Antiinfective Antiinflammatory Drugs

1. Antiinfective & Antiinflammatory Drugs Antibiotics Antiviral Antifungal Antimalarial Antiseptic & Disinfectant Agents Antiinflammatory & Antirheumatic

2. AntibioticsDefinition Medications used to treat bacterial infections Ideally, before beginning antibiotic therapy, the suspected areas of infection should be cultured to identify the causative organism and potential antibiotic susceptibilities

4. Antibiotic Therapy Empiric therapy: treatment of an infection before specific culture information has been reported or obtained Prophylactic therapy: treatment with antibiotics to prevent an infection, as in intra-abdominal surgery or after trauma

5. Antibiotic Therapy Therapeutic response Decrease in specific signs and symptoms of infection are noted (fever, elevated WBC, redness, inflammation, drainage, pain) Subtherapeutic response Signs and symptoms of infection do not improve

6. Antibiotic Therapy Superinfection Antibiotic resistance Host factors Genetic host factors G6PD deficiency Slow acetylation Allergic reactions

7. AntibioticsClasses Sulfonamides Penicillins Cephalosporins Tetracyclines Aminoglycosides Quinolones Macrolides

8. Other Antibiotics Classes clindamycin (Cleocin) dapsone linezolid (Zyvox) metronidazole (Flagyl) nitrofurantoin (Macrodantin) quinupristin and dalfopristin (Synercid) daptomycin (Cubicin)

9. Antibiotic Therapy Four common mechanisms of action Interference with cell wall synthesis Interference with protein synthesis Interference with DNA replication Acting as a metabolite to disrupt critical metabolic reactions inside the bacterial cell

11. Actions of Antibiotics Bactericidal: kill bacteria Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately; will eventually lead to bacterial death

12. AntibioticsSulfonamides One of the first groups of antibiotics Sulfadiazine (Coptin) Sulfamethoxazole Sulfisoxazole (Gantrisin) Used to treat otitis media, UTIs, other conditions Often combined with another antibiotic Sulfamethoxazole-trimethoprim (Bactrim)

13. Sulfonamides: Mechanism of Action 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

14. Sulfonamides Indications Treatment of UTIs caused by susceptible strains of: Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus Nocardiosis (caused by Nocardia - pneumonia) Pneumocystis jiroveci pneumonia (PJP) co-trimoxazole (Bactrim, Septra) Upper respiratory tract infections

15. Sulfonamides:Combination Products trimethoprim/sulfamethoxazole (co-trimoxazole, Bactrim, Septra) Used to treat UTIs, PJP, otitis media, other conditions erythromycin/sulfisoxazole (Pediazole) Used to treat otitis media

16. SulfonamidesAdverse Effects Body System Adverse Effects Blood Hemolytic and aplastic anemia, agranulocytosis, thrombocytopenia Integumentary Photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, epidermal necrolysis GI Nausea, vomiting, diarrhea, pancreatitis Other Convulsions, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria

17. Nursing Implications Sulfonamides Should be taken with at least 2000 mL of fluid per day, unless contraindicated Oral forms should be taken with food or milk to reduce GI upset

18. Penicillins Natural penicillins Penicillinase-resistant penicillins Aminopenicillins Extended-spectrum penicillins

20. Penicillins Natural penicillins penicillin G, penicillin V potassium Penicillinase-resistant drugs cloxacillin, dicloxacillin, nafcillin, oxacillin Aminopenicillins amoxicillin, ampicillin, bacampicillin Extended-spectrum drugs piperacillin, ticarcillin, carbenicillin

21. Penicillins First introduced in the 1940s Bactericidal: inhibit cell wall synthesis Kill a wide variety of bacteria Also called “ß-lactams” Bacteria produce enzymes capable of destroying penicillins These enzymes are known as ß-lactamases As a result, the medication is not effect

