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

5/5/2012 1DR.GIRISH MB


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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

5/5/2012 DR.GIRISH MB 4


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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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Other Agents Used in Gm Positive Infections

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