ANTIBIOTICS- CLASS

2
MACROLIDES
Group 2 Presentation
Macrolides are a class of antibacterial agents that are produced by members
of the Actinomycetales order of bacteria.
Their chemical structure is characterized by a large lactone ring, which can
vary from 12 to 16 atoms, with one or more sugar chains attached.
Macrolides are actively concentrated within leukocytes and thus are
transported into the site of infection.
What Are Names of Macrolide Drugs?

Names of Macrolide drugs include:

• Azithromycin

• Clarithromycin

• Difficid

• E.E.S

• Ery-Tab

• EryPed

• Erythrocin lactobionate

• Erythrocin stearate

• Erythromycin base

• Erythromycin ethylsuccinate

• Erythromycin lactobionate

• Erythromycin stearate

• Fidaxomicin

• PCE dispertab
• Zithromax
Macrolide antibiotics such as erythromycin, clarithromycin, and
azithromycin have been used widely to combat primarily
respiratory diseases caused by Gram-positive pathogens and
fastidious Gram-negative pathogens. The popularity of this class
of antibiotics is largely due to their spectrum of activity and
their relative safety.
The second-generation macrolides, clarithromycin and
azithromycin, are derived from erythromycin, and have a
broader spectrum of activity and improved pharmacokinetic
properties.
MECHANISM OF ACTION
Macrolide antibiotics inhibit bacterial protein synthesis by interfering with
ribosome function, and details of the inhibitory mechanisms have been
clarified by recent advances in the x-ray structure of the ribosome–macrolide
complexes
Macrolides react with the peptidyl transferase enzyme of the 50S ribosomal
subunit, inhibiting protein-chain elongation. Active macrolide efflux is
common in most Gram-positive pathogens. During the protein synthesis, the
hydrophobic side of the macrolide molecule links to specifically the sidewall of
the exit tunnel and leads to premature release of short peptidyl-tends.
Another potential mechanism is premature dissociation of the peptidyl-tRNA
from the ribosome.
USES OF MACROLIDES
One of the major uses for macrolides is atypical and intracellular pathogenic infections
such as Chlamydia and Legionella spp. in parenchymal lower respiratory tract infections
or nongonococcal urethritis
Other major advantages of macrolides compared to other compounds is their safety in
β-lactam-allergic patients, oral bioavailability, tolerability when used during pregnancy,
and in the pediatric setting as well as in adult and elderly patients.
The antimicrobial spectrum of macrolides is slightly wider than that of penicillin, and,
therefore, macrolides are a common substitute for patients with a penicillin
allergy.Beta-hemolytic streptococci, pneumococci, staphylococci, and enterococci are
usually susceptible to macrolides. Unlike penicillin, macrolides have been shown to be
effective against Legionella pneumophila, mycoplasma, mycobacteria, some rickettsia,
and chlamydia.
Macrolides are not to be used on nonruminant herbivores, such as horses and rabbits.
They rapidly produce a reaction causing fatal digestive disturbance. It can be used in
horses less than one year old, but care must be taken that other horses (such as a foal's
mare) do not come in contact with the macrolide treatment.
How Are Macrolides Used?
Macrolides are used for treating the following:

• Mycoplasma pneumonia
• Rhinosinusitis (inflammation of the nasal cavity and paranasal sinuses)
• Pertussis (highly contagious respiratory tract infection)
• Diphtheria (inflammation of the mucous membranes of the throat)
• Respiratory infections caused by Chlamydia trachomatis
• Bronchiectasis (a condition where the bronchial tubes of lungs are permanently damaged)
• Cystic fibrosis (a disorder that produces abnormally thick mucus leading to blockage of
bronchi in the lungs)
• Pharyngitis (inflammation of the back of the throat, often referred to as sore throat)
• Tonsillitis (inflammation of the tonsils)
• Acute exacerbation of COPD (chronic inflammatory lung disease)
• Genital ulcer disease
HOW MICROBES SHOW RESISTANCE TO MACROLIDES.
The primary means of bacterial resistance to macrolides occurs by post-
transcriptional methylation of the 23S bacterial ribosomal RNA. This acquired
resistance can be either plasmid-mediated or chromosomal, i.e., through
mutation, and results in cross-resistance to macrolides, lincosamides, and
streptogramins (an MLS-resistant phenotype)
Two other forms of acquired resistance include the production of drug-
inactivating enzymes (esterases or kinases. as well as the production of active
ATP-dependent efflux proteins that transport the drug outside of the cell.
Azithromycin has been used to treat strep throat (Group A streptococcal (GAS)
infection caused by Streptococcus pyogenes) in penicillin-sensitive patients;
however, macrolide-resistant strains of GAS occur with moderate frequency.
Cephalosporin is another option for these patients.