Anti-Infective Agents

1. Anti-Infective Agents Antibiotics: Sulfonamides Penicillins Cephalosporins Tetracyclines Aminoglycosides Macrolides Quinolones

2. Antibiotics • Medications used to treat bacterial infections • Culture and sensitivity before therapy

3. Antibiotics Definitions • Empiric therapy: treatment of an infection before culture • Prophylactic therapy: treatment with antibiotics to prevent an infection • Broad spectrum- effective against several groups of microorganisms • Narrow spectrum- effective against a few groups

4. Antibiotics Definitions • Bactericidal: kill bacteria • Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately; will eventually lead to bacterial death • Superinfection: elimination of normal bacteria and other bacteria take over

5. Nosocomial • Hospital Acquired Infections • Patients with decreased resistance • Often drug resistant strains • Staph (Skin, Lungs) • Psuedomonas (Lungs, Wounds) • Proteus (Wound, UTI)

6. http://www.fda.gov/fdac/features/2002/402_bugs.html

7. Antibiotic Resistant Microorganisms

8. Antibiotics: Sulfonamides One of the first groups of antibiotics • sulfadiazine • sulfamethizole • Sulfamethoxazole • sulfisoxazole

9. Sulfonamides: Mechanism of Action • Bacteriostatic action • Prevent synthesis of folic acid required for synthesis of purines and nucleic acid • Does not affect human cells or certain bacteria—they can use preformed folic acid

10. Sulfonamides: sulfamethoxazole Therapeutic Uses Bactrim • Combined with trimethoprim. • Used to treat UTIs, Pneumocystis carinii pneumonia, ear infections, bronchitis, gonorrhea, etc.

11. Sulfonamides: Side Effects • Photosensitivity • Crystalluria • Delayed skin reactions

12. Antibiotics: Penicillins • Natural penicillins • Penicillinase-resistant penicillins • Aminopenicillins • Extended-spectrum penicillins

13. Penicillins • Inhibit the synthesis of bacterial cell wall • Bactericidal • Therapeutic levels are not usually obtained in intraocular and cerbrospinal fluid • Rapidly excreted in through the kidneys

14. Antibiotics: Penicillins • First introduced in the 1940s • Bactericidal: inhibit cell wall synthesis • Kill a wide variety of bacteria • Also called “beta-lactams”

15. Antibiotics: Penicillins • Bacteria produce enzymes capable of destroying penicillins. • These enzymes are known as beta-lactamases. • As a result, the medication is not effective.

16. Antibiotics: Penicillins • Chemicals have been developed to inhibit these enzymes: • clavulanic acid • These chemicals bind with beta-lactamase and prevent the enzyme from breaking down the penicillin

17. Prototype: Penicillin G • Widely used • Effectiveness and minimal toxicity • Available IV & IM • Natural PCN

18. Antibiotics: Penicillins: Augmentin • Penicillin-beta-lactamase inhibitor combination drugs: • amoxicillin + clavulanic acid = Augmentin • Inactivate beta-lactamase enzymes • Protects PCN and extends spectrum • Available PO

19. Penicillins: Mechanism of Action • Penicillins enter the bacteria via the cell wall. • Inside the cell, they bind to penicillin-binding 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.

20. Penicillins: Therapeutic Uses • Prevention and treatment of infections caused by susceptible bacteria

21. Penicillins: Adverse Effects • Allergic reactions occur in 0.7% – 8% of treatments • urticaria, pruritus, angioedema • 10% of allergic reactions are life-threatening and • 10% of these are fatal

22. Penicillins: Side Effects • Common side effects: • nausea, vomiting, diarrhea, abdominal pain • Other side effects are less common

23. Antibiotics: Cephalosporins • First Generation • Second Generation • Third Generation • Fourth Generation

24. Antibiotics: Cephalosporins • Semisynthetic derivatives from a fungus • Structurally and pharmacologically related to penicillins • Bactericidal action • Broad spectrum • Divided into groups according to their antimicrobial activity

25. Cephalosporins: First Generation cefazolin cephalexin (Ancef and Kefzol) (Keflex and Keftab) IV and PO PO used for surgical prophylaxis, URIs, otitis media

