Antimicrobial & Chemotherapeutic Agents

Antimicrobial and Chemotherapeutic Agents

• Chemotherapeutic drugs are chemical agents used in the treatment or prevention of disease.
• Antimicrobial agents, used in chemotherapy, control infection.
• Antibiotics are produced by microorganisms to inhibit or destroy other microorganisms.
• Synthetic drugs are antimicrobial substances from dyes and/or other organic compounds.
• Antimicrobials include all antimicrobial drugs.
• Narrow spectrum drugs target a limited array of microbial types: Bacitracin affects certain Gram-positive bacteria, and griseofulvin treats skin infections.
• Broad-spectrum drugs act against a wide range of microbes: Tetracyclines target various Gram-positive and Gram-negative bacteria, including rickettsia and mycoplasma.

Range of Antibiotics Action

• Primarily affects Gram-positive organisms such as Penicillin, erythromycin, novobiocin, vancomycin, and bacitracin.
• Primarily active against Gram-negative organisms such as Polymyxin, neomycin, and streptomycin.
• Active against both Gram-positive and Gram-negative organisms such as Tetracycline, chloramphenicol, sulphonamide, and ampicillin.

Characteristics of Ideal Antimicrobial Drugs

• Exhibits selective toxicity to microbes but does not harm vertebrate cells.
• Microbicidal action is preferred over microbistatic action.
• Soluble and effective even when highly diluted in body fluids.
• Potent and not broken down or prematurely excreted.
• Not prone to developing antimicrobial resistance.
• Complements or aids the host's defense mechanisms.
• Remains active despite the presence of organic materials.
• Does not disrupt the host's health by causing allergies or predisposing to other infections.

Factors Influencing Antimicrobial Agent Effectiveness

• Temperature: Activity is enhanced at the optimal temperature. Spore formers need high temperatures.
• Exposure Duration: Longer exposure to microbicidal agents results in more organisms killed.
• Concentration: Higher concentrations generally kill microorganisms more rapidly, but effectiveness isn't always directly proportional.
• Population Size: Larger populations require longer exposure times. Aggregation hinders drug penetration.
• Population Composition: Effectiveness varies based on the type of organism due to differences in susceptibility.
• Environmental Factors: Conditions around the organisms impact destruction, and organic matter in biofilms protects microorganisms.

Resistance to Antibiotics

• Antibiotics effectively controlled diseases like tuberculosis, pneumonia, syphilis, and gonorrhea.
• Organisms evolving resistance pose a challenge.
• Penicillin's use led to resistant bacteria evolution.
• Resistant organisms maintain pathogenicity but are unaffected by penicillin.

Reasons Microorganisms Become Resistant

• Adaptability allows survival under environmental stress.
• Natural selection favors organisms that withstand control methods.
• Penicillin use selected strains resistant due to penicillinase enzyme production.
• Natural resistance occurs when the organism lacks the structure the antibiotic targets, like Mycoplasma lacking a cell wall.
• Acquired resistance happens when microorganisms produce substances that inactivate the antibiotic: Staphylococcus aureus produces penicillinase.
• Mutation can alter cellular structures, preventing antibiotic binding: staphylococci mutating to prevent penicillin binding.
• Plasmids carrying resistance information can transfer antibiotic resistance between bacteria.
• Repeated Exposure can create mutant organisms in subinhibitory antibiotic concentrations: These mutants survive and multiply in lethal concentrations for parent strains.
• Resistance development varies. S. aureus resists penicillin, chloramphenicol, and tetracyclines slowly, while resistance to streptomycin and isoniazid can rapidly increase in Mycobacterium tuberculosis.

Quality Control and Aseptic Techniques

Definitions

• Disinfection: Destroys or removes pathogenic organisms rendering an object non-infectious; some organisms or spores may survive.
• Sterilization: Destroys or removes all living organisms; sterility is absolute.

Physical Methods of Sterilization - Heat

• Effective as it's rapid, reliable, controllable and leaves no harmful substances.

Dry Heat

• Incineration/Destruction by Fire: Best for contaminated materials, such as infected animals; platinum/iron wire loops sterilized by heating in a flame.
• Hot Air Oven: Maintained at 160°C for an hour for sterilizing dry glassware, metal objects, and syringes.
• Infrared Radiation: Maintained at 180°C for 10 minutes and used for large-scale syringe sterilization.

