I was first introduced to infectious diseases (ID) during my hospital pharmacy rotation this past March. As my preceptor and the ID team completed rounds for difficult-to-treat patients, I was pretty lost most of the time, to say the least!
Now that I am in the midst of this new class, I am able to connect my rotation experiences to the content we are learning.
This post is a simple overview of common antibiotic classes, examples of each, and how they work!
Cell Wall Inhibitors
These agents target the cell wall of microorganisms. As seen below, the cell wall is found outside the plasma membrane. Because eukaryotes (including humans) do not have this layer, bacterial cell walls are a great target for antibiotics without causing harm to our own cells!
- The cell wall is composed of peptidoglycan, which is made by these enzymes:
- Transglycosylase alternates 2 sugars
- Transpeptidase (aka penicillin-binding protein) cross links peptides to the sugars
- These enzymes and the process of cell wall synthesis are inhibited by some of the antibiotics we use!
There are 2 main cell wall inhibitors: Beta Lactams and Glycopeptides.
Beta Lactams
All of these agents have a beta lactam ring, which is seen in green below. There are 4 classes of beta lactams: penicillins, cephalosporins, carbapenems, and monobactams.
Mechanism Of Action
Covalently and irreversibly bind the bacteria’s transpeptidase enzyme = inhibit peptidoglycan and cell wall synthesis = bacterial death
Examples
Penicillins: Penicillin V, amoxicillin, nafcillin
Cephalosporins: Cefazolin, cefuroxime, ceftriaxone, cefepime, ceftaroline
Carbapenems: Imipenem-cilastatin, meropenem, doripenem
Monobactam: Aztreonam
Key Points About Beta Lactams:
- They are bactericidal against gram (+) AND gram (-)
- Aztreonam only has activity against gram (-)!
- All are time-dependent antibiotics. We administer smaller doses multiple times a day to increase the amount of time the drug is in the body.
- Penicillin G is very unstable when given orally and is degraded by stomach acids
- Penicillin V is stable in acid! This is due to a stabilizing electron-withdrawing oxygen in the R group.
- Resistance
- Bacteria with the enzyme β lactamase can open the β ring and deactivate the drug
- To overcome this, we also give β lactamase inhibitors! These include clavulanate, sulbactam, and tazobactam
- Bind the β lactamase (to “distract it”) so the antibiotic is not deactivated
- Allergies
- Allergic reactions are driven by the R1 side chain!
- Aztreonam and 3rd-, 4th-, and 5th-generation cephalosporins are safe in people with a penicillin allergy.
Glycopeptides (Peptide Antibiotics)
Mechanism of Action
These antibiotics bind a pair of specific amino acids (D-alanine, D-alanine) found on a sugar needed for peptidoglycan synthesis.
This hinders the cross-linking of peptides = cell wall cannot be built
Examples
Vancomycin, telavancin, dalbavancin, oritavancin
Key Points About Glycopeptides
- Vancomycin is bactericidal, but can be bacteriostatic against certain organisms
- Vancomycin has many OH groups which make it very hydrophilic! This means it has poor absorption in the GI
- It is given IV multiple times a day
- It needs therapeutic drug monitoring (serum concentrations taken to adjust dose and reduce side effects)
- Spectrum: Gram (+) Only!
- Resistance
- Some bacteria can change one of the D-alanine amino acids to D-lactate = Vancomycin cannot bind = peptidoglycan/cell wall built normally
- Daptomycin and Oritavancin are effective against vancomycin-resistant enterococcus (VRE).
Protein Synthesis Inhibitors
Another target of antibiotics is the synthesis of bacterial proteins. This happens in the ribosomes:
- Bacterial ribosomes have 2 subunits: 30S and 50S
- Human cells do not have the same subunits and therefore are not affected!
- The main steps of protein synthesis (translation) are:
- Initiation- an mRNA strand binds the small subunit (30S) along with a start tRNA. The large subunit (50S) then binds to complete the ribosome
- Elongation- Peptidyl transferase attaches amino acids to the growing polypeptide
- Termination- A stop codon triggers the detachment of the polypeptide. The subunits dissociate and recruited to another translation.
There are 6 main types of protein synthesis inhibitors, classified by their mechanism of action and by the ribosome subunit they inhibit.
Macrolides
Mechanism of Action
They bind to the 50S subunit = peptidyl transferase cannot elongate the peptide
This inhibits the elongation step of protein synthesis!
Examples: Azithromycin, clarithromycin
Key Points About Macrolides
- They are bacteriostatic, but can have bactericidal activity depending on the microorganism
- Broad Spectrum: Gram (+), gram (-), and atypical bacteria
- Atypicals include mycoplasma, chlamydophila, legionella
Oxazolidinones and Lincosamides
Mechanism of Action
They bind to the 23S subunit within 50S
- Oxazolidinones block the initiation step = ribosome complex does not form
- Lincosamides block the elongation cycle = premature polypeptide dissociation
Examples: Linezolid, tedizolid, clindamycin (only lincosamide)
Key Points About Oxazolidinones & Clindamycin
- They are bacteriostatic = inhibit growth
- Spectrum: Gram (+) only
- Clindamycin also covers anaerobes
- Linezolid & tedizolid also cover VRE
- Clindamycin is the most common culprit of Clostridium difficile
Tetracyclines, Aminoglycosides, Glycylcyclines
Mechanism of Action
They bind to the 30S subunit! This prevents the correct synthesis of proteins
- Aminoglycosides bind irreversibly and may also interfere with proofreading
Examples:
Tetracyclines: Tetracycline, doxycycline, Minocycline
Aminoglycosides: Amikacin, tobramycin, gentamicin, plazomicin
Glycylcyclines: Eravacycline, tigecycline
Key Points
- They are bacteriostatic = inhibit growth
- Aminoglycosides may also be bactericidal against some organisms
- Spectrum:
- Tetracyclines have broad activity: gram (+), gram (-), and atypicals
- Aminoglycosides only have gram (-) activity if used alone, but can be added to other medications for synergy (gram + activity)
- Glycylcyclines have broad activity: gram (+), gram (-), atypicals, and anaerobes
- Aminoglycosides require therapeutic drug monitoring
- They are concentration-dependent
- Tigecycline has a BBW for death in pneumonia patients
DNA Synthesis Inhibitors
Another target of antibiotics is the replication and synthesis of DNA. There are multiple ways antibiotics achieve this:
There are 3 major types of DNA synthesis inhibitors:
Fluoroquinolones
Mechanism of Action
They bind and inhibit DNA gyrase, which is used by bacteria to release tension during replication
Examples: Delafloxacin, levofloxacin, moxifloxacin, ciprofloxacin
Key Points
- They are bactericidal!
- Spectrum:
- Streptococci (+), gram (-), and atypicals
- Ciprofloxacin, levofloxacin & delafloxacin cover pseudomonas
- Delafloxacin covers Staph. aureus
- Moxifloxacin covers anaerobes
- Should be avoided in patients < 12 y.o
Nitroimidazoles
Mechanism of Action
Have a nitro group that absorbs extra electrons = reduced by ferredoxin = toxic metabolites produced = DNA fragmentation
Examples: Metronidazole, nitrofurantoin
Key Points
- Metronidazole is bactericidal! Nitrofurantoin is bacteriostatic!
- Spectrum:
- Metronidazole covers anaerobes
- Nitrofurantoin used exclusively for UTIs (enterococci & gram (-))
Sulfonamides & Trimethoprim
Mechanism of Action
Indirectly inhibit bacterial DNA: interferes with folic acid pathway
- Bacteria need folic acid for the synthesis of base pairs and DNA
- Dihydropteroate synthetase = combines dihydropteridine + PABA
- Inhibited by Sulfonamides
- Dihydrofolate reductase is inhibited by Trimethoprim
Examples: Trimethoprim-Sulfamethoxazole
Key Points
- They are bacteriostatic!
- Spectrum:
- Gram (+) except enterococci and gram (-)
Hope this is helpful to anyone reading!! I will certainly review it to refresh my memory in the future 🙂
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