1. Antimicrobial Agents Chapter 7

2. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 2 Anti-infective Therapy Modern age  Discovery of sulfanilamide in 1936  Commercial introduction of penicillin in 1941

3. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 3 Antimicrobial Therapy Original antimicrobials: derived from microorganisms Newer agents: chemically synthesized

4. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 4 Factors Leading to Infection Age: young and elderly Increased exposure to pathogenic organisms Disruption of the normal barriers Inadequate immunological defenses Impaired circulation Poor nutritional status

5. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 5 Sources of Infection Bacteria Fungi Viruses

6. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 6 Administering Antimicrobial Agents Consider the following:  Location of the infecting organism in the body  Status of the client’s organ function (continues)

7. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 7 Administering Antimicrobial Agents Consider the following:  Age of the client  Pregnancy and/or lactation  Likelihood of developing organisms resistant to the antimicrobial agent (continued)

8. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 8 Overuse Overuse of antimicrobial agents can lead to the development of severely resistant organisms.  Promoted the development of organisms that are not affected by any of the available therapies

9. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 9 Resistant Organisms MRSA/VRSA: methicillin/vancomycin- resistant Staphylococcus aureus VRE: vancomycin-resistant Enterococcus ORSA: oxacillin-resistant Staphylococcus aureus

10. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 10 Antimicrobial Therapy Prevent infections. Use Universal Precautions.

11. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 11 Classifications Antimicrobial agents are classified based on the following factors:  Bactericidal or bacteriostatic  Site of action  Narrow or broad spectrum  Adverse effects

12. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 12 Antimicrobial Classes Sulfonamides Penicillins Cephalosporins Tetracyclines Macrolides Aminoglycosides Fluoroquinolones Carbapenem Ketolides

13. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 13 Sulfonimides First group of antibiotics  General action  Bacteriostatic effect  Inhibit para-aminobenzoic acid (PABA) PABA is essential for bacterial growth  Broad spectrum

14. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 14 Sulfonamides: Therapeutic Uses Treatment of urinary tract infections Otitis media Certain vaginal infections Some respiratory infections

15. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 15 Sulfonamides: Adverse Effects Hypersensitivity Renal dysfunction Hematological changes

16. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 16 Sulfonamides: Nursing Implications Consume at least 1 liter of fluid/day Avoid sunlight and tanning beds Reduce the effectiveness of oral contraceptives

17. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 17 Sulfonamide Combinations Sulfonamides also combined with:  Antimicrobials, diuretics, oral hypoglycemics, and carbonic anhydrase inhibitors

18. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 18 Penicillins Part of a large group of chemically related antibiotics  Derived from fungus or mold Cephalosporins currently used instead of the penicillins

19. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 19 Penicillins: Action Inhibit synthesis of the bacterial cell wall  Most effective on newly forming and actively growing cell walls  Some of the penicillins are rapidly destroyed in the stomach.  Given IM or IV (continues)

20. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 20 Action of penicillin on bacteria (from Medicines and You, U.S. Department of Health and Human Services) (continued)

21. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 21 Resistance to Penicillins Frequent early use of penicillin caused:  Penicillinase  The bacteria to produce penicillin-destroying enzymes  Potassium clavulanate inhibits penicillinase: combined with penicillin

22. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 22 Penicillins: Therapeutic Uses Prevention and treatment of gram (+) bacterial infections:  Enterococcus, Streptococcus, and Staphylococcus bacteria

23. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 23 Penicillins: Adverse Effects Hypersensitivity Gastrointestinal symptoms Neurotoxicity Renal dysfunction

24. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 24 Cephalosporins Chemically and pharmacologically related to penicillins Action: prevent bacterial cell wall synthesis

25. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 25 Cephalosporins: Action Either bactericidal or bacteriostatic; depends on:  Susceptibility of organism  Dose of drug  Tissue concentration  Rate of bacteria multiplication

26. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 26 Classes of Cephalosporin Include several generations:  First: good gram-positive coverage  Second: good gram-positive coverage; some gram-negative coverage  Third: less gram-positive coverage; more gram-negative coverage  Fourth: good gram-negative coverage

27. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 27 Treatment with Cephalosporins Treat infections of:  Skin  Bone  Heart  Blood  Respiratory tract  Gastrointestinal tract  Urinary tract

28. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 28 Cephalosporins: Adverse Effects Hypersensitivity Cross-sensitivity reaction to penicillin Thrombophlebitis (when given IV) Sterile abscess (when given IM) Nephrotoxicity

29. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 29 Tetracyclines Action: inhibit protein synthesis in the bacterial cell; bacteriostatic Broad spectrum  Bacteria: gram – and gram + Effective against: protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease

30. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 30 Tetracyclines: Nursing Implications Bind to Ca 2+, Mg 2+, and Al 3+ ions and form insoluble complexes Do not give tetracycline with:  Dairy products, antacids, or iron salts

31. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 31 Tetracyclines: Toxic Effects Do not give to children. Affects tooth development from:  Fourth month of fetal development to 8 years old  Temporary and permanent discoloration of developing teeth Photosensitivity Superinfection

32. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 32 Macrolides Action  Bacteriostatic: inhibits protein synthesis in the bacterial cell Primarily used for respiratory, gastrointestinal, urinary, skin, and soft tissue infections

33. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 33 Treatment with Macrolides Treat both gram + and some gram – organisms  Erythromycin: preferred (pertussis) Primarily metabolized by the liver and excreted in the urine

34. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 34 Macrolides: Adverse Effects Hypersensitivity Gastrointestinal effects Hepatotoxicity Jaundice

35. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 35 Aminoglycosides Poor oral absorption  Given intravenously, not orally Action  Bactericidal: inhibit cell wall protein synthesis  Effective: gram – and some gram +  Narrow therapeutic range  Potent antibiotics with serious toxicities!

36. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 36 Aminoglycosides: Toxicities Serious toxicities: caution  Nephrotoxicity  Ototoxicity  Block neuromuscular action, which can lead to respiratory paralysis Monitor drug levels, both peak and trough

37. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 37 Fluoroquinolones First oral antibiotics effective against gram-negative bacteria Excellent oral absorption

38. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 38 Fluoroquinolones: Action Bactericidal: alter DNA Broad spectrum: effective against gram- negative organisms and some gram- positive organisms

39. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 39 Treatment with Fluoroquinolones Treat infections of:  Lower respiratory tract  Bone and joint  Infectious diarrhea  Urinary tract  Skin  Sexually transmitted diseases

40. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 40 Fluoroquinolones: Nursing Implications Consume at least 1 liter of fluid/day

41. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 41 Carbapenems Action: Inhibit synthesis of the bacterial cell wall Broad spectrum Effective:  Gram negative  Gram positive Treat community acquired pneumonia

42. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 42 Carbapenems: Nursing Considerations Given intravenously and intramuscularly Cross-sensitivity to penicillins Advantage  Given once every 24 hours

43. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 43 Carbapenems: Adverse Effects Hypersensitivity Diarrhea Local reactions at intramuscular and intravenous sites

44. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 44 Ketolides FDA approved in 2004 New class  Developed from macrolides  Semisynthetic  Treat macrolide-resistant strep pneumonia

45. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 45 Ketolides: Adverse Effects Hypersensitivity Headache Diarrhea

46. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 46 Urinary Tract Anti-infectives Trimethoprim  Most common  Blocks the synthesis of folate in bacteria, thus inhibiting formation of nucleic acid and protein (continues)

47. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 47 Urinary Tract Anti-infectives Others  Methenamine products: produces local bactericidal effect  Nitrofurantoin: stops CHO metabolism  Produces yellow-brown urine (continued)

48. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 48 Antimicrobial Therapy General nursing implications Instructions take as prescribed:  Length of time: do not stop before antimicrobials are gone Assess for signs and symptoms of returning infection

49. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 49 Antimicrobials: Nursing Implications Obtain cultures from appropriate sites before beginning therapy.

50. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 50 Antitubercular Agents Tuberculosis (TB)  Mycobacterium tuberculosis  An aerobic bacillus  Requires oxygen to survive Antitubercular agents treat all forms of Mycobacterium

51. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 51 Tuberculosis TB close to eradication; new resistant strain developed in immunocompromised individuals and immigrants to the U.S. Drug therapy is given in two forms:  Preventive therapy  Active therapy

52. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 52 TB: Preventive Therapy Preferred agent  INH (Isoniazid)  Known as chemoprophylaxis  Safest  Low cost  Action: tuberculostatic and tuberculocidal  Treatment: 18 months to 2 years

53. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 53 Isoniazid INH  Action: inhibits the synthesis of mycolic acid Adverse effects of INH  Hepatotoxicity: jaundice  Peripheral neuritis  Nausea  Skin rashes

54. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 54 Multiple Drug Therapy Required: combination of two or three agents Helps prevent development of resistant strains

55. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 55 Antitubercular Therapy Effectiveness depends on:  Where  Strain  Effective drug combination  Sufficient duration  Effective drug compliance

56. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 56 Antitubercular Agents: Nursing Implications Client education is critical. Therapy may last for up to 24 months. Take medications exactly as ordered. Emphasize the importance of strict compliance.

57. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 57 Antitubercular Agents: Nursing Implications Do not consume alcohol. Diabetic: monitor blood glucose levels INH and rifampin :  Oral contraceptives ineffective

58. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 58 Lyme Disease Spirochete Borrelia burgdorferi  Transmitted from a deer tick Symptoms  Rash  Flulike symptoms, followed by arthritis and fatigue

59. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 59 Treatment for Lyme Disease Oral doxycycline  Adults: 100 mg b.i.d  Length: 10 to 14 days Adverse effect  Photosensitivity

60. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 60 Fungi Contracted  Air  Skin to skin Due to normal flora being killed off:  Antibiotics  Corticosteroid therapy  Antineoplastic agents  Suppressed immune system

61. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 61 Mycotic Infections Three general types  Cutaneous  Subcutaneous  Systemic (can be life threatening)

62. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 62 Antifungal Agents Treatment  Antibiotic therapy will not work.  Requires prolonged treatment  Human cell structure resembles fungi cell structure. Action  Antifungal agents take advantage of the slight differences of the cell structures.

63. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 63 Antifungal Agents: General Adverse Effects Topical: irritation and redness Oral: nausea, vomiting, and diarrhea May potentiate antihistamines

64. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 64 Antifungal Agents: Adverse Effects IV: hepatotoxicity, renal toxicity, and phlebitis IV drugs must be diluted and administered slowly: amphotericin B

65. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 65 Antifungal Agents: Nursing Implications IV  Monitor vital signs every 15 to 30 minutes.  Monitor input and output.  Monitor urinalysis findings.

66. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 66 Antiviral Agents Viruses cause many infectious disorders:  Acute: common cold  Chronic: herpes  Slow growing: AIDS Available vaccines  Polio, rabies, and smallpox

67. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 67 Viral Replication A virus cannot replicate on its own. It must attach to and enter a host cell.  Uses the host cell’s energy to synthesize protein: DNA and RNA (continues)

68. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 68 Life cycle of a virus (continued)

69. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 69 Interferons Normally, interferons protect the cells from infecting viruses.  Interferon: continuous research Recent antifungal agents end in “vir”

70. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 70 Antiviral Agents: Key Characteristics Inhibit viral replication by interfering with:  Viral nucleic acid synthesis and/or regulation  Ability of virus to bind to cells Interferon: stimulates immune system

71. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 71 Treatment with Antiviral Agents Antiviral agents treat:  Influenzae A  Herpes simplex  RSV  AIDS, HIV

72. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 72 Antiviral Agents: Adverse Effects Bone marrow suppression Nephrotoxicity Hepatotoxicity Gastrointestinal effects Central nervous system effects

73. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 73 Antiviral Agents: Nursing Implications Be sure to teach proper application:  Ointments  Aerosol powders Emphasize handwashing. Wear gloves for topical application. (continues)

74. Copyright 2007 Thomson Delmar Learning, a division of Thomson Learning Inc. All rights reserved. 7 - 74 Antiviral Agents: Nursing Implications Usually not a cure  Replications cease: remain in nerve fibers Therapeutic effects vary  Range from delayed progression of AIDS and ARC to decrease in flulike symptoms  Frequency of herpes-like flare-ups decrease (continued)