If you took a double take at this title, you know that vancomycin is not classified as an aminoglycoside. Instead, vancomycin is a glycopeptide antibiotic used to treat Gram-positive infections, while aminoglycosides are usually used to treat Gram-negative infections.¹  Vancomycin is the most frequently used antibiotic in the hospital.² Understanding antibiotic classification is important to ensure selection of the right antibiotic that will improve patient outcomes and reduce the risk of side effects and antibiotic resistance. 

In 2019, almost 5 million deaths were associated with antimicrobial resistance.³ Global data on antimicrobial resistance from the World Health Organization (WHO) 2022 report found high levels of resistance in several pathogenic bacteria to the antibiotics used to treat bloodstream and other common infections.³

A thorough understanding of antibiotic classification is one of the best weapons we have in the fight against infectious diseases.

Key Takeaways

• Vancomycin is a glycopeptide antibiotic used to treat Gram-positive infections.
• Antibiotic classification helps choose the right antibiotic while avoiding adverse effects and antibiotic resistance.
• Antibiotic resistance results in worse patient outcomes and increased costs.
• Bayesian dosing software such as DoseMeRx accomplishes one of the main goals of dosing antibiotics like vancomycin, which is to achieve a therapeutic dose as quickly and safely as possible .
  
  

What Are Antibiotics?

Antibiotics are antimicrobial agents used to treat bacterial infections and diseases. They work by destroying or inhibiting bacterial growth.⁴ Antibiotics are antibacterial agents and only work against bacteria; they do not treat infections caused by other pathogens such as viruses, fungi, or parasites.

Antibiotic side effects may differ depending on the type of antibiotic used. Common side effects of many antibiotics include:⁴

• Nausea
• Diarrhea
• Rashes
• Yeast infections
  

More serious possible side effects include Clostridium difficile infection, severe allergic reactions, and antibiotic-resistant infections.⁴

Understanding antibiotic classification can help clinicians choose the right therapeutic drug for the infection and avoid or reduce the incidence of side effects.

Antibiotic Classification

Antibiotics are grouped into classes based on their effect on bacteria in vitro (outside of a living organism). The two main classes of antibiotics are bacteriostatic and bactericidal antibiotics. In general, bacteriostatic antibiotics stop or slow bacterial growth, and bactericidal antibiotics kill bacteria.⁵

Antibiotics are grouped as bacteriostatic or bactericidal based on their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The MIC is the lowest concentration of an antimicrobial agent required to inhibit bacterial growth in vitro. The MBC is the lowest concentration of an antimicrobial agent required to kill a particular bacterium in vitro. An antibiotic is considered bacteriostatic if its MBC to MIC ratio is greater than 4. If its MBC to MIC ratio is less than or equal to 4, it is considered bacteriocidal.⁵

Antibiotics can be further grouped based on their mechanism of action, chemical structure, and target bacteria. 

Bacteriostatic Antibiotics

Antibiotics that prevent the growth of bacteria by inhibiting cellular activity without directly causing cell death are bacteriostatic antibiotics.⁶ 

To be clinically effective, bacteriostatic antibiotics usually work best in patients with a functioning immune system. The patient’s immune system must be capable of fully clearing the infection after a bacteriostatic antibiotic inhibits bacterial growth.⁶

Antibiotics classified as bacteriostatic include:⁵

• Tetracyclines — such as doxycycline, minocycline, tigecycline, and tetracycline 
• Glycylcyclines — such as tigecycline
• Lincosamides — such as clindamycin
• Macrolides — such as erythromycin, clarithromycin, azithromycin, fidaxomicin, and telithromycin
• Oxazolidinones — such as linezolid and tedizolid
• Sulfonamides — such as sulfamethoxazole
  

