Chapter 38-42 Antibiotics & Infections PDF

Copyright © 2020 Elsevier Inc. All Rights Reserved. CHAPTER 38 ANTIBIOTICS PART 1 2 Microorganisms are everywhere. Can be harmful or beneficial under normal circumstances MICROBIAL INFECTION Defenses Physical barriers (e.g., intact skin or ciliated respiratory mucosa) Physiologic defenses (e.g., sto...

Copyright © 2020 Elsevier Inc. All Rights Reserved. CHAPTER 38 ANTIBIOTICS PART 1 2 Microorganisms are everywhere. Can be harmful or beneficial under normal circumstances MICROBIAL INFECTION Defenses Physical barriers (e.g., intact skin or ciliated respiratory mucosa) Physiologic defenses (e.g., stomach gastric acid, antibodies) Phagocytic cells Copyright © 2020 Elsevier Inc. All Rights Reserved. 3 Copyright © 2020 Elsevier Inc. All Rights Reserved. Gram positive stain purple very thick cell wall, known as peptidoglycan, and they also have a thick outer capsule. Gram negative BACTERIA stain red cell wall structure that is more complex, with a smaller outer capsule and peptidoglycan layer and two cell membranes: an outer and an inner membrane more difficult to treat Categorizing bacteria is on the basis of their response to the Gram stain procedure. Copyright © 2020 Elsevier Inc. All Rights Reserved. 4 Copyright © 2020 Elsevier Inc. All Rights Reserved. 5 INFECTIONS Community-associated infections An infection that is acquired by a person who has not been hospitalized or had a medical procedure (e.g., dialysis, surgery, catheterization) within the past year Copyright © 2020 Elsevier Inc. All Rights Reserved. 6 INFECTIONS: SITES OF ORIGIN Health care–associated infections Were not present or incubating in the patient on admission to the facility Occurs more than 48 hours after admission More difficult to treat because causative microorganisms are often drug resistant and the most virulent Methicillin-resistant Staphylococcus aureus (MRSA) is most common. Copyright © 2020 Elsevier Inc. All Rights Reserved. 7 HEALTH CARE–ASSOCIATED INFECTIONS: PREVENTION Handwashing Antiseptics Generally, only inhibits the growth of microorganisms but does not necessarily kill them Applied exclusively to living tissue Static agents Disinfectants Kills organisms Used only on nonliving objects Cidal agent Copyright © 2020 Elsevier Inc. All Rights Reserved. Medications used to treat bacterial infections 8 ANTIBIOTICS Ideally, before beginning antibiotic therapy, the suspected areas of infection should be cultured to identify the causative organism and potential antibiotic susceptibilities. Copyright © 2020 Elsevier Inc. All Rights Reserved. 9 ANTIBIOTIC THERAPY Empiric therapy: treatment of an infection before specific culture information has been reported or obtained Definitive therapy: antibiotic therapy tailored to treat organism identified with cultures Prophylactic therapy: treatment with antibiotics to prevent an infection, as in intraabdominal surgery or after trauma Copyright © 2020 Elsevier Inc. All Rights Reserved. Therapeutic response 10 ANTIBIOTIC THERAPY (CONT.) Decrease in specific signs and symptoms of infection are noted (fever, elevated white blood cell count, redness, inflammation, drainage, pain) Subtherapeutic response Signs and symptoms of infection do not improve. Copyright © 2020 Elsevier Inc. All Rights Reserved. 11 ANTIBIOTIC THERAPY (CONT.) Superinfection C. difficile infection Formerly called pseudomembranous colitis Secondary infection Resistance Food–drug interactions Tetracycline & _____; Quinolones & _____ Host factors age, allergy history, kidney and liver function, pregnancy status, genetic characteristics, site of infection, and host defenses Copyright © 2020 Elsevier Inc. All Rights Reserved. 12 ANTIBIOTIC THERAPY (CONT.) Allergic reactions Most common severe reactions Pregnancyrelated host factors Copyright © 2020 Elsevier Inc. All Rights Reserved. 13 ANTIBIOTIC THERAPY (CONT.) Genetic host factors genetic abnormalities that result in various enzyme deficiencies glucose-6-phosphate dehydrogenase deficiency (sulfonamides, nitrofurantoin, and dapsone - may result in the hemolysis) Slow acetylation-certain drugs to be metabolized more slowly ; leading to toxicity- drug accumulation Anatomic site of the infection Copyright © 2020 Elsevier Inc. All Rights Reserved. 14 ANTIBIOTICS: CLASSES Sulfonamides Macrolides Penicillins Quinolones Tetracyclines Cephalosporins Aminoglycosides Copyright © 2020 Elsevier Inc. All Rights Reserved. Interference with cell wall synthesis 15 ANTIBIOTIC THERAPY: MECHANISM OF ACTION Interference with protein synthesis Interference with DNA replication Acting as a metabolite to disrupt critical metabolic reactions inside the bacterial cell Copyright © 2020 Elsevier Inc. All Rights Reserved. 16 BASIC SITES OF ANTIBIOTIC ACTIVITY Cell wall synthesis Antimetabolites Copyright © 2020 Elsevier Inc. All Rights Reserved. 17 Copyright © 2020 Elsevier Inc. All Rights Reserved. Bactericidal: kill bacteria 18 ACTIONS OF ANTIBIOTICS Bacteriostatic: inhibit growth of susceptible bacteria rather than killing them immediately; eventually leads to bacterial death Copyright © 2020 Elsevier Inc. All Rights Reserved. 