22. Penicillins Chemicals used to inhibit these enzymes: Clavulanic acid Tazobactam Sulbactam Bind with ß-lactamase and prevent the enzyme from breaking down the penicillin -- making the drug more effective Penicillin-ß-lactamase inhibitor combination drugs ampicillin + sulbactam = Unasyn amoxicillin + clavulanic acid = Augmentin ticarcillin + clavulanic acid = Timentin piperacillin + tazobactam = Zosyn

23. 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

24. Penicillins Indications Prevention and treatment of infections caused by susceptible bacteria, such as: Gram-positive bacteria Streptococcus, Enterococcus, Staphylococcus

25. Penicillins Adverse Effects Allergic reactions occur in 0.7% to 4% of cases Urticaria, pruritus, angioedema Those allergic to penicillins have a fourfold to sixfold increased risk of allergy to other ß-lactam antibiotics Cross-reactivity between penicillins and cephalosporins is between 1% and 18% Common adverse effects Nausea, vomiting, diarrhea, abdominal pain Other adverse effects are less common

26. PenicillinsInteractions MANY interactions! NSAIDs Oral contraceptives warfarin Others

27. Nursing Implications Penicillins Any patient taking a penicillin should be carefully monitored for an allergic reaction for at least 30 minutes after its administration The effectiveness of oral penicillins is decreased when taken with caffeine, citrus fruit, cola beverages, fruit juices, or tomato juice Administer with at least 6 ounces of water

28. Cephalosporins Four Generations: Semisynthetic derivatives from a fungus Structurally and pharmacologically related to penicillins Bactericidal action Broad spectrum Divided into groups according to antimicrobial activity

29. CephalosporinsFirst Generation Used for surgical prophylaxis, URIs, otitis media cefazolin (Ancef and Kefzol): IV or IM cephalexin (Keflex): PO

30. Cephalosporins: Second Generation Good gram-positive coverage Better gram-negative coverage than first generation Cefmetazole IV Cefprozil (Cefzil) PO Cefoxitin (Mefoxin) IV Cefaclor (Ceclor) PO cefoxitin (Mefoxin): IV and IM Used prophylactically for abdominal or colorectal surgeries Also kills anaerobes cefuroxime (Kefurox and Ceftin): PO Surgical prophylaxis Does not kill anaerobes

31. Cephalosporins Third Generation ceftriaxone (Rocephin) IV and IM, long half-life, once-a-day dosing Elimination is primarily hepatic Easily passes meninges and diffused into CSF to treat CNS infections ceftazidime (Fortaz, Tazidime) IV and IM forms Excellent gram-negative coverage Used for difficult-to-treat organisms such as Pseudomonas Eliminated renally instead of biliary route Excellent spectrum of coverage

32. Cephalosporins Fourth Generation Newest cephalosporin drugs Broader spectrum of antibacterial activity than third generation, especially against gram-positive bacteria Tx: UTI, Skin infections, pneumonia cefepime (Maxipime) GM +/- cefdinir cefditoren pivoxil (Spectracef)

33. Cephalosporins Adverse Effects Similar to penicillins Mild diarrhea, abdominal cramps, rash, pruritis, redness, edema Potential cross-sensitivity with penicillins if allergies exist

34. Nursing ImplicationsCephalosporins Orally administered forms should be given 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

35. Carbapenems Very broad-spectrum antibacterial action Reserved for complicated body cavity and connective tissue infections May cause drug-induced seizure activity All given parenterally imipenem-cilastatin (Primaxin) Used for treatment of bone, joint, skin, and soft tissue infections Cilastatin inhibits an enzyme that breaks down imipenem meropenem (Merrem) – bacterial meningitis ertapenem (Invanz) - newest

36. Monobactams aztreonam (Azactam) Synthetic ß-lactam antibiotic Primarily active against aerobic gram-negative bacteria (E. coli, Klebsiella spp., Pseudomonas spp.) Bactericidal Used for moderately severe systemic infections and UTIs

