Infectious Processes PDF

BIO3310-30 Human Physiology and Pharmacology The Infectious Process  Readings ATI Online Module: Infection ATI Text: Chapters 43-47 Abrams: Ch. 15, 18-20, 23-25 Drug Classes Overview: Drug classifications:  Penicillins  Cephalosporins  Carbapenems  Vancom...

BIO3310-30 Human Physiology and Pharmacology The Infectious Process  Readings ATI Online Module: Infection ATI Text: Chapters 43-47 Abrams: Ch. 15, 18-20, 23-25 Drug Classes Overview: Drug classifications:  Penicillins  Cephalosporins  Carbapenems  Vancomycin (unique drug)  Tetracyclines  Macrolides  Aminoglycosides  Oxazolidinones  Sulfonamides  Trimethoprim/sulfonmethoxazole (unique drug)  Fluoroquinolones  Metronidazole (unique drug)  Antifungal drugs (Amphotericn B, Azoles)  Antiviral drugs (non-HIV) FYI:  Epidemiology: Study distribution and patterns of disease in populations  Pathogens: cause infectious diseases ◦ What are the types of pathogens?  Pathogenicity: ability of an organism to cause disease  Types of Pathogen Spread ◦ Communicable ◦ Non-communicable Describe the Transmission Process of Infection Reservoir Portal of Exit & Mode of Transmission Portal of Entry Susceptible victim Transmission of Infection (Cont.) 6 Injury to the Body Occurs  Directly ◦ By toxins released from the microorganism  Indirectly ◦ Body’s immune response Host Defense Systems  Innate and specific immune response  Mechanical (cilia/coughing)  Epithelial Barriers (skin)  Block foreign material entering the body  Provide multilayer protection  Dry surface does not promote organism growth  Sloughing of skin/mucosal cells aids in microorganism removal  Biochemical barriers (ph)  Phagocytes  Chemical mediators 8 Explain Risk Factors for Infection 1. Nutritional Status 2. Poor Habits (smoking, alcohol, drug use) 3. Chronic Illness 4. Age 5. Immunosuppression/compromise 6. Drug Therapy Role of Environment Environmental factors influence the likelihood of exposure and infection by microorganisms 1. Sanitation 2. Air quality 3. Living conditions 4. Climate 10 Discuss 2 Goals of Immunization 1. Confer immunity to a host by immunizations (exposure to the pathogens). 2. Decrease the number of susceptible hosts in the population (herd immunity). Bacteria in our lives   Colonization: harmless inhabitation of resident flora  Opportunistic infections: normal flora that cause infections if immunosuppressed  Iatrogenic infections (CA or HAI) Virulent organisms: cause illness Microorganism Characteristics that allows them to survive and thrive! 1. Microbial Adherence ◦ Ability of a microorganism to latch onto and gain entrance into its host  Direct penetration  Sticks to tissue surface  Slime layer (glycocalyx) also facilitates adherence 2. Bacterial enzymes ◦ Help microorganism to spread or invade tissues 13 1. Encapsulation ◦ Prevents opsonization by antibodies ◦ Prevents microorganism from being phagocytized 2. Endospore formation ◦ Allows microorganism to survive under harsh environmental conditions 3. Virulence ◦ Microorganism consistently causes disease in all infected hosts ◦ Interaction between host/pathogen harms host 14 Bacterial Survival of the Fittest!  Bacterial mobility  Exotoxins  Endotoxins Microbial Resistance Microorganism’s ability to mutate in response to environment changes in host Mutation allows successful host infection We will come back to this later! 