19 ANTIBIOTICS: SULFONAMIDES One of the first groups of antibiotics Often combined with another antibiotic Sulfamethoxazole combined with trimethoprim (a nonsulfonamide antibiotic), known as Bactrim, Septra, or co-trimoxazole and often abbreviated as SMX-TMP, is used commonly in clinical practice. Copyright © 2020 Elsevier Inc. All Rights Reserved. Bacteriostatic action Prevent synthesis of folic acid required for synthesis of purines and nucleic acid Do not affect human cells or certain bacteria; they can use preformed folic acid Only affect organisms that synthesize their own folic acid 20 SULFONAMIDES: MECHANISM OF ACTION Copyright © 2020 Elsevier Inc. All Rights Reserved. 21 SULFONAMIDES: INDICATIONS Effective against both gram-positive and gram-negative bacteria Treatment of urinary tract infections (UTIs) caused by susceptible strains of: Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus Upper respiratory tract infections SMX-TMP is commonly used for outpatient Staphylococcus infections because of the high rate of community-acquired MRSA infections. Copyright © 2020 Elsevier Inc. All Rights Reserved. 22 SULFONAMIDES: ADVERSE EFFECTS Hemolytic and aplastic anemia, agranulocytosis, thrombocytopenia Urticaria Stevens-Johnson Syndrome Copyright © 2020 Elsevier Inc. All Rights Reserved. 23 BETA-LACTAM ANTIBIOTICS Penicillins Cephalosporins Carbapenems Monobactams Copyright © 2020 Elsevier Inc. All Rights Reserved. 24 PENICILLINS First derived from a mold (fungus) often seen on bread or fruit. Natural penicillins Penicillinase-resistant penicillins Aminopenicillins Extended-spectrum penicillins Copyright © 2020 Elsevier Inc. All Rights Reserved. 25 BETA-LACTAMASE INHIBITORS Some bacteria have acquired the capacity to produce enzymes capable of destroying penicillins. These enzymes are called beta-lactamases, and they can inactivate the penicillin molecules by opening the beta-lactam ring. These drugs bind with the beta-lactamase enzyme itself to prevent the enzyme from breaking down the penicillin molecule. Copyright © 2020 Elsevier Inc. All Rights Reserved. Ampicillin/sulbactam (Unasyn) 26 EXAMPLES OF COMBINATION AGENTS Amoxicillin/clavulanic acid (Augmentin) Piperacillin/tazobactam (Zosyn) 27 Copyright © 2020 Elsevier Inc. All Rights Reserved. Penicillins enter the bacteria via the cell wall. PENICILLINS: MECHANISM OF ACTION Inside the cell, they bind to penicillinbinding protein. Once bound, normal cell wall synthesis is disrupted. Result: Bacteria cells die from cell lysis. Penicillins do not kill other cells in the body. Copyright © 2020 Elsevier Inc. All Rights Reserved. PENICILLINS: INDICATIONS Prevention and treatment of infections caused by susceptible bacteria, such as: Gram-positive bacteria, including Streptococcus spp., Enterococcus spp., Staphylococcus spp. 28 Copyright © 2020 Elsevier Inc. All Rights Reserved. 29 known drug allergy PENICILLINS: CONTRAINDICATIONS Type of reaction that occurs in patients who state they are allergic to penicillins Not all end in “cillin” (e.g., Zosyn, Augmentin) Many medication errors have occurred when a penicillin drug called by its trade name is given to a patient with a penicillin allergy. Copyright © 2020 Elsevier Inc. All Rights Reserved. PENICILLINS: ADVERSE EFFECTS 30 Allergic reactions: 0.7% to 4% of treatment courses. Urticaria, pruritus, angioedema increased risk of allergy to other betalactam antibiotics. History of throat swelling or hives from penicillin should not receive cephalosporins. Common adverse effects Nausea, vomiting, diarrhea, abdominal pain Other adverse effects are less common. Copyright © 2020 Elsevier Inc. All Rights Reserved. 31 PENICILLINS: INTERACTIONS MANY interactions! NSAIDS Oral contraceptives-why is this important? Warfarin-enhanced effect Copyright © 2020 Elsevier Inc. All Rights Reserved. 32 CEPHALOSPORINS Semisynthetic antibiotics Structurally and pharmacologically related to penicillins Bactericidal action Broad spectrum Divided into groups according to their antimicrobial activity 5 generations! Copyright © 2020 Elsevier Inc. All Rights Reserved. 33 CEPHALOSPORINS: FIRST GENERATION Good gram-positive coverage Poor gram-negative coverage Parenteral and oral (PO) forms Examples Cefazolin (Ancef) Cephalexin (Keflex) Copyright © 2020 Elsevier Inc. All Rights Reserved. CEPHALOSPORINS: FIRST GENERATION (CONT.) 34 Used for surgical prophylaxis and for susceptible staphylococcal infections Cefazolin (Ancef and Kefzol): intravenous (IV) or intramuscular (IM) Cephalexin (Keflex): PO Copyright © 2020 Elsevier Inc. All Rights Reserved. 35 CEPHALOSPORINS: ADVERSE EFFECTS Similar to penicillins Mild diarrhea, abdominal cramps, rash, pruritus, redness, edema Potential crosssensitivity with penicillins if allergies exist 36 CARBAPENEMS Broadest antibacterial action of any antibiotics to date Reserved for complicated body cavity and connective tissue infections in acutely ill hospitalized patients Must be infused over 60 minutes May cause drug-induced seizure activity This risk can be reduced with proper dosage. Copyright © 2020 Elsevier Inc. All Rights Reserved. Copyright © 2020 Elsevier Inc. All Rights Reserved. 37 MACROLIDES Erythromycin (E-mycin, E.E.S, others) Azithromycin (Zithromax) Fidaxomicin (Dificid, Dificlir) Copyright © 2020 Elsevier Inc. All Rights Reserved. Prevent protein synthesis within bacterial cells 38 MACROLIDES: MECHANISM OF ACTION Considered bacteriostatic Bacteria will eventually die In high enough concentrations, may also be bactericidal Copyright © 2020 Elsevier Inc. All Rights Reserved. MACROLIDES: INDICATIONS 39 Strep infections Streptococcus pyogenes (group A betahemolytic streptococci) Mild to moderate upper and lower respiratory tract infections Haemophilus influenzae Spirochetal infections Syphilis and Lyme disease Gonorrhea, Chlamydia, Mycoplasma Clostridium Difficile Copyright © 2020 Elsevier Inc. All Rights Reserved. MACROLIDES: ADVERSE EFFECTS GI effects, primarily with erythromycin Nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia Azithromycin and clarithromycin: fewer GI adverse effects, longer duration of action, better efficacy, better tissue penetration 40 Copyright © 2020 Elsevier Inc. All Rights Reserved. 41 TETRACYCLINES Natural and semisynthetic Obtained from cultures of Streptomyces Bacteriostatic: inhibit bacterial growth Inhibit protein synthesis Stop many essential functions of the bacteria Examples Tetracycline Doxycycline (Doryx, Vibramycin) Minocycline (Minocin) Tigecycline (Tygacil) Copyright © 2020 Elsevier Inc. All Rights Reserved. 42 TETRACYCLINES (CONT.) Bind (chelate) to Ca+++ and Mg++ and Al+++ ions to form insoluble complexes Dairy products, antacids, and iron salts reduce oral absorption of tetracyclines. Should not be used in children younger than age 8 years or in pregnant or lactating women because tooth discoloration will occur if the drug binds to the calcium in the teeth Copyright © 2020 Elsevier Inc. All Rights Reserved. 43 TETRACYCLINES: INDICATIONS Wide spectrum Gram-negative and grampositive organisms, protozoa, Mycoplasma spp., Rickettsia spp., Chlamydia, syphilis, Lyme disease, acne, others 44 TETRACYCLINES: ADVERSE EFFECTS Strong affinity for calcium Discoloration of permanent teeth and tooth enamel in fetuses and children or nursing infants if taken by the mother May retard fetal skeletal development if taken during pregnancy Alteration in intestinal flora may result in: Superinfection (overgrowth of nonsusceptible organisms such as Candida spp.) Diarrhea Pseudomembranous colitis May also cause: Vaginal candidiasis, Gastric upset, Enterocolitis, Maculopapular rash Copyright © 2020 Elsevier Inc. All Rights Reserved. Copyright © 2020 Elsevier Inc. All Rights Reserved. 45 NURSING IMPLICATIONS Assess Before-Drug allergies; renal, liver, and cardiac function; and other lab studies. Obtain Thorough patient health history, including immune status. Assess Conditions that may be contraindications to antibiotic use or that may indicate cautious use. Assess Potential drug interactions. Copyright © 2020 Elsevier Inc. All Rights Reserved. 46 NURSING IMPLICATIONS (CONT.) It is essential to obtain cultures from appropriate sites before beginning antibiotic therapy. Instruct patients to take antibiotics exactly as prescribed and for the length of time prescribed; they should not stop taking the medication early because they feel better. Assess for signs and symptoms of superinfection: fever, perineal itching, cough, lethargy, or any unusual discharge. Copyright © 2020 Elsevier Inc. All Rights Reserved. 47 NURSING IMPLICATIONS Sulfonamides Take with 2000 to 3000 mL of fluid/24 hour. Assess red blood cell count before beginning therapy. Take oral doses with food. Penicillins Take oral doses with water (not juices) because acidic fluids may nullify the drug’s antibacterial action. Monitor patients taking penicillin for an allergic reaction for at least 30 minutes after administration. Copyright © 2020 Elsevier Inc. All Rights Reserved. 48 NURSING IMPLICATIONS (CONT.) Cephalosporins Assess for penicillin allergy; may have cross-allergy. Give orally administered forms with food to decrease GI upset even though this will delay absorption. Some of these drugs may cause a disulfiram (Antabuse)-like reaction when taken with alcohol. Copyright © 2020 Elsevier Inc. All Rights Reserved. 49 NURSING IMPLICATIONS (CONT.) Macrolides These drugs are highly protein bound and will cause severe interactions with other protein-bound drugs. The absorption of oral erythromycin is enhanced when taken on an empty stomach, but because of the high incidence of GI upset, many drugs are taken after a meal or snack. Copyright © 2020 Elsevier Inc. All Rights Reserved. 50 NURSING IMPLICATIONS (CONT.) Tetracyclines Avoid milk products, iron preparations, antacids, and other dairy products because of the chelation and drug-binding that occur. Take all medications with 6 to 8 oz of fluid, preferably water. Because of photosensitivity, avoid sunlight and tanning beds. Copyright © 2020 Elsevier Inc. All Rights Reserved. 51 NURSING IMPLICATIONS (CONT.) Monitor for therapeutic effects: Improvement of signs and symptoms of infection Return to normal vital signs Negative culture and sensitivity tests Disappearance of fever, lethargy, drainage, and redness Monitor for adverse reactions. CHAPTER 39 ANTIBIOTICS PART 2 Copyright © 2020 Elsevier Inc. All Rights Reserved. Copyright © 2020 Elsevier Inc. All Rights Reserved. Organisms that are resistant to one or more classes of antimicrobial drugs 53 MULTIDRUG- RESISTANT ORGANISMS Methicillin-resistant Staphylococcus aureus (MRSA) Vancomycin-resistant Enterococcus (VRE) Organisms producing extendedspectrum beta-lactamases (ESBLs) Carbapenem-resistant Enterobacteriaceae (CRE) MULTIDRUG-RESISTANT ORGANISMS (CONT.) Copyright © 2020 Elsevier Inc. All Rights Reserved. 