1. CHAPTER 37 Antibiotics Part 1

2. Antibiotics: Definition
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 intraabdominal surgery or after trauma

5. Antibiotic Therapy (cont’d)
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 (cont’d)
Superinfection
Antibiotic resistance
Host factors
Genetic host factors
G6PD deficiency
Slow acetylation
Allergic reactions

7. Sulfonamides Penicillins Cephalosporins Tetracyclines
Antibiotics: Classes
Sulfonamides
Penicillins
Cephalosporins
Tetracyclines
Aminoglycosides
Quinolones
Macrolides
Others

8. 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

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

11. Antibiotics: Sulfonamides
One of the first groups of antibiotics
sulfadiazine
sulfamethoxazole
sulfisoxazole
Often combined with another antibiotic
trimethoprim

12. 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

13. 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 spp.)

14. Sulfonamides: Indications (cont’d)
Pneumocystis jiroveci pneumonia (PJP)
co-trimoxazole
Upper respiratory tract infections
Other uses

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
sulfisoxazole (Gantrisin)
Used to treat otitis media, UTIs, other conditions

16. Sulfonamides: Adverse Effects
Body System Adverse Effects
Blood Hemolytic and aplastic anemia, agranulocytosis, thrombocytopenia
Integumentary Photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, epidermal necrolysis

17. Sulfonamides: Adverse Effects (cont’d)
Body System Adverse Effects
GI Nausea, vomiting, diarrhea, pancreatitis
Other Convulsions, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria

18. β-Lactam Antibiotics Penicillins Cephalosporins Carbapenems
Monobactams

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

21. Penicillins (cont’d) Natural penicillins Penicillinase-resistant drugs
penicillin G, penicillin V potassium
Penicillinase-resistant drugs
cloxacillin, dicloxacillin, nafcillin, oxacillin

22. Penicillins (cont’d) Aminopenicillins Extended-spectrum drugs
amoxicillin, ampicillin, bacampicillin
Extended-spectrum drugs
piperacillin, ticarcillin, carbenicillin

23. Penicillins (cont’d) First introduced in the 1940s
Bactericidal: inhibit cell wall synthesis
Kill a wide variety of bacteria
Also called “β-lactams”

24. Penicillins (cont’d)
Bacteria produce enzymes capable of destroying penicillins
These enzymes are known as β-lactamases
As a result, the medication is not effective

25. Penicillins (cont’d)
Chemicals have been developed to inhibit these enzymes:
Clavulanic acid
Tazobactam
Sulbactam
These chemicals bind with β-lactamase and prevent the enzyme from breaking down the penicillin, thus making the drug more effective

26. Penicillins (cont’d)
Penicillin-β-lactamase inhibitor combination drugs
ampicillin + sulbactam = Unasyn
amoxicillin + clavulanic acid = Augmentin
ticarcillin + clavulanic acid = