Glycopeptide Antibiotics

GLYCOPEPTIDE ANTIBIOTICS

Vancomycin

It is a glycopeptide antibiotic discovered in 1956 as a penicillin substitute which has assumed special significance due to efficacy against MRSA, Strep. viridans, Enterococcus and Cl. difficile. It is bactericidal to gram-positive cocci, Neisseria, Clostridia and diphtheroids. However, in hospitals where it has been extensively used for surgical prophylaxis, etc., vancomycin-resistant Staph. aureus (VRSA) and vancomycin-resistant Enterococcus (VRE) have emerged. These nosocomial bacteria are resistant to methicillin and most other antibiotics as well.

Vancomycin acts by inhibiting bacterial cell wall synthesis. It binds to the terminal dipeptide ‘Dala-Dala’ sequence of peptidoglycan units— prevents its release from the bactoprenol lipid carrier so that assembly of the units at the cell membrane and their cross linking to form the cell wall cannot take place. Enterococcal resistance to vancomycin is due to a plasmid mediated alteration of the dipeptide target site, reducing its affinity for vancomycin.

Vancomycin is not absorbed orally. After i.v. administration, it is widely distributed, penetrates serous cavities, inflamed meninges and is excreted mainly unchanged by glomerular filtration with a t½ of 6 hours. Dose reduction is needed in renal insufficiency.

Toxicity: Systemic toxicity of vancomycin is high. It can cause plasma concentrationdependent nerve deafness which may be permanent. Kidney damage is also doserelated. Other oto and nephrotoxic drugs like aminoglycosides must be very carefully administered when vancomycin is being used. Skin allergy and fall in BP during i.v. injection, due to histamine release from mast cells, are the other problems. Rapid i.v. injection has caused chills, fever, urticaria and intense flushing—called ‘Red man syndrome’.

Uses:

Given orally (125–500 mg 6 hourly), it is the second choice drug to metronidazole for antibiotic associated pseudomembranous enterocolitis caused by C. difficile.

Systemic use (500 mg 6 hourly or 1 g 12 hourly infused i.v. over 1 hr) is restricted to serious MRSA infections for which it is the most effective drug, and as a penicillin substitute (in allergic patients) for enterococcal endocarditis along with gentamicin. For empirical therapy of bacterial meningitis, i.v. vancomycin is usually combined with i.v. ceftriaxone/cefotaxime. It is also used in dialysis patients and those undergoing cancer chemotherapy. Penicillin-resistant pneumococcal infections and infection caused by diphtheroids respond very well to vancomycin.

It is the preferred surgical prophylactic in MRSA prevalent areas and in penicillin allergic patients.

VANCOCIN-CP 150 mg tab, 500 mg/vial inj; VANCOGEN, VANCORID-CP 500 mg/vial inj; VANCOLED 0.5, 1.0 g inj.

Teicoplanin

It is a newer glycopeptide antibiotic which in fact is a mixture of 6 similar compounds. It is active against gram-positive bacteria only; mechanism of action and spectrum of activity is similar to vancomycin. Notable features are:

·  It is more active than vancomycin against enterococci, and equally active against MRSA.

·     Some VRE but not VRSA are susceptible to teicoplanin.

·     It can be injected i.m. as well; is excreted by kidney; dose needs to be reduced in renal insufficiency; has a very long t½ (3–4 days).

·  Toxicity is less than vancomycin; adverse effects are rashes, fever, granulocytopenia and rarely hearing loss. Reactions due to histamine release are rare (1 in 2500).

Teicoplanin is indicated in enterococcal endocarditis (along with gentamicin); MRSA and penicillin resistant streptococcal infections, osteomyelitis, as alternative to vancomycin.

Dose: 400 mg first day—then 200 mg daily i.v. or i.m.; severe infection 400 mg × 3 doses 12 hourly—then 400 mg daily.

TARGOCID 200, 400 mg per vial inj. for reconstitution.