USMLE Step 1 Antimicrobials

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USMLE Step 1 Antimicrobials
2010-05-24 19:18:08
USMLE antibiotics antimicrobials microbiology pharmacology

USMLE Step 1 Antimicrobials
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  1. Inhibition of peptidoglycan cross-linking in cell wall
    the -cillins plus -penems, aztreonam, cephalosporins
  2. Block peptidoglycan synthesis
    • bacitracin
    • vanc
  3. Disrupt bacterial cell membranes
  4. Block nucleotide synthesis
    • Sulfonamides
    • Trimethoprim
  5. Block topoisomerase II (gyrase)
    Fluoroquinolones (-floxacin, like cipro)
  6. Block mRNA synthesis
  7. Block 50s ribosomal subunit
    • Chloramphenicol
    • Macrolides
    • Clindamycin
    • Streptogramins
    • Linezolid
  8. Block 30S subunit
    • aminoglycosides (gent, neomycin, amikacin, tobramycin, streptomycin)
    • tetracyclines
  9. Bacteriostatic antibiotics
    • Erythromycin
    • Clindamycin
    • Sulfamethoxazole
    • Trimethoprim
    • Tetracyclines
    • Chloramphenicol
  10. Bactericidal
    • vanc
    • fluroquinolones
    • penicillin
    • aminoglycosides
    • cephalosporins
    • metronidazole
  11. Nafcillin, methicillin, dicloxacillin
    • Penicillinase-resistant penicillins
    • Use for s. aureas but not MRSA
    • Methicillin causes AIN
  12. Ampicillin, amoxicillin (aminopenicillins) use and toxicity
    • Combine with clavulanic acid to enhance spectrum
    • Amoxicillin has greater oral bioavailability than ampicillin
    • HELPS cover gram-neg rods: H. flu, E. coli, Listeria, Proteus, Salmonella, enterococci
  13. Ticarcillin, carbenicillin, piperacillin
    • anti-pseudomonals
    • use with clavulanic acid
  14. Anti-pseudomonals
    • ticarcillin, carbenicillin, piperacillin
    • aztreonam
    • fluoroquinolones - oral
    • (carbapenems
    • polymyxins
    • 3rd and 4th generation cephalosporins
    • aminoglycosides)
  15. 1st generation cephalosporins
    • cefazolin and cephalexin
    • cover: gram + cocci, proteus, e. coli, Kleb (PEcK)
  16. 2nd generation cephalosporins
    • cefoxitin, cefaclor, cefuroxime
    • gram + cocci, H. flu, Enterobacter, Neisseria, Proteus, E. coli, Kleb, Serratia
    • From 1st gen, added haemophilus, enterobacter, neisseria, and serratia
  17. 3rd generation cephalosporins
    • ceftriaxone, cefotaxime, ceftazidime
    • coverE: serious gram-neg infxn, meningitis
    • e.g. pseudomonas, gonorrhea
  18. 4th generation cephalosporin
    • cefepime
    • has increased activity against pseudomonas
  19. aztreonam
    • For penicillin allergic patients or renal insuff
    • Gram-neg rods: Kleb, pseudomonas, serratia
    • No activity against gram+ or anerobes
  20. Carbapenems
    • Administer imipenem with cilastatin to decrease inactivation in kidney
    • DOC for enterobacter
    • Gram+ cocci, gram- rods, anaerobes
    • Tox: seizures, GI, rash
  21. vancomycin
    • Binds D-ala-D-ala portion of cell wall precursors
    • Resistance: d-ala-d-lac
    • For s. aureus, c. diff
    • Tox: nephro, oto, thrombophlebitis, redman
  22. Aminoglycosides
    • Inhibit formation of initiation complex
    • Require O2 (use for aerobic organisms only)
    • For gram- rods
    • Tox: nephro, oto, teratogen
  23. Tetracycline
    • Prevents aminoacyl-tRNA attachment at 30S
    • Use doxy in renal failure
    • Use democlocycline as an ADH antagonist in SIADH
    • Use: vibrio, acne, chlamydia, ureaplasma, mycoplasma, tularemia, h. pylori, borrelia, rickettsia
    • Tox: teeth and photosensitivity
  24. Macrolides
    • e.g. erythromycin, azithromycin, clarithromycin
    • Block translocation at 50S
    • Use: strep, mycoplasma, legionella, chlamydia, neisseria
    • Tox: QT, GI, cholestatic hepatitis, eosinophilia
    • Increases theophylline & oral anticoagulants
  25. Chloramphenicol
    • Inhibits 50S peptidyltransferase activity
    • Tox: aplastic anemia, gray baby syndrome (infants lack UDP-glucuronyl transferase)
  26. Clindamycin
    • Blocks peptide bond at 50S
    • For aerobes above the diaphragm
    • Tox: pseudomembranous colitis, fever
  27. Sulfonamides
    • PABA antimetabolites inhibit dihydropteroate synthetase
    • gram+ and - and nocardia, chlamydia
    • UTI
    • Tox: hypersensitivity, G6PDD hemolysis, AIN, photosensitivity, kernicterus in infants
    • Displaces warfarin from albumin
    • Allergic pts also cannot take sulfonylureas, sulfasalazine, thiazide diuretics, acetazolamide, furosemide
  28. Trimethoprim
    • Inhibits bacterial DHF reductase
    • For UTI, shigella, salmonella, pneumocystis jiroveci
    • Tox: marrow toxicity; supplement folinic acid
  29. Fluoroquinolones
    • Inhibit DNA gyrase (topo II). avoid antacids.
    • Gram- rods including pseudomonas, neisseria
    • Tox: GI, superinfections, rash, HA, dizziness. Cartilage/tendon damage esp in fetus
  30. Metronidazole
    • Forms toxic metabolites that damage DNA
    • For anaerobes below the diaphragm and protozoans, h. pylori
    • Tox: metallic taste, doesn't mix with alcohol
  31. Polymyxins
    • Disrupt cell membrane osmotic properties (detergent)
    • For resistant gram- infxns
    • Tox: neuro, ATN
  32. How to prophylax and treat TB
    • Px: INH
    • Tx: RIF, INH, pyrazinamide, ethambutol
    • Cycloserine is 2nd line
    • All are bad for liver; Ethambutol tox: optic neuropathy
  33. How to prophylax and treat M. avium intracellulare
    • Px: azithromycin
    • Tx: azithro, RIF, ethambutol, streptomycin
  34. How to treat leprosy (M. leprae)
    Dapson, RIF, clofazimine
  35. INH
    • Decreases synthesis of mycolic acid
    • Tox: neuro, hepato. Give B6 to prevent neurotox.
  36. RIF
    • Inhibits DNA-dependent RNA polymerase
    • Revs up P-450
    • Red/orange body fluid
    • Rapid resistance if used alone
  37. How a bug gets resistant to penicillins/cephalosporins
    Beta-lactamase cleavage of beta-lactam ring, or aletred PBP (MRSA, s. pneumoniae)
  38. How a bug gets resistant to aminoglycosides
    Modification via acetylation, adenylation, or phosphorylation
  39. How a bug gets resistant to vancomycin
    Change terminal D-ala of cell wall to d-lac, which decreases affinity
  40. How a bug gets resistant to chloramphenicol
    Modifies it via acetylation
  41. How a bug gets resistant to macrolides
    Methylates the rRNA near erythromycin's ribosome-binding site. Sneaky sneaky!
  42. How a bug gets resistant to tetracycline
    Decreased uptake or increased export. Pushy pushy!
  43. How a bug gets resistant to sulfonamides
    Alters its enzyme (dihydropteroate synthetase), or decreases uptake, or increases PABA synth
  44. How a bug gets resistant to quinolones
    It alters its gyrase or reduces uptake
  45. Meningococcal prophylaxis
    RIF or minocycline
  46. Gonorrhea prophylaxis
  47. Syphilis prophylaxis
    Benzathine penicillin G
  48. Pneumocystis jiroveci pneumonia prophylaxis
    TMP-SMX (also px for UTI) or aerosolized pentamidine
  49. Endocarditis prophylaxis
  50. How do you treat VRE?
    with linezolid and streptogramins (quinupristin/dalfopristin)
  51. Amphotericin B
    • Binds ergosterol and tears holes in fungal membrane
    • Use for systemic mycoses
    • Tox: shake and bake, hypotension, nephrotox, arrhythmias, anemia, phlebitis.
