Pharm- Antibiotics

  1. mutation
    responsible for most resistance in an organism

    occurs constantly in nature, unrelated to antibiotics
  2. transduction
    transfer of drug resistance gene from one cell to another via a phage
  3. transformation
    uptake of drug resistance plasmids (DNA), present in the immediate environment
  4. conjugation
    transfer of resistance genes via direct contact through a sex pilus or bridge

    involves resistance factor (RF) and resistance transfer factor (RTF)

    a single plasmid can confer multiple drug resistance
  5. MIC vs. MBC
    minimal inhibatory concentration shows no growth in 24 hours

    minimal bacteriocidal concentration (99.9% killed)

    MIC usually sufficient in choosing dose, unless using a drug with low threapeutic index on a severe infection
  6. importance of the location of infection when choosing a drug
    must always have the MIC at the site of infection, since not all drugs penetrate equally into all parts of the body
  7. importance of renal function in choosing an antibiotic
    most antimicrobials are excreted by the kidneys

    impaired renal function = sustained blood levels
  8. route of administration in choosing abx
    determined by properties of the drug and severity of infection

    some drugs are not well absorbed after oral dosing, like vancomycin
  9. neutropenic patients and abx
    pt w/ immune disorder not usually given bacteriostatic drug
  10. drug allergies when choosing abx
    all antimicrobial agents have the potential to cause a reaction

    most common offenders are penicillins


    skin tests are not always diagnostic
  11. indications to treat with combined antimicrobial agents
    • 1. Tx of mixed infections
    • 2. Tx of severe infections when etiology is not known (CYA principle)
    • 3. Enhancement of antimicrobial activity in treating a known infection (synergy)
    • - penicillin and streptomycin in treating enterococcal endocarditits
    • 4. Prevention of emergence of resistant organisms (often in TB Tx)
  12. disadvantages of combined antimicrobial therapy
    • 1. Drug antagonism (bacteriostatic drug used with a bacteriocidal drug)
    • 2. Unnecessary patient exposure (toxic effects can also be synergistic)
  13. most extensive use of antimicrobial prophylaxis
    prevention of wound infection during surgery
  14. misuses of antimicrobial agents
    • 1. Treatment of untreatable infections (viral, etc)
    • 2. Therapy of a fever of undetermined orgins
    • 3. Improper dose (can be from lack of pt compliance)
    • 4. Reliance on chemotherapy with omission of surgical drainage
    • 5. Lack of adequate bacteriological information (ID of MO, sensitivity, etc)
  15. def. of suprainfections
    emergence of resistant organisms, often in the GI tract, after reduction by antimicrobial agents of the more susceptable organisms

    often from Clostridium difficile

  16. common use of sulfonamides
    treatment of urinary tract infections due to susceptable bacteria
  17. sulfonamides are all structural analogs of ....
    PABA, which is needed to make folic acid
  18. mechanism of action of sulfanomides
    inability to make folic acid

    without folic acid, the cell has less tetrahydrofolate available

    therefore, cell is unable to convert dUMP to TMP

    therefore, inhibition of folic acid synthesis prevents bacteria from replicating DNA
  19. action of sulfanomides

    therefore, sulfanomides have little or no effect without a competant immune system

    can't be used with bacteriocidal drugs, b/c will reduce their effectiveness
  20. microbial resistance to sulfanomides
    microbes with greatly enhanced levels of PABA and folic acid

    the increased levels of these substrates bypass the metabolic block caused by the drug
  21. toxicity of sulfanomides
    • 1. agranulocytosis (rare, usually can be reversed)
    • 2. thrombocytopenia (mild)
    • 3. aplastic anemia (very rare, can be fatal)
    • 4. acute hemolytic anemia (assoc. w/ lack of erythrocyte glucose-6-phosphate dehydrogenase activity; most commonly seen in blacks)
  22. most severe hypersensitivity to sulfonamides
    Stevens-Johnson syndrome
  23. major use of sulfonamide today is with...
  24. how trimethoprim works
    inhibits dihydrofolate reductase

    the mammalian DHFR is only inhibited at concentrations over 10,000x higher than the bacterial enzymes, therefore safe in humans
  25. cause of trimethoprim resistance
    mutant DHFR enzyme which will no longer bind the drug
  26. therapeutic uses of sulfonamide plus trimethoprim
    uncomplicated lower urinary tract infections

