The document discusses several classes of antibacterial drugs, including glycopeptides (vancomycin, teicoplanin, telavancin, dalbavancin, oritavancin), polymyxins, lipopeptides (daptomycin), polypeptides (bacitracin, mupirocin). It covers their mechanisms of action, spectra of activity, mechanisms of resistance, pharmacokinetics, therapeutic uses, dosages, and adverse effects. The glycopeptides are effective against gram-positive bacteria including MRSA. Polymyxins target gram-negative aerobes, while daptomycin and mupirocin have activity against staphylococci and enter

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