16 Test Yourself Define These Characteristics of Microorganisms  Microbial adherence  Bacterial enzymes  Encapsulation Label the Following Slides With  Bacteria  Virus  Fungi  Parasite Types of Pathogenic Organisms 19  Who am I? I am nonphotosynthetic I live in the environment I cause mycotic infections or mycoses I colonize an area first, then invade epithelium I like to invade breaks in your skin I live normally in or on your body If your body’s defenses are compromised, I will grow I cause superficial, subcutaneous or systemic infections Who am I? I am a protozoa or single-celled animal I am a helminth or arthropod I live on or in your body for food and shelter Symptoms of infection with me depend on where I am I like to infect your GI tract, blood, or skin Parasites 22 Who am I? I am a single cell with no internal organelles I live in intestines & participate in digestion I am responsible for soil’s fertility I breakdown dead tissue for other organisms to use Only a few of me & my family are harmful to humans You identify me by: morphology (cocci, bacilli, spiral) response to gram staining (gram positive or negative) Who Am I? I am the smallest known infective agent I am composed of DNA or RNA A capsule surrounds my genetic material I am totally dependent on my host for energy & to replicate myself I cause the common cold and AIDS You can’t touch me with antibiotics Viruses 27 Viruses 28 Antimicrobials  Used to treat infectious diseases  Up to 30% of all hospitalized patients receive antimicrobials  Modern antimicrobials – 1930s and 1940s  Significantly reduced morbidity and mortality from infection Basic Terminology of Antimicrobial Therapy  Chemotherapy ◦ Use of chemicals against invading organisms  Antibiotic ◦ Strictly speaking – a chemical that is produced by one microbe and has the ability to harm other microbes  Antimicrobial agent ◦ Any agent that has the ability to kill or suppress microorganisms Lab Studies  Microscopy  Dyes (Gram stain, KOH)  Culture and sensitivity (takes 48-72 hours)  Serology (antibody levels)  Assess for microbial RNA/DNA  CBC (white count especially) Choose drug based on results of the C & S Able to give drugs that kill bacteria without injuring human cells. Classification of Antibiotics  Drugs work on: 1. Cell wall synthesis 2. Cell membrane permeability 3. Protein synthesis (lethal) 4. Nonlethal inhibitors of protein synthesis 5. Synthesis of nucleic acids 6. Antimetabolites 7. Viral enzyme inhibitors Compare These Terms Bactericidal Bacteriostatic Broad Spectrum Narrow Spectrum Acquired Drug Resistance  Organism can become less and less susceptible or lose sensitivity entirely over time.  Describe 4 bacterial modifications contributing to resistance 1. Reducing drug concentration (active uptake or active export) 2. Drug inactivation 3. Target molecule alteration 4. Antagonist production Organisms With Microbial Drug Resistance  Enterococcus faecalis (VRE)  Enterococcus faecium  Staphylococcus aureus (MRSA, VRSA)  Staphylococcus epidermidis,  Streptococcus pneumoniae (PRSP, MDRSP)  Klebsiella pneumoniae  MDR-TB Acquired Drug Resistance Describe how these factors contribute to drug resistance Antibiotic use More & more broad spectrum antibiotics HAI: healthcare acquired infections (nosocomial infections) Superinfection  Discuss These Ways to Delay Resistance Prevent infection (vaccinations, handwashing) Diagnose & treat infection effectively Wise antibiotic use (also including AB additives in livestock feed to promote growth) Prevent transmission  REVIEW AND UNDERSTAND THIS CHART Fig. 82-1. Pocket card from the CDC’s Campaign to Prevent Antimicrobial Resistance. Selection of Antibiotics  Identify organism  Drug sensitivity of organism  Host factors  Drug may be ruled out due to: ◦ Allergy ◦ Inability to penetrate the site of infection ◦ Patient variables Considerations when choosing treatment 1. Host defences 2. Site of infection 3. Age 4. Pregnancy & lactation 5. Previous Allergic Reaction 6. Genetic Factors Prophylactic Use of Antimicrobials  Agents given to prevent infection rather than to treat an established infection ◦ Surgery ◦ Bacterial endocarditis ◦ Neutropenia ◦ Other indications Antibiotic Combinations  Antimicrobial effects of antibiotic combinations ◦ Additive, potentiated, antagonistic  Indications for Combination Therapy ◦ Initial Therapy for Severe Infections ◦ Used for mixed infections ◦ Prevention of Resistance ◦ Decrease Toxicity ◦ Enhanced Antibacterial Action Disadvantages of Combination