Pharm CH 29

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Pharm CH 29
2013-10-15 15:57:49
Pharm 29

Pharm CH 29 Antibacterial Agents Penicillins Cephalosporins
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  1. Bacteria:
    single celled organisms

    reproduce by cell division about q 20 mins

    have a rigid cell wall and the structure of the wall determines the shape of
    the bacteria.


    –Cocci- spherical

    –Cocci in clusters-

    –Cocci in chains-
  2. Another classification of bacteria involves staining.

    •Gram staining is determined by the ability of the cell wall to retain a purple stain
    by a basic dye.

    Gram + bacteria turn purple (retain the dye)



    Group B streptcoccus

    Gram– bacteria not stained by dye

    Neisseria meningitides

    Escherichia coli

    Haemophilus influenzae
  3. Types of Antibiotic Therapy

    •Empiric therapy: prior to definitive dianosis
    prescribed antibiotic w/o test of cultures

    •Prophylactic therapy:
    treatment before a problem, ex. Amoxicilin when go to a dentist before oral treatment

    •Therapeutic therapy:
    Know exactly what it is and treat it with exact antibiotic
  4. Beta-lactamase

    •Many bacteria produce the enzyme beta-lactamase, which destroys beta-lactam antibiotics such as PCN ( penicilin) and cephalosporins.

  5. Antibacterial Drugs

    •Antibacterial, antimicrobial, antibiotics, are used interchangeably.

    •Do not act alone:

    –Natural body defenses ( immune system, if immune compromized very difficult to fight bacteria)

    –Surgical procedures to excise infected tissue (remove dead tissue, form of debride)

    –Dressing changes (when you change it, all the puss gets cleaned out, remains on the dressing)

    •Obtained by either natural resources or manufactured.

    •PCN marketed in 1945 ( mas marketed to soldiers , dying on the field)

    •Sulfonamide a synthetic antibacterial introduced in 1935

  6. Bacteriostatic/Bactericidal

    Bacteriostatic drugs inhibit the
    growth of bacteria

    Bactericidal drugs kill bacteria

    –Tetracycline and sulfonamides are bacteriostatic

    –PCN and cephalosporins are bactericidal

    –Some drugs can be both
  7. Mechanisms of Antibacterial Action

    5 mechanisms of antibacterial action are responsible for the inhibition of growth
    and destruction of microorganisms:

    • –Inhibition of bacterial cell wall synthesis

    –Alteration of membrane permeability

    –Inhibition of protein synthesis

    –Inhibition of the synthesis of bacterial RNA and DNA

    –Interference with metabolism within the cell
  8. Pharmacokinetics (ADME)

    •Antibacterial drugs must penetrate the cell wall with sufficient concentration and have an affinity to the binding sites on the bacterial cell.

    –The longer it is there the better it works.

    Antibacterials that have a longer
    half life usually maintain a greater concentration at the binding site;
    therefore frequent dosing is not required.

    –Remember steady state of antibacterials occur after the 4th or 5th half lives

  9. Pharmacodynamics

    •The drug concentration at the site and length of time at site plays an important
    role in bacterial eradication.  Antibacterials drugs are used to
    achieve the MEC necessary to halt the growth of a microorganism.

    •With some severe infections, a continuous infusion regimen is more effective than
    intermittent dosing because of the constant drug concentration and time
  10. Pharmacodynamics (con’t)

    The effect of antibacterial drugs has on an infection depends not only on the drug
    but also on:





    •Organ function

    •Circulation- if circulation is impeded- the drug may not be distributed properly to the infected area

    if poor circulation the drug is not going there

  11. Resistance to Antibacterials

    •Bacteria may be sensitive or resistant to certain

    –When bacteria are sensitive to a drug, the pathogen is inhibited or destroyed.

    –If bacteria are resistant to an antibacterial, the pathogen continues to grow,
    despite administration of the antibacterial drug.

    •Resistance may result naturally (occurs without previous exposure)  or it may be acquired (prior exposure to the

  12. Resistance to Antibacterials

    Penicillinase, an enzyme produced
    by the microorganism, is responsible for causing its Penicillin resistance (penicilinaze breaks down penicilin structure).

    •Penicillinase metabolizes penicillin G,
    causing the drug to be ineffective.

    •Penicillinase-resistant penicillins that are effective against S. aureus are currently

  13. Nosocomial Infections

    •Infections acquired while clients are hospitalized.

    –In large healthcare institutions, there is a tendency toward drug resistance in

    –Mutant strains of bacteria have developed, thus increasing their resistance to
    antibiotics that were once effective against them.
  14. Antibiotic resistance (con’t)

    can transfer their genetic instruction to another bacterial species.

    •The other bacterial species becomes resistant to that antibiotic as well.

    Methicillin was the first penicillinase-resistant PCN developed.  

    –MRSA –highly resistant bacteria became resistant not only to methicillin, but to all PCN’s
    and cephalosporins.

    –In 1981 seen in the community

    –Methicillin no longer on the
    market- drug of choice in tx
    of MRSA vancomycin.
  15. •VREF:
    vanco resistant enterococci faecium

    –reported strain resistant to vanvo-VRSA- If this becomes prevalent, a major medical
    problem could result

    •Linezolid (Zyvox), is effective
    against MRSA, VREF, and PCN resistant strptococci.

    •Synercid IV- used against
    life threatening infections caused by VREF, tx of bacteremia.

    •In development bacterial vaccines- the bacterial vaccine against pneumococcus has been effective in decreasing the occurrence of pneumonia and meningitis.
  16. Remember

    •When antibiotics are taken unnecessarily, incorrectly, or stops prematurely, one may
    develop resistance to antibacterials.

    •Antibiotics are ineffective against viruses
  17. Cross- Resistance

    •Can occur between antibacterial drugs that have similar actions such as the penicillins and cephalosporins.

    •To assure the effectiveness of a drug prescribed for a certain microorganism,
    culture and sensitivity testing is performed.

    •A C&S can detect the ineffective microorganism present in a sample and what
    drug can kill it.

  18. C&S

    The organism causing the infection is determined by culture.

    •The antibiotic the organism  is sensitive
    to are determined by sensitivity.

  19. Antibiotic Combinations

    •Combination antibiotics should not be routinely prescribed or administered except for
    specific uncontrollable infections.

    –Usually a single antibiotic will successfully treat a bacterial infection

    –Take C&S before beginning any antibiotic!!

  20. Spectrums of Antibiotics

    •Narrow Spectrum are primarily effective against one type of organism.

    Example: PCN, erythro are used to tx infections caused by
    Gram + bacteria

    –Broad Spectrum can be effective against Gram +/- organisms.

    –Broad Spectrum ABX’s are frequently used to treat infections when the offending microorganisms has not been identified by C&S.

  21. Penicillin

    •A natural antibacterial agent obtained from mold genus Penicillium.

    beta-lactam structure interferes
    with bacterial wall synthesis by inhibiting the bacterial enzyme that is necessary for cell division and cellular synthesis

  22. Let’s Clarify

    •Penicillians are mainly referred
    to as beta-lactam antibiotics.

    –Bacteria can produce a variety of enzymes, such as beta-lactamases, that can inactivate penicillin and other beta lactam antibiotics such as cephalosporins.

    The beta lactamases, which attack penicillins, are called penicillinases
  23. Penicillin G

    •First PCN given PO and IM.

    –PO only about 1/3 of the dose is absorbed

    –Therefore given IM and IV- more effective in achieving a therapeutic serum penicillin

    –Short duration of action

    –IM painful because it is an aqueous soln.

  24. Penicillin V

    •Next type produced

    2/3 absorbed by GI tract however less potent than PCN G.

    PCN V is effective
    against mild to moderate infections, including anthrax.

    resistant- therefore the development of broad spectrum ABX with structures
    similar to PCN were created. They too combat infections resistant to PCN G and V.

  25. Broad Spectrum Penicillin
    (not broad anymore, old name, now just Penicilin)

    •Used to treat both Gram +/- bacteria.

    •Not all that broad after all.

    •Are effective against some Gram – organisms but these drugs are not penicillinase resistant.

    •They are readily inactivated by beta-lactamases, thus ineffective against S. aureus


    (prototype for penicilin)


  26. Penicillinase-Resistant Penicillins

    •Penicillinase-resistant penicillins  are used to treat penicillinase-producing S. aureus.

    •Not effective against Gram – organisms and is less effective than penicillin G
    against Gram + organisms.

    Dicloxacillin sodium (Dynapen)


    •Oxacillin sodium
  27. Amoxicillin and Dicloxacillin

    Amoxicillin: upper resp tract infections, Urinary Tract Infection (UTI), otitis media, sinusitis

    Dicloxacillin: Staphylococcus aureus infection
    Amoxicillin and Dicloxacillin

    •Pregnancy Category B

    Drug-Lab-Food interactions

    Increase effect with aspirin

    • Decrease effect with  tetracycline
    • and erythromycin

    Decrease effect with acidic juices(orange juice is acidic, no good with meds)

    Side effects:

    A/D: N/V/D and rash

    A: edema, stomatitis(infection or inflamation)

    D: abdominal pain and flatulence(farting)


    Allergy to PCN

    Severe renal disorder

    Caution: allergy to cephalosporin

    •Adverse reactions:

    A/D: Super infections, blood dyscrasias, bone marrow depression

    A: resp distress

    D: liver toxicity(liver function test)
  28. Amoxicillin and Dicloxacillin

    Mode of action: inhibition of cell wall

    synthesis, bactericidal effect

    • look for protein binding Diclocacillin is (95%)
    • Onset and duration not imp
  29. Drug Interactions

    The broad spectrum penicillins (amoxicillin and ampicillin) may decrease the effectiveness of oral contraceptives (need to have barrier contraceptive risk for HIV)

    •When PCN is mixed with an aminoglycoside in IV soln, the actions of both are inactivated.

