antimicrobial

• Antimicrobial agents


  Primitive medications concocted from plant, animal, and mineral products that had been found through trial and error or accident, to have some curative effect
• Some primitive medications were effective, but others either had no effect or were harmful
• Pharmakeutikos


  Practice of witchcraft
• Introduction of drugs to control infections in the 1930s


  • Began as a medical revolution
  • Added significantly to the lifespan and health of humans
  • For many years, antibiotics were regarded as the miracle cure-all for infectious diseases
• Narrow-spectrum antimicrobials


  Effective against a limited array of different microbial types

  
• Narrow-spectrum antimicrobials


  • Bacitracin
  • Griseofulvin

  
• Medium-spectrum antimicrobials


  Effective against a wider range of microbes

  
• Medium-spectrum antimicrobial


  • Ampicillin
• Broad-spectrum antimicrobials


  • Have the greatest range of activity
  • Usually exert their effects on common cell components such as ribosomes, which are found in all cells and mitochondria

  
• Broad-spectrum antimicrobial


  • Tetracycline
• Disk Diffusion Tests (Kirby-Bauer method)


  1. Freshly grown bacteria are used to inoculate the entire surface of a Mueller-Hinton agar plate

  2. Appropriate antibiotic test disks are placed on it

  3. After 16 to 18 hours of incubation at 35°C, the diameters of the zones of inhibition are measured to the nearest millimeter

  
• Penicillin


  • First antibiotic
  • Parent compound for all "-cillin" drugs
  • Narrow spectrum and cannot be given by mouth
  • Often considered the drug of choice for infections by sensitive gram-positive bacteria (streptococci) and some gram-negative bacteria (meningococci)

  
• Problems in Penicillin therapy


  • Resistant strains of pathogens
  • Allergy
• Showing an allergy to any of the penicillin drugs will require avoidance of all of them, regardless of the type
• Cephalosporins


  • Beta-lactam drugs
  • Currently account for one-third of all antibiotics administered
  • Relatively broad spectrum
  • Cause fewer allergic reactions than penicillin
  • Many are poorly absorbed from the intestine and must be administered parenterally (by injection into a muscle or a vein)

  
• Recent additions to cephalosporins


  • Combination of broad spectrum cephalosporin & beta-lactamase inhibitor
  • Examples: Zerbaxa (ceftolozene + tazobactam), Avycaz (ceftizadime + avibactam)
• Carbapenems and Monobactams


  • Beta-lactam drugs
  • Imipenem and ertapenem are broad-spectrum antibiotics with greater resistance to beta-lactamases
  • Aztreonam is a monobactam with a narrow spectrum for treating gram-negative aerobic bacilli

  
• Starting in 2001, some carbapenem-resistant strains of gram-negative enteric bacteria (CRE) began to emerge in hospitals and continued to increase in numbers, causing concern in some clinical settings

  
• Vancomycin


  • Narrow-spectrum antibiotic most effective in treating staphylococcal infections in cases of penicillin and methicillin resistance or in patients with an allergy to penicillins
  • Used for the treatment of Clostridium infections in children and endocarditis caused by Enterococcus faecalis
  • Very toxic and hard to administer, usually restricted to the most serious, life-threatening conditions

  
• Bacitracin


  • Narrow-spectrum peptide antibiotic produced by a strain of Bacillus subtilis
  • Blocks the elongation of the peptidoglycan in gram-positive bacteria
  • A major ingredient in antibiotic ointment (Neosporin) for combating superficial skin infections by streptococci and staphylococci

  
• Isoniazid (INH)


  • Interferes with the synthesis of mycolic acid, a necessary component of the cell wall of acid-fast organisms
  • Used to treat infections with Mycobacterium tuberculosis but is effective only against growing cells

  
• Polymyxins


  • Narrow-spectrum peptide antibiotics with a unique fatty acid component that contributes to their detergent activity
  • Two polymyxins- B and E (also known as colistin)
  • Have any routine applications, even these are limited by their toxicity to the kidney
  • Indicated to treat drug-resistant infections caused by gram-negative rods such as Pseudomonas aeruginosa

  
• Fluoroquinolones


  • Norfloxacin and ciprofloxacin (Cipro) are more commonly used
  • Prescribed in many cases of urinary tract infections, sexually transmitted diseases, gastrointestinal infections, osteomyelitis, respiratory infections, and soft tissue infections
  • Sparfloxacin and levofloxacin are newer drugs in this category, especially recommended for pneumonia, bronchitis, and sinusitis
  • Concerns have arisen regarding the overuse of quinolone drugs
  • Other side effects include damage to tendons and brain disturbances

  
• Rifampin


  • Blocks the action of RNA polymerase, thereby preventing transcription
  • Used in treating mycobacterial infections, especially tuberculosis and leprosy
  • Given in combination with other drugs to prevent development of resistance

  
• Aminoglycosides


  Act on DNA or RNA
• Gram-negative rods


  Such as Pseudomonas aeruginosa
• Fluoroquinolones


  • Norfloxacin and ciprofloxacin (Cipro)
  • More commonly used quinolones
  • Prescribed in many cases of urinary tract infections, sexually transmitted diseases, gastrointestinal infections, osteomyelitis, respiratory infections, and soft tissue infections

  
• Fluoroquinolones


  • Sparfloxacin and levofloxacin
  • Newer drugs in this category
  • Especially recommended for pneumonia, bronchitis, and sinusitis

  
• Concerns have arisen regarding the overuse of quinolone drugs
• Other side effects of quinolone drugs include damage to tendons and brain disturbances
• Rifampin


  • Blocks the action of RNA polymerase, thereby preventing transcription
  • Used in treating mycobacterial infections, especially tuberculosis and leprosy
  • Given in combination with other drugs to prevent development of resistance

  
• Streptomycin


  One of the oldest drugs but has gradually been replaced by newer forms with less mammalian toxicity
• Gentamicin


  • Less toxic
  • Widely administered for infections caused by Escherichia, Pseudomonas, Salmonella, and Shigella

  
• Tobramycin and Amikacin


  • Two relatively new aminoglycosides
  • Used for gram-negative infections
  • Tobramycin is especially useful for treating Pseudomonas infections in cystic fibrosis patients

  
• Doxycycline and Minocycline


  • Administered orally to treat several sexually transmitted diseases, Rocky Mountain spotted fever, Lyme disease, typhus, Mycoplasma pneumonia, cholera, leptospirosis, acne, and even some protozoan infections
  • Low in cost and easy to administer

  
• Side effects of tetracycline antibiotics include gastrointestinal disruption due to changes in the normal microbiota, staining of the teeth, and interference with fetal bone development during pregnancy

  
• Chloramphenicol


  • Entirely synthesized through chemical processes
  • Used to treat typhoid fever, brain abscesses, and rickettsial and chlamydial infections for which an alternative therapy is not available
  • Toxic to human cells so its uses are restricted
  • A small number of people undergoing long-term therapy incur irreversible damage to the bone marrow that usually results in a fatal form of aplastic anemia
  • Should never be given in large doses repeatedly over a long time period, and the patient's blood must be monitored during therapy

  
• Erythromycin


  • Has a moderate spectrum and fairly low toxicity
  • Administered orally for Mycoplasma pneumonia, legionellosis, Chlamydia infections, pertussis, and diphtheria, and as a prophylactic drug prior to intestinal surgery

  
• Clarithromycin and Azithromycin


  • Useful for middle ear, respiratory, and skin infections
  • Have been approved for Mycobacterium (MAC) infections in AIDS patients
  • Clarithromycin has additional applications in controlling infections and gastric ulcers caused by Helicobacter pylori
  • Azithromycin is one of the most prescribed antibiotics in the world, used to treat respiratory, gastrointestinal, and sexually transmitted infections
  • Serious side effect of azithromycin is heart arrhythmias

  
• Clindamycin


  • Broad-spectrum antibiotic
  • For the treatment of serious infections in the large intestine and abdomen due to anaerobic bacteria (Bacteroides and Clostridium), infections with penicillin-resistant staphylococci and acne
  • May cause adverse reactions in the gastrointestinal tract