54 MRSA Threat of MRSA becoming resistant to all antibiotics currently available No longer seen just in hospitals; it has spread to the community setting, and approximately 50% of staphylococcal infections contracted in the community involve MRSA VRE usually seen in urinary tract infections (UTIs) Newer antibiotics have been developed to successfully treat VRE and MRSA. Copyright © 2020 Elsevier Inc. All Rights Reserved. 55 AMINOGLYCOSIDES Natural and semisynthetic Produced from Streptomyces spp. Poor oral absorption; no oral forms (exception: neomycin) Very potent antibiotics with serious toxicities Bactericidal; prevent protein synthesis Examples Gentamicin Neomycin (Neo-Fradin) Copyright © 2020 Elsevier Inc. All Rights Reserved. 56 AMINOGLYCOSIDES: INDICATIONS Used to kill gramnegative bacteria, such as Pseudomonas spp., Escherichia coli, Proteus spp., Klebsiella spp., Serratia spp. Often used in combination with other antibiotics for synergistic effects (beta-lactams or vancomycin) Exception: neomycin Poorly absorbed through GI tract and are given parenterally. Given orally to decontaminate the GI tract before surgical procedures Also used as an enema for this purpose Used to treat hepatic encephalopathy Copyright © 2020 Elsevier Inc. All Rights Reserved. 57 AMINOGLYCOSIDES: ADVERSE EFFECTS Cause serious toxicities Nephrotoxicity (renal damage) Ototoxicity (auditory impairment and vestibular impairment [eighth cranial nerve]) Superinfections Must monitor drug levels to prevent toxicities Minimum inhibitory concentration (MIC) AMINOGLYCOSIDES: THERAPEUTIC DRUG MONITORING Copyright © 2020 Elsevier Inc. All Rights Reserved. 58 Serum levels measured to prevent toxicity Serum level needs to be at least eight times higher than the MIC. (minimum inhibitory concentration) lowest concentration of drug needed to kill a certain standard amt of bacteria Time-dependent killing Time-dependent killing the amt of time the drug is above the MIC is critical for maximum bacterial growth Concentration-dependent killing -dependent killing (aminoglycosides) drug plasma concentration that is a certain level above the MIC Peak: highest drug levels for once-daily regimens Trough: lowest to ensure adequate renal clearance of the drug and avoid toxicity Copyright © 2020 Elsevier Inc. All Rights Reserved. Postantibiotic effects 59 AMINOGLYCOSIDES: THERAPEUTIC DRUG MONITORING (CONT.) Resistance Drug interactions Copyright © 2020 Elsevier Inc. All Rights Reserved. 60 QUINOLONES Also called fluoroquinolones Excellent oral absorption Absorption reduced by antacids Effective against gram-negative organisms and some grampositive organisms Examples Ciprofloxacin (Cipro) Levofloxacin (Levaquin) Copyright © 2020 Elsevier Inc. All Rights Reserved. 61 QUINOLONES: MECHANISM OF ACTION Bactericidal Alter DNA of bacteria, causing death Do not affect human DNA Used to treat S. aureus, Serratia marcescens, and Mycobacterium fortuitum Bacterial resistance Copyright © 2020 Elsevier Inc. All Rights Reserved. 62 QUINOLONES: INDICATIONS Gram-negative bacteria such as Pseudomonas spp. Complicated urinary tract, respiratory, bone and joint, GI, skin, and sexually transmitted infections Copyright © 2020 Elsevier Inc. All Rights Reserved. 63 QUINOLONES: INTERACTIONS Oral quinolones: antacids, calcium, magnesium, iron, zinc preparations, or sucralfate Patients need to take the interacting drugs at least 1 hour before or after taking quinolones. Dairy products Enteral tube feedings Probenecid Nitrofurantoin Oral anticoagulants Copyright © 2020 Elsevier Inc. All Rights Reserved. 64 QUINOLONES: ADVERSE EFFECTS Prolonged QT interval Increased LFT (Liver function studies) *Black box warning: increased risk of tendonitis and tendon rupture Copyright © 2020 Elsevier Inc. All Rights Reserved. 65 MISCELLANEOUS ANTIBIOTICS Clindamycin (Cleocin) Linezolid (Zyvox) Daptomycin (Cubicin) Metronidazole (Flagyl) Vancomycin (Vancocin, Vancoled) Copyright © 2020 Elsevier Inc. All Rights Reserved. 66 MISCELLANEOUS ANTIBIOTICS Vancomycin (Vancocin) Treatment of choice for MRSA and other gram-positive infections Oral vancomycin is indicated for the treatment of antibiotic-induced colitis (C. difficile) and for the treatment of staphylococcal enterocolitis. Must monitor blood levels to ensure therapeutic levels and prevent toxicity May cause ototoxicity and nephrotoxicity Copyright © 2020 Elsevier Inc. All Rights Reserved. 67 MISCELLANEOUS ANTIBIOTICS Vancomycin (Vancocin) Red man syndrome may occur Flushing or itching of head, neck, face, upper trunk Antihistamine may be ordered to reduce these effects. Additive neuromuscular blocking effects in patients receiving neuromuscular blockers Should be infused over 60 minutes Rapid infusions may cause hypotension. Copyright © 2020 Elsevier Inc. All Rights Reserved. 