    GI infections

    pneumocystis carnii infections (common in AIDS patients)

    prophylaxis in neutropenic patients (organ transplant patients)
  27. common action of both sulfonamides and trimethoprim
    prevent the production of tetrahydrofolate-C1 and threfore inhibits synthesis of DNA

    both are bacteriostatic
  28. major mechanism of resistance for sulfanomides and trimethoprim
    sulfa: overproduction of PABA

    TMP: mutant DHFR enzyme will not bind the drug
  29. how beta lactam drugs work
    inhibit cell-wall synthesis in bacteria
  30. enzyme inhibited by penicillin
    transpeptidase (inserts bridge in the last step in formation of the cell wall)
  31. acid stable penicillins
    penicillin V (same action, but better absorbed in GI tract)
  32. penicillinase resistant penicillins
    methicillin (these drugs should be used only when it is known that the infecting bacteria produces penicillinase)
  33. broader spectrum penicillins
    ampicillin, amoxicillin

    active against gram negative bacteria, but are destroyed by beta lactamases
  34. penicillin metabolism
    all penicillins are excreted almost unchanged

    through glomerular filtration

    the exception is cloxacillin (metabolized in liver)
  35. penicillin hypersensitivity
    often mild, but can include anaphylaxis
  36. MRSA
    major cause of hospital-acquired infections

    do not produce penicillinases

    resistant to other beta-lactam antibiotics as well as other antimicrobial agents of diverse structures and modes of action

    can be acquired by mecA gene
  37. mode of action of cephalosporins
    identical to penicillins

    very similar side effects

    there is a high cross-over of penicillin allergic patients that are also allergic to cephalosporins
  38. 1st generattion cephalosporins
    • 1. cephalothin (parenteral only, easily broken down by staphylococcal beta lactamase)
    • 2. cefazolin (more susceptable to beta lactamase)
  39. 2nd generation cephalosporins
    more active against gram negative than first generation

    • 1. cefamandole (can't drink alcohol on this drug due to "disulfuram reaction")
    • 2. cefuroxime (like the first, but longer acting)
  40. 3rd generation cephalosporins
    ceftriaxone (long half life, very effective in treating gonorrhea)
  41. therapeutic uses of cephalosporins
    prophylaxis during and after surgery

    3rd generation groups are DOC for meningitis caused by gram negative bacteria

    ceftriaxone used to treat gonorrhea, unless strain is tested to be sensitive to penicillin

    sometimes used as penicillin alternative in patients that can't take PCN (although some are allergic to both)
  42. adverse rxn to cephalosporins

    "disulfuram" reaction with alcohol (cefamandole, cefoperazone)
  43. beta-lactamase inhibitors
    clavulanic acid

    has no bacteriostatic or cidal features

    combined with amoxicillin to make Augmentin
  44. bacitracin
    inhibitors of cell-wall synthesis by inhibiting a phosphatase enzyme

    very few side effects
  45. fosfomycin
    inhibits MurA, which catalyzes the first step in making peptidoglycan


    can be used as a single dose Tx for urinary tract infections

    safe to use in pregnancy
  46. vancomycin
    binds to D-ALA-D-ALA, so cell wall can't polymerize

    "red man syndrome" if given rapidly IV (anaphylaxis, fever, shock-like state)

    very expensive

    resistance is a growing problem
  47. major uses of vancomycin
    DOC for MRSA

    DOC for antibiotic associated colitis (AAC)
  48. enzyme involved in linking reaction of protein synthesis
    peptidyl transferase
  49. major uses of aminoglycosides
    treatment of infections caused by aerobic gram negative bacteria

    often given with beta lactam drug, but not in the same solution
  50. mechanism of action of aminoglycosides
    • 1. streptomycin (interacts with the 30s subunit of the ribosome)
    • - blocks protein synthesis at the level of initiation

    ALL aminoglycosides are bacteriocidal
  51. aminoglycoside resistance
    most important mechanism is "resistance caused by aminoglycoside modifying enzymes" which inactivate the drug

    the genes for these enzymes are carried on plasmids which are conjugally transmitted

  52. aminoglycoside side effects
    • damage to 8th cranial nerve (irreversible)
    • - loss of sensory cells in vestibulocochlear organs
  53. therapeutic index of aminoglycosides
    very narrow
Card Set
Pharm- Antibiotics