Antimicrobial & Chemotherapeutic Agents

• Chemotherapy uses chemicals or drugs to treat diseases/conditions

Chemotherapeutic Agent

• Drugs are used to treat conditions/diseases

Antimicrobial Agent

• Chemicals/drugs inhibit or kill pathogens in vivo to treat infectious diseases
• Some antimicrobial agents are antibiotics

Antibacterial Agents

• Drugs treat bacterial diseases

Antifungal Agents

• Treat fungal diseases

Antiprotozoal Agents

• Treat protozoal diseases

Antiviral Agents

• Treat viral diseases

Antibiotics

• Substances produced by microorganisms that kill or inhibit the growth of other microorganisms

Semisynthetic Antibiotics

• Chemically modified antibiotics broaden pathogen targets or reduce side effects
• Examples include ampicillin and amoxicillin

Ideal Antimicrobial Agent Characteristics

• Should kill/inhibit pathogen growth without harming the host
• Should not cause allergic reactions and needs to be stable in storage
• Needs to remain effective in body tissues long enough and kill pathogens before resistance develops

Antimicrobial Agent Actions

• Inhibit cell wall synthesis
• Damage cell membranes
• Inhibit nucleic acid synthesis (DNA/RNA)
• Inhibit protein synthesis
• Inhibit enzyme activity

Antibacterial Agents

• Bacteriostatic drugs inhibit bacteria growth
• Bactericidal drugs kill bacteria

Sulfonamide Drugs

• These inhibits folic acid production in bacteria requiring p-aminobenzoic acid for folic acid synthesis
• Bacteria cannot produce specific proteins without folic acid, leading to death

Sulfa Drugs

• They are competitive inhibitors and also bacteriostatic

Penicillin

• It interferes with peptidoglycan synthesis/cross-linking in Gram-positive bacteria
• Disrupting their cell wall synthesis, ultimately destroying the bacteria

Peptidoglycan

• It is a component of cell walls

Colistin and Nalidixic Acid

• These destroy Gram-negative bacteria
• These are also narrow-spectrum antibiotics

Broad-Spectrum Antibiotics

• These counteract Gram-positive and Gram-negative bacteria
• Includes Ceftriaxone, Ciprofloxacin, and Tetracycline

Multidrug Therapy

• Sometimes one drug is not enough
• Combines two+ drugs simultaneously, such as in tuberculosis treatment

Synergism

• This is when combined antimicrobials enhance pathogen killing, surpassing individual drug effectiveness
• It is a good thing

Antagonism

• This is when drugs counteract each other, reducing pathogen killing compared to individual drug effectiveness
• It is a bad thing

Antibacterial Agent Categories

• Penicillins: bactericidal, interfere with cell wall synthesis
• Cephalosporins: bactericidal, interfere with cell wall synthesis
• Carbapenems: bactericidal, interfere with cell wall synthesis
• Tetracyclines: bacteriostatic, inhibit protein synthesis
• Aminoglycosides: bactericidal, inhibit protein synthesis
• Macrolides: bacteriostatic (lower doses), bactericidal (higher doses), inhibit protein synthesis
• Fluoroquinolones: bactericidal, inhibit DNA synthesis

Antifungal Agents

• Agents function by binding to cell membrane sterols, interfering with sterol synthesis, or blocking mitosis or nucleic acid synthesis
• They are more toxic because both humans and infected organisms are eukaryotic

Antiprotozoal Agents

• These are generally toxic to the host
• They function by interfering with DNA/RNA synthesis or protozoal metabolism

Antiviral Agents

• They are newer antimicrobial tools that inhibit replication but has development challenges due to viral production inside host cells

"Cocktails"

• Uses multiple antiviral drugs simultaneously, such as in HIV treatment

Superbugs

• Microbes, often bacteria, are resistant to ≥1 antimicrobial agents
• Infections from these are not easily treatable
• Include: MRSA, VRE, MDRTB, multidrug-resistant strains of Acinetobacter/Burkholderia/Pseudomonas, and Neisseria gonorrhoeae and KPC

Intrinsic Resistance

• Natural resistance occurs if bacteria lack the drug's target or the drug can't reach its action site

Acquired Resistance

• Bacteria that were once susceptible to a drug have become resistant

Drug-Binding Sites

• Proteins on the cell's surface where drugs bind before entering bacterial cell
• Resistance develops through chromosomal mutations altering drug-binding sites or cell membrane permeability

Enzyme Production

• Bacteria may develop enzymes to destroy/inactivate drugs, leading to resistance
• Bacteria resistant to penicillin acquired the gene for penicillinase production through conjugation

Resistance Factor (R-factor)

• Plasmids containing multiple drug resistance genes

MDR (Multidrug-Resistance) Pumps

• Bacteria become resistant by developing MDR pumps to expel drugs

MDR Pump Mechanism

• This enables bacteria to pump drugs out of the cell, preventing damage

Resistance Acquisition

• It occurs through chromosomal mutation or new gene acquisition via transduction, transformation, or conjugation

β-Lactamases

• Penicillin, cephalosporin, and carbapenem molecules have a double-ringed structure
• Some bacteria produce enzymes (β-lactamases) to destroy the β-lactam ring, rendering the drug ineffective
• Three types of β-lactamases: Penicillinases, Cephalosporinases, and Carbapenemases
• Drug companies are combining β-lactam antibiotics with β-lactamase inhibitors

Strategies Against Drug Resistance

• Educate health professionals/patients, avoid patient pressure for unnecessary antibiotics, and prescribe narrow-spectrum drugs based on lab results
• Destroy expired medications, avoid prophylactic antibiotic use, practice infection control, and adhere to prescribed drug regimens

Empiric Therapy

• Initiates drug therapy before lab results on pathogen identity/susceptibility
• It is done when necessary to save lives
• Clinicians make educated guesses based on experience, also considering factors before prescribing antimicrobials

Factors for Consideration During Empiric Therapy

• Check available antimicrobial susceptibility data, consider patient allergies, age, pregnancy status, and if the patient is an inpatient or outpatient
• Account for hospital formulary, infection site, other medications, medical problems, leukopenia, immunocompromisation, and also drug costs

Undesirable Effects of Antimicrobial Agents

• Indiscriminate use causes organisms to die but resistant ones survive
• Patients may develop allergies and agents may be toxic
• Prolonged broad-spectrum use can destroy normal flora, leading to superinfections like Clostridium difficile-associated diarrhea

Selecting for Resistant Organisms

• Susceptible organisms die, but resistant ones survive and thrive