must be given with other medicines for tuberculosis (TB).
- Treatment of bacterial infections :
- Adults: 250 to 500 milligrams of streptomycin is injected into a muscle every six hours; or 500 milligrams to 1 gram of streptomycin is injected into a muscle every twelve hours.
- Children and adolescents: Dose is based on body weight and must be determined by your doctor. This dose is injected into a muscle every six to twelve hours.
- Treatment of tuberculosis (TB) :
- For tobramycin
- For all dosage forms:
- Adults and adolescents: The dose is given every six to eight hours for seven to ten days or more.
- Older infants and children: The dose is given every six to sixteen hours.
- Premature and full-term newborn babies: The dose is given every twelve to twenty-four hours.
Side Effects of This Medicine
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your health care professional immediately if any of the following side effects occur:
Any loss of hearing; clumsiness or unsteadiness; dizziness; greatly increased or decreased frequency of urination or amount of urine; increased thirst; loss of appetite; nausea or vomiting; numbness, tingling, or burning of face or mouth (streptomycin only); muscle twitching, or convulsions (seizures); ringing or buzzing or a feeling of fullness in the ears
Any loss of vision (streptomycin only); skin rash, itching, redness, or swelling
Rare—Once-daily or “high dose” gentamicin only-
Shaking; chills; fever
Difficulty in breathing; drowsiness; weakness
In addition, leg cramps, skin rash, fever, and convulsions (seizures) may occur when gentamicin is given by injection into the muscle or a vein, and into the spinal fluid.
For up to several weeks after you stop receiving this medicine, it may still cause some side effects that need medical attention. Check with your doctor if you notice any of the following side effects or if they get worse:
Any loss of hearing; clumsiness or unsteadiness; dizziness; greatly increased or decreased frequency of urination or amount of urine; increased thirst; loss of appetite; nausea or vomiting; ringing or buzzing or a feeling of fullness in the ears
Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.