Therapy  Increased risk of toxic and allergic reactions  Possible antagonism of antimicrobial effects  Increased risk of superinfection  Selection of drug-resistant bacteria  Increased cost 5 Misuses of Antimicrobial Drugs 1. Treatment of an untreatable infection 2. Treatment of FUO 3. Improper Dosage 4. Treatment without adequate bacteriologic information 5. Omission of surgical drainage Monitoring of Antimicrobial Therapy  Monitor clinical responses and laboratory results  Frequency of monitoring should increase with severity of infection  Clinical indicators of success ◦ Reduction of fever, resolution of signs/symptoms related to the affected organ  Serum drug levels for toxicity Types of Antibacterials 1) Beta-lactams ◦ Penicillins—end in “cillin” ◦ Cephalosporins (5 generations)—often begin with “cef-” ◦ Carbapenems 2) Aminoglycosides—end in “mycin or micin” 3) Fluoroquinolones-end in “”floxacin” 4) Tetracyclines---end in “cycline” Types of Antibacterials (con’t) 1) Sulfonamides—often begin with “sulfa-” 2) Urinary Antiseptics 3) Macrolides—end in “thromycin” 4) Ketolides 5) Miscellaneous drugs Universal Client Teaching for Anti-infective Therapy  Make sure you check the drug names, dose, route, schedule and if it is taken with/without food.  Take it in evenly spaced intervals  Take the full course even if you feel better  Do not double if you skip a dose  Discard any unused drug, do not use past the expiration date (decreased potency)  Take OTC meds only after checking with health care provider  Monitor for s/s of superinfections Penicillins  Mechanism of action ◦ Weaken the cell wall, causing bacteria to take up excessive water and rupture ◦ Active only against bacteria that are undergoing growth and division ◦ Bactericidal ◦ Bacterial resistance  Inability of penicillins to reach their target  Inactivation of penicillins by bacterial enzymes  Production of penicillin-binding proteins (PBPs) that have a low affinity for penicillins Penicillin Allergy  Development of penicillin allergy  Skin tests for penicillin allergy  Management of patients with a history of penicillin allergy  Assess for penicillin allergy in each patient who will be receiving penicillin ◦ If history of mild reaction – consider cephalosporin ◦ If history of anaphylaxis – avoid administration of penicillin or cephalosporins Classification of Penicillins (“- cillin”)  Narrow-spectrum penicillins ◦ Pencillinase-sensitive  Penicillins G and V  Narrow-spectrum penicillins ◦ Pencillinase-resistant  Dicloxacillin, Nafcillin, Oxacillin  Broad-spectrum penicillins ◦ Aminopenicillins  Amipicillin (Prototype)  Amoxicillin, Ticarcillin, Piperacillin  Penicillins Most Common Adverse Effects Hypersensitivity reactions GI: diarrhea, N/V, abdominal pain, gastritis (less if take with food Drug interactions: (in book) ◦ Penicillin inactivates IV aminoglycosides (gentamycin) so don't mix (often given together for serious infections) **Cross Sensitivity with other classes with similar chemical structure—cephalosporins and carbapanems** Combo Drugs  Penicillin-Beta-Lactamase Inhibitor Combinations ◦ Beta-lactamase inhibitor given to bind with the beta-lactamases (enzyme that degrades beta- lactam ring in the cell wall) to prevent inactivation of the beta-lactam antibiotics  Unasyn  Augmentin  Zosyn  Timentin Cephalosporins ( “cef-”)  Most widely used group of antibiotics  Beta-lactam antibiotics  Disrupt cell wall synthesis  Similar to penicillin structure  Bactericidal  Usually given parentally but are also given orally  Toxicity is low  Grouped into 5 generations  Work against gram positive and gram negative-more active against gram negative Classification of Cephalosporins  First generation ◦ Cefazolin (Ancef)---Prototype  Second generation ◦ Cefaclor (Ceclor) ◦ Cefotetan (Cefotan)  Third generation ◦ Cefoperazone (Cefobid) ◦ Ceftriaxone (Rocephin)  Fourth generation ◦ Cefepime (Maxipime)  Fifth generation ◦ Ceftaroline (Used to treat MRSA) Cephalosporins  First generation mostly used for prophylaxis  Fifth generation used against MRSA and VRE  Side Effects: ◦ Hypersensitivity reactions ◦ Superinfections ◦ GI complaints (less if take with food)  Give with caution ◦ If pt on anticoagulants (causes dec Vit K) Carbapenems (“-penem”)  Beta-lactam antibacterial  Inhibits cell wall synthesis  Broad spectrum, bactericidal  Work differently than PCN so can be used if PCN/Cephalosporin resistant  Must be given parentally  Used MDR microbs  Examples: Imipenem-cilastatin, meropenem  Adverse Reactions ◦ GI: N/V/D ◦ Rash/hypersensitivity reactions ◦ Phlebitis at infusion site ◦ Risk for superinfections Vancomycin (Vancocin, Vancoled)  Action ◦ Inhibits cell wall synthesis ◦ bactericidal  Uses ◦ Severe infections only ◦ Methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis ◦ Oral dose used for Clostridium difficile if metronidazole was tried and found ineffective Vancomycin  Side Effects ◦ Ototoxicity (may be permanent) ◦ Nephrotoxicity ◦ Hepatotoxicity (slight chance) ◦ Anemia ◦ Red man syndrome ◦ Thrombophlebitis ◦ Thrombocytopenia (rare) ◦ Allergic reactions ***Need to monitor peak and trough levels Aminoglycosides (“-micin” or –”mycin”)  Most commonly employed agents ◦ Gentamicin, tobramycin, neomycin, streptomycin  Narrow-spectrum antibiotics  Bactericidal, disrupts protein synthesis  Use – aerobic gram-negative bacilli  Have shown stability in face of resistance  Can cause serious injury to inner ear and kidney  LOW therapeutic index-monitor drug levels  Not absorbed from the GI tract-give how?  Microbial resistance Aminoglycosides  Adverse effects ◦ Nephrotoxicity ◦ Ototoxicity ◦ Hypersensitivity reactions ◦ Neuromuscular blockade ◦ Blood dyscrasias  Drug Interactions ◦ Penicillins, cephalosporins and vancomycin, ototoxic drugs, nephrotoxic drugs, skeletal muscle relaxants, ASA, NSAIDS, acyclovir, loop diuetics Gentamicin - Prototype  Used to treat serious infections caused by aerobic gram-negative bacilli ◦ Pseudomonas aeruginosa ◦ Escherichia coli ◦ Klebsiella ◦ Serratia ◦ Proteus mirabilis  Nursing Implications ◦ Monitor serum levels (peak and trough) ◦ Monitor kidney function ◦ Monitor for tinnitus and verigo Fluoroquinolones (“- floxacin”)  Broad-spectrum with multiple applications  Disrupt DNA replication and cell division  All can be administered orally or IV  Not approved for those under 18  Side effects generally mild but can cause ◦ Tendon rupture (low risk) and arthropathy* ◦ Hypersensitivity* ◦ Superinfections* ◦ Photosensitivity ◦ GI ◦ QT prolongation* ◦ CNS (dizziness, H/A, confusion, somulence, esp in elderly) Fluoroquinolones: Ciprofloxacin (Cipro)  Ciprofloxacin (Cipro) ◦ Broad-spectrum antibiotic (gram-negative and some gram-positive) ◦ Inhibits bacterial DNA  Uses: multiple systems ◦ Drug of choice for anthrax and other biologic warfare pathogens ◦ Infections: respiratory, UTI, GI, bones, joints, skin, and soft tissue Fluoroquinolones: Ciprofloxacin  Drug and food interactions ◦ Absorption reduced by:  Aluminum antacids  Magnesium antacids  Iron salts  Zinc salts  Sucralfate  Milk and dairy products ◦ Elevation of drug levels Theophylline (used for asthma) Warfarin (an anticoagulant) Tinidazole (an antifungal drug) 68 Other Fluoroquinolones  Ofloxacin  Moxifloxacin  Norfloxacin  Levofloxacin  Gemifloxacin Tetracyclines (“-cycline”)  Tetracyclines ◦ Broad-spectrum antibiotics ◦ Inhibit protein synthesis ◦ Increasing bacterial resistance has emerged ◦ bacteriostatic  Uses (Rarely the drug of choice except for certain diseases) ◦ Rickettsial disease ◦ Chlamydia trachomatis ◦ Brucellosis ◦ Cholera ◦ Used for treatment of acne Tetracyclines  Absorption – chelation ◦ Calcium supplements, milk products, iron supplements, magnesium-containing laxatives, and most antacids  Adverse effects ◦ Gastrointestinal irritation (take on empty stomach) ◦ Effect on bone and teeth (do not use in children