Antimicrobial Chemotherapy Lecture Notes PDF

Okay, here is the converted markdown output of the document in the images: ### Lecture 6: Antimicrobial & Chemotherapy #### Antimicrobial Chemotherapy * The use of drugs to treat infectious diseases * **Chemotherapy:** The use of chemicals or drugs to treat diseases. * Kill or inhibit the gr...

Okay, here is the converted markdown output of the document in the images: ### Lecture 6: Antimicrobial & Chemotherapy #### Antimicrobial Chemotherapy * The use of drugs to treat infectious diseases * **Chemotherapy:** The use of chemicals or drugs to treat diseases. * Kill or inhibit the growth of microorganisms. * **Goal:** Kill / Destroy the pathogen, but don't harm the host. * Selective toxicity. * The perfect drug does not exist. * Ancient Remedies #### Lecture 6 - Learning Goals * Explain the general principles of antimicrobial chemotherapy. * Describe the purpose of antimicrobial chemotherapy. * Define chemotherapy, antimicrobial and antibioitc. * Describe the contributions of Paul Ehrlich, Gerhard Domagk, Alexander Fleming, Selman Waksman to the development of antimicrobial therapy. * Ideintify sources of the most common antimicrobial drugs. * Explain the concept of selective toxicity. * Distinguish between broad-spectrum and narrow-spectrum antimicrobials and explain the significance of the distinction. * Discuss the factors that must be considered whe choosing an antimicrobial drug. * Describe the major categories of Antimicrobial agents. * Describe the five major targets of Antibacterial agents, and list major drugs associated with each. * List the four categories of drugs used to treat fungal infections and describe how they work. * Provide examples of antiprotozoal and anthelminthic drugs currently in use. * Describe the major modes of action of antiviral drugs. * Summarize the ways in which antimicrobial drugs are evaluated for use. * Define therapeutic index and identify whether a high or a low index is preferable in a drug. * Distinguish between toxicity to drugs and allergic responses to drugs. * Describe methods used for assessing antimicrobial susceptibility. * Define antimicrobial resistance. * Differentiate between inherent and acquired resistance. * Discuss the ways that microbes acquire antimicrobial resistance. * List five cellular or structural mechanisms that microbes use to resist antimicrobials. * Describe the action of beta-lactamases and explain their importance in drug resistance. * Explain how clavulanic acid is used to counteract antimicrobial resistance. | Name | Contribution | |-----------------|--------------------------------------------------------------------| | Paul Ehrlich | Magic Bullet. Salvarsan - First antimicrobial drugs. | | Gerhard Domagk | Prontosil. | | Alexander Flemmin | Discovered penicillin. | | Dorothy Hodgkin | Discovered structure of the **β**-Lactam ring. | | Selman Waksman | Discovered antibiotics by Actinomycetes. | ### Antimicrobial Timeline The image shows the evolution of antimicrobial drug discovery, peaking in the mid-20th century and declining. ### Characterizing Antimicrobial Drugs * Mode of action. * Spectrum of activity. * Bioavailability. * Unintended consequences. #### Mode of Action * Selective toxicity: Inhibit microbial growth without affecting host. * Common targets: * Cell wall. * Ribosomes. * Nucleic acid synthesis. * Enzymes. * **Bactericidal:** Kills microorganism. * **Bacteriostatic:** Slows microbial growth. * Synergism with the host immune response. * **Broad Spectrum:** Kills a large majority of microorganisms. * **Narrow Spectrum:** Kills a specific class of microorganisms. #### Unintended Consequences * Disruption of the microbiota. * Superinfections. * Toxicity. * Allergic reactions. * Drug interactions. * Immunosuppression → infection. * Antimicrobial resistance. #### Targeting the Bacterial Cell Wall * **β-Lactams:** * Penicillins. * Cephalosporins. * Carbapenems. * Monobactams. * Prevent peptidoglycan crosslinking. * **Glycopeptides:** * Different Mechanism * Poor oral bioavailability * Example: Vancomycin #### Targeting Protein Synthesis * **30S ribosome:** * Aminoglycosides (target gram -) * Bactericidal. * Examples: Streptomycin, gentamicin, and neomycin. * Inner ear toxicity. * Tetracyclines: * Bacteriostatic. * Examples: Tetracycline and doxycycline. * **50S ribosome:** * Phenicols: * Chloramphenicol. * Macrolides: * Erythromycin, Azithromycin. * Lincosamides * Clindamycin #### Drug of last resort *Polypeptide antibiotics* * Inhibit transport of cell wall components * Kidney toxicity * Topical use Example: Bacitracin ### Targeting Nucleic Acid Synthesis * DNA synthesis * RNA synthesis #### Quinolones * Inhibit topoisomerases and DNA gyrase * Examples: nalidixic acid, ofloxacin #### Metronidazole * Directly damages DNA under anaerobic conditions ### Targeting Metabolic Pathways * Folic Acid Synthesis * Sulfa Drugs - First steps * Trimethoprim - Last steps * Mycolic Acid Synthesis * Isoniazid ### Treating Eukaryotic Infections * Fewer differences * Increased toxicity * Goal: Selective Toxicity **Antifungal Agents** | Category | Action | Example | |-----------------|----------------------------------------------------|---------------------------------| | Ergosterol | Directly interact with ergosterol | Polyenes | | Polyenes | Amphotericin B, Nystatin | Directy interact with ergosterol | | Ergosterol synthesis | Azoles Allylamines | Miconazole Terbinafine Tolnaftate Fluconazole | | Cell wall synthesis | Inhibit cell wall synthesis |Echinocandins | | Nucleic synthesis | Inhibit nucleic acid synthesisFlucytosi | Flucytosine | | Microtubule assembly | Inhibits Microtubule assembly | Griseofulvin | #### Anti-Protozoan Infections * Antimalarial Drugs * Quinine * Chloroquine. * Hydroxychloroquine. * Artemisinin. *Other Anti-Protozoan Drugs* *Metronidazole* *Trimethoprim-Sulfamethoxazole* ##### Anti-Helminthic Agents * Animal parasites. * Immobilize, disintegrate, inhibit metabolism. * Examples: *Albendazole* *Praziquantel* *Ivermectin* #### Antiviral Agents *Obligate Intracellular Parasites* *Targets of Antiviral threpies* *Entry and Uncoating* *Viral Replication* *Assembly* ### Neuraminidase Inhibitors * Influenza treatment. * Zanamivir (Relenza) and oseltamivir (Tamiflu). ### Nucleoside Analogues * Inhibit nucleic acid synthesis. * Examples: * Acyclovir (Herpes viruses). * Ribavirin (Hepatitis C). * Remdesivir (COVID-19). ### HIV Treatments * Inhibit specific steps in the virus replication cycle. ### Assessing Antimicrobial Sensitivity * Kirby-Bauer. * Tube-dilution method (MIC) - Minimum Inhibitory Concentration. * Microdilution tray. * E test. ### Antimicrobial Resistance * When a microbe is not affected by a particular antimicrobial therapy. ### Combatting Beta Lactamases *clavulanic Acid* ### Inactivating Enzymes *batalactamases* ### Altered Targets *Ex. methicillin resistant S. aureus* ### Reduced Drug Penetration -Ex. Carbapenam resistance in P.aeruginos via OprD -Mutation-Reduced expression ### Efflux Pumps -Ex. Multidrug Resistant S.aureus --- ### Lecture 7 Skin & Eye Infections #### Staphylococcus aureus * Gram positive cocci * "Grape-like clusters" * Golden colonies * Facultative anaerobic * Mesophile * Facultative halophile #### S. aureus toxins * Enterotoxins: Heat-stable, acid resistant, cause gastroenteritis. * Exfoliative toxins: Cause the superficial layers of skin to peel off. * Toxic shock syndrome toxin: Heat & protease-resistant toxins, targets multiple organs. #### Diseases caused by *S. aureus* * Localized, pyogenic (mediated by hydrolytic enzymes & cytotoxins). * Skin infections * Pneumonia * Meningitis * Endocarditis * Osteomyelitis * Septic arthritis * Systemic (toxins-superantigens). * Food poisoning. * Toxic shock syndrome. * Scalded skin syndrome. * **Folliculitis:** Infections of the hair follicles. * **Sty:** Folliculitis of an eyelash. * **Furuncle (boil):** Absess, pus by inflamed tissue. * **Carbuncle:** Inflammation of tissue under the skin. * **Impetigo:** Crusting (nonbullous) sores, spread by autoinoculation. * **Surgical Site Infections** #### Virulence Factors * Capsule-protects against opsonization & phagocytosis * Catalase positive * Coagulase positive * Hydrolytic enzymes (hyaluronidase, lipase, DNase) * Hemolysins & leukocidins #### Epideiology * Known as Ritters Disease * Caused by exfoliative toxin * Children <6 * Immunosupression * Indey Disease Diagram of different types of skin lesions. #### Diagnose * Microscopy (pyogenic infections) * Culture * Blood Agar, MSA * Nuckic acid amplification tests * Catalase * Coagulase * Protein A --- ### Treatment, control & prevention #### Treatment * Incision & drainage (localized infections) * Antibiotic