Micropara 9

• Chemotherapy


  The use of any chemical (drug) to treat any disease or condition
• Chemotherapeutic agent


  Any drug used to treat any condition or disease
• Antimicrobial agent


  Any chemical (drug) used to treat an infectious disease, either by inhibiting or killing pathogens in vivo
• Antibiotic


  A substance produced by a microorganism that kills or inhibits growth of other microorganisms
• Semisynthetic antibiotics


  Antibiotics that have been chemically modified to kill a wider variety of pathogens or reduce side effects
• The discovery of penicillin by Alexander Fleming
• Characteristics of an ideal antimicrobial agent

  • Kill or inhibit the growth of pathogens
  • Cause no damage to the host
  • Cause no allergic reaction in the host
  • Be stable when stored in solid or liquid form
  • Remain in specific tissues in the body long enough to be effective
  • Kill the pathogens before they mutate and become resistant to it
• Mechanisms of action of antimicrobial agents

  • Inhibition of cell wall synthesis
  • Damage to cell membranes
  • Inhibition of nucleic acid synthesis (either DNA or RNA synthesis)
  • Inhibition of protein synthesis
  • Inhibition of enzyme activity
• Bacteriostatic drugs


  Inhibit growth of bacteria
• Bactericidal drugs


  Kill bacteria
• Sulfonamide drugs


  Inhibit production of folic acid (a vitamin) in those bacteria that require p-aminobenzoic acid to synthesize folic acid; without folic acid bacteria cannot produce certain essential proteins and die

  
• Sulfa drugs


  Competitive inhibitors; they are bacteriostatic
• Penicillin


  In most Gram-positive bacteria, interferes with the synthesis and cross-linking of peptidoglycan, a component of cell walls. By inhibiting cell wall synthesis, penicillin destroys the bacteria
• Colistin and nalidixic acid

  Destroy only Gram-negative bacteria; they are referred to as narrow-spectrum antibiotics
• Broad-spectrum antibiotics


  Antibiotics that are destructive to both Gram-positive and Gram-negative bacteria (examples: ampicillin, chloramphenicol and tetracycline)
• Major categories of antibacterial agents

  • Penicillins (bactericidal; interfere with cell wall synthesis)
  • Cephalosporins (bactericidal; interfere with cell wall synthesis)
  • Tetracyclines (bacteriostatic; inhibit protein synthesis)
  • Aminoglycosides (bactericidal; inhibit protein synthesis)
  • Macrolides (bacteriostatic at lower doses; bactericidal at higher doses; inhibit protein synthesis)
  • Fluoroquinolones (bactericidal; inhibit DNA synthesis)
• Synergism


  When 2 antimicrobial agents are used together to produce a degree of pathogen killing that is greater than that achieved by either drug alone
• Antagonism


  When 2 drugs actually work against each other. The extent of pathogen killing is less than that achieved by either drug alone
• How most antifungal agents work

  • By binding with cell membrane sterols (e.g., nystatin and amphotericin B)
  • By interfering with sterol synthesis (e.g., clotrimazole and miconazole)
  • By blocking mitosis or nucleic acid synthesis (e.g., griseofulvin and 5-flucytosine)
• Antiprotozoal agents


  Usually toxic to the host
• How antiprotozoal agents work

  • Interfering with DNA and RNA synthesis (e.g., chloroquine, pentamidine, and quinacrine)
  • Interfering with protozoal metabolism (e.g., metronidazole)
• Antiviral agents


  The newest weapons in antimicrobial methodology. Difficult to develop these agents because viruses are produced within host cells. Some drugs have been developed that are effective in certain viral infections, but not others; they work by inhibiting viral replication within cells
• Superbugs


  Microbes (mainly bacteria) that have become resistant to one or more antimicrobial agent. Infections caused by superbugs are difficult to treat!
• Examples of bacterial superbugs

  • methicillin-resistant Staphylococcus aureus (MRSA)
  • vancomycin-resistant Enterococcus spp. (VRE)
  • multidrug-resistant Mycobacterium tuberculosis (MDRTB)
  • multidrug-resistant strains of Acinetobacter, Burkholderia, E. coli, Klebsiella, Pseudomonas, Stenotrophomonas, Salmonella, Shigella. and N. gonorrhoeae
  • β–lactamase-producing strains of Streptococcus pneumoniae and Haemophilus influenzae
  • carbapenemase-producing Klebsiella pneumoniae

  
• Intrinsic resistance


  Bacteria are naturally resistant because they lack the specific target site for the drug or the drug is unable to cross the organism's cell wall or cell membrane and thus, cannot reach its site of action
• Acquired resistance


  Bacteria that were once susceptible to a particular drug become resistant
• How bacteria become resistant to drugs

  • Chromosomal mutation that affects the structure of a drug-binding site can prevent the drug from binding
  • Chromosomal mutations may alter the structure of the cell membrane, thus preventing the drug from entering the cell
  • Bacteria can develop the ability to produce an enzyme that destroys or inactivates a drug
  • Bacteria can develop the ability to produce multidrug-resistance (MDR) pumps that enable the cell to pump out drugs before they can damage or kill the cell
• Resistance factor (R-factor)


  A plasmid that contains multiple genes for drug resistance
• β-lactamases


  Enzymes produced by some bacteria that destroy the β-lactam ring in penicillin and cephalosporin molecules, rendering the drugs ineffective
• Strategies in the war against drug resistance

  • Education of healthcare professionals and patients
  • Patients should stop demanding antibiotics every time they are, or their child is, sick
  • Physicians should not be pressured by patients and should prescribe drugs only when warranted
  • Clinicians should prescribe a narrow-spectrum drug if lab results indicate that it kills the pathogen
  • Patients should destroy any excess or out-dated medications
  • Antibiotics should not be used in a prophylactic manner
  • Healthcare professionals should practice good infection control
  • Patients should take drugs in manner prescribed
• Empiric therapy


  Drug therapy initiated before laboratory results are available (i.e., before the pathogen is identified and/or before susceptibility test results are available)
• Factors to be considered in empiric therapy

  • If pathogen identity is known, use the "pocket chart" of antimicrobial susceptibility test data from past year
  • Is the patient allergic to any antimicrobial agents?
  • What is the age of the patient?
  • Is the patient pregnant?
  • Inpatient or outpatient?
  • In the hospital formulary?
  • Site of the infection?
  • What other medication(s) is the patient taking?
  • What other medical problems does the patient have?
  • Is the patient leukopenic or immunocompromised?
  • What is the cost of the drug(s)?

  
• Reasons why antimicrobial agents should not be used indiscriminately: