Lecture 6

• bactericidal 


  "cidal" kills susceptible bacteria (host cells not needed)
• bacteriostatic

  "static" stops bacterial growth and relies on host cells to clear bacteria
• narrow spectrum antibiotics

  active against small group of bacteria; snipers
• broad spectrum antibiotics

  active against big group of bacteria; bazookas
• resistance

  organisms that no longer response to a therapy or is associated with failure (from tests)
• gives as much as you want, won't do anything

  resistant
• sensitive

  when organisms response to an antimicrobial or has activity in test tube (susceptible and can be wiped out with antibiotics)
• antimicrobial targets

  best one = cell wall synthesis

  Second most = protein synthesis

  Third = nuceic acid synthesis
• Against beta lactams?cell wall synthesis


  Penicillins, cephalosporins, carbapenems, monobactams
• Against cell wall


  Vancomycin, bacitracin
• against cell membrane(cell wall synthesis)


  polymyxins
• Against 30S unit

  tetracyclines, aminoglycosides
• against 50S unit

  macrolides, clindamycin, linezolid
• against RNA polymerase


  rifampin
• against DNA gyrase

  quinolones
• Against folate synthesis

  sulfonamides, trimethoprim
• Beta-lactam antibiotics

  central component of all beta-lactam antibiotics is beta-lactam ring
• What stops cell wall synthesis?

  transpetidase enzyme is inhibited, so no bond between NAM and NAG can be built so there is no support for cell wall
• types of penecillins

  penicillinG, penicillinV, cloxacillin, amoxicillin, piperacillin
• types of cephalosporins

  1st gen = ampicillin

  2nd gen = cefazolin

  3rd gen = ceftazidime, ceftriazone, cefizime
• types of cerbapenems

  ertapenem, meropenem
• beta-lactum facts?

  active against gram + and -; penicillins and 1st gen cephalosporins are narrow spectrum; 3rd and 4th cephalosporins are broad spectrum and for more resistant organisms; carbapenems are VERY broad (last resort antibiotics)
• glycopeptides

  non beta-lactams for gram positive organisms, stops growth of peptidoglycan unit of wall (vancomycin, teicoplanin)
• protein synthesis inhibitors


  binds to ribosomes (30S and 50S to stop reproduction in bacteria)
• Nucleic acid inhibitors (fluoroquinolones)?

  great drugs with broad spectrum, tissue penetration is good on most tissues
• fluoroquinolones

  1st gen = nalidizix acid

  2nd gen = ciprofloxcin, ofloxacin

  3rd gen = gatifloxacin

  4th gen = moxifloxacin
• metabolic inhibitors

  trimethoprim (DHF)/sulfamethoxazole (stops PABA); stops active form of folic acid
• Intristic resistance


  already had the gene in its genome to be resistant to drug, cannot stop this
• acquired resistance


  bacteria gains genome/ability to be resistant to drug, we can stop this
• antibiotic testing?

  in vitro, tested as either sensitive (S), intermediate (I, not really used) or resistant (R)
• presence of antibiotics?


  will grow if it is resistant, will not grow if it is sensitive
• resistance detection

  the larger the disc is around the antibiotic means it is more susceptible (sensitive to antibiotics)
• micro-broth dilution


  is bacteria grows in well of antibios then it is resistant
• mutations?

  happens in about 1 in 10 million cells, a colony of bacteria has 100 million cells, up to 10 mutation events in one colony
• resistance mechanisms

  efflux pump, reduced permeability, enzymatic inactivation, altered binding site
• antibiotic pressure?

  can cause resistance to antibiotics since it has more time to build resistance mechanisms
• sharing of resistance mechanisms

  direct spread = plasminds, conjugation, transformation

  transduction happens too
• Conjugation


  gene transfer and recombinaiton that needs direct contact (cell to cell), builds a bridge so plasmid donated genes can move over
• transformation


  naked DNA is taken up by competent bacterial cell and mixes with recipients genome. either DNA fragments or DNA plasmids
• transduction (rare)


  bacteriophage infects bacteria (virus to bacteria) and gives its resistance