68 NURSING IMPLICATIONS Assess Before- drug allergies; hepatic, renal, and cardiac function; and other laboratory study results. Be Obtain a thorough patient health history, including immune status. Assess Conditions that may be contraindications to antibiotic use or that may indicate cautious use. Assess Potential drug interactions. Copyright © 2020 Elsevier Inc. All Rights Reserved. It is essential to obtain cultures from appropriate sites before beginning antibiotic therapy. Instruct patients to take antibiotics exactly as prescribed and for the length of time prescribed Assess for signs and symptoms of superinfection: fever, perineal itching, cough, lethargy, or any unusual discharge 69 NURSING IMPLICATIONS (CONT.) Copyright © 2020 Elsevier Inc. All Rights Reserved. 70 NURSING IMPLICATIONS Monitor for therapeutic effects: Improvement of signs and symptoms of infection Return to normal vital signs Monitor for adverse reactions. Negative culture and sensitivity tests Disappearance of fever, lethargy, drainage, and redness Chapter 40 Antiviral Drugs Copyright © 2020 Elsevier Inc. All Rights Reserved. Viral replication A virus cannot replicate on its own. General Principles of Virology It must attach to and enter a host cell. It then uses the host cell’s energy to synthesize protein, DNA, and RNA. Copyright © 2020 Elsevier Inc. All Rights Reserved. 72 Viruses enter the body through at least four routes: 73 General Principles of Virology (Cont.) Inhalation Ingestion Transplacentally Inocculation Viruses are difficult to kill because they live inside the cells. Any drug that kills a virus may also kill cells. Copyright © 2020 Elsevier Inc. All Rights Reserved. Smallpox (poxviruses) Sore throat Conjunctivitis (adenoviruses) Warts (papovaviruses) Influenza (orthomyxoviruses) 74 Viral Illnesses Respiratory infections (coronaviruses, rhinoviruses) Gastroenteritis (rotaviruses, Norwalk-like viruses) Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (retroviruses) Herpes (herpesviruses) Hepatitis (hepadnaviruses) Copyright © 2020 Elsevier Inc. All Rights Reserved. Most viral illnesses are bothersome but survivable. Effective vaccines have prevented some illnesses. Effective drug therapy is available for a small number of viral infections. Copyright © 2020 Elsevier Inc. All Rights Reserved. 75 Viral Illnesses (Cont.) Antiviral Drugs Antiviral drugs kill or suppress the virus by destroying virions or inhibiting the ability of viruses to replicate; controlled by current antiviral therapy. Immunoglobulins are concentrated antibodies that can attack and destroy viruses. 76 Copyright © 2020 Elsevier Inc. All Rights Reserved. Viruses controlled by current antiviral therapy Cytomegalovirus (CMV) Hepatitis viruses 77 Antiviral Drugs (Cont.) Herpesviruses HIV Influenza viruses (the “flu”) Respiratory syncytial virus (RSV) Copyright © 2020 Elsevier Inc. All Rights Reserved. Key characteristics of antiviral drugs Able to enter the cells infected with virus 78 Antiviral Drugs (Cont.) Interfere with viral nucleic acid synthesis, regulation, or both Some drugs interfere with ability of virus to bind to cells. Some drugs stimulate the body’s immune system. Copyright © 2020 Elsevier Inc. All Rights Reserved. Antiviral drugs 79 Antiviral Drugs (Cont.) Used to treat infections caused by viruses other than HIV Antiretroviral drugs Used to treat infections caused by HIV, the virus that causes AIDS Copyright © 2020 Elsevier Inc. All Rights Reserved. Best responses to antiviral drugs are in patients with competent immune systems. 80 Antiviral Drugs (Cont.) A healthy immune system works synergistically with the drug to eliminate or suppress viral activity. Copyright © 2020 Elsevier Inc. All Rights Reserved. 81 Antiviral Drugs Con’t. Opportunistic infections Occur in immunocompromised patients Would not normally harm an immunocompetent person Require long-term prophylaxis and antiinfective drug therapy Can be other viruses, fungi, bacteria, or protozoa Copyright © 2020 Elsevier Inc. All Rights Reserved.  Herpesviridae 82 Herpes Simplex and VaricellaZoster Virus Infections  HSV-1 (oral herpes)  HSV-2 (genital herpes)  Chickenpox and shingles (HHV-3 or VZV)  Epstein-Barr (HHV-4)  CMV (HHV-5)  Human herpesviruses 6 and 7 are not especially clinically significant; immunocompromised patients  Kaposi’s sarcoma (HHV-8) Copyright © 2020 Elsevier Inc. All Rights Reserved. Herpesviridae (cont.) Shingles (HHV-3 or VZV) Painful: opioids for pain control Postherpetic neuralgias 83 Herpes Simplex and VaricellaZoster Virus Infections (Cont.) Acyclovir may speed recovery; best results are generally seen when the antiviral drug is started within 72 hours of symptom onset. Zostavax Copyright © 2020 Elsevier Inc. All Rights Reserved. Hepatitis B Mild, without symptoms or chronic hepatitis or liver failure and death Transmission of hepatitis B virus occurs through blood and body fluid exposure. Transmission to infants Hepatitis B vaccine Antiviral drug therapy for hepatitis B: lamivudine, tenofovir, and telbivudine, and alfa-interferon (we don’t need to know these medications) 84 Copyright © 2020 Elsevier Inc. All Rights Reserved. Hepatitis C Leading cause of liver failure leading to liver transplantation Symptoms Transmission: infected blood and sexual contact Alcoholic disease can lead to development of hepatitis C. Treatment: interferon, ribavirin, simeprevir, and sofosbuvir (do not need to know medications) 85 Copyright © 2020 Elsevier Inc. All Rights Reserved. 