37. Macrolides Prevent protein synthesis within bacterial cells Considered bacteriostatic - Bacteria will eventually die In high enough concentrations, may also be bactericidal erythromycin (E-mycin azithromycin (Zithromax) clarithromycin (Biaxin) Adverse Effects: GI effects, primarily with erythromycin Nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia Newer drugs, azithromycin and clarithromycin: fewer GI adverse effects, longer duration of action, better efficacy, better tissue penetration

38. Nursing ImplicationsMacrolides 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

39. Ketolide telithromycin (Ketek) Only drug in this class Better antibacterial coverage than macrolides Active against gram-positive bacteria, including multi-drug resistant strains of S. pneumoniae Active against selected gram-negative bacteria Indications: Community-acquired pneumonia, acute bacterial sinusitis, bacterial exacerbations of chronic bronchitis Adverse reactions include: Headache, dizziness, GI discomfort, altered potassium levels, prolonged QT intervals

40. Tetracyclines Natural and semisynthetic Obtained from cultures of Streptomyces Bacteriostatic—inhibit bacterial growth Inhibit protein synthesis Stop many essential functions of the bacteria demeclocycline (Declomycin) oxytetracycline tetracycline doxycycline (Doryx, Vibramycin) Minocycline

41. TetracyclinesAdverse 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) Diarrhea Pseudomembranous colitis

42. Nursing ImplicationsTetraclyclines Milk products, iron preparations, antacids, and other dairy products should be avoided because of the chelation and drug-binding that occurs All medications should be taken with 6 to 8 ounces of fluid, preferably water Due to photosensitivity, avoid sunlight and tanning beds

43. Nursing Implications Before beginning therapy, assess drug allergies; renal, liver, and cardiac function; and other lab studies Be sure to obtain patient health history, including immune status Assess for conditions that may be contraindications to antibiotic use or that may indicate cautious use Assess for potential drug interactions It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy

44. Nursing Implications Each class of antibiotics has specific adverse effects and drug interactions that must be carefully assessed and monitored The most common adverse effects of antibiotics are nausea, vomiting, and diarrhea All oral antibiotics are absorbed better if taken with at least 6 to 8 ounces of water

45. Nursing Implications 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

46. Antibiotic Therapy Concepts Therapeutic drug monitoring Minimum inhibitory concentration (MIC) Concentration-dependent killing Once-daily dosing vs. multi-daily dosing Peak and trough blood levels Synergistic effects Post-antibiotic effect (PAE)

47. Antibiotic TherapyToxicities Ototoxicity Temporary or permanent hearing loss, balance problems Nephrotoxicity Varying degrees of reduced renal function Rising serum creatinine may indicate reduced creatinine clearance Monitor trough levels every 3 days while on therapy or as ordered

48. Aminoglycosides gentamicin (Garamycin) kanamycin neomycin (Neo-Fradin) streptomycin tobramycin (Nebcin) amikacin (Amikin) netilmicin paromomycin

49. Aminoglycosides Natural and semisynthetic Produced from Streptomyces Poor oral absorption; no PO forms Very potent antibiotics with serious toxicities Bactericidal; prevents protein synthesis Kill mostly gram-negative; some gram-positive

50. Aminoglycosides Indications Used to kill gram-negative bacteria Pseudomonas, E. coli, Proteus, Klebsiella, Serratia Often used in combination with other antibiotics for synergistic effects Certain gram-positive infections that are resistant to other antibiotics Aminoglycosides poorly absorbed through the GI tract - given IV Exception: neomycin Given orally or by enema - decontaminate the GI tract before surgical procedures

51. Aminoglycosides Adverse Effects Ototoxicity and nephrotoxicity are the most significant Headache Paresthesia Fever Superinfections Vertigo Skin rash Dizziness

52. Fluoroquinolones ciprofloxacin (Cipro) norfloxacin (Noroxin) levofloxacin (Levaquin) gatifloxacin (Tequin) moxifloxacin (Avelox) gemifloxacin (Factive)

