other agents used in gm positive infections
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Other agents used ingram positive
infections
DR GIRISH M BengalorkarAssociate professor
Sri Devaraj Urs medcial college tamaka kolar
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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, toxoplamagondii
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CLINDAMYCIN- good oral absorption, IM/IV,90% PPB, do not cross BBB, it can penetrate
into abscess and also phagocytes. Secretedinto 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)
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Unwanted effects:
1 GIT diarrhoea and pseudomembranouscolitis (metronidazole 2500mg QID for 5-10 days or
vancomycin 125mg QID orally for 5 days)
2. Hepatotoxic
jaundice3. increases the action of NM blockers
4. hypersensitivity
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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, corynebacteruim, clostridium, enterococi fecalisand faecium
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PK not absorbed orally but still given for localeffects on GIT- antibiotic assoc. diarrhea withC.difficile
Does not cross BBB
Given IV, 75%excreted unchanged(glfiltration)
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
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Adverse effects
Allergy- skin rash, urticaria- histaminerelease- flushing and hypotension----redman syndrome
Nerve deafness and nephrotoxicity
Thrombophlebitis
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Streptogramins B/Aquinpristin 30 /dalfopristin 70
Semisynthetic derivatives of pristinamycin
M/A- bactericidal Q binds to 50s andinhibit protein synthesis thus inhibitingpolypeptide elongation
D binds to a site close to 50s and bringsabout conformational change in 50s thusenhancing binding of Q-----synergisticaction
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Spectrum Gm + cocci staph MSSA andMRSA
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
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uses
Skin infections caused by MSSA, MRSAvancomycin resistant E.faecium (softtissue, UTI ,bacteremia)
Adv infusion related- pain, phlebitis,arthralgia, myalgia
- cyt. P450 3A4- terfenadine , astemizole,
cyclosporine.
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linezolid Synthetic agent oxazolidinone cidal drug
Inhibit protein synthesis binds to 23s and 50 sand prevents 70s formation that is required forinitiation of protein synthesis because of unique
binding site No cross resistance with other drugs
Spectrum- Gm+ staph, strepto ,enterococci,
Gm+ bacilli
listeria,B.anthracis andcorynebacterium
Gm+ anaerobic cocci- clostridium
No action on Gm- bacteria5/5/2012 11DR.GIRISH MB
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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
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Unwanted effects- GI disturbances,headache , thrombocytopenia, monitorplatelet count
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Glycopeptides Teicoplanin
Actinoplanes teichomyeticous Mixture of 6 closely related compounds
Similar to vanco in structure and mechanismand 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
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daptomycin
Cyclic lipopetide
MA binds to bacterial plasma membranecausing membrane depolarization andrelease intracellular ions cell damage
MRSA, VRSA ,penicillin resistantpneumonia ,VRE
Uses same as that of vancomycin
Adv- rash headache GI disturbances
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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 phospholipidsand penetrate the cell wall and disruptscell membrane and increased permeability
and leak.(detergent action) Spectrum- gr-ve bact-enterobacter, E. coli,
Klebsiella, salmonellae, pseudomonas
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Not absorbed orally(given for local action orally)
Given IV, do not cross BBB, excreted unchanged
Uses:
1. topical skin, ocular and mucous membraneinfections
2. orally- enteritis due to shigella, kleb,
enterobacter, pseudomonas3. UTI-(pseudomonas and not proteus)
SE: 1. nephrotoxicity: proteinuria and renal failure
2. Ototoxic3. Increased NM blocking action
4. Histamine release- bronchospasm,
hypotension, flushing5/5/2012 19DR.GIRISH MB
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BACITRACIN
MIXTURE OF POLYPEPTIDES Antibiotic obtained from bacillus
subtilis(tracy strain 1943)
Bactericidal- inhibit cell wallsynthesis(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
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Uses- skin, eye, wound infections caused bygm+ve organisms including
staphylococcus(not on unbroken skin) Unwanted effects-
1. highly nephrotoxic
2. potentiates NM blocking
Bacitracin (gram +ve)
Polymyxin(gm-ve)
Neomycin(gm-ve bacilli and gm+ve cocci)
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mupirocin
Topical antimicrobial against S.aureus isan effective agent for such infectionsespecially MRSA strains
Source- pseudomonas fluorescens
MA inhibits protein synthesis by binding tobacterial isoleucyl tRNA synthetase(mammalinan enzymes is 8000 times lesssensitive)
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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 , lowresistance and no cross resistance
Adverse irritation , erythematic and burning
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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 itsabsorption
Excreted in bile, does not cross BBB
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Topical boils , folliculitis
Resistant staph infections of bone andjoint 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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