Chemotherapy of Infections Quiz

Chemotherapy of Infections

• The term chemotherapy was developed by Ehrlich at the beginning of the 20th century to describe using chemicals to treat diseases
• Antibiotics are substances produced naturally by microorganisms or synthetically that kill or inhibit the growth of other microorganisms

Selective Toxicity

• Chemotherapeutic drugs should be toxic to invading organisms and innocuous to the host
• This is based on biochemical differences between pathogens and the host
• Drug concentration must be carefully controlled to prevent damage to the host

Empiric Therapy

• When a patient requires urgent therapy, empiric therapy is used
• Empiric therapy involves choosing a drug in the absence of sensitivity data, influenced by the site of infection and patient history
• Therapy should be initiated after specimens for laboratory analysis are taken and before culture results are available

Antimicrobial Drugs

• Bacteriostatic Drugs: inhibit bacterial growth
• Bactericidal Drugs: kill bacteria

Chemotherapeutic Spectra

• Narrow Spectrum: affects a single or limited group of microorganisms, e.g., Isoniazid against mycobacteria only
• Extended Spectrum: affects gram + and a significant number of gram - bacteria, e.g. Ampicillin
• Broad Spectrum: affects a wide variety of microbial species, e.g., Tetracyclines and Chloramphenicol

Drug Resistance

• Drug resistance is the ability of a microorganism to withstand an antibiotic to which they were once sensitive
• Resistance can be accelerated by a variety of factors, including human practices

Mechanism of Drug Resistance

• Mutations: changes in the DNA sequence of the bacteria
• Gene Amplifications: an increase in the number of copies of a gene, which leads to increased expression of the gene product
• Plasmids: extrachromosomal DNA that can transfer resistance genes
• Transposons: mobile DNA elements that can insert into the bacterial chromosome and transfer resistance genes
• Gene Cassettes and Integrons: provide a mechanism for the acquisition and expression of multiple resistance genes
• Conjugation: transfer of genetic material between bacteria through direct contact
• Transductions: transfer of genetic material between bacteria through a bacteriophage
• Transformation: uptake of free DNA by a bacterium

Biochemical Mechanisms of Resistance

• Alteration of drug-sensitive binding site: The target for the antibiotic can be altered, preventing the antibiotic from binding
• Production of enzymes that inactivate the drug: Bacteria can produce enzymes that break down or inactivate the antibiotic
• Decreased drug accumulation in bacteria: Bacteria can decrease the uptake of the antibiotic or increase the efflux of the antibiotic
• Alteration of enzyme pathways: The antibiotic can be prevented from working by altering the pathway that the antibiotic targets

Antimicrobial Combinations and Prophylaxis

• It is therapeutically advisable to treat patients with one agent specific for the infecting microorganism
• Using antibiotics prophylactically is generally unadvisable
• Antibiotic combinations are necessary in some situations:
  • Mixed infections
  • Life-threatening conditions
  • When there is a risk of developing resistant microorganisms

Prophylactic Antibiotics

• Prophylactic antibiotics are used to prevention of infections in certain situations:
  • Prevention of streptococcal infections in patients with rheumatic heart disease
  • Pretreatment of patients undergoing dental extractions who have implanted prosthetic devices
  • Prevention of TB or Meningitis in individuals in close contact with infected patients
  • Treatment prior to certain surgical procedures

Complications of Antibiotic Therapy

• Direct Toxicity: can be a side effect of the antibiotic, e.g., Aminoglycoside ototoxicity
• Hypersensitivity: allergic reactions can occur, ranging from urticaria to anaphylactic shock
• Superinfection: can occur with broad-spectrum antibiotics, allowing opportunistic organisms to overgrow

Classification of Antimicrobial Agents

• Antibiotics are classified by their mechanism of action which defines their target
• Classes include:
  • Beta-lactam antibiotics
  • Macrolide antibiotics
  • Aminoglycoside antibiotics
  • Fluoroquinolones
  • Tetracyclines