Lecture 1

• Antibiotics fight bacteria, while antimicrobial compounds work against various microorganisms like protozoa, yeast, fungi, viruses, algae, and some worms
• Modern era in Antibiotics begins with Fleming
• Classification of antibiotics based on spectrum of action

  • Narrow spectrum - only against a single or limited group of microorganisms
  • Extended spectrum - against G+ organisms and a significant number of G- bacteria
  • Broad spectrum - affecting a wide range of microorganisms
• Chemotherapy is the killing of a living organism, including cancer cells, bacteria, fungi, protozoa, or viruses
• Differences between prokaryotic and Eukaryotic cells

  Bacterial cells lack membrane-bound organelles, have single chromosome in the cytoplasm, thick cell wall of peptidoglycan; Animal cells have membrane-bound organelles like nucleus and mitochondria
• Classification of antibiotics based on source

  • Natural compounds: e.g. penicillin, chloramphenicol
  • Synthetic compounds: e.g. sulfonamides, quinolones
  • Semisynthetic compounds: e.g. Ampicillin
• Antibiotic


  Compounds able to fight bacteria; antimicrobial compounds can work against various microorganisms
• Bacteria


  Prokaryotic cells; some are pathogenic to humans and can cause serious infections, treated with antibiotics
• Classification of antibiotics

  1. Based on source

  2. Based on spectrum of activity

  3. Based on chemical nature

  4. Based on mode of action
• Mechanisms responsible for acquired resistance include production of enzymes that inactivate the drug, alteration of drug binding site, reduction in drug uptake, and development of altered metabolic pathways
• Broad spectrum antibiotics affect a wide variety of microbial species and alter the normal bacterial flora, potentially leading to super-infections like candida
• According to the effect on microorganisms

  1. Bactericidal agents: kill the microorganism e.g. penicillin

  2. Bacteriostatic agents: arrest growth of the microorganism e.g. sulfonamides
• Antibiotic resistance is a major problem in clinical practice, with examples like Methicillin-resistant Staph aureus (MRSA) and multidrug-resistant bacteria
• Acquired resistance occurs when previously sensitive microorganisms develop resistance through spontaneous mutations or acquisition of new genes
• Extended spectrum antibiotics are effective against G+ organisms and also against a significant number of G- bacteria
• According to Chemical Structure


  1. Groups of B-lactams: Penicillin, Cephalosporins, Carbapenem, Monobactam

  2. Groups of aminoglycosides: Streptomycin, Neomycin, Kanamycin, Gentamicin

  3. Groups of chloramphenicol: Chloramphenicol

  4. Groups of tetracycline: Chlortetracycline, Oxytetracycline

  5. Groups of macrolides: Erythromycin, Azithromycin

  6. Groups of Lincomycins: Lincomycin, Clindamycin

  7. Groups of quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin

  8. Groups of sulfonamides: Sulfamethoxazole, Sulfadiazine

  9. Groups of polymyxin: Polymyxin B

  10. Groups of Peptides and Glycopeptides: Vancomycin, Bacitracin
• Classification of bacteria on the basis of MOA
• INH is active only against mycobacteria
• According to mode of action

  1. Inhibit cell wall synthesis

  2. Inhibit protein synthesis

  3. Inhibit nucleic acid synthesis

  4. Injury to plasma membrane

  5. Inhibit synthesis of essential metabolites
• Mutation of the target site can lead to altered expression of proteins in drug-resistant organisms
• Innate resistance is a feature of a particular species of bacteria, e.g., Pseudomonas, which are inherently resistant to certain antibiotics
• Clinical Approaches for Rational Prescribing of Antibiotics

  1. Right Patients: Confirm the presence of an infection by Fever and White blood cell count

  2. Right Antimicrobial Drug: Identification of the infecting organism through Antibiotic sensitivity test, Empirical therapy, and Patient factors
• Superbugs

  • MRSA - Methicillin/oxacillin-resistant Staphylococcus aureus
  • VISA - Vancomycin intermediate resistant Staphylococcus
  • PRSP - Penicillin-resistant Streptococcus pneumonia
• Superbugs are microorganisms with multiple resistance
• MRSA causes 19,000 deaths annually in the USA
• In 1952, 100% of Staphylococcus infections were cured by penicillin, but by 1982, only 10% were cured
• Introduction to Antibiotic Therapy

  1. Mutation of the target: Altered expression of proteins in drug-resistant organisms

  2. Actively transporting the drug from the cells: Efflux systems that pump out the drugs (e.g., tetracycline)

  3. Inactivation of the drug: The ability to destroy or inactivate the antimicrobial agent

  4. Prevention of the drug to enter the cells: Decreased penetrability of an agent
• In old age (> 65 years) the incidence of renal toxicity with aminoglycosides is greater than in younger patients
• Post-antibiotic effect (PAE)


  • The PAE is a persistent bacterial suppression after levels of antibiotic fall below the MIC. Antimicrobials with long PAE (e.g. Azithromycin and fluoroquinolones) usually require one dose per day
• Pregnancy: many antibiotics cross the placenta and cause adverse effects to the fetus e.g. aminoglycosides and tetracyclines
• Misuses of antibiotics

  • Treatment of insensitive infections
  • Viral infection
  • Treatment of fever of undetermined origin
  • Treatment without adequate bacteriological data
  • Improper dosage
• Time-dependent killing

  • β-lactam antibiotics, macrolides, clindamycin, and linezolid do not exhibit concentration-dependent property; instead, the clinical efficacy depends on the time the drug concentration remains above the MIC. Preparations with long duration kill more bacteria
• Adverse Effects of Antimicrobial Drugs: 1. Allergic Reactions: some people develop hypersensitivities to antimicrobials 2. Toxic Effects: some antimicrobials are toxic at high concentrations or cause adverse effects 3. Suppression of normal flora: when normal flora killed, other pathogens may be able to grow to high numbers leading to hypovitaminosis especially vitamin K and Superinfection
• The use of tetracycline can bind to growing bones and teeth resulting in abnormal teeth and bone formation
• Concentration-dependent killing

  • Certain antibiotics (e.g. Gentamycin) show enhanced bacterial killing in concentration above the MIC. Giving this antibiotic by a single large dose per day achieves high peak levels and causes rapid killing of bacteria. Gentamycin 160 mg once daily is the most effective
• Prophylactic use of antibiotics is required in certain clinical situations for the prevention rather than the treatment of infections
• SUPERINFECTION (Opportunistic infection): Administration of antimicrobials usually alter bacterial flora but with no ill effect in most cases however, broad-spectrum antibiotics if used for a long time may alter or kill bacterial flora. So, the bacteria and fungi that are normally inhibited by bacterial flora will multiply leading to superinfection (its early manifestation may be diarrhea). It is caused by staphylococci, Pseudomonas, proteus, Candida albicans or Clostridia difficile... Treatment: Stop the causative agent and give a drug that kills the organisms responsible for superinfection e.g. staphylococcal enterocolitis, which is treated by metronidazole or vancomycin orally, antifungal nystatin for candidiasis
• In immunocompromised patients, the use of bactericidal agents is necessary, as the host’s immune system is not capable of final elimination of the bacteria
• What works against only limited or single microorganism

  Narrow spectrum antibiotic