  52. Nystatin
    • Binds ergosterol to disrupt fungal membrane
    • No systemic use; swish and swallow or topical
  53. Azoles
    • Inhibit ergosterol synthesis
    • Use for systemic mycoses, cryptococcal meningitis (crosses BBB)
    • Tox: hormone synth inhibition causing gynecomastia, liver dysfunction (p-450 inhib)
  54. Flucytosine
    • Converts to 5-FU and inhibits DNA (pyrimidine) synthesis
    • Use in combination with amphotericin B
    • Tox: nausea, vomiting, bone marrow suppression
  55. Capsofungin
    • Inhibits cell wall syntehsis by inhibiting synthesis of beta-glucan
    • Use for invasive aspergillosis
    • Tox: GI, flushing
  56. Terbinafine
    • Inhibits fungal enzyme squalene epoxidase
    • Treat dermatophytoses like onychomycosis
  57. Griseofulvin
    • Interferes with microtubule function to dirupt mitosis
    • Oral tx of superficial infections
    • Tox: deposits in nails, teratogen, carinogen, confusion, HA, induces P-450/warfarin metabolism
  58. Amantadine
    • Blocks influenza A uncoating by buffering endosome. M2 protein (mutated for resistance).
    • Can treat Parkinson's because it causes release of DA from intact nerves
    • Tox: ataxia, dizziness, slurred speech
  59. Zanamivir and oseltamivir
    Inhibit influenza neuraminidase for influenza A and B. Baby viruses can't swim free.
  60. Ribavirin
    • Inhibits IMP dehydrogenase to inhibit synth of guanine nucleotides
    • Use for RSV, chronic hep C
    • Tox: hemolytic anemia, teratogen
  61. Acyclovir
    • HSV/VZV thymidine kinase phosphorylates it so it can inhibit viral DNA polymerase and terminate its chain
    • Use for herpesviruses except not CMV
  62. Ganciclovir
    • CMV viral kinase monophosphorylates it, becomes guanosine analog.
    • Use for CMV
    • Tox: more than acyclovir. marrow and renal.
  63. Foscarnet
    • PyroFOSphate analogue; viral DNA polymerase inhibitor (can mutate); does not require viral kinase
    • Use for CMV retinitis in IC patients when ganciclovir fails or for resistant HSV
    • Tox: nephro
  64. Protease inhibitors end in:
    -navir. ritonavir, indinavir, nelfinavir, saquinavir.
  65. Reverse transcriptase inhibitors: name the nucleosides
    Zidovudine (AZT), didanosine, zalcitabine, stavudine, lamivudine, abacavir
  66. Reverse transcriptase inhibitors: name the non-nucleosides
    • Nevirapine, Efavirenze, Delaviridine
    • Never Ever Deliver nucleosides
  67. Reverse transcriptase inhibitors: mech and tox
    • Prevent incorporation of DNA copy of viral genome into host DNA
    • Tox: bone marrow, neuropathy, lactic acidosis (nucleosides), rash (non nucleosides), megaloblastic anemia (ZDV)
    • Use in pregnancy to reduce transmission
  68. Enfuvirtide
    • Fusion inhibitor for HIV; binds viral gp41 subunit so it can't enter CD4 cell
    • Use when replication continues despite other drugs
    • Tox: hypersensitivity, risk of pneumonia
  69. How do interferons work as therapy?
    • They induce ribonuclease that degrades viral mRNA
    • But they can cause neutropenia
  70. Use for IFN-alpha
    chronic HBV, HCV, Kaposi's sarcoma
  71. Use for IFN-beta
  72. Use for IFN-gamma
    NADPH oxidase deficiency