26. CephalosporinsPrototype: Cephalexin (Keflex) • Broad spectrum • First generation • Respiratory, soft tissue, bones, urinary tract, and bloodstream infections • Tx pcn resistant GC • Contraindicated with prior severe anaphylactic reaction to PCN

27. Cephalosporins: Side Effects • similar to penicillins

28. Antibiotics: Tetracyclines • doxycycline (Doryx, Doxy-Caps, Vibramycin)

29. Antibiotics: Tetracyclines • Natural and semi-synthetic • Bacteriostatic—inhibit bacterial growth • Inhibit protein synthesis • Stop many essential functions of the bacteria

30. Tetracyclines: Therapeutic Uses • Wide spectrum: • gram-negative, gram-positive, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease

31. Antibiotics: Tetracyclines • Bind to Ca2+ and Mg2+ and Al3+ ions to form insoluble complexes • Thus, dairy products, antacids, and iron salts reduce absorption of tetracyclines

32. Tetracyclines: Side Effects Strong affinity for calcium • Discoloration of permanent teeth and tooth enamel in fetuses and children • May retard fetal skeletal development if taken during pregnancy

33. Tetracyclines: Side Effects Alteration in intestinal flora may result in: • Superinfection (overgrowth of nonsusceptible organisms such as Candida) • Diarrhea • Pseudomembranous colitis

34. Tetracyclines: Side Effects May also cause: • Vaginal moniliasis • Gastric upset • Enterocolitis • Maculopapular rash

35. Antibiotics: Aminoglycosides • gentamicin (Garamycin)

36. Aminoglycosides • Natural and semi-synthetic • Poor oral absorption; no PO forms • Very potent antibiotics with serious toxicities • Bactericidal • Kill mostly gram-negative; some gram-positive also

37. Aminoglycosides • Used to kill gram-negative bacteria such as Pseudomonas spp., E. coli, Proteus spp., Klebsiella spp., Serratia spp. • Often used in combination with other antibiotics for synergistic effect. • BIG GUN!!!!

38. Aminoglycosides Cause serious toxicities: • Nephrotoxicity (renal failure) • Ototoxicity (auditory impairment and vestibular [eighth cranial nerve]) • Must monitor drug levels, pg 581

39. Adverse Effects Aminoglycosides Page 583 • Nephrotoxicity • Ototoxicity • Neurotoxicity • Hypersensitivity

40. Aminoglycosides: Side Effects Ototoxicity and nephrotoxicity are the most significant

41. Antibiotics: Quinolones • ciprofloxacin (Cipro)

42. Quinolones • Excellent oral absorption • Absorption reduced by antacids • First oral antibiotics effective against gram-negative bacteria

43. Quinolones: Mechanism of Action • Bactericidal • Effective against gram-negative organisms and some gram-positive organisms • Alter DNA of bacteria, causing death • Do not affect human DNA

44. Quinolones: Therapeutic Uses • Lower respiratory tract infections • Bone and joint infections • Infectious diarrhea • Urinary tract infections • Skin infections • Sexually transmitted diseases

45. Quinolones: Side Effects • Dizziness • Photosensitivity • Constipation • Rash, pruritis • Flushing

46. Drug Interactions • Cimetidine • Probenicid • Antacids • Iron

47. Antibiotics: Macrolides • erythromycin • azithromycin (Zithromax)

48. Macrolides: Therapeutic Uses Strep infections • Streptococcus pyogenes (group A beta-hemolytic streptococci) Mild to moderate URI • Haemophilus influenzae Spirochetal infections • Syphilis and Lyme disease Gonorrhea, Chlamydia, Mycoplasma

49. Macrolides: Side Effects GI effects, primarily with erythromycin: • nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia • Newer agents, azithromycin and clarithromycin: fewer side effects, longer duration of action, better efficacy, better tissue penetration

50. Antibiotics: Nursing Implications • Before beginning therapy, assess drug allergies; other labs • Be sure to obtain thorough patient health history,. • Assess for conditions that may be contraindications to antibiotic use • Assess for potential drug interactions.