86 Copyright © 2020 Elsevier Inc. All Rights Reserved. Mechanism of action 87 Antiviral Drugs (NonHIV) Most of the current antiviral drugs work by blocking the activity of a polymerase enzyme that normally stimulates the synthesis of new viral genomes. Used to treat non-HIV viral infections Influenza viruses HSV, VZV CMV Hepatitis Copyright © 2020 Elsevier Inc. All Rights Reserved. Adverse effects Vary with each drug 88 Antiviral Drugs (NonHIV) (Cont.) Healthy cells are often killed also, resulting in serious toxicities. Interactions Copyright © 2020 Elsevier Inc. All Rights Reserved. Antiviral Drugs (Non-HIV) (Cont.) Acyclovir (Zovirax) Synthetic nucleoside analogue Used to suppress replication of HSV-1, HSV-2, VZV Drug of choice for treatment of initial and recurrent episodes of these infections Oral, topical, parenteral forms 89 Copyright © 2020 Elsevier Inc. All Rights Reserved. Antiviral Drugs (Non-HIV): Neuraminidase Inhibitors Oseltamivir (Tamiflu) and zanamivir (Relenza) Active against influenza types A and B Reduce duration of illness Oseltamivir: causes nausea and vomiting Zanamivir: causes diarrhea, nausea, sinusitis Treatment should begin within 2 days of influenza symptom onset. 90 Copyright © 2020 Elsevier Inc. All Rights Reserved. 91 HIV and AIDS New cases of HIV have decreased by 19% since between 2005 and 2014. Retrovirus Transmitted by sexual activity, intravenous drug use, perinatally from mother to child The risk for transmission to health care workers via percutaneous (needlestick) injuries is currently calculated at approximately 0.3%. Prophylactic therapy for accidental exposure Copyright © 2020 Elsevier Inc. All Rights Reserved. Stage 1: asymptomatic infection Stage 2: early, general symptoms of disease 92 Four Stages of HIV Infection* Stage 3: moderate symptoms Stage 4: severe symptoms, often leading to death *World Health Organization model Copyright © 2020 Elsevier Inc. All Rights Reserved. 93 Opportunistic Infections Protozoal Fungal Toxoplasmosis of the brain, others Candidiasis of the lungs, esophagus, trachea Pneumocystis jiroveci pneumonia, others Viral Bacterial CMV disease, HSV infection, others Various mycobacterial infections, others Extrapulmonary TB Opportunistic neoplasias HIV wasting syndrome Kaposi’s sarcoma, others Major weight loss, chronic diarrhea, chronic fever Copyright © 2020 Elsevier Inc. All Rights Reserved. Highly active antiretroviral therapy 94 Antiretroviral Drugs Includes at least three medications These medications work in different ways to reduce the viral load. Copyright © 2020 Elsevier Inc. All Rights Reserved. Numerous and vary with each drug Drug therapy may need to be modified because of adverse effects. 95 Antiretroviral Drugs: Adverse Effects Goal is to find the regimen that will best control the infection with a tolerable adverse effect profile Medication regimens change during the course of the illness. Copyright © 2020 Elsevier Inc. All Rights Reserved. Before beginning therapy, assess underlying disease and medical history, including allergies. 96 Nursing Implications Assess baseline vital signs and nutritional status. Assess for contraindications, conditions that may indicate cautious use, and potential drug interactions. Copyright © 2020 Elsevier Inc. All Rights Reserved. 97 Nursing Implications (Cont.) Teach Emphasize Instruct proper application technique for ointments, aerosol powders, and so on. Handwashing before and after administration of medications to prevent site contamination and spread of infection. Patients to wear a glove or finger cot when applying ointments or solutions to affected areas. Copyright © 2020 Elsevier Inc. All Rights Reserved. Instruct Emphasize Inform Instruct patients to consult their prescribers before taking any other medication, including overthe-counter medications. Emphasize the importance of good hygiene. Inform patients that antiviral drugs are not cures but do help to manage symptoms. 98 Nursing Implications (Cont.) Copyright © 2020 Elsevier Inc. All Rights Reserved. 99 Nursing Implications (Cont.) Instruct patients on the importance of taking these medications exactly as prescribed and for the full course of treatment. Instruct patients to start therapy with antiviral drugs at the earliest sign of recurrent episodes of genital herpes or herpes zoster. Copyright © 2020 Elsevier Inc. All Rights Reserved. Monitor for adverse effects: Effects are varied and specific to each drug. 100 Nursing Implications con’t Monitor for therapeutic effects: Effects vary depending on the type of viral infection. Effects range from delayed progression of AIDS and other viruses to a decrease in flulike symptoms, decrease in frequency of herpes-like flare-ups, or crusting over of herpetic lesions. Copyright © 2020 Elsevier Inc. All Rights Reserved. CHAPTER 41 ANTITUBERCULAR DRUGS Copyright © 2020 Elsevier Inc. All Rights Reserved. ANTITUBERCULAR DRUGS TUBERCULOSIS (TB) CAUSED BY MYCOBACTERIUM TUBERCULOSIS ANTITUBERCULAR DRUGS TREAT ALL FORMS OF MYCOBACTERIUM (MTB). TB IS MOST COMMONLY CHARACTERIZED BY GRANULOMAS IN THE LUNGS: NODULAR ACCUMULATIONS OF INFLAMMATORY CELLS (E.G., MACROPHAGES, LYMPHOCYTES) THAT ARE DELIMITED (“WALLED OFF” WITH CLEAR BOUNDARIES) AND HAVE A CENTER THAT HAS A CHEESY OR CASEATED CONSISTENCY. Copyright © 2020 Elsevier Inc. All Rights Reserved. 102 MYCOBACTERIUM (MTB) INFECTIONS COMMON INFECTION SITES LUNG (PRIMARY SITE) BRAIN (CEREBRAL CORTEX) BONE (GROWING END) LIVER KIDNEY GENITOURINARY TRACT Copyright © 2020 Elsevier Inc. All Rights Reserved. 