Tetracyclines

Tetracyclines are broad-spectrum antibiotics that inhibit protein synthesis by binding to the 30S ribosomal subunit, stopping the cell from further growing or replicating. Tetracyclines are administered orally and are widely distributed into body tissues and fluids, making them useful in treating a variety of infections caused by Gram-positive, Gram-negative, and atypical bacteria. Common side effects of tetracyclines include photosensitivity and gastrointestinal (GI) distress.⁷

Glycylcyclines

Glycylcyclines are derived from tetracyclines and have the same mechanism of action. However, they may still be active against tetracycline-resistant organisms, allowing them to be used for complicated skin infections and intra-abdominal infections as well as community-acquired pneumonia. Adverse events are similar to tetracyclines.⁸

Lincosamides

Similarly to tetracyclines, lincosamide antibiotics stop bacterial cell growth by inhibiting protein synthesis. However, lincosamides bind to the 50S ribosomal subunit instead of the 30S ribosomal subunit.⁹ At high concentrations, lincosamides can exhibit bactericidal activity. Licosamides are administered orally and have a large volume of distribution. They have activity against Gram-positive bacteria, anaerobic bacteria, and some protozoa. However, they have little activity against Gram-negative bacteria. Common adverse events include GI distress and Clostridium difficile infection.¹⁰

Macrolides

Macrolides also inhibit protein synthesis by binding to the 50S ribosomal subunit. At high doses, macrolides can exhibit bactericidal activity. Macrolides have activity against many Gram-positive bacteria and some atypicals. They are commonly administered orally with good bioavailability but can also be administered by IV. Common side effects include GI distress, diarrhea, and QT prolongation.¹¹

Oxazolidinones

Oxazolidinones inhibit protein synthesis by binding to the 50S ribosomal subunit. Many drug-resistant Gram-positive bacteria maintain susceptibility to this class. This class can be administered orally with almost 100% bioavailability and a large volume of distribution. Possible adverse events include bone marrow suppression and diarrhea.¹²

Sulfonamides

Sulfonamides inhibit bacterial cell growth by blocking bacteria’s ability to use folic acid.¹³ Sulfamethoxazole is commonly combined with trimethoprim, which blocks folic acid in a bactericidal manner. Although sulfonamides have a broad spectrum of activity against many Gram-positive and Gram-negative bacteria, there is widespread antimicrobial resistance in the community setting.⁶ Common side effects include GI distress, photosensitivity, and dizziness. There is also a possibility of serious skin rashes, such as those due to Stevens-Johnson syndrome and toxic epidermal necrolysis.¹³

Bactericidal Antibiotics

Bactericidal antibiotics kill bacteria. There are several antibiotic classes with various mechanisms of action that have bactericidal activity.⁵ 

Antibiotics classified as bactericidal include:⁵

• Beta-lactams — including penicillins, cephalosporins, carbapenems, and monobactams
• Fluoroquinolones — such as ciprofloxacin, levofloxacin, and moxifloxacin
• Cyclic lipopeptides — such as daptomycin
• Nitroimidazoles — such as metronidazole and tinidazole
• Aminoglycosides — such as tobramycin, gentamicin, neomycin, streptomycin, kanamycin, netilmicin, and amikacin
• Glycopeptides — such as vancomycin, teicoplanin, dalbavancin, oritavancin, and telavancin
  

Bactericidal antibiotics can be further grouped by their pharmacokinetics. Bactericidal activity can be concentration-dependent or time-dependent. Concentration-dependent antibiotics have increased efficacy as their concentration increases. Time-dependent antibiotics depend on the duration of the effective concentration to determine their bactericidal activity.⁵

Concentration-dependent antibiotic classes include:⁵

• Fluoroquinolones
• Cyclic lipopeptides
• Nitroimidazoles
• Aminoglycosides
  

Time-dependent antibiotic classes include:⁵

• Beta-lactams
• Glycopeptides

Beta-Lactams

Beta-lactams (β-lactams) inhibit bacterial cell wall synthesis. This process is conserved in Gram-positive and Gram-negative bacteria, giving beta-lactams a broad spectrum of activity. However, bacteria have many mechanisms of resistance, necessitating the addition of beta-lactam inhibitors in some cases. Beta-lactams are generally well tolerated but can cause diarrhea and allergic reactions.¹⁴

