can alter microbial flora, leadin to resistant organisms

• mutate with time
• strains can appear and disappear

• cell wall inhibitor
• cell membrane inhibitors/modifiers
• protein syn. inhibitors
• DNA syn. inhibitors
• alteration in energy metabolism

• protein syn.
  • 70S
  • 80S
• DNA syn- enzymes different
• cell wall (microbe)

• stop growth
• so you need the immune system to eliminate the infection
• clinical application- it works really well if patient is not immunocompromised

• conc. dep. killing (more killing with a higher concentration of drug)
• you can get a post antibiotic effect
  • even after drug is removed, you will still inhibit bacterial growth
  • it will eventually where off, and bug can start growing again
• drug must allow MIC to be reached first in plasma, then at infection site
  • clinical application- without this property, the antibiotic effect of limited

• ineffective therapy (leads to failure/relapse)
• forces use of newer, more expensive agents
  • newer agents may be more toxic
• resistant bacteria may thrive and spread in hospital
• untreatable infections due to development of resistance of new agents

• intrinsic (due to biology of organism)
• acquired
  • organism was sensitive but became resistant due to
    • mutation of existing gene
    • acquisition of new genes
      • conjugation (most common mechanism of acquiring drug resistance)
      • transduction
      • transformation

• target
  • mutation of target site
  • making of a "fake" target site
• decreased influx
• increased efflux
• metabolism of drug by the bug
• bypass pathway
  • you have enough of an intermediate product to counteract the drugs effect
  • it could also switch to an alternative pathway

• various results
  • synergy
  • indifference
  • antagonism]

Combination therapy ofen overused

• combination of cell wall inhibitor with aminoglycoside antibiotic
  • improve influx of aminoglycoside
• combination of agents acting on sequential steps in metabolic pathway
  • ex: sulfonamides and trimethaprim
• combination of agents in which one agent inhibits the destruction of another
  • ex: amoxicillin and clavulanic acid

• life threatening infection
• polymicrobial infection
• empiric therapy with no single agent is active against potential pathogens
• synergy
• prevent emergence of resistant bacteria
• permit use of lower dose of one of the antimicrobial agents
  • avoid toxicity

• cyclosoporin
• vancomycin
• penicillin
• cephalosporins
• bacitracin

• trimethoprim
• sulfonamides

• tetracyclin
• streptomycin
• gentamycin
• spectinomycine
• tobramycin

• erythromycin
• clindomycin
• chloromphenical
• Linezolid

quinolones

aolidixic acid

• bacteria may infect host
• host can respond with active or passive imunity
• drug administered with "selective toxicity"
  • interplay between effect of drug on bug and patient
• host can respond to drug with allergy or toxicity

• broad spectrum- condition where life threatinin situation, patient unstable, so you need to start therapy ASAP
• narrow spectrum- when you have identified to bacteria

• when you cannot get spectrum
• based on knowledge of antibacterial spectrum of drug and likely pathogen
• usually broad spectrum
  • downside- they have greater risk of disturbing normal flora, leading to development of resistance

• takes time: 18-48 hrs
• find most appropriate antibiotic in the appropritate concentration
  • MIC (minimal inh. conc.)