53. Fluoroquinolones Also called “quinolones” Excellent oral absorption Absorption reduced by antacids Effective against gram-negative organisms and some gram-positive organisms Mechanism of Action: Bactericidal Alter DNA of bacteria, causing death Do not affect human DNA

54. Fluoroquinolones Indications Lower respiratory tract infections Bone and joint infections Infectious diarrhea Urinary tract infections Skin infections Sexually transmitted diseases Anthrax

55. Fluoroquinolones: Adverse Effects Body System Adverse Effects CNS Headache, dizziness, fatigue, depression, restlessness, insomnia GI Nausea, vomiting, diarrhea, constipation, thrush, increased LFTs Integumentary Rash, pruritus, urticaria, flushing, photosensitivity (with lomefloxacin) Other Fever, chills, blurred vision, tinnitus

56. Other Antibiotics clindamycin (Cleocin) dapsone linezolid (Zyvox) metronidazole (Flagyl) nitrofurantoin (Macrodantin) quinupristin and dalfopristin (Synercid) daptomycin (Cubicin)

57. Other Antibiotics clindamycin (Cleocin) Used for chronic bone infections, GU infections, intraabdominal infections, other serious infections May cause pseudomembranous colitis

58. Other Antibiotics dapsone Used for leprosy (Hansen’s disease), PJP pneumonia associated with HIV/AIDS, other uses

59. Other Antibiotics linezolid (Zyvox) New class: oxazolidinones Used to treat vancomycin-resistant Enterococcus faecium (VREF, VRE), hospital-acquired skin and skin structure infections, including those with MRSA May cause hypotension, serotonin syndrome if taken with SSRIs, and reactions if taken with tyramine-containing foods

60. Other Antibiotics nitrofurantoin (Macrodantin) Primarily used for UTIs (E. coli, S. aureus, Klebsiella spp., Enterobacter spp.) Use carefully if renal function is impaired Drug concentrates in the urine Usually well-tolerated if patient is kept well-hydrated

61. Other Antibiotics quinupristin and dalfopristin (Synercid) 30:70 combination, work synergistically Used for bacteremia and infections caused by vancomycin-resistant Enterococcus (VRE) and other complicated skin infections May cause arthralgias, myalgias

62. Other Antibiotics daptomycin (Cubicin) New class: lipopeptide Used to treat complicated skin and soft-tissue infections

63. Other AntibioticsVancomycin Natural, bactericidal antibiotic - Destroys cell wall Treatment of choice for MRSA, and other gram-positive infections Must monitor blood levels to ensure therapeutic levels and prevent toxicity May cause ototoxicity and nephrotoxicity Should be infused over 60 minutes -- Monitor IV site closely Red man syndrome may occur Flushing/itching of head, neck, face, upper trunk Antihistamine may be ordered to reduce these effects Ensure adequate hydration (2 L fluids/24 hr) if not contraindicated to prevent nephrotoxicity

64. Nursing Implications Before beginning therapy, assess drug allergies; hepatic, renal, and cardiac function Be sure to obtain thorough patient health history, including immune status Assess for conditions that may be contraindications to antibiotic use or that may indicate cautious use Assess for potential drug interactions

65. Nursing Implications It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy

66. Nursing Implications Patients should be instructed to take antibiotics exactly as prescribed and for the length of time prescribed; they should not stop taking the medication early when they feel better Assess for signs and symptoms of superinfection: fever, perineal itching, cough, lethargy, or any unusual discharge For safety reasons, check the name of the medication carefully because there are many drugs that sound alike or have similar spellings

67. Nursing Implications Each class of antibiotics has specific adverse effects and drug interactions that must be carefully assessed and monitored

68. Nursing Implications Aminoglycosides Monitor peak and trough blood levels of these drugs to prevent nephrotoxicity and ototoxicity Symptoms of ototoxicity include dizziness, tinnitus, and hearing loss Symptoms of nephrotoxicity include urinary casts, proteinuria, and increased BUN and serum creatinine levels

69. Nursing Implications 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