Fluoroquinolones

Fluoroquinolones inhibit DNA synthesis by inhibiting DNA gyrase and topoisomerase IV enzymes that help to control DNA structure and facilitate replication. They are broad-spectrum antibiotics with high oral bioavailability and a large volume of distribution that can be used to treat many different types of infections. The spectrum of activity differs between drugs in this class but includes Gram-negative and Gram-positive bacteria. Fluoroquinolones are prone to overuse, and many bacteria have developed resistance to this antibiotic. They can cause several side effects, such as GI distress, Clostridium difficile infection, QT prolongation, and tendonitis.¹⁵

Cyclic Lipopeptides

Cyclic lipopeptides work by disrupting the bacterial cell membrane. These antibiotics bind to the bacterial membrane and cause depolarization, leading to a loss of membrane potential and eventual cell death. Cyclic lipopeptides have activity against only Gram-positive organisms but maintain effectiveness against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Possible side effects include constipation, headache, insomnia, and myopathy.¹⁶

Nitroimidazoles

Nitroimidazoles kill anaerobic bacteria and some parasites and protozoa by disrupting DNA and inhibiting protein synthesis. They can be administered orally or intravenously. Common side effects include GI upset, constipation, and a bitter taste in the mouth.¹⁷

Aminoglycosides

Aminoglycoside antibiotics bind the 30S ribosomal subunit, causing the inhibition of protein synthesis.¹⁸ Their spectrum of activity includes aerobic Gram-negative bacteria, some Gram-positive bacteria, and mycobacteria but is enhanced when combined with other antibiotic classes, such as beta-lactams. Side effects include ototoxicity, nephrotoxicity, and neuromuscular blockade.¹⁹

Glycopeptides

Glycopeptides inhibit cell wall synthesis in Gram-positive bacteria.²⁰ Possible side effects include flushing, hypotension, ototoxicity, and nephrotoxicity.²¹

Is Vancomycin an Aminoglycoside?

Vancomycin is classified as a glycopeptide antibiotic, not an aminoglycoside. It has a different mechanism of action, spectrum of activity, and clinical use than aminoglycoside antibiotics.²¹

Mechanism of Action

Vancomycin works by inhibiting cell wall biosynthesis. It binds to D-alanyl-D-alanine and blocks the synthesis and polymerization of the peptidoglycan layer of the cell wall. This weakens the bacterial cell wall, causing the intracellular contents to spill out, thus killing the cell.²¹

Gram-negative bacteria are naturally resistant to vancomycin due to their outer membrane, which blocks access to the cell wall.²⁰

Administration

Vancomycin is FDA-approved to be administered intravenously or orally in pediatric and adult populations.

The dosage and frequency of intravenous vancomycin administration are based on individual patient factors and pharmacokinetics.²¹

Oral administration is typically 125 mg – 250 mg four times daily for 7 to 10 days.²¹

Side Effects

Common side effects of vancomycin include:²⁰

• Nausea
• Stomach pain
• Vomiting
• Back pain
• Headache
• Gas
• Diarrhea
• Flushing
• Hypotension
  

Serious side effects can also occur, including:²¹

• Acute kidney injury (AKI)
• Temporary or permanent hearing loss
• Thrombocytopenia
• Vasculitis
• Stevens-Johnson syndrome
  

Contraindications

Vancomycin should not be used in patients with a history of allergic or hypersensitivity reactions to the medication or any of its ingredients.²¹

Special considerations should also be given to the following patients:²¹

• Elderly patients
• Patients who are pregnant or breastfeeding
• Patients with renal impairment
• Patients taking other nephrotoxic agents
  

Monitoring

Patients receiving vancomycin therapy require drug monitoring to ensure efficacy and avoid adverse events such as nephrotoxicity and the development of antibiotic resistance.

