Chapter 9: Controlling the Growth of Pathogens In Vivo Using Antimicrobial Agents PDF

Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN Controlling Microbial Growth in Vivo Types of Antimicrobial Agents Using Antimicrobial Agents...

Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN Controlling Microbial Growth in Vivo Types of Antimicrobial Agents Using Antimicrobial Agents Antimicrobial agents are classified based on Vivo-within the type of pathogen they target: Antimicrobial resistant (AMR) 1. Antibacterial agents: Treat bacterial infections. Chemotherapy- The use of any chemicals 2. Antifungal agents: Treat fungal or drugs to treat any diseases or conditions, infections. including infections and cancer. 3. Antiprotozoal agents: Target protozoal diseases. Historical Note: 4. Antiviral agents: Treat viral Father of Chemotherapy—Paul infections Ehrlich Antibiotics: A subset of Antimicrobial Neosalvarsan/Compound Agents 606—were used to treat syphilis. Definition: Antibiotics are substances rosaniline was useful for treating produced by microorganisms that kill or African trypanosomiasis. inhibit other microorganisms. All antibiotics are antimicrobial agents, but not all antimicrobial Chemotherapeutic agents: Drugs used to agents are antibiotics. treat diseases. Note: Therefore, the terms are not Historical Examples: synonyms, and care should be taken to use Indigenous practices: the terms correctly. ○ Ipecac root: Treated dysentery. Streptomycin: kill bacteria ○ Quinine: Extracted from Bacteria from bats- ability to kill or prevent cinchona bark to treat E-coli. malaria. Sources of Antibiotics: Early European alchemists: Used Produced by soil-dwelling mercury and arsenic compounds, microorganisms to gain a often causing severe side effects. competitive advantage. Modern Developments: Examples of antibiotic-producing Chemotherapeutic agents targeting organisms: infectious diseases are collectively ○ Moulds: Produce penicillin called antimicrobial agents. These and cephalosporins. drugs either inhibit the growth of ○ Bacteria: Produce pathogens or kill them. bacitracin, erythromycin, and chloramphenicol. JULATON, ALEA BIANCA B. I REVIEWER  Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN Modern Production: Historical Note: Antibiotics were traditionally Alexander Fleming, a Scottish extracted from microorganisms but bacteriologist, accidentally are now often synthesized or discovered the first antibiotic when modified in laboratories. he noticed that the growth of contaminant Penicillium notatum Also, many antibiotics have been mould colonies on his culture plates chemically modified to kill a wider was inhibiting the growth of variety of pathogens or reduce side Staphylococcus bacteria. effects; these modified antibiotics a: During World War II, two semisynthetic antibiotics. biochemists, Sir Howard Walter Florey and Ernst Boris Chain, Semisynthetic antibiotics: purified penicillin and demonstrated Chemically altered antibiotics with its effectiveness in the treatment of improved properties, such as: various bacterial infections. Broader activity against Selman Waksman who first used pathogens. the term "antibiotic.” Reduced side effects For their outstanding contributions to Examples: medicine, these Ampicillin, Investigators-Ehrlich, Fleming, Carbenicillin Florey, Chain, Waksman, and Domagk-were all Nobel Prize Primary Use recipients at various times. Antibiotics are primarily antibacterial, making them essential for treating How Antimicrobial Agents Work bacterial diseases. To be acceptable, an antimicrobial agent must inhibit or destroy the Characteristics of an Ideal Antimicrobial pathogen without damaging the Agent host. The ideal antimicrobial agent should: To accomplish this, the agent must Kill or inhibit the growth of target a metabolic process or pathogens structure possessed by the Cause no damage to the host pathogen but not possessed by the Cause no allergic reaction in the host (i.e., the infected person). host Be stable when stored in solid or The five most common mechanisms of liquid form action of antimicrobial agents are as follows: Remain in specific tissues in the Inhibition of cell wall synthesis body long enough to be effective Damage to cell membranes Kill the pathogens before they Inhibition of nucleic acid synthesis mutate and become resistant to it. (either DNA or RNA synthesis) JULATON, ALEA BIANCA B. I REVIEWER  Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN Inhibition of protein synthesis metabolic pathways, leaving human Inhibition of enzyme activity cells unharmed. Mechanisms of Action 1. Competitive Inhibition (Sulfonamides) Kapag walang folic acid, walang DNA. a. Mechanism: Sulfa drugs mimic p-aminobenzoic acid (PABA), a precursor for folic acid synthesis in bacteria. b. Outcome: Bacteria are unable to synthesize folic acid, a necessity for protein production, leading to cell Antibacterial Agents: Mechanisms, death. Types, and Strategies c. Impact on Humans: Sulfonamide drugs inhibit production Humans obtain folic acid of folic acid (a vitamin) in those from diet, so sulfa drugs bacteria that require p-aminobenzoic have no harmful effects on acid (PABA) to synthesize folic acid. human cells. ○ Because the sulfonamide d. Type: Sulfa drugs are molecule is similar in shape bacteriostatic (inhibits to the PABA molecule, growth, does not kill bacteria attempt to bacteria). metabolize sulfonamide to produce folic acid (Fig. 9-3). However, the enzymes that convert PABA to folic acid cannot produce folic acid from the sulfonamide molecule. ○ Without folic acid, bacteria cannot produce certain essential proteins and finally die. Antibacterial agents are essential in combating bacterial infections. Their effectiveness is based on selectively targeting bacterial structures or JULATON, ALEA BIANCA B. I REVIEWER  Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN 2. Cell Wall Inhibition (Penicillins 3. Protein Synthesis Inhibition and Cephalosporins) Tetracyclines: Bind to In most Gram-positive bacteria, bacterial ribosomes, halting including streptococci and protein synthesis staphylococci, penicillin interferes (bacteriostatic). with the synthesis and cross-linking Aminoglycosides: Disrupt of peptidoglycan, a component of bacterial protein synthesis in bacterial cell walls. Thus, by Gram-negative aerobes inhibiting cell wall synthesis, (bactericidal). penicillin destroys the bacteria. Macrolides: Inhibit bacterial protein production; Why doesn't penicillin also destroy dosage-dependent effects human cells? (bacteriostatic or - Because human cells do not bactericidal). have cell walls 4. DNA Synthesis Inhibition (Fluoroquinolones) Penicillin: Inhibits synthesis Mechanism: Inhibit bacterial and cross-linking of DNA replication, leading to peptidoglycan, leading to cell death. bacterial lysis. Example: Ciprofloxacin, Cephalosporins: Similar effective against action to penicillin but vary in Gram-negative pathogens. their effectiveness against Type: Bactericidal. Gram-positive and Gram-negative bacteria. Type: Bactericidal (kills bacteria). Dapat pineprescribe ng doctor ilang dose ang need. (ang pagbudbod ng penicillin sa sugat is not good). JULATON, ALEA BIANCA B. I REVIEWER  Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN Spectrum Activity Bacteriostatic agents should be used only in patients whose host defense 1. Narrow-Spectrum Antibiotics mechanisms (see Chapters 15 and Target specific types of 16) are functioning properly (i.e., bacteria. only in patients whose bodies are Examples: capable of killing the pathogen once Vancomycin: Effective its multiplication is stopped). against Gram Positive bacteria. Bacteriostatic agents should not be Colistin and nalidixic acid: used in immunosuppressed or Targets Gram-negative leukopenic patients (patients having bacteria an abnormally low number of white 2. Broad-Spectrum Antibiotics blood cells) because the host Effective against a wide defense mechanisms of such range of bacteria, including patients would be unable to both Gram Positive and eliminate the nongrowing bacteria. Gram-negative species. Examples: Virtually all of the antibacterial Ampicillin, agents currently available either kill chloramphenicol, bacteria or inhibit their growth. Tetracycline Researchers are attempting to ceftriaxone, develop antibacterial agents that Ievofloxacin, and target bacterial virulence factors, tetracycline. rather than targeting the pathogens themselves. Bacterial virulence factors include various harmful substances, such as toxins and enzymes, produced by bacteria. Key Categories of Antibacterial Agents 1. Penicillins Antimicrobial agents work well against Mechanism: Block cell wall bacterial pathogens because the bacteria synthesis. (being prokaryotic) have different cellular Effective Against: structures and metabolic pathways that can Gram-positive cocci (e.g., be disrupted or destroyed by drugs that do Staphylococcus aureus), not damage the eukaryotic host's cells. some Gram-negative cocci, and spirochetes. JULATON, ALEA BIANCA B. I REVIEWER  Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN Notable Forms: like Enterobacteriaceae and Extended-spectrum Pseudomonas aeruginosa penicillins target Gram-negative bacilli. Strategies in Antibacterial