Drugs and Infectious Diseases (Antibiotics)

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Drugs and Infectious Diseases (Antibiotics)
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2013-10-24 13:55:38
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Drugs Infectious Antibiotics
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Exam 1 (basic science)
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  1. Penicillin G and V action
    • bactericidal
    • Time-dependent (T>MIC)
    • inhibits Transpeptidase activity of PBP1a, 1b, thus inhibiting cell wall synthesis
  2. PEN G and V do NOT work against:
    • PBP2a (MRSA)
    • PBP2x(S. pneumoniae)
    • PBP5 (E. faecium)
  3. PEN G and V Elimination
    Rapidly, unchanged into urine
  4. Most common side effects of Pen G and V
    GI and Allergic manifestations
  5. PEN G Gram + Spectrum
    • Strept. ABCG
    • S. pneumoniae (pen sensitive only)
    • E. faecalis (with gentamicin)
    • C. diptheriae
    • L. monocytogenes (secondary)
    • B. anthracis (secondary)
  6. Pen G Gram negative coverage
    • N. meningitids
    • T. pallidum
    • P. multocida
    • H. ducreyi
  7. Pen G Anaerobe coverage
    • Actinomyces
    • Clostridium spp.
    • Peptostreptococus
    • Prevotella (not all)
  8. Penicillinase Resistant Penicillins
    • Nafcillin
    • Dicloxacillin
    • Cloxacillin
    • Oxacillin
  9. Penicllinase-Resistant Penicillins Action
    • Time-dependent
    • Bactericidal
    • same MOA as PEN G
  10. Aminopenicillin Drugs
    • Ampicillin
    • Amoxicillin
  11. Extended Spectrum Penicillins
    Carboxypenicillin Class ==> Ticarcillin

    Ureidopenicillin Class ==> Piperacillin
  12. Extended Spectrum Penicillins and MSSA
    DOES NOT COVER MSSA
  13. Category D and X Drugs:
    Tetracyclines (includes Tetracycline, Doxycycline, Minocycline) ===> D

    Tigecycline ===> D

    Aminoglycosides (Gentamicin, Tobramycin, Amikacin) ===> D

    Cidofovir (anti-herpetic drug) ===> X

    Ribavirin (HCV treatment) ===> X
  14. First Generation Cephalosporin Coverage:
    PRIMARILY GRAM POSITIVE: (Strept ABCG, S. pneumoniae (NOT PEN-resistant strains), MSSA, NOT MRSA)

    Limited gram negative: (CA Protues mirabilis, E. coli, Klebsiella

    Anaerobes: (MOST PEN-sensitive mouth anaerobes (B. fragilis is resistant))
  15. Penicillin G Spectrum
    Gram Positives (Step. ABCG; S. pneumoniae; L. monocytogenes; B. anthracis; E. faecalis w/ gentamicin)

    Gram Negatives (T. pallidum; N. meningitidis; P. multocida; H. ducreyi)

    Anaerobes (Actinomyces; Clostridium; Peptostreptococcus; Prevotella)
  16. Pen V spectrum compared to G
    • narrower than G
    • does not cover L. monocytogenes or T. pallidum
  17. Does Pen G or V cover MSSA, MRSA, or Gut Anaerobes?
    • NO
    • NO
    • NO
  18. Pen G Clinical Use
    Syphilis (DRUG OF CHOICE; T. pallidum)

    Primary/Secondary prophylaxis of Rheumatic heart disease.

    Erysipelas (NON DIABETICS)

    Strept. pyogenes (Group A Strep. pharyngitis; necrotizing fascitis)

    Clostridial infections (NOT C. diff)
  19. PEN V Clinical Use
    Strept. A, C, G (pharyngitis; tonsilitis)

    P. multocida

    Erysipelas (DIABETICS; better than Pen G)
  20. Jarish-Herxheimer Rxn:
    • - NOT AN ALLERGIC REACTION
    • Systemic Reaction occurring 1-2 hours after initial treatment of syphilis with effective antibiotics
    • - Pen G has a rapid rxn against T. palladium, releasing heat stable pyrogens

    -Flu-like symptoms, tachycardia, hyperventilation, vasodilation, self-limiting

    -Caution in patients (pregnancy, highly debilitated pts.; pts. with CV or neurological symptoms)
  21. Pen G and V D-D interactions
    Oral contraceptives decrease efficacy

    Colestipol decreases PEN V absorption (separate the doses)

    Probenecid blocks active tubular secretion of many drugs (prolongs PEN T 1/2)
  22. Penicillinase Resistant Drugs
    • Nafcillin
    • Dicloxacillin
    • Cloxacillin
    • Oxacillin
  23. Penicllinase-Resistant Penicillin MOA
    • BACTERICIDAL
    • TIME-DEPENDENT
    • SAME MOA AS PEN G
  24. Penicillinase Resistant Penicillin Spectrum
    • NO GRAM NEGATIVES
    • NOT MRSA, MSSA, or S. epidermidis (gram positives)
  25. Penicillinase-Resistant Penicllins PK
    • unchanged into urine
    • IF RENALLY IMPAIRED: BILE (no need to renally adjust the dose)
  26. Nafcillin (Penicillinase-Resistant Penicillin) Adverse Effect
    Reversible Neutropenia (esp. if > 21 days with >2 g/day)
  27. Oxacillin (PRP) AE
    reversible hepatic dysfunctin with doses > 2 g/day
  28. Aminopenicllin Drugs
    • Ampicillin
    • Amoxicillin
  29. Aminopenicillin MOA
    SIMILAR TO PEN G
  30. Aminopenicillin Spectrum
    Gram Positives (SAME as PEN G: PLUS: E. faecium; S. epidermidis; L. monocytogenes; S. pneumoniae (PEN sensitive)

    Gram Negatives (N. meningitids; P. mirabilis; P. multocida; H. pylori (AMOX ONLY); H. influenzae (non-ß-lactamase strains))

    Anaerobes: same as PEN G

    Other: B. burgdoferri (Lyme Disease; Amox only)
  31. Aminopenicllin PK
    Excreted into urine and bile (enterohepatic circulation)

    DECREASE DOSE if CrCl < 10-20 mL/min
  32. Aminopenicllin Adverse Effects
    • same as PEN G and V
    • PLUS: INCREASED RISK OF C. difficile (Amp > Amox); increased risk of serum sickness; rash
  33. Extended Spectrum Penicillins (ESPs) Drugs
    • Carboxypenicillins (Ticarcillin)
    • Ureidopenicillins (Piperacillin)
  34. ESPs Spectrum
    • COVERS MSSA in combination with BLI
    • AEROBIC GRAM NEGATIVE (esp. Enterobacter)
    • Gram Negatives:
    • -N. meninigitis
    • -Enterobacter (Shigella, Salmonella, Serratia)
    • -Aeromonas, P. aeruginosa (depends on local sensitivity, need testing
    • -P. multocida
    • Piperacillin ==> also E. coli, NOT Serratia

    • Gram Positives:
    • -Same as PEN G; except E. faecalis for Ticarcillin

    Anaerobes: same as Pen G
  35. ESP PK
    • mostly unchanged in urine
    • BILIARY EXCRETION INCREASES AS RENAL FUNCTION DECREASES (no need to adjust the dose)
  36. Adverse Effects of ESP (Ticarcillin and Piperacillin)
    GI and allergic manifestations

    • Bleeding (binds ADP receptor on platelets (Tic>Pip)
    • Neutropenia (Pip)
    • Phlebitis (inflamed vascular walls of veins)
  37. 1st Gen. Cephalosporin Drugs
    • Cefazolin (Parenteral)
    • Cephalexin
    • Cefadroxil
    • Cephradine
  38. Cephalosporin MOA
    • BACTERICIDAL
    • TIME-Dependent Action
  39. 1st Gen Cephalosporin Spectrum
    • Gram Positives (VERY ACTIVE AGAINST GRAM POSITIVE AEROBIC COCCI)
    • -Strept. (ABCG; pneumoniae; viridans)
    • Staph. (MSSA; NOT MRSA)

    • Gram Negatives:
    • -CA Proteus mirabilis
    • -E. coli
    • -Klebsiella

    • Anaerobes:
    • -similar to PEN G (i.e. oral only)
  40. Cefazolin
    • 1st gen cephalosporin
    • parenteral only
    • surgical wound prophylaxis (foreign body implantation)
  41. 2nd Generation Cephalosporin Drugs
    • Laracarbef
    • Cefaclor
    • Cefonicid
    • Ceforanide
    • Cefprozil
    • Cefuroxime axetil
    • Cefoxitin (Cephamycin)
    • Cefotetan (Cephamycin)
  42. Cephamycins (not really 2nd gen. cephalosporins)
    Cefoxitin and Cefotetan

    • Gram +
    • -LESS ACTIVE AGAINST GRAM +

    • Gram Negative
    • - LESS vs. Proteus, E. coli, Klebsiella
    • -EXTENDED COVERAGE vs. Enterobacteriaceae
    • ORAL AND GI Anaerobes

    • Cefotetan < Cefoxitin vs. gram + aerobes
    • Cefotetan < Cefoxitin vs. NON B. fragilis spp.

    UNCHANGED into urine
  43. TRUE 2nd gen. cephalosporins spectrum
    • NOT MRSA or Enterococci spp.
    • LESS active vs. gram + compared to 1st gen
    • EXCEPTIONS: (in which 2nd gen is > 1st gen)
    • - cefprozil > vs. Strept. and Staph.
    • -Cefuroxime > vs. S. pneumoniae and S. pyogenes
    • -Cefaclor = Cefazolin

    • Gram Negative:
    • > vs. Proteus, E. coli, Klebsiella
    • PLUS M. cararrhalis, H. influenzae

    Anaerobes: ORAL, NOT GI
  44. 3rd Generation Cephalosporin Drugs
    • Parenteral:
    • -Cefoperazone
    • -Cefotaxime
    • -Ceftriaxone
    • -Cefizoxime
    • -Ceftiazidime

    • Oral Suspension
    • -Cefixime

    • Oral Prodrug: take with food
    • -Cefpodoxime proxetil
    • -Cefditoren pivoxil

    • Ceftibuten (take WITHOUT food)
    • Cefdinir (red stools)
    • Cefditoren
  45. BIG FOUR 3rd Gen. Cephalosporin
    • Cefotaxime
    • Ceftriaxone
    • Ceftizoxime
    • Ceftazidime

    EXCELLENT GRAM NEGATIVE COVERAGE and GRAM POSITIVE

    NO GI ANAEROBES, QUESTIONABLE vs. ORAL ANAEROBES
  46. Cephalosporin with MTT Moiety
    Cefotetan (Cephamycin class)

    • MTT (Methyltetrathiazole) = competitive inhibitor of Vitamin K Carboxylase (VKC)
    • -VKC is needed for anticoagulation pathway (chelation of calcium)
    • -also blocks Vitamin K Epoxide Reductase

    INCREASES RISK OF BLEEDING

    • Drug-Drug interactions:
    • -increases effect of anticoagulants
    • -induced ethanol intolerance (Acetylaldehyde dehydrogenase is blocked)
    • -probenecid decreases excretion of Cefotetan
  47. 4th Generation Cephalosporins
    Cefepime

    • DOES NOT COVER MRSA
    • EXCELLENT VS. GRAM NEGATIVE (except B. fragilis)

    ZWITTERION ZWITTERION ZWITTERION (increases penetration via porin channel through outer membrane of gram-negative organisms)

    mostly unchanged in urine (excretion)

    MAJOR CLINICAL USE: moderate to severe nosocomial infections (P. aeruginosa and Enterobacteriaceae)
  48. 5th Gen. Cephalosporin
    Ceftibiprole Medocaril; Ceftaroline Fosamil

    COVERS MSSA, MRSA, VISA

    NOT FOR C. dfficile

    • Clinical Uses:
    • -Complicates SSTI
    • -Nosocomial Pneumonias
    • -CAP requiring hospitalization
  49. ß-lactamase inhibitors
    • Serine-dependent
    • -A
    • -C
    • -D
    • SerOH group attacks C=O of lactam ring

    • Metallo-Dependent (zinc)
    • -B
    • anionic intermediate is stabilized by interactions with zinc

    • Clavulunate
    • Tazobactam
    • Sulbactam
  50. ß-Lactamase Inhibitors/ß-Lactam Antibiotic Combinations
    • TAPA
    • CCTS

    • Ticarcillin/Clavulunate
    • Amoxicillin/Clavulunate
    • Pipercillin/Tazaobactam
    • Ampicillin/Sulbactam

    Tazobactam > Clavulunate >>> Sulbactam

    TRANSIENT (not irreversible) inhibition of ß-lactamase

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