103 MYCOBACTERIUM (MTB) INFECTIONS (CONT.) AEROBIC BACILLUS PASSED FROM INFECTED: HUMANS COWS (BOVINE) AND BIRDS (AVIAN) MUCH LESS COMMON Copyright © 2020 Elsevier Inc. All Rights Reserved. 104 MYCOBACTERIUM (MTB) INFECTIONS (CONT.) TUBERCLE BACILLI ARE CONVEYED BY DROPLETS. DROPLETS ARE EXPELLED BY COUGHING OR SNEEZING, AND THEY THEN GAIN ENTRY INTO THE BODY BY INHALATION. TUBERCLE BACILLI THEN SPREAD TO OTHER BODY ORGANS VIA BLOOD AND LYMPHATIC SYSTEMS. TUBERCLE BACILLI MAY BECOME DORMANT, OR WALLED OFF BY CALCIFIED 105 OR FIBROUS TISSUE. Copyright © 2020 Elsevier Inc. All Rights Reserved. MTB: very slow-growing organism More difficult to treat than most other bacterial infections MYCOBACTERIUM (MTB) INFECTIONS (CONT.) First infectious episode: primary TB infection Reinfection: chronic form of the disease Dormancy: may test positive for exposure but are not necessarily infectious because of this dormancy process Copyright © 2020 Elsevier Inc. All Rights Reserved. 106 Diagnosis of tuberculosis DIAGNOSIS Step 1 Tuberculin skin test (Mantoux test) Step 2 If skin test results are positive, then chest x-ray Step 3 If chest x-ray shows signs of tuberculosis, then culture of sputum* or stomach secretions *The acid-fast bacillus smear test is performed on sputum as a quick method of determining whether tuberculosis treatment and precautions are needed until a more definite diagnosis is made. Copyright © 2020 Elsevier Inc. All Rights Reserved. 107 MULTIDRUG-RESISTANT TUBERCULOSIS (MDR-TB) TB INFECTS ONE THIRD OF THE WORLD’S POPULATION. MDR-TB THAT IS RESISTANT TO BOTH ISONIAZID (INH) AND RIFAMPIN EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS (XDR-TB): RELATIVELY RARE TYPE OF MDR-TB, RESISTANT TO ALMOST ALL DRUGS USED TO TREAT TB, INCLUDING THE TWO BEST FIRST-LINE DRUGS, INH AND RIFAMPIN, AS WELL AS TO THE BEST SECOND-LINE MEDICATIONS XDR-TB IS OF SPECIAL CONCERN FOR PATIENTS WHO HAVE AIDS OR ARE OTHERWISE IMMUNOCOMPROMISED. USE OF MULTIPLE MEDICATIONS TO TREAT TB DUE TO INCREASING PRESENCE OF RESISTANCE Copyright © 2020 Elsevier Inc. All Rights Reserved. 108 ANTITUBERCULAR DRUGS FIRST-LINE DRUGS : INH: PRIMARY DRUG USED RIFAMPIN STREPTOMYCIN Copyright © 2020 Elsevier Inc. All Rights Reserved. 109 Major effects of drug therapy: reduction of cough and, therefore, reduction of the infectiousness of the patient ANTITUBERCULAR DRUG THERAPY CONSIDERATIONS Normally occurs within 2 weeks of the initiation of drug therapy if TB strain is drug sensitive Most cases of TB can be cured. Successful treatment: several antibiotic drugs for at least 6 months and sometimes for as long as 12 months Copyright © 2020 Elsevier Inc. All Rights Reserved. 110 ANTITUBERCULAR DRUG THERAPY CONSIDERATIONS (CONT.) Perform drug-susceptibility testing on the first Mycobacterium spp. that is isolated from a patient specimen to prevent the development of MDR-TB. Even before the results of susceptibility tests are known, begin a regimen with multiple antitubercular drugs (to reduce the chances of development of resistance). Copyright © 2020 Elsevier Inc. All Rights Reserved. 111 Adjust drug regimen after the results of susceptibility testing are known. ANTITUBERCULAR DRUG THERAPY CONSIDERATIONS Monitor patient compliance closely during therapy. Problems with successful therapy occur because of patient nonadherence to drug therapy and the increased incidence of drug-resistant organisms. Copyright © 2020 Elsevier Inc. All Rights Reserved. 112 MECHANISM OF ACTION THREE GROUPS: PROTEIN WALL SYNTHESIS INHIBITORS: STREPTOMYCIN, RIFAMPIN, RIFABUTIN CELL WALL SYNTHESIS INHIBITORS: CYCLOSERINE, ETHIONAMIDE, INH Copyright © 2020 Elsevier Inc. All Rights Reserved. 113 Effectiveness depends on: ANTITUBERCULAR THERAPY Type of infection Adequate dosing Sufficient duration of treatment Adherence to drug regimen Selection of an effective drug combination Problems: Drug-resistant organisms Drug toxicity Patient nonadherence Copyright © 2020 Elsevier Inc. All Rights Reserved. 114 Drug of choice for TB Resistant strains of Mycobacterium emerging Metabolized in the liver through acetylation—watch for “slow acetylators” Used alone or in combination with other drugs Contraindicated with liver disease ISONIAZID 115 Copyright © 2020 Elsevier Inc. All Rights Reserved. Rifamycin antibiotic Also used to treat infections caused by non-TB mycobacterial species Adverse effects: turns urine, feces, saliva, skin, sputum, sweat, and tears a red-orange-brown color Oral use only RIFABUTIN , RIFAMPIN, AND RIFAPENTINE Copyright © 2020 Elsevier Inc. All Rights Reserved. 116 NURSING IMPLICATIONS Obtain a thorough medical history and assessment. Perform liver function studies in patients who are to receive INH or rifampin (especially in older patients and those who use alcohol daily). Assess for contraindications to the various drugs, conditions for cautious use, and potential drug interactions. Therapy may last for up to 24 months. Take medications exactly as ordered at the same time every day. Strict adherence to regimen for improvement of condition or cure. 117 NURSING IMPLICATIONS Remind patients that they are contagious during the initial period of their illness—instruct in proper hygiene and prevention of the spread of infected droplets. Teach patients to take care of themselves, including getting adequate nutrition and rest. Copyright © 2020 Elsevier Inc. All Rights Reserved. 118 Should not consume Alcohol NURSING IMPLICATIONS (CONT.) Rifampin causes oral contraceptives to become ineffective; another form of birth control is needed. Copyright © 2020 Elsevier Inc. All Rights Reserved. 119 Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become reddish orange; even contact lenses may be stained. NURSING IMPLICATIONS (CONT.) Pyridoxine may be needed to combat neurologic adverse effects associated with INH therapy. Oral preparations may be given with meals to reduce gastrointestinal upset even though recommendations are to take them 1 hour before or Copyright © 2020 Elsevier Inc. All Rights Reserved. 2 hours after meals. 120 Monitor for adverse effects. NURSING IMPLICATIONS (CONT.) Instruct patients on the adverse effects that should be reported to the prescriber immediately. These include fatigue, nausea, vomiting, numbness and tingling of the extremities, fever, loss of appetite, depression, and jaundice. Monitor for therapeutic effects. Decrease in symptoms of TB, such as cough and fever Laboratory study results (culture and sensitivity tests) and chest radiographs should confirm clinical findings. Copyright © 2020 Elsevier Inc. Allof Rights Reserved. 121 Watch for lack clinical response to therapy, indicating possible drug resistance. Copyright © 2020 Elsevier Inc. All Rights Reserved. 122 Antifungal Drugs Copyright © 2020 Elsevier Inc. All Rights Reserved. Chapter 42 Four general types:  Cutaneous  Subcutaneous  Superficial  Systemic  Can be life threatening  Usually occur in immunocomprom ised host Mycotic Infections 124 Candida albicans  May follow antibiotic therapy, antineoplastics, or immunosuppressants (corticosteroids)  May result in overgrowth and systemic infections  Growth in the mouth is called thrush or oral candidiasis.  Common in newborn infants and immunocompromised patients Vaginal candidiasis  Yeast infection  Pregnancy, women with diabetes mellitus, women taking oral contraceptives Copyright © 2020 Elsevier Inc. All Rights Reserved. Mycotic Infections (Cont.) 125 Drugs used to treat infections caused by fungi Systemic  Amphotericin B, fluconazole, griseofulvin, nystatin, Topical  nystatin Ophthalmic: natamycin Copyright © 2020 Elsevier Inc. All Rights Reserved. Antifungal Drugs 126 Mechanism of Action (Cont.)  amphotericin B and nystatin  Bind to sterols in cell membrane lining  Result: fungal cell death  Do not bind to human cell membranes or kill human cells Copyright © 2020 Elsevier Inc. All Rights Reserved. Polyenes 127 Imidazoles and triazoles  ketoconazole, fluconazole  Inhibit fungal cell cytochrome P-450 enzymes, resulting in cell membrane leaking  Result: altered cellular metabolism and fungal cell death Copyright © 2020 Elsevier Inc. All Rights Reserved. Mechanism of Action (Cont.) 128 Indications Drug of choice for the treatment of many severe systemic fungal infections is amphotericin B. Choice of drug depends on type and location of infection Fluconazole: passes into the cerebrospinal fluid and inhibit the growth of cryptococcal fungi, effective in the treatment of cryptococcal meningitis Copyright © 2020 Elsevier Inc. All Rights Reserved. Systemic and topical fungal infections 129 Contraindication allergy, liver failure, kidney failure Antifungal Drugs: Contraindications/Adverse Effects Fluconazole Nausea, vomiting, diarrhea, stomach pain Increased liver enzymes Use with caution in patients with renal and liver dysfunction Nystatin Nausea, vomiting, anorexia, diarrhea, rash Copyright © 2020 Elsevier Inc. All Rights Reserved. Adverse Effects 130 Copyright © 2020 Elsevier Inc. All Rights Reserved. Antifungal Drugs: Interactions 131 Many antifungal drugs are metabolized by the cytochrome P-450 enzyme system. Co-administration of two drugs that are metabolized by this system may result in competition for these enzymes and thus higher levels of one of the drugs. Assess Before-hypersensitivity, possible contraindications, and conditions that require cautious use. Nursing Implications Baseline vital signs, complete blood count, liver and renal function studies, and electrocardiography. Assess Other medications used (prescribed and over the counter) to avoid drug interactions. Copyright © 2020 Elsevier Inc. All Rights Reserved. Obtain 132 Follow manufacturer’s directions carefully for reconstitution and administration. vital signs of patients receiving intravenous (IV) infusions every 15 to 30 minutes. Monitor Monitor input and output to identify adverse effects, during IV infusion Copyright © 2020 Elsevier Inc. All Rights Reserved. Nursing Implications (Cont.) Monitor 133 Nystatin given as an oral lozenge or troche should be slowly and completely dissolved in the mouth (not chewed or swallowed whole). Nystatin suspension should be swished thoroughly in the mouth as long as possible before swallowing. Copyright © 2020 Elsevier Inc. All Rights Reserved. Nursing Implications 134 Nursing Implications (Cont.) Easing of symptoms of infection Improved energy levels Normal vital signs, including temperature Monitor carefully for adverse effects. Copyright © 2020 Elsevier Inc. All Rights Reserved. Monitor for therapeutic effects. 135