Therapy 2. Cephalosporins 1. Multidrug Therapy Gram-positive bacteria. Combining two or more Increased Gram-negative drugs can improve efficacy activity. and prevent resistance. Broad Gram-negative activity Example: Treatment of (Pseudomonas aeruginosa). tuberculosis often involves Activity against both multiple drugs (e.g., Gram-positive and isoniazid, rifampin) Gram-negative bacteria 2. Synergism and Antagonism 3. Tetracyclines Synergism: Two drugs work Broad-spectrum, together, enhancing bacteriostatic drugs targeting pathogen killing (e.g., ribosomes. trimethoprim + Effective Against: sulfamethoxazole = Chlamydias, mycoplasmas, co-trimoxazole). and spirochetes. Antagonism: Two drugs 4. Aminoglycosides counteract each other, Broad-spectrum, bactericidal reducing efficacy. drugs inhibiting protein synthesis. Considerations for Antibacterial Use Effective Against: Aerobic Gram-negative bacteria, 1. Bactericidal vs. Bacteriostatic such as E. coli and a. Bactericidal Agents: Pseudomonas aeruginosa Preferred for 5. Macrolides immunocompromised Dosage-dependent patients or severe infections. (bacteriostatic or b. Bacteriostatic Agents: bactericidal). Effective when the patient’s Effective Against: immune system is functional. T. pallidum, Legionella spp., and mycoplasmas. 6. Fluoroquinolones Broad-spectrum bactericidal drugs. Effective Against: Gram-negative pathogens 2. Targeting Virulence Factors JULATON, ALEA BIANCA B. I REVIEWER  Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN Emerging strategies focus on Example: neutralizing bacterial Metronidazole (brand virulence factors (e.g., toxins name: Flagyl). and enzymes) instead of directly targeting bacteria. ANTIVIRAL AGENTS Viruses replicate within host cells, Neutralizing the toxins or enzymes that can cause derulence/pagkakasakit sa tao. making treatment challenging. Antiviral drugs act by: ANTIFUNGAL AGENTS ○ Inhibiting viral replication Fungi are eukaryotic cells, so within cells: antifungal drugs often pose toxicity Examples: Various risks to the host. drugs against HIV, These drugs work by: herpes simplex virus, ○ Binding to cell membrane and influenza. sterols: ○ HIV Treatment: Examples: Nystatin, a. The first effective Amphotericin B drug: Zidovudine ○ Inhibiting sterol synthesis: (AZT). Examples: b. Modern treatments Clotrimazole, often involve drug Miconazole. cocktails, though ○ Blocking mitosis or nucleic resistance can acid synthesis: develop. Examples: Griseofulvin, 5-Flucytosine Dandruff- Ketoconazole-based shampoos targeting dandruff because dandruffs are fungus. ANTIPROTOZOAL AGENTS DRUG RESISTANCE Antiprotozoal drugs are usually toxic Superbugs to the host due to their effects on Drug-resistant pathogens, termed eukaryotic cells. They work by: "superbugs," pose significant challenges. ○ Interfering with DNA/RNA Notable examples: synthesis: MRSA (Methicillin-resistant Examples: Staphylococcus aureus). Chloroquine, VRE (Vancomycin-resistant Pentamidine, Enterococcus spp.). Quinacrine MDR-TB (Multidrug-resistant ○ Interfering with metabolism Mycobacterium tuberculosis). JULATON, ALEA BIANCA B. I REVIEWER  Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN XDR-TB (Extensively drug-resistant β-LACTAMASES tuberculosis). Mechanism: Carbapenemase-producing β-lactam antibiotics (e.g., penicillins, Klebsiella pneumoniae. cephalosporins) contain a β-lactam ring, essential for their function. βlactamases are enzymes that: ○ Destroy the β-lactam ring, rendering the antibiotic ineffective. Two types: Penicillinases: Target penicillins. Cephalosporinases: Target cephalosporins Hindi magwowork kapag ang pinainom ay same b-lactam antibiotics Mechanisms of Resistance 1. Intrinsic Resistance: Bacteria naturally lack the drug's target site or cannot allow drug entry. Example: Mycoplasmas (no cell wall → resistant to cell wall inhibitors). 2. Acquired Resistance: Mutations alter drug-binding sites or membrane permeability. Gene acquisition through: 1. Conjugation (e.g., plasmid exchange for penicillinase Countermeasures: production). Drugs combining β-lactam antibiotics 2. Transformation (uptake of with β-lactamase inhibitors: environmental DNA). Clavulanic acid + Amoxicillin 3. Transduction (Augmentin). (bacteriophage-mediated Clavulanic acid + Ticarcillin DNA transfer). (Timentin). MDR pumps expel drugs, conferring Sulbactam + Ampicillin multidrug resistance. (Unasyn). Tazobactam + Piperacillin (Zosyn). JULATON, ALEA BIANCA B. I REVIEWER Chapter 9: Controlling the Growth of Pathogens In Vivo using Antimicrobial Agents FIRST SEMESTER I ACADEMIC YEAR 2024-2025 I PROF. JOHN LEONARD CHAN JULATON, ALEA BIANCA B. I REVIEWER