Other Agents Used in GM Positive Infections

Other agents used in gram positive infections
DR GIRISH M Bengalorkar Associate professor Sri Devaraj Urs medcial college tamaka kolar
5/5/2012 DR.GIRISH MB 1
LINCOSAMIDES
Antibiotics with polybasic structure Lincomycin from St.Lincolnensis Clindamycin- chlorine substitued Bactericidal: protein synthesis inhibited (like erythromycin) Spectrum: 1.Gram positive cocci including Staph. Producing penicillinase 2. Anaerobes-bacteriodes, peptococcus, peptostreptococcus 3. Pneumocystis jeroveci, toxoplama gondii
CLINDAMYCIN- good oral absorption, IM/IV, 90% PPB, do not cross BBB, it can penetrate into abscess and also phagocytes. Secreted into bile and urine. Uses: 1. post op. sepsis 2.UTI 3.Septicemia 4. Osteomyelitis(Staph) 5. pelvic and lung abscess(bacteriodes) 6. P. jerovoci pneumonia in AIDS (clinda+primaquine) 7. toxoplasmosis of brain in AIDS(clinda+primaquine)
Unwanted effects: 1 GIT diarrhoea and pseudomembranous colitis (metronidazole 2500mg QID for 510 days or vancomycin 125mg QID orally for 5 days) 2. Hepatotoxic jaundice 3. increases the action of NM blockers 4. hypersensitivity
VANCOMYCIN
A GLYCOPEPTIDE ANTIBIOTIC St. orientalis Bactericidal: inhibit peptidoglycan synthesis and thus inhibit cell wall synthesis Spectrum gm+ve bacilli, S. aureus even MRSA, S. epidermidis, S. pyogenes, Pneumococci and viridans, coryne bacteruim, clostridium, enterococi fecalis and faecium
PK not absorbed orally but still given for local effects on GIT- antibiotic assoc. diarrhea with C.difficile Does not cross BBB Given IV, 75%excreted unchanged(gl filtration) Reduce the dose in renal failure Uses: oral;- staph enterocolitis, pseudomemb . Colitis (125mg QID for 5 d) IV -endocarditis by MRSA and enterococci Serious bacteremia- S. epidermidis infection
Adverse effects
Allergy- skin rash, urticaria- histamine release- flushing and hypotension----red man syndrome Nerve deafness and nephrotoxicity Thrombophlebitis
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Streptogramins B/A quinpristin 30 /dalfopristin 70

