Anti-infective Agents

Drug Therapy Across the Lifespan

Drug Therapy Across the Lifespan

Development of Anti-infective Therapy

• 1920s
  • Paul Ehrlich worked on developing a synthetic chemical effective against infection-causing cells only
  • Scientists discovered penicillin in a mold sample
• 1935
  • The sulfonamides were introduced

Mechanisms of Action

• Interfere with biosynthesis of the bacterial cell wall
• Prevent the cells of the invading organism from using substances essential to their growth and development
• Interfere with steps involved in protein synthesis
• Interfere with DNA synthesis
• Alter the permeability of the cell membrane to allow essential cellular components to leak out

Mechanism of Anti-infective Agents

Mechanism of Anti infective Agents

Anti-infective Activity

• Anti-infectives vary in their effectiveness against invading organisms
• Some are selective: they are effective only for a small number of organisms
• Bactericidal: kill the cell
• Bacteriostatic: prevent reproduction of the cell

Narrow Spectrum vs Broad Spectrum

• Narrow spectrum of activity
  • Effective against only a few microorganisms with a very specific metabolic pathway or enzyme
• Broad spectrum of activity
  • Useful in treating a wide variety of infections

Human Immune Response

• Goal of anti-infective therapy is reduction of the population of the invading organism
• Drugs that eliminate all traces of any invading pathogen might be toxic to the host as well
• Immune response is a complex process involving chemical mediators, leukocytes, lymphocytes, antibodies, and locally released enzymes and chemicals

Problems With Treating Infections in Immunosuppressed Patients

• Anti-infective drugs cannot totally eliminate the pathogen without causing severe toxicity in the host
• These patients do not have the immune response in place to deal with even a few invading organisms

Resistance

• Anti-infectives act on a specific enzyme system or biological process; many microorganisms that do not act on a specific system are not affected by the particular drug
• This is considered natural or intrinsic resistance to that drug

Acquired Resistance

• Microorganisms that were once sensitive to the particular drug have begun to develop acquired resistance
• This results in serious clinical problems

Ways Resistance Develops

• Producing an enzyme that deactivates the antimicrobial drug
• Changing cellular permeability to prevent the drug from entering the cell
• Altering transport systems to exclude the drug from active transport into the cell
• Altering binding sites on the membranes or ribosomes, which then no longer accept the drug
• Producing a chemical that acts as an antagonist to the drug

Preventing Resistance

• Limit the use of antimicrobial agents to the treatment of specific pathogens sensitive to the drug being used
• Make sure doses are high enough, and the duration of drug therapy long enough
• Be cautious about the indiscriminate use of anti-infectives

Identification of the Pathogen

• Identification of the infecting pathogen is done by culture
• A culture of a tissue sample from the infected area is done
  • A swab of infected tissue is allowed to grow on an agar plate
  • Staining techniques and microscopic examination identify the bacterium
• Stool can be examined for ova and parasites

Sensitivity of Pathogen

• Shows which drugs are capable of controlling the particular microorganism
• Important to be done for microorganisms that have known resistant strains
• Along with a culture, identifies the pathogen and appropriate drug for treatment

Factors Affecting Prescribing Anti-infective Agents

• Identification of the correct pathogen
• Selection of the right drug
  • One that causes the least complications for that particular patient
  • One that is most effective against the pathogen involved

Combination Therapy

• Use of a smaller dosage of each drug
• Some drugs are synergistic
• In infections caused by more than one organism, each pathogen may react to a different anti-infective agent
• Sometimes, the combined effects of the different drugs delay the emergence of resistant strains

Adverse Reactions to Anti-infective Therapy

• Kidney damage
• Gastrointestinal (GI) tract toxicity
• Neurotoxicity
• Hypersensitivity reactions
• Superinfections

Prophylaxis of Anti-infective Agents

• People traveling to areas where malaria is endemic
• Patients who are undergoing gastrointestinal or genitourinary surgery
• Patients with known cardiac valve disease, valve replacements, and other conditions requiring invasive procedures