  30. Beta Lactamase Inhibitors

    When a broad spectrum
    Abx is combined with a
    beta lactamase inhibitor, the
    resulting antibiotic inhibits the bacterial beta-lactamases, making the antibiotic effective and extending its
    antimicrobial effect.

    •Three beta-lactamase inhibitors(not antibiotics):

    –clavulanic acid

    These are not given alone


    –amioxicillin/clavulanic acid (Augmentin)

    –Ampicillin/sulbactam (Unasyn)

    –Piperacillin/tazobactam (Zosyn)

  31. Extended Spectrum Penicillins

    •AKA antipseudomonal penicillins

    •Broad spectrum penicillins

    •Effective against Pseudomonas
    aeruginosa (Gram- bacillus)
    which is difficult to eradicate

    •Also useful against
    many Gram -  organisms example Klebsiella pneumoniae.

    •These penicillins are not penicillinase resistant


    •Piperacillin/tazobactam (Zosyn)

    •Ticarcillin/clavulanate (Timentin)

  32. Cephalosporins(sister and brother to penicilin 10% crosover sensitivity, same backbone as in penicilin)

    Like PCN, the cephalosporins have a beta-lactam structure and act by inhibiting the bacterial enzyme necessary
    for cell wall synthesis. Lysis to the cell occurs, and the bacterial
    cell dies.

    •10% cross over sensitivity!

  33. Generations

    Four groups of cephalosporins have been developed, identified as generations.

    •Each generation is effective against a broader spectrum of bacteria.

    NOT ALL CEPHALOSPORINS  are affected by the beta lactamases
  34. First Generation Cephalosporins

    Destroyed by the beta lactamases

    •Effective against gram + bacteria

    •Effective against most gram – bacteria

    –Cefadroxil (Duricef)

    Cefazolin sodium (Ancef)

    –Cephalexin (Keflex)

  35. Second Generation Cephalosporins

    •Same effectiveness as first generation

    Not all are affected by beta lactamases(not destroyed by beta lactamaze)

    •These antibiotics possess a broader spectrum against other gram – bacteria.

    –Cefaclor (Ceclor)

    –Cefotetan (Cefotan)

    –Cefprozil monohydrate (Cefzil)

    –Cefuroxime (Ceftin)

  36. Cefazolin and Cefaclor

    Therapeutic uses: resp, urinary, skin infections

    Cefazolin: bone and joint
    infections, genital infections, endocarditis

    Cefaclor: ear infections,
    certain gram – and gram + strains.
    • Cefazolin (1st)
    • Cefaclor (2nd)

    •Pregnancy B

    Drug-Lab-Food Interactions:

    Increase toxicity with loop diuretics, aminoglycosides, vanco

    Decrease effect with tetracycline, erythromycin

    •Side effects:

    Both: anorexia(w/o apetite), N/V/D rash

    Cefazolin: abd cramps fever

    Cefacol: pruritis(itching), headaches, vertigo, weakness

    Contraindications: Both: hypersensitivity to cephs

    Caution: hypersensitive to PCN, renal disease, lactation

    •Adverse reactions: superinfections, urticaria(hives),

    Cefazolin: seizures, anaphylaxis

    Cefaclor: renal failure
  37. Cefazolin and Cefaclor

    Mode of action:
    inhibition of cell wall synthesis, causing cell death, bactericidal effect
    • cefaclor rapid PO, don't take if you have renal problems
  38. Third Generation Cephalosporins

    •Resistant to beta lactamases

    •Most are effective in treating sepsis and many strains of gram – bacilli.

    •Same effectiveness as first and second generations.

    •Also effective against gram – bacteria and less effective against gram + bacteria

    –Cefdinir (Omnicef)

    –Cefixime (Suprax)

    –Ceftazidime (Fortaz)

    –Cefpodoxime (Vantin)

    –Cefoperazone (Cefobid)

    Ceftriaxone (Rocephin
  39. Fourth Generation Cephalosporins

    •Similar to third generation

    •Most are effective in treating sepsis and many strains of gram – bacilli.

    •Resistant to most beta-lactamase bacteria

    •Broader gram + coverage than the third generations.

    –Cefepime (Maxipime)

  40.  Side Effects and Adverse Reactions

    •GI disturbances (N/V/D)

    •Alteration in blood clotting time (increased bleeding)

    •Nephrotoxicity in individuals withpreexisting renal disorder.
  41. Drug Interactions

    •ETOH- alcohol

    –Flushing(very miserable),
    dizziness, headaches, N/V and muscular cramps