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    Aminoglycoside & Cephalosporins

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    krishnakumar
    The document discusses aminoglycoside and cephalosporin antibiotics. It provides details on their mechanisms of action, spectra of activity, pharmacokinetics, toxicities and clinical uses. Aminoglycosides interfere with bacterial protein synthesis and are used for aerobic gram-negative infections. Cephalosporins inhibit bacterial cell wall synthesis and include both narrow and broad-spectrum agents used for various bacterial infections. Both drug classes can cause ototoxicity, nephrotoxicity and neuromuscular blockade, requiring monitoring and dosage adjustment.

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    Aminoglycoside & Cephalosporins

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    krishnakumar
    18 views30 pages
    The document discusses aminoglycoside and cephalosporin antibiotics. It provides details on their mechanisms of action, spectra of activity, pharmacokinetics, toxicities and clinical uses. Aminoglycosides interfere with bacterial protein synthesis and are used for aerobic gram-negative infections. Cephalosporins inhibit bacterial cell wall synthesis and include both narrow and broad-spectrum agents used for various bacterial infections. Both drug classes can cause ototoxicity, nephrotoxicity and neuromuscular blockade, requiring monitoring and dosage adjustment.

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    The document discusses aminoglycoside and cephalosporin antibiotics. It provides details on their mechanisms of action, spectra of activity, pharmacokinetics, toxicities and clinical uses. Aminoglycosides interfere with bacterial protein synthesis and are used for aerobic gram-negative infections. Cephalosporins inhibit bacterial cell wall synthesis and include both narrow and broad-spectrum agents used for various bacterial infections. Both drug classes can cause ototoxicity, nephrotoxicity and neuromuscular blockade, requiring monitoring and dosage adjustment.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    18 views30 pages

    Aminoglycoside & Cephalosporins

    Uploaded by

    krishnakumar
    The document discusses aminoglycoside and cephalosporin antibiotics. It provides details on their mechanisms of action, spectra of activity, pharmacokinetics, toxicities and clinical uses. Aminoglycosides interfere with bacterial protein synthesis and are used for aerobic gram-negative infections. Cephalosporins inhibit bacterial cell wall synthesis and include both narrow and broad-spectrum agents used for various bacterial infections. Both drug classes can cause ototoxicity, nephrotoxicity and neuromuscular blockade, requiring monitoring and dosage adjustment.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 30

    Aminoglycoside &

    Cephalosporins

    Krishna Kumar .M.J


    Aminoglycosides
    Bactericidal antibiotics
    Interfere with protein synthesis
    Used to treat aerobic Gram –ve bacteria
    Sulfate salts,higly water soluble.
    Resemble each other in MOA,
    pharmacokinetic therapeutic and toxic
    properties
    Relatively low margin of safety
    Exhibit ototoxicity and nephrotoxicity
    Chemistry
    Amino - 2- - Amino
    sugar o- deoxystreptam o- sugar
    ine
    Aminoglycosides
    Structure

    Streptidi - Streptose - N-Methyl-


    ne o- amino sugar o- L
    glucosam
    ine amino
    Streptomycin sugar
    structure
    Streptobiosam
    ine
    Aminoglycosides
    Systemic Topical
    a) Streptomycin a) Neomycin
    b) Gentamicin b) Framycetin
    c) Kanamycin
    d) Amikacin
    e) Sisomicin
    f) Tobramycin
    g) Netilimicin
    Mechanism of action
    • Initially they penetrate
    bacterial cell wall, to
    reach periplasmic space
    through porin channels
    (passive diffusion)
    • Further transport across
    cytoplasmic membrane
    takes place by active
    transport by proton
    pump; an oxygen-
    dependent process
    Mechanism of resistance
    Synthesis of plasmid mediated bacterial
    transferase enzyme: Inactivate
    aminoglycosides
    ↓ transport into bacterial cytosol
    Deletion/alteration of receptor protein on 30 S
    ribosomal unit by mutation: prevents
    attachment
    Antibacterial spectrum
     Primarily against Gm –ve aerobic bacilli
    Proteus, pseudomonas
    E.Coli,enterobacter
    Klebsiella
    Shigella
    Only few Gm +ve cocci:
    staph aureus, strepto viridans
    Not effective against Gm +ve bacilli, Gm-ve
    cocci and anaerobes
    Pharmacokinetics
    Highly polar basic drugs: poor oral BA
     Administered parenterally or applied
    locally
    Poorly distributed and poorly protein bound
    Do not undergo any significant metabolism
    Nearly all IV dose is excreted unchanged in
    urine
    Dose adjustment is needed in renal
    insufficiency
    Shared toxicities

