Antibiotics

• Antimicrobial therapy


  Takes advantage of the biochemical difference that exist between microorganisms and human beings
• Antimicrobial drugs


  • They are effective in the treatment of infections because of their selective toxicity; that is, they have the ability to injure or kill an invading microorganism without harming the cells of the host
  • The selective toxicity is relative rather than absolute, requiring that the concentration of the drug be carefully controlled to attack the microorganism, while still being tolerated by the host

  
• Selection of the most appropriate antimicrobial agent

  1. Knowing the organism's identity

  2. Knowing the organism's susceptibility to a particular agent

  3. Knowing the site of infection

  4. Considering patient factors

  5. Considering the safety of the agent

  6. Considering the cost of therapy

  
• Some patients require empiric therapy - immediate administration of drug/s prior to bacterial identification and susceptibility testing
• Identification of the infecting organism

  1. Characterizing the organism is central to selection of the proper drug

  2. A rapid assessment can sometimes be made on the basis of the Gram stain

  3. It is generally necessary to culture the infective organism to arrive at a conclusive diagnosis and determine the susceptibility to antimicrobial agents
• When a person has a cough for 2 weeks, you do not automatically give the person an anti-tuberculosis antibiotic. Instead, the sputum is first collected and cultured to identify the bacteria present in order to come up with the conclusive diagnosis that will lead to proper treatment.
• Determining antimicrobial susceptibility of infective organisms

  1. Ideally, the antimicrobial agent used to treat an infection is selected after the organism has been identified and its drug susceptibility established

  2. In the critically ill patient, immediate empiric therapy is indicated

  3. Antimicrobial susceptibility tests are used to determine which specific antibiotics a particular bacteria or fungus is sensitive to

  4. The zone of inhibition is the area that is transparent, where the bacteria has been inhibited

  
• Site of infection

  Adequate levels of an antibiotic must reach the site of infection for the invading microorganisms to be effectively eradicated
• Patient factors to consider when selecting an antibiotic

  • Status of the patient's immune system
  • Kidneys (major organ of elimination)
  • Liver (site where the drug is metabolized when it is taken orally)
  • Circulation (blood carries the drug in the plasma)
  • Age (certain antibiotics should not be given to infants)
  • Pregnancy or breast-feeding (in women)

  
• FDA categories of antimicrobials and fetal risk

  • Category A: No human fetal risk or remote possibility of fetal harm
  • Category B: No controlled studies show human risk; animal studies suggest potential toxicity
  • Category C: Animal fetal toxicity demonstrated; human risk undefined
  • Category D: Human fetal risk present, but benefits may outweigh risks
  • Category X: Human fetal risk clearly outweighs benefits; contraindicated in pregnancy
• Antibiotics such as penicillin/s are among the least toxic of all drugs because they interfere with a site or function unique to the growth of microorganisms

  
• Other antimicrobial agents (for example, chloramphenicol) have less specificity and are reserved for life-threatening infections because of the potential for serious toxicity to the patient
• Often several drugs may show similar efficacy in treating an infection but vary widely in cost
• Rational dosing of antimicrobial agents

  Based on their pharmacodynamics (the relationship of drug concentrations to antimicrobial effects) and pharmacokinetic properties (the absorption, distribution, metabolism, and elimination of the drug)
• Concentration-dependent killing


  • Certain antimicrobial agents, including aminoglycosides and daptomycin, show a significant increase in the rate of bacterial killing as the concentration of antibiotic increases from 4- to 64-fold the MIC (minimum inhibitory concentration) of the drug for the infecting organism

  
• Time-dependent killing


  Also called Concentration-Independent Killing. The clinical efficacy of these antimicrobials is best predicted by the percentage of time that blood concentrations of a drug remain above the Minimum Inhibitory Concentration (MIC)
• Post-antibiotic effect (PAE)