Semisynthetic derivatives of pristinamycin M/A- bactericidal Q binds to 50s and inhibit protein synthesis thus inhibiting polypeptide elongation D binds to a site close to 50s and brings about conformational change in 50s thus enhancing binding of Q-----synergistic action
Spectrum Gm + cocci staph MSSA and MRSA S.Pneumo , E.faecium, atypical pneumonia (mycoplasma , legionella ,chlamydiae) PK- only IV infusion over 1 hr with 5% dextrose in water Q -0.8 hrs D-0.7 hrs Mostly metabolized in liver and eliminated in bile Some through kidney Given every 8 hrs or 12h
uses
Skin infections caused by MSSA, MRSA vancomycin resistant E.faecium (soft tissue, UTI ,bacteremia) Adv infusion related- pain, phlebitis, arthralgia, myalgia - cyt. P450 3A4- terfenadine , astemizole, cyclosporine.
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Synthetic agent oxazolidinone cidal drug Inhibit protein synthesis binds to 23s and 50 s and prevents 70s formation that is required for initiation of protein synthesis because of unique binding site No cross resistance with other drugs Spectrum- Gm+ staph, strepto ,enterococci, Gm+ bacilli listeria,B.anthracis and corynebacterium Gm+ anaerobic cocci- clostridium No action on Gm- bacteria
linezolid
Because of its unique action it is active against penicillin resistant S.pneumonia, MRSA, VRSA, VRE. PK- ORAL AND IV T half 4 to 6 hrs Distributed to perfused tissue Metabolized by non enzymatic oxidation Excreted by urine
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Dose complicated infections 600 mg BD Uncomplicated - 400 mg BD VRE - soft tissue , UTI and bacteremia Nosocomial pneumonia- MSSA , MRSA Community acquired pneumonia Skin infections- staph infections Osteomyelitis Reserved drug for MDR strains
Unwanted effects- GI disturbances, headache , thrombocytopenia, monitor platelet count
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Glycopeptides Teicoplanin
Actinoplanes teichomyeticous Mixture of 6 closely related compounds Similar to vanco in structure and mechanism and spectrum and route of elimination It can be given IM PBB more than 90% once a day Active only on Gm + pneumoniae, S. fecalis, MRSA, Listeria , Corynebacterium, Clostridia Synergistic with amino glycosides Osteomyelitis, endocarditis, bacteremia Adv-skin rash
daptomycin
Cyclic lipopetide MA binds to bacterial plasma membrane causing membrane depolarization and release intracellular ions cell damage MRSA, VRSA ,penicillin resistant pneumonia ,VRE Uses same as that of vancomycin Adv- rash headache GI disturbances
Dalvancin
Derived form teicoplanin MA same as Vancomycin MRSA VRSA t half 6-11 days once a week IV Telvancin derived from vancomycin
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POLYMYXINS
Large polypeptide antibiotics Colistin or polymyxin E bacillus colistinus Polymyxin B bacillus polymyxa Bactericidal: interacts with phospholipids and penetrate the cell wall and disrupts cell membrane and increased permeability and leak.(detergent action) Spectrum- gr-ve bact-enterobacter, E. coli, Klebsiella, salmonellae, pseudomonas
Not absorbed orally(given for local action orally) Given IV, do not cross BBB, excreted unchanged Uses: 1. topical skin, ocular and mucous membrane infections 2. orally- enteritis due to shigella, kleb, enterobacter, pseudomonas 3. UTI-(pseudomonas and not proteus) SE: 1. nephrotoxicity: proteinuria and renal failure 2. Ototoxic 3. Increased NM blocking action 4. Histamine release- bronchospasm, hypotension, flushing
BACITRACIN
MIXTURE OF POLYPEPTIDES Antibiotic obtained from bacillus subtilis(tracy strain 1943) Bactericidal- inhibit cell wall synthesis(different from that of penicillin) Spectrum-gr+ve cocci and bacilli, neisseria, H.influenza, trepo are sensitive Oral absorption poor. Used topically. Systemically highly toxic
Uses- skin, eye, wound infections caused by gm+ve organisms including staphylococcus(not on unbroken skin) Unwanted effects1. highly nephrotoxic 2. potentiates NM blocking Bacitracin (gram +ve) Polymyxin(gm-ve) Neomycin(gm-ve bacilli and gm+ve cocci)
mupirocin
Topical antimicrobial against S.aureus is an effective agent for such infections especially MRSA strains Source- pseudomonas fluorescens MA inhibits protein synthesis by binding to bacterial isoleucyl tRNA synthetase (mammalinan enzymes is 8000 times less sensitive)
Active all Staph and strepto(except group D) Invitro activity H.influenzae , gonococci P.multocida ,moraxella catarrhalis, B. pertusis Uses impetigo, folliculitis, infected eczema , wound infections , infected burns , Activity is enhanced by acid pH of skin 2% mupicrocin ointment applied 3 times daily Advantage- unique structure-good activity , low resistance and no cross resistance Adverse irritation , erythematic and burning
Fusidic acid
A steroidal antibiotic from fungus fusidium cocecineum genus Bactericidal decrease protein synthesis by inhibiting ribosomal function Penicillin producing staph, Gm + aerobes and anaerobes Orally effective and milk decrease its absorption Excreted in bile, does not cross BBB
Topical boils , folliculitis Resistant staph infections of bone and joint and soft tissue Septicemia and endocarditis staph Adv epigastria pain , skin rash , jaundice CI peptic ulcer , Available with betamethasone valerate , and hydrocortisone acetate
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Other Agents Used in GM Positive Infections

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Other Agents Used in GM Positive Infections

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Other agents used in gram positive infections

Streptogramins B/A quinpristin 30 /dalfopristin 70

Unwanted effects- GI disturbances, headache , thrombocytopenia, monitor platelet count

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