    Ototoxicity
    Vestibular damage
    Cochlear damage
    Nephrotoxicity
    Neuromuscular blockade
    Ototoxicity
    May be irreversible
    Cochlear damage
    Hearing loss and tinnitus
    More with neomycin , amikacin and kanamycin
    Vestibular damage
    Vertigo, ataxia, loss of balance
    More with Streptomycin, gentamycin
    Tobramycin has both types of toxicity
    Netilimycin claimed to have low ototoxicity
    Nephrotoxicity
    Reversible if drug promptly discontinued
    Gentamicin, amikacin and tobramycin are
    more toxic than streptomycin
    Responsible for 10-15% of all renal failure
    cases
    ↓ GFR, ↑ sr creatinine
    ↓clearance of antibiotic → ↑ ototoxicity
    Neuromuscular blockade
    Cause N-M junction blockade by
    Displacing Ca2+ from NM junction
    By blocking post synaptic NM receptors
    Inhibiting Ach release from motor nerve
    Neomycin & streptomycin: more propensity
    Tobramycin least likely to produce it
    Myasthenic weakness ↑by these drugs
    Precautions /
    Contraindications
    Pregnancy: foetal ototoxicity
    With other ototoxic drugs: furosemide,
    minocycline
    With nephrotoxic drugs: vancomycin ,cisplatin
    Elderly patients
    Those with kidney disease
    Cautious use of muscle relaxants
    Do not mix with any other drug in same
    syringe
    Streptomycin
     Ribosomal resistance develops fast

     Active against aerobic gram –ve bacteria


     H.ducreyi,brucella,yersinia,norcardia,M.tb,E.coli,V.cholera,shigella,
    Klebsiella & some gram +ve cocci

     Limited usefulness as single agent

     Plague, tularemia and brucellosis


     In combination with tetracycline
     SABE: due to Streptococcus Viridans & faecalis
     With penicillin but gentamicin preferred

     Reserve first line drug for tuberculosis used only in combination


    Gentamicin
     Obtained from Micromonospora purpurea

     Most commonly used aminoglycoside for Acute infections


    a) More potent than Streptomycin

    b) Broader spectrum: pseudomonas, proteus, E.coli, klebsiella,


    enterobacter, serratia,UTI,osteomyelitis,ear inf,meningitis

    c) Low cost, reliability of use, long experience

    d) Acts synergistically with ampicillin, penicillin G, Ticarcillin,


    ceftriaxone, Vancomycin

     Relatively more nephrotoxic


    Gentamicin (Uses)
     Use restricted to serious Gm-ve bacillary infections

     Septicaemia, sepsis, fever in immunocompromised patients


     Used with penicillins

     Pelvic infections : with metronidazole

     SABE: with Penicillin G or ampicillin or vancomycin

     Coliform infection: with ampicillin or ceftriaxone

     Pseudomonal infections: with ticarcillin

     Meningitis by Gm-ve bacilli : III generation cephalosporin alone or with


    gentamicin
    Guideline for adjustment of dose in
    renal insufficiency
    Tobramycin
    Identical to gentamicin
    Used in pseudomonas and proteus infections
    Ototoxicty and nephrotoxicity probably lower

    Sisomicin
    • Identical to gentamicin
    • More potent on pseudomonas and -hemolytic
    streptococci
    • Combined with penicillin for SABE
    • Used interchangeably with gentamicin
    Amikacin
    Less toxic semisynthetic derivative of
    kanamycin
    Resistant to enzymes that inactivate gentamicin
    and tobramcyin
    Widest spectrum of activity
    Uses:
    Same as gentamicin
    Reserve drug for hospital acquired Gm-ve bacillary
    infections
    Multidrug resistant TB along with other drugs
    Dose : 15mg/kg/day in 1-3 doses
    Netilimicin
    Semisynthetic derivative of sisomicin
    Relatively resistant to aminoglycoside
    inactivating enzymes
    More active against klebsiella, enterobacter &
    staphylococci
    Less active against pseudomonas aeruginosa
    Doses and pharmacokinetics similar to
    gentamicin
    Neomycin
     wide spectrum active against Gm-ve bacilli and some gm+ve
    cocci
     Pseudomonas and strep.pyogenes not sensitive

     Too toxic for parenteral use , limited to topical use

     Topically used in skin, eye and external ear infections


    combined with bacitracin or polymyxin-B to widen antibacterial
    spectrum and to prevent emergence of resistant strains

     Orally
    Preparation of bowel before surgery 1 gm TDS
    Hepatic coma: Supresses ammonia forming coliforms
    prevents encephalopathy (Lactulose more preferred)
    Cephalosporins
    Any of various broad-spectrum beta- lactam
    antibiotics closely related to the Penicillins,
    that were originally derived from the fungus,
    Cephalosporium acremonium
    Bactericidal
    Inhibition of bacterial cell wall synthesis.
    Mech of Resistance :
    Alteration in PBPs
    Decrease permeability
    Production of b-lactamase enzyme (enzyme
    inactivation).
    Adverse Effect
    Thromboflebitis
    Diarrhoea – common with oral cepharidine,IV
    cefoperazone
    Hypersestivity rxn
    Nephrotoxicity – high in cephaloridine,low with
    cephalothin.
    Bleeding – cefoperazone,ceftriaxone
    Prolong BT
    Neutropenia & Thrombocytopenia - Ceftazidime

    Indications
    Resp.tract inf, UTI,soft tissue inf : gram –ve
    org(Enterobacter,Serratia,Proteus,Kleb)
    :cefuroime,cefotaxime,ceftriaxone.
    Penicillinase producing Stah inf : cephalothin.
    Septicemia : aminoglycoside + cephalo
    Surgical prophylaxsis – Ist gen cephalo
    Meningitis(H.inf,Enterobacter):cefuroxime,cefotaxime,ceftriax
    one
    Pseudo. Meningitis – ceftazidime + genta
    Gonorrhoea
    Typhoid
    Mixed aerobic – anaerobic inf – cefuroxime or 3rd gen
     prophylaxis & Rx in neutropenic pts – ceftazidime or 3rd gen
    or with aminoglycoside.
    Good activity v
    Staphs and Streps

    Increased activity v Gram Nega


    Slightly less activity
    against Gram Positives
    Cefuroxime-ampicillin rest H.inf,meningitis
    caused by h.influ ,meningococci,pneumococci,G
    +ve cocci
    CEFACLOR : H.inf,E.coli,proteus
    Very good Gram negative coverag
    Reasonable against Gram Positive
    Ceftazidime has anti-pseudomonal ac

    CEFOTAXIME :aerobic G –ve & +ve,,indicate in


    menigitis,hospital acq if,septicemia & inf in
    immunocompromised children
    Dose : 1 – 2 iv or im 6-12 hrly.

    CEFTRIAXONE : long duration of action,good CSF


    penetration,menigitis,multires. Typhoid
    fever,UTI,Abd.sepsis,
    Adv effect- bleeding

    CEFOPERAZONE : against
    Pseudomonas,S.typhi,Brucella
    UTI,Resp,skin,soft tissue inf,Adv effect –
    hypoprthrominemia.

    CEFIXIME : against
    enterobacter,H.inf,S.pyogenes,pnumoniae,
    Longer acting,Adv effect – diarrhoea,Dose – 200 -
    400mg BD
    Very broad spectrum activity
    including Pseudomonas

    CEFEPIME – pseduomonas,S.aureus,in hospital


    acq pneumonia,sepicemia,
    Dose – 1-2 g iv 8-12hrly

    S.aureus,Srept.pneu
    moniae,Pseudo,Enter
    ococci,
    M/C in MRSA
    Thank
    You

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