  A persistent suppression of microbial growth that occurs after levels of antibiotic have fallen below the MIC
• Medically important microorganisms


  • Gram (+) cocci
  • Gram (+) bacilli
  • Gram (-) cocci
  • Gram (-) rods
  • Anaerobic organisms
  • Spirochetes
  • Mycoplasma
  • Chlamydia
  • Other
• Narrow-spectrum antibiotic


  Chemotherapeutic agents acting only on a single or a limited group of microorganisms

  
• Isoniazid: narrow-spectrum antimicrobial drug


  • Effective only against Mycobacterium tuberculosis

  
• Extended-spectrum antibiotic


  Antibiotics that are modified to be effective against gram-positive organisms and also against a significant number of gram-negative bacteria

  
• Ampicillin: extended-spectrum antimicrobial drug


  • Acts against gram-positive and some gram-negative bacteria

  
• Broad-spectrum antibiotic


  Drugs such as tetracycline, fluoroquinolones and carbapenems that affect a wide variety of microbial species

  
• Administration of broad-spectrum antibiotics can drastically alter the nature of the normal bacterial flora and precipitate a superinfection due to organisms such as Clostridium difficile
• Types of microorganisms

  • Chlamydia
  • Mycobacteria
  • Other
• Extended-spectrum antibiotic


  Antibiotics modified to be effective against gram-positive organisms and also against a significant number of gram-negative bacteria

  
• Extended-spectrum antibiotic


  • Ampicillin

  
• Gram-positive organisms affected by ampicillin

  • Enterococci
  • Listeria monocytogenes
• Gram-negative organisms affected by ampicillin

  • Escherichia coli
  • Haemophilus influenzae
  • Proteus mirabilis
  • Salmonella typhi
• Broad-spectrum antibiotic


  Drugs that affect a wide variety of microbial species
• Administration of broad-spectrum antibiotics can drastically alter the nature of the normal bacterial flora and precipitate a superinfection due to organisms such as Clostridium difficile</b>
• Microorganisms affected by tetracycline

  • Gram-positive cocci
  • Gram-positive bacilli
  • Gram-negative cocci
  • Gram-negative rods
  • Anaerobic organisms
  • Spirochetes
  • Mycoplasma
  • Chlamydia
  • Actinomyces
  • Rickettsiae
  • Amoebae
• Classes of antibiotics

  • Protein Synthesis Inhibitors
  • Cell Wall Inhibitors
  • Fluoroquinolones
  • Folate Synthesis Inhibitors
• Protein synthesis inhibitors


  • They target bacterial ribosomes and inhibit bacterial protein synthesis
  • Bacterial ribosomes differ structurally from mammalian cytoplasmic ribosomes

  
• Protein synthesis

  Has two steps: Transcription (replicating DNA & mRNA) and Translation

  
• Protein synthesis inhibitor drugs

  • Tetracyclines
  • Glycylcyclines
  • Aminoglycosides
  • Macrolides/Ketolides
  • Macrocyclic
  • Lincosamides
  • Oxazolidinones
  • Chloramphenicol
  • Quinupristin/Dalfopristin

  
• Tetracyclines


  They bind reversibly to the 30S subunit of the bacterial ribosome, preventing binding of tRNA to the mRNA-ribosome complex, thereby inhibiting bacterial protein synthesis

  
• Tetracycline adverse effects

  • Gastric discomfort
  • Effects on calcified tissues
  • Hepatotoxicity
  • Phototoxicity
  • Vestibular dysfunction
  • Pseudotumor cerebri
  • Contraindicated in pregnancy and children under 8
• Glycylcycline


  Tigecycline is a derivative of minocycline, it exhibits bacteriostatic action by reversibly binding to the 30S ribosomal subunit and inhibiting protein synthesis

  
• Aminoglycosides


  They bind the 30S ribosomal subunit, interfering with assembly of the functional ribosomal apparatus and/or causing the 30S subunit to misread the genetic code