therapy - Supportive therapy #### Prevention * Cleansing of wounds - Topical antiseptics * Hand washing - No vaccine ### Streptococci pyogenes: * Group A, **β**-hemolytic streptococci: * Capsule (hyaluronic acid) - protects against phagocytosis. * M proteins - prevent phagocytosis, adhesins. * Catalase. * Cytolysins - Hemolysins - Streptolysins * Erythrogenic toxins - proinflammatory, stimulate cytokine release, damage capillaries. ##### Erythema nodosum * Inflammation of the subcutaneous fat cells of the hypodermis. * Painful red nodules on the skin. * Often on the skins. ### Pseudomonas aeruginosa * Gram red * Obligate aerobes (although can use nitrate or arginine as a terminal electron acceptor) * Oxidase (Different from Enterobacteriacea) * Grape Soda Scent * -2-amino acetophenone * Some strains produce pigments (ex. pyocyanin & pyroverdin) - Siderophores ### Pseudomonas control * Resevoir *Disinfectants Respiratory equipment Water, soil * Control *Proper Cleaning, Patient isolation, Aseptic Techn, wound care, no vaccine Image showing 3 states of Acne ### Streptococci * Facultative anaerobes * Some capnophies * Catase #### Classifications * Hemolysis-Lancefield (Sexological)-Biochemical ### Cellulitus * Infection of dermis or hypodermis. * Painful, red rash * Warm to the touch. *(can also be caused by Staphylococci)* ### Erysipelas * Raised red rash, clear borders. * Often face or legs St. Anthony's fire. * Painful localized skin infection w/ systemic symptoms. ### Necrotizing Fasciitis * Infection of the fascia * Can rapidly progress * Treatment involves debridement & sometimes amputation * Other Causes: S.aureus, Clostridia, Acromonas hydrophilia. *Primarily Opportunistc* #### P.Aeruginosa infection *Virluence factors* * Phosholipase ExoenzymeS ExotosinA -Frimbrea * Antibiotic resistance *Porin protest, B-lactamases, Efflux pumps * Bioflim death Pseydomands dermatitis Otitus carner Nosocomial infection- Especially burn patients * Cystic Fibrosis Particnts #### Anthrax: *Causatin agent facillus Anthracis* *Zoonotic resorce poor countries* Reservoirs cattle, sheep, horses, masks 8 traits #### Bacillius Anthracis * Enderspore forming Rod * Virulence determinants * Catagories of digans, Edemation responsible for fluid accumulation, protein -polypeptide cupsele, phospolipase C, toxins plsimid encoded Protective antijen. Lethal toxin- primflammatory toxm --- ### Cutaneons Anthrax *Pamless papple progress to ulceratian *Pamful Swollen lymph nodes *Maydevelop systemic signs #### Antrax - Diganosis *Microscopy Grow th in culture *positive direct -gentetic Test #### Anthrox - Treatmenf & Control -Coproflaxcm or Donycylline #### Human Harpes Wiruses -Alpha Herpes viruses (latent im nourons) * Herpes simpley virus, typel 1 (Hsv-1) * Herpes simplea virus type 2 (HSV-2) * Varicella zoster virus (VZ-V) Bumus ### Gastrointestine Anthrax Olcars form at site of imuasian ( Mouth cosphags Intastime) Regional swollen lymph nodes fluid accumulation seprs ### inhatation anthran Initial non specific Signs . High case fality fate *Rapid onset sepris feuer edema, Swollen lymph nodes. Maimingits *pappillomas- (Cacsed by human papiloma ulrusrs) #### herpes virus structure *Foor levels *Double stranded DNA genome *Icosapenla hedral Capsid -Auphous protest #### herpes virus replication (Hsv) *Wiral envelope Fusian Uy Cell membrane via Surface glycol Proleins cy toskelital transpote mt nuclearis relese of viral Dia circularizatisar of jamanre ### tincas ( ak aringworm) * cutansass intertians caused by dermatophytes . Requies Keratin for grow th tracophyton Epodemapfyfan 8 Micus poram diagnosis woods lamp *skin scraping/ direct mucroscopy +culture Sourand dextrose ce agur creatment topical ointonants pral jrosetuloin -CCC= Chloamphaninal & cyslohusamude --- ###acterial conjunctivits aka pinkage commonly caused hy Haemphis influenzae extramly contogions self limiting characterised ###acunthar noeba kerativ protozian inferlian of eye can lead to severe carnal demage --###Neonatal conjunctivites Opthalmia neonaturam meissena gonerae inclusion conjunctivites chlymiala thachamatis ### tracoma -leaderig cause of blindness chlymiala teschomates inferlian cavses perminunt scarring --- ###onchocerca wolvules- disemse Onchocleamatits ###agnastsic toural history ###diasis ###onchoceca medinesis Guimca worm gemel info the fery serpent :::