Polypeptide antibiotics

Polypeptide antibiotics

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  Miscellaneous Antibiotics Dr. D.K. Brahma Associate Professsor Department of Pharmacology NEIGRIHMS, Shillong
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  ??? • Name someantibacterial agents having topical preparations • Sulfacetamide sod. (20 – 30% eye drop & oint., Mafendie & Silver sulfadiazine (1% cream) • Ciprofloxacin eye/ear drop (3 mg/ml) • Freshly prepared penicillin solution • Chlorampheincol eye drop (0.4-0.5%), otic solution (10%), cream (10%) • Gentamicin eye/ear drop (0.3%), 0.1% cream; Tobramycin & sisomycin 0.3% eye drop, Neomycin – skin cream-oint-eye oint-ear drop etc.
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  Polypeptide Antibiotics • Lowmolecular weight cationic polypeptide • Powerful bactericidal agents – toxicity • Elaborated from bacteria • Names – 1. Polymyxin B - Bacillus polymyxa 2. Colistin - B. Colistinus 3. and Bacitracin - Bacillus subtillis
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  Polymyxin B andColistin • Antibacterial spectrum: Gm -ve bacteria only, except Proteus, Serratia and Neisseria – Colistin more potent in Pseudomonas, Shigella and Salmonella • MOA: Rapidly acting bactericidal – Detergent like action – high affinity for phospholipids – Orient between phospholipid and protein layers – membrane distortion or pseudopore formation – Leakage of ions and amino acids etc. – also inactivate endotoxins – Exhibits synergism with other AMA - penetration
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  Polymyxin B andColistin • ADRs: No oral absorption or denuded skin absorption – Applied topically – safe - no systemic effects or sensitization – Orally ? - Nausea, Vomiting and diarrhea – Systemic on parenteral – flushing and parasthesia (Histamine?), Kidney damage neurological disturbances and NM blockade • Preparations: Polymyxin B – in combination with neomycin and bacitracin/hydrocortisone – powder, eye/ear drop and ointment; Colistin – Dry syrup • Uses: – Topically: in combination with others in skin infections, burns, otitis externa, conjunctivitis and corneal ulcer – Orally: Gm-ve bacillary diarrhea – Salmonella, Shigella, E. coli etc) in children and also pseudomonas superinfection enteritis
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  Bacitracin • Bactericidal • Source– Bacillus subtillis • Spectrum: Gm +ve cocci and bacilli; also Neisseria and H. influenzae • MOA: Inhibits cell wall synthesis (Penicillin) – efflux of ions • Kinetics: Not absorbed orally, high toxicity parenterally (kidney) – topical only • Uses: Infected wounds – ulcers, eye infections – in combination with neomycin and polymyxin – Does not penetrate intact skin – NEBASULF, NEOSPORIN
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  Others … • Spectinomycin:Spectromyces spectabilis – narrow spectrum antibiotic similar to aminoglycosides – effective against limited no. of gm-ve bacteria – MOA: Inhibits bacterial protein synthesis – 30S rhibozome – Uses: IV - Drug resistant gonorrhoea / beta lactum allergy or contraindicated • Quinupristine/Daflopristine – semisynthetic antibiotic – like macrolides and lincosamides - • Streptogramins group – Gr. A and Gr. B – naturally occurring bacteriostatic • 30: 70 mixture – bactericidal – administered parenterally – MOA: Inhibition of bacterial protein synthesis – (i) 50S fraction - inhibition of incorporation of aminoacyl tRNA and mRNA translation – Spectrum: Gm +ve cocci including MRSA, VRSA, VRE, Neisseria, Legionella and Chlamydia pneumoniae – not in E. faecium – Uses: Nosocomial MRSA, VRE and other resistant gm+ve infections
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  Mupirocin and Fusidicacid • Mupirocin: Topical antibiotic - Obtained from Pseudomonas (pseudomonic acid) – Specturm: Gm +ve bacteria – Stre. pyogenes (sensitive penicillin & resistant), Staph. aureus, MRSA – Bacteriostatic – at high conc. bactericidal – Uses: furunculosis, folliculitis, impetigo, infected insect bites and small wounds – Preparation – 2% ointment – local use only – BACTROBAN, MUPIN, T-BACT • Fusidic acid: narrow spectrum steroidal antibiotic – blocks protein synthesis – Effective against penicillinase producing Staph. aureus and few gm +ve bacteria – Uses: Boils, furunculosis and other cutaneous infections – FUSIDERM, FUSIBACT
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  Oxazolindinone • Linezolid -New Class of syntheic antibiotic - 2 rings – Oxazolidine and Oxazoline • Spectrum: Useful in resistant gm+ve coccal (aerobic and anaerobic) and bacillary infection – MRSA, VRSA, VRE, penicilin resistant – Strep. pyogens, Strep. Viridans, Strep. pneumoniae, M. tuberculosis, Corynebacterium, Listeria, Clostridia and Bact. Fragilis • MOA: Binds to 23S fraction (p site) of 50S ribosome and interfere with formation of N-formylmethionine – tRNA (tRNAfMet ) -70S initiation complex – Distorts tRNA binding site – overlapping of 50S and 30S ribosomal subunits – stops protein synthesis – (Resistance – mutation of 23S)
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  Linezolid • Kinetics: Completetlyabsorbed orally, metabolized non- enzymatically and excreted in urine – half life – 5 hours • Uses: Complicated and uncomplicated skin and soft tissue infections, community and hospital acquired pneumonias, bacteraemias and other gm+ infections – However – hospital acquired pneumonias, febrile neutropenia, wound infections others due to multidrug resistant gm +ve bacteria – VRE, VRSA etc. • ADRs: Mild – abdominal pain, nausea, taste disturbance – Rash, pruritus, headache, oreal/vaginal candidiasis – Neutropenia, thrombocytopenia and optic neuropathy – MAO inhibitor
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  Khublei shibun