The recommendations for intravenous vancomycin monitoring have shifted over the years from peak and trough serum concentrations to just serum trough concentrations to the current recommendation based on the area under the curve (AUC).²²  It is now recommended healthcare providers shift to AUC-based dosing for vancomycin utilizing Bayesian software programs such as DoseMeRx.

Renal function and serum creatinine should also be monitored during vancomycin therapy. Close monitoring may be required for patients with risk factors for vancomycin-associated AKI such as:²

• Older age
• Female
• Chronic kidney disease
• Liver disease
• Heart failure
• Diabetes
• Obesity
• Immunosuppression
  

Aminoglycosides vs. Glycopeptides

While aminoglycosides and glycopeptides are both bactericidal antibiotics, they have different mechanisms of action, uses, and side effects.

Mechanism of Action

The mechanism of action of aminoglycosides and glycopeptides influences their spectrum of activity.

Aminoglycoside Mechanism of Action

Aminoglycosides inhibit protein synthesis by binding the 30S ribosomal subunit, causing the misreading of transfer RNA. Aminoglycoside antibiotics are most effective against Gram-negative bacteria because of the thinner peptidoglycan layer in their cell walls compared to Gram-positive bacteria. This allows aminoglycosides to penetrate the cell wall more easily and reach their target. Additionally, Gram-negative bacteria have a higher concentration of negatively charged molecules in their outer membrane, which attracts the positively charged aminoglycoside molecules and facilitates their entry into the cell.¹⁸

Aminoglycosides‘ broad spectrum of activity includes:¹⁸

• Enterobacteriaceae species, including Escherichia coli and Klebsiella pneumoniae
• Pseudomonas aeruginosa
• Acinetobacter baumannii
• Mycobacterium species
• Staphylococcus aureus
  

Glycopeptide Mechanism of Action

Glycopeptides inhibit cell wall synthesis instead of protein synthesis to kill bacteria. They are unable to penetrate the outer membrane of Gram-negative bacteria, so glycopeptides only have bactericidal activity against Gram-positive bacteria.²¹

Glycopeptides have activity against Gram-positive bacteria, including:²¹

• Enterococcus species
• Staphylococcus species (including methicillin-resistant strains)
• Streptococcus species (including drug-resistant strains)
• Clostridium species
  

Uses

FDA-approved uses may differ between each antibiotic in each respective class. Antibiotics from both classes are considered broad-spectrum and may be used for empiric therapy until culture and sensitivity tests can be performed.

Antibiotics from either class are not absorbed through oral administration, so intravenous administration is required for systemic treatment. Oral therapy may be appropriate for GI infections.^19,21

In general, aminoglycosides are used to treat infections caused by aerobic Gram-negative bacteria, such as:²³

• Complicated urinary tract infections (UTIs)
• Pneumonia
• Endocarditis
• Sepsis
• Skin and soft tissue infections
• Abdominal infections
• Tuberculosis
• Cystic fibrosis
• Zoonotic infections
• Pelvic inflammatory disease
• Surgical prophylaxis
  

Glycopeptides are used to treat Gram-positive bacterial infections, such as:²⁰

• Endocarditis
• Enterocolitis
• Diarrhea associated with Clostridium difficile
• Skin and soft tissue infections
• Pneumonia
• Sepsis
  

Side Effects

Although aminoglycosides and glycopeptides have very different mechanisms of action and spectrums of activity, they both have a risk of kidney function deterioration caused by nephrotoxicity and hearing loss caused by ototoxicity.^19,21

Other possible side effects of aminoglycoside therapy include:²³

• Neurotoxicity
• Anemia
• Thrombocytopenia
• Tinnitus
• Headache
  

Possible side effects of glycopeptide therapy include:²¹

• Electrocardiogram (ECG) changes
• Hypotension
• Vancomycin flushing syndrome (VFS)
• Skin rash
  

Antibiotic Classification and Antibiotic Resistance

Proper antibiotic classification is essential to ensure appropriate treatment and prevent antibiotic resistance.

Antibiotic resistance occurs when bacteria are able to resist the effect of antibiotics. An increasing number of infections have become harder to treat due to antibiotic resistance, creating a global health threat.²⁴

What Causes Antibiotic Resistance?

Antibiotic resistance occurs when bacteria change in a way that allows them to resist the effect of an antibiotic. The bacteria that survive can multiply and pass on these resistance traits. Although this is a normal and expected process, overuse and misuse of antibiotics can speed up the process.²⁴

Effects of Antibiotic Resistance

Antibiotic resistance is associated with worse patient outcomes, such as longer recovery times, excess morbidity and mortality, and increased costs.^24,25 

The Centers for Disease Control and Prevention (CDC) estimates that antimicrobial resistance costs the United States up to $55 billion every year in healthcare and loss of productivity.²⁶

Preventing Antibiotic Resistance

Antibiotic resistance is a global health threat requiring action from individuals in the community, healthcare professionals, and policymakers to prevent or mitigate the problem.²⁴

Individuals can prevent antibiotic resistance in the following ways:²⁴

• Follow health worker’s advice on taking antibiotics
• Don’t share or use leftover antibiotics
• Stay up to date with vaccinations
• Prevent infections by using proper hygiene and avoiding close contact with sick individuals
• Practice safe sex
• Prepare and store food hygienically
  

Healthcare professionals can prevent antibiotic resistance by:²⁴

• Educating patients about the proper use of antibiotics and how to prevent infections
• Prescribing antibiotics only when necessary and according to appropriate guidelines
• Practicing proper hygiene
• Reporting antibiotic-resistant infections to antibiotic stewardship teams

Policymakers can prevent antibiotic resistance by doing the following:²⁴

• Creating a national plan to tackle antibiotic resistance
• Improving surveillance and research on antibiotic resistance
• Regulating and ensuring appropriate use and disposal of medicines
  

Did you know? One of the first antibiotics to ever be discovered was penicillin. Alexander Fleming, a Scottish physician and microbiologist, discovered it by accident in 1928. He was inspecting Staphylococcus culture plates when he noticed one of them had a spot with some mold growing on it. The area surrounding the mold was clear, implying that it had inhibited bacterial growth.

Ensure Accurate Antibiotic Dosing Through Proper Classification

Antibiotic classification helps healthcare providers select the most appropriate antibiotic for treating bacterial infections. Different classes of antibiotics have different mechanisms of action, spectrums of activity, and pharmacokinetic properties. Understanding these differences can help clinicians choose the most effective antibiotic to treat a particular infection while minimizing the risk of side effects, toxicity, and the development of antibiotic resistance.

DoseMe provides the tools to simplify your dosing and monitoring efforts to improve efficacy and decrease side effects. Built-in analytics within the DoseMeRx platform can also help you monitor and optimize dosing practices and patient outcomes with real-time data, including:

• Time to therapeutic target
• Patient risk indicators
• Trough vs. AUC outcomes
• Average daily dose amounts

Simplify your dosing and drug monitoring processes with user-friendly software. Contact DoseMe today.

FAQs on Antibiotic Classification

What is the difference between antibiotic resistance and antimicrobial resistance?

Antimicrobial agents include antibiotics, antivirals, antifungals, and antiparasitics. Antimicrobial resistance is when bacteria, viruses, fungi, or parasites change in a way that allows them to resist an antimicrobial agent. Antibiotic resistance is a type of antimicrobial resistance where bacteria change in a way that allows them to resist an antibiotic.²⁴

Are antibiotics necessary for treating all bacterial infections?

Antibiotics are not always necessary when treating a bacterial infection. It is important to weigh the potential benefits and harms of antibiotics when treating infections that may clear on their own, such as sinus infections or ear infections.

It is also important to note that antibiotics do not treat infections caused by viruses, fungi, or parasites.²⁷

How do health professionals determine antibiotic dosage?

Healthcare professionals determine the appropriate antibiotic, dosage, and frequency based on the following:²⁸

• Signs and symptoms of bacterial infection
• Patient demographics and comorbidities
• Local antibiotic resistance patterns
• Pharmacokinetic and pharmacodynamic characteristics of the appropriate antibiotic
  

DoseMeRx can help clinicians find the safest and most effective dose for patients requiring intravenous antibiotic therapy with several infectious disease drug models, including vancomycin and several aminoglycoside antibiotics.

References

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2. Kan WC, Chen YC, Wu VC, Shiao CC. Vancomycin-associated acute kidney injury: A narrative review from pathophysiology to clinical application. Int J Mol Sci. 2022;23(4):2052. https://doi.org/10.3390/ijms23042052
3. World Health Organization. (2022). Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022. https://www.who.int/publications/i/item/9789240062702
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7. Shutter MC, Akhondi H. Tetracycline. StatPearls [Internet]. Last update July 2022.
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9. Murphy PB, Bistas KG, Le JK. Clindamycin. StatPearls [Internet]. Last update June 2022.
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11. Patel PH, Hashmi MF. Macrolides. StatPearls [Internet]. Last update February 2022.
12. Foti C, Piperno A, ScalaA, et al. Oxazolidinone antibiotics: Chemical, biological and analytical aspects. Molecules. 2021;26(14):4280. https://doi.org/10.3390/molecules26144280
13. Jacob D. How Do Sulfonamides Work? RxList. (2022, December 29). Available from: https://www.rxlist.com/how_do_sulfonamides_work/drug-class.htm
14. Pandey N, Cascella M. Beta Lactam Antibiotics. StatPearls [Internet]. Last update September 2022.
15. Yan A, Bryant EE. Quinolones. StatPearls [Internet]. Last update January 2023.
16. Patel S, Saw S. Daptomycin. StatPearls [Internet]. Last update December 2022.
17. Memon N. What Are Names of Nitroimidazoles Drugs? RxList. (2021, October 22). Available from: https://www.rxlist.com/what_are_names_of_nitroimidazoles_drugs/drug-class.htm
18. Krause KM, Serio AW, Kane TR, et al. Aminoglycosides: An overview. Cold Spring Harbor Perspectives in Medicine. 2016;6(6):a027029. https://doi.org/10.1101/cshperspect.a027029
19. Block M, Blanchard DL. Aminoglycosides. StatPearls [Internet]. Last update July 2022.
20. Kahn S. How Do Glycopepties Work? RxList. (2021, October 21). Available from: https://www.rxlist.com/how_do_glycopeptides_work/drug-class.htm
21. Patel S, Preuss CV, Bernice F. Vancomycin. StatPearls [Internet]. Last update January 2023.
22. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2020;77(11):835-864. doi:10.1093/ajhp/zxaa036
23. Sruthi M. How Do Aminoglycosides Work? RxList. (2021, May 5). Available from: https://www.rxlist.com/how_do_aminoglycosides_work/drug-class.htm
24. World Health Organization. (2021, November 17). Antimicrobial Resistance. Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
25. de Kraker ME, Davey PG, Grundmann H. Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe. PLoS Med. 2011;8(10):e1001104. doi:10.1371/journal.pmed.1001104
26. Dadgostar P. Antimicrobial resistance: Implications and costs. Infection and Drug Resistance. 2019;12:3903-3910. https://doi.org/10.2147/IDR.S234610
27. Centers for Disease Control and Prevention. (2021, October 6). Antibiotic Use Questions and Answers. Available from: https://www.cdc.gov/antibiotic-use/q-a.html
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