Moist Heat

• Pasteurization: Uses 65°C for 30 minutes or 72°C for 15 seconds in a water bath, killing pathogens in milk but leaving some vegetative organisms and spores.
• Boiling: Uses 100°C for 5 minutes, destroys vegetative organisms but spores may survive; suitable for disinfecting contaminated items when autoclaving is unavailable.
• Intermittent Steaming/Tyndallization: Uses 100°C for 30 minutes on three consecutive days to sterilize media damaged by autoclaving, targeting vegetative organisms and spore formers over multiple cycles.

Steam Under Pressure/Autoclaving

• Used for sterilizing surgical instruments, dressings, gowns, towels, gloves, and bacteriological media via steam at pressures above atmospheric pressure exceeding 100°C.
• Effective autoclave sterilization requires a minimum of 15 psi at 121°C for 15 minutes, 20 psi at 126°C for 10 minutes, or 30 psi at 134°C for 3 minutes.

Control of Absolute Sterilization

• Automatic recording of pressure, temperature, and time during each sterilizing cycle.
• Heat-sensitive tape is fixed to the outside of each pack.
• Chemical indicators placed in inaccessible parts turn colors when the appropriate temperature is achieved.
• Heat-resistant spores of Bacillus stearothermophilus are used as sterility checks.
• Thermocouple measurement is performed outside the loads.
• Unprotected sterile swabs are used to check for possible recontamination.

Sterilization - Radiation

• Direct Sunshine: Kills vegetative organisms but is less effective against spores; disinfection from ultraviolet rays.
• Ultraviolet Light: Used to sterilize surfaces like inoculation cabinets; reduces airborne bacteria.
• Ionizing Radiation: Uses gamma radiation from isotopes like cobalt-60 and cesium-137 or high-energy electrons, sterilizing articles up to 2 ft thick, pre-packaged items, and pharmaceuticals.

Sterilization - Filtration

• Bacterial Filter Papers: Sterilize heat-sensitive fluids, separate bacteria from enzymes/toxins, and remove bacteria from suspensions containing viruses with various filters made of different materials and porosities.
• Water Filtration: Uses sand beds with a slimy coating of organisms to filter water.
• Air Filtration: Uses glass wool and finer filters in operating theaters, with electrostatic precipitators for small particles and cotton for bacteriological work.

Chemical Methods or Agents

• Many chemicals kill or inhibit microorganisms, but practical use varies with the situation.

Assessment of Disinfectant Properties

• Kills: Spores are highly resistant exceptions are formaldehyde, halogens, and ethylene oxide. Mycobacterium tuberculosis resists more than other vegetative organisms. Gram-negative organisms are often more resistant than Gram-positive, specifically Pseudomonas aeruginosa.
• Inhibits: High dilutions of mercury salts and quaternary compounds have bacteriostatic effects, while chlorine, formaldehyde, and ethylene oxide are primarily bactericidal.
• Action Rate: Disinfectants act over time, with some acting in seconds and others in days; higher temperatures, concentrations, and fewer organisms accelerate the process.
• Side Effects: Factors like toxicity, vapors, corrosiveness, staining, handling, quality, and cost impact suitability.
• Standardized Testing: Rideal-Walker test compares a disinfectant's ability to kill Salmonella typhi relative to phenol expressed as a phenol coefficient.

Major Chemical Disinfectants

• Salts: Sodium chloride, mercuric chloride (HgCl), and oxycyanate.
• Acids and Alkalis: Vinegar, sulfur dioxide, and benzoic acid for food preservation.
• Halogens: Chlorine, bromine, and iodine.
• Oxidizing Agents: Potassium permanganate and hydrogen peroxide.
• Ether: Cleanses skin before injection.
• Alcohol: Ethyl alcohol kills vegetative bacteria and glycerol preserves vaccinia virus.
• Dyes: Aniline, malachite green, crystal violet, acridine, proflavine, and acriflavine sterilize clinical samples.
• Others: Soaps, detergents, chlorhexidine, formaldehyde, glutaraldehyde, and ethylene oxide.