1) Vancomycin and daptomycin are glycopeptides and lipopeptides respectively that are used to treat infections caused by gram-positive bacteria like MRSA. They work by inhibiting cell wall synthesis. 2) Vancomycin has side effects of fever, redness, and hearing loss while daptomycin can cause muscle damage. 3) Newer drugs like lipoglycopeptides have dual mechanisms of inhibiting cell wall synthesis and disrupting membranes. They are generally more potent than vancomycin against gram-positives.

1. Antibacterial Agents
Manual of Clinical Microbiology, 11th Edition
Done By: Dr. Abdullatif Al Rashed (Clinical Microbiology Resident)
• Glycopeptides:
1) Vancomycin:
Mechanisms of Action:
• Blocking the formation of precursors of peptidoglycans by complexing with the D-
alanyl-D-alanine portion of the cell wall.
Spectrum of Activity:
Active only against aerobic and anaerobic Gram-positive organisms
• It is not active against Gram-negative organisms or mycobacteria.
• The emergence of vancomycin resistant enterococci (VRE) has been increasing.
• Vancomycin is useful in the prevention and treatment of endocarditis due to Gram-
positive bacteria in patients who are allergic to penicillin.
• Itis the drug of choice for treating Corynebacterium jeikeium infections.
• It is useful for treating antibiotic associated C. difficile colitis.
• It acts synergistically with aminoglycosides or rifampin against staphylococci,
streptococci, and enterococci.
Pharmacology:
o Vancomycin can be administered orally or parenterally. After oral administration, the
drug is poorly absorbed, and high concentrations in stools are achieved, accounting
for its efficacy in treating pseudomembranous colitis
o Therapeutic levels of Vancomycin are achieved in synovial, ascitic, pericardial, and
pleural fluids, with variable penetration into the CSF only in the presence of inflamed
meninges
Side effects:
o Fever, chills, and phlebitis at the site of infusion. (Most Common)
MSSA
MRSA
Streptococci
Enterococci
Coagulase
Negative
Staphs
N
Corynebacterium spp., Bacillus
spp., L. monocytogenes
Clostridium spp.
Actinomyces
spp.

2. Antibacterial Agents Manual of Clinical Microbiology, 11th Edition
o Red man syndrome. (Rapid or bolus infusion of vancomycin causes tingling and
flushing of the face, neck, and thorax due to histamine release)
o Allergic maculopapular or diffuse erythematous rashes
o High-frequency hearing loss due to ototoxicity (in daily high doses)
o Vancomycin-induced nephrotoxicity. (RARE)
2) Teicoplanin:
• It is a complex glycopeptide chemically related to vancomycin.
• Currently available for clinical use in most countries of the world except the United
States.
• Lipopeptides:
1. Daptomycin:
Mechanisms of Action:
• It binds irreversibly to the cytoplasmic membrane of susceptible bacteria via a
calcium ion-dependent insertion of the hydrophobic tail of the molecule and causes
generalized disruption of membrane permeability.
• The end effect is cell death without cell lysis, providing this drug with potent
bactericidal activity.
• It can’t to penetrate the outer membrane of Gram-negative bacteria.
Spectrum of Activity:
Active only against aerobic and anaerobic Gram-positive organisms
• Daptomycin is 2- to 4-fold more active than vancomycin against these Gram-
positive cocci
• It is not active against Gram-negative organisms or mycobacteria.
MSSA
MRSA
Streptococci
Enterococci
Coagulase
Negative
Staphs
N
Corynebacterium spp., Bacillus
spp., L. monocytogenes
Clostridium spp., peptostreptococci
Actinomyces spp., Propionibacterium

3. Antibacterial Agents Manual of Clinical Microbiology, 11th Edition
• It acts synergistically with aminoglycosides or rifampin against staphylococci,
streptococci, and enterococci.
• Since the optimal in vitro activity of daptomycin depends on the calcium ion
concentration in the growth medium, media used for susceptibility testing with this
drug should contain the recommended calcium concentration of 50 μg/ml.
Pharmacology:
o Daptomycin shows poor penetration into the CSF and alveolar space, where it is
bound by surfactant, so it is not use for the treatment of meningitis and pneumonia.
Side effects:
o Diarrhea, rash, dizziness, and dyspnea. (Most Common)
o Elevated serum creatinine phosphokinase levels causing myalgias, and myopathy but
are reversible (Significantly reduced if lower dosages and once-daily dosing
frequency)
• Lipoglycopeptides:
Types • Dalbavancin, oritavancin, and telavancin.
Mechanism of
Action
• They have a dual mechanism of action:
1. Inhibition of the transglycosylation process of peptidoglycan cell wall synthesis by
formation of a complex with the D-alanyl-D-alanine residues.
2. Depolarization of the bacterial cell membrane.
Spectrum of
Activity
• Active only against aerobic and anaerobic Gram-positive organisms.
• More potent than vancomycin and teicoplanin against a broad range of Gram-positive
bacteria.
• Dalbavancin and telavancin are not active against VRE, while Oritavancin is active
against VRE.
Pharmacology • Oritavancin is rapid bactericidal while Dalbavancin is slow bactericidal.
Side Effects
• Taste disturbance, nausea, vomiting, and foamy urine (most common adverse reactions
in telavancin)
• Telavancin is labeled as a category C agent with regard to use in pregnant women.

4. Antibacterial Agents Manual of Clinical Microbiology, 11th Edition
• POLYMYXINS:
Types:
Mechanisms of Action:
1. They interact with the phospholipids of the bacterial cell membrane, thus increasing
cell permeability and disrupting osmotic integrity.
2. This process results in leakage of intracellular components, leading to cell death.
The bactericidal action is reduced in the presence of calcium, which
interferes with the attachment of drugs to the cell membrane.
Spectrum of Activity:
Polymyxins are active only against select Gram-negative bacilli,
especially Pseudomonas spp. and Acinetobacter spp.
• Proteus, Providencia, Serratia, and Neisseria isolates are usually resistant.
• The combination of polymyxins with TMP-SMX may be synergistic in the treatment
of serious infection due to resistant Serratia spp., P. aeruginosa, B. cepacia, and S.
maltophilia
• Aerosolized polymyxins have been used successfully to treat respiratory tract
colonization and nosocomial pneumonia due to MDR Gram-negative bacilli or P.
aeruginosa in patients with or without cystic fibrosis or bronchiectasis.
Pharmacology:
• Polymyxins are usually administered parenterally, orally, or topically.
• They do not penetrate well into pleural fluid, synovial fluid, or CSF even in the presence
of inflammation.
polymyxin
A
polymyxin B polymyxin C
polymyxin
D
polymyxin E
(Colistin)
Only polymyxins B and E (colistin) are used clinically in humans.

5. Antibacterial Agents Manual of Clinical Microbiology, 11th Edition
Side effects:
o Neurotoxicity and nephrotoxicity. (Most Common)
o Paresthesia with flushing, dizziness, vertigo, ataxia, slurred speech, drowsiness, or
mental confusion. (if levels in serum exceed 1 to 2 μg/ml)
o Curare-like effect that can block neuromuscular transmission.
o Allergic reactions, such as fever and skin rashes, are rare, but urticaria and shock after
rapid intravenous infusion have occurred.