For MBBS Students

1. MISCELLANEOUS
ANTIBACTERIALS
Dr. J.N. Chaturvedi

2. Glycopeptides
◦ Agents:
◦ Vancomycin
◦ Tiecoplanin
◦ Lipoglycopeptides-
◦ Telavancin,
◦ Dalbavancin, and
◦ Oritavancin

3. Glycopeptides
◦ Vancomycin, a tricyclic glycopeptide antibiotic produced by
Streptococcus orientalis.
◦ Teicoplanin is a mixture of related glycopeptides.
◦ telavancin, dalbavancin, and oritavancin are the new generation of
glycopeptide congeners, the lipoglycopeptides.

4. Glycopeptides- Antimicrobial activity
◦ Vancomycin
◦ Vast majority of gram +ve bacteria including MRSA, penicillin-resistant streptococci, and
ampicillin-resistant enterococci.
◦ Lactobacillus, Leuconostoc, Pediococcus, Erysipelothrix, all species of gram-negative bacilli
and mycobacteria are resistant to glycopeptides.
◦ Teicoplanin, Telavancin, Dalbavancin and Oritavancin
◦ Similar to Vancomycin and are also active against some vancomycinresistant enterococci

5. Glycopeptides- Mechanism of action
Binds with high affinity to the d-alanyl-d-alanine terminus of cell wall precursor units
interferes with process of transglycosylation
Cell wall synthesis inhibition
◦ Telavancin and oritavancin possess a second mechanism of action: direct disruption of the bacterial
cell membrane.

6. Glycopeptides- Mechanism of resistance
◦ Alteration of the d-alanyl-d-alanine target to d-alanyl-d-lactate or d-alanyl d-serine  bind
glycopeptides poorly.

7. Glycopeptides- Pharmacokinetics
◦ Route of administration:
◦ Vancomycin: Oral (local action), i.v.
◦ Teicoplanin: i.m/i.v
◦ Telavancin, Dalbavancin & oritavancin: i.v.
P/K Parameters Vancomycin Teicoplanin Telavancin Dalbavancin &
oritavancin
Absorption Poor oral absorption Poor oral absorption Poor oral absorption Poor oral absorption
Distribution 30 % plasma protein
bound; ECF (Blood,
interstitial &
transcellular)
90-95% plasma protein
bound
>90% plasma protein
bound
>90 % plasma protein
bound.
Bone
Metabolism - - NS
Excretion 90% Renal 90% Renal 70-80% Renal 33-50% Renal
T1/2 6h 100h 7h 10days

8. Glycopeptides- Dosage
◦ Dosage:
◦ Vancomycin (Parenteral)
◦ In adults: 30-45md/kg/d in 2-3 divided dosage as i.v infusion over 60mins.
◦ In paediatric age group:
◦ 0-7 days: 15mg/kg f/b 10mg/kg q12h.
◦ 8-30 days: 15mg/kg f/b 10mg/kg q8h.
◦ Older infants & children: 10-15mg/g q6h.
◦ Vancomycin (Oral)
◦ 125 mg q6h with escalation upto 500 mg q6h for life threatening diseases.
◦ Teicoplanin
◦ In adults: 6-12mg/kg q12h for 4 doses f/b 6-12mg/kg/d.
◦ Telavancin
◦ In adults: 10mg/kg/d
◦ Dalbavancin
◦ In adults: 1000 mg i.v f/b 500 mg/d.
◦ Oritavancin:
◦ In adults:1200 mg/d

9. Glycopeptides- Therapeutic uses
1. Skin/soft tissue/ bone/ joint infection:
◦ Vancomycin is DOC where gram +ve bacteria including MRSA are suspected.
2. Respiratory tract infection:
◦ Nosocomial pneumonia causes by MRSA.
3. CNS infection:
◦ Vancomycin is key component of empirical treatment of community acquired bacterial meningitis.
◦ Nosocomial meningitis is stetting of V-P shunts.

10. Glycopeptides- Therapeutic uses
4. Endocarditis & vascular catheter infection:
◦ Staphylococcal endocarditis: Vancomycin is DOC.
◦ Endocarditis caused by viridians streptococci in patients allergic to penicillin.
◦ Enterococcal endocarditis (in combination with aminoglycosides)
◦ Vascular catheter infection caused by gr+ve bacteria.
5. Other infections:
◦ Moderate to severe pseudomembranous enterocolitis caused by C.difficile.
◦ Empiric therapy for fever in neutropenic patients.
◦ Surgical prophylaxis in patients allergic to penicillin.

11. Glycopeptides- Adverse drug reactions
1. Infusion related
◦ Rapid i.v. injection of vancomycin causes urticarial reactions, flushing, tachycardia & hypotension- “Red man”
or “Red neck” syndrome. It is due to release of histamine form mast cells.
2. Nephrotoxicity
3. Other toxic & irritative effects:
◦ QT- prolongation : Telavancin
◦ Teratogenic effects: Telavancin
◦ Auditory impairment: Vancomycin

12. Polymyxins
◦ The polymyxins are a group of closely related antibiotics elaborated by strains of Bacillus polymyxa.
◦ Polymyxin B is a mixture of polymyxins B1 and B2.
◦ Colistin, also known as polymyxin E, is produced by Bacillus colistinus.
◦ Antimicrobial activity:
◦ Gram –ve aerobes:
◦ Most Pseudomonas,
◦ Acinetobacter, and
◦ Enterobacteriaceae (except Proteus and Serratia spp. Stenotrophomonas and Burkholderia)

13. Polymyxins
◦ Mechanism of action:
◦ Surface-active amphipathic agents that act as cationic detergents.
◦ Interact strongly with phospholipids and disrupt the structure of cell membranes.
◦ Mechanism of resistance:
◦ Rare & not known
◦ Pharmacokinetics:
◦ Poor oral & topical absorption.
◦ Colistimethate (CMS) is available for parenteral/ inhalational use.
◦ CMS is excreted renally, polymyxin has nonrenal excretion.

14. Polymyxins-Therapeutic Uses
◦ Systemic Use:
◦ Only in serious infections due to pathogens resistant to other effective therapies.
◦ bacteremia, pneumonia, bone/joint infections, burns, cellulitis, cystic fibrosis, endocarditis,
gynecologic infections, meningitis, and ventriculitis.
◦ Topical Use:
◦ Polymyxin B sulfate is available for ophthalmic, otic, and topical use in combination with a variety of
other compounds.
◦ Colistin is available as otic drops.
◦ Infections of the skin, mucous membranes, eye (infection of corneal ulcers), and Ear (External otitis).

15. Polymyxins-Adverse Effects
◦ Dose-related nephrotoxicity.
◦ Neurological reactions include muscle weakness, apnea, paresthesias, vertigo, and slurred speech

16. Lipopeptides- Daptomycin
◦ Derived from Streptomyces roseosporus.
◦ Antimicrobial Activity:
◦ gram-positive bacteria: Strep., Staph. (including MRSA, VRSA), Enterococci (incl. VRE).
◦ Mechanism of Action:
◦ Binds to bacterial membranes, resulting in depolarization, loss of membrane potential, and cell death.
◦ Concentration-dependent bactericidal activity.
◦ Mechanism of Resistance:
◦ Not fully characterized.
◦ May be related to changes in cell surface charge that impede daptomycin binding.
◦ coadministration of β-lactams with daptomycin (even when the pathogen is resistant to the β-lactam) can
reverse this resistance.

17. Lipopeptides- Daptomycin
◦ Pharmacokinetics:
◦ Poor oral absorption, given i.v. only.
◦ Widely distributed including lung parenchyma (but inactivated by lung surfactant)
◦ 80% renal excretion.
◦ T1/2 = 8-9h.
◦ Therapeutic uses & dosage:
◦ Complicated skin & soft tissue infection (4mg/k/d)
◦ Complicated bacteraemia & right sided endocarditis (6mg/k/d)
◦ Adverse effects:
◦ Musculoskeletal toxicity: Elevation in creatine kinase. Rhabdomyolysis has also been reported.

18. Polypeptide-Bacitracin
◦ Produced by the Tracy-I strain of B. subtilis.
◦ Mechanism of action:
◦ Cell wall synthesis inhibition by interfering dephosphorylation in phospholipid carrier cycle.
Inhibits mucopeptide transfer to growing cell.
◦ Antimicrobial activity:
◦ Very effective against gram-positive cocci and bacilli, Neisseria, H. influenzae, and T.
pallidum.
◦ Moderate activity against Actinomyces and Fusobacterium.

19. Polypeptide-Bacitracin
◦ Therapeutic Uses:
◦ Current use is restricted to topical application.
◦ Available as ophthalmic and dermatologic ointments, powder for the extemporaneous compounding
of topical solutions.
◦ Skin & corneal infection.
◦ Eradication of nasal carriage of staphylococci.
◦ Toxicity:
◦ Nephrotoxicity with parenteral use.

20. Mupirocin
◦ First isolated from Pseudomonas fluorescens.
◦ Mechanism of action:
◦ Inhibits bacterial protein synthesis by reversible binding and inhibition of isoleucyl tRNA synthase.
◦ Antimicrobial Activity:
◦ S. pyogenes, MSSA, and MRSA
◦ Mechanism of resistance:
◦ Production of Ile tRNA synthase that binds mupirocin poorly.
◦ Dosage:
◦ 2% cream and a 2% ointment for dermatologic use and as a 2% ointment for intranasal use.

21. Mupirocin
◦ Therapeutic uses:
◦ Dermatological preparations for traumatic skin lesions and impetigo secondarily infected
with S. aureus or S. pyogenes.
◦ Nasal ointment is approved for eradication of S. aureus nasal carriage.
◦ Adverse effects:
◦ Irritation and sensitization at the site of application.
◦ Polyethylene glycol present in the ointment can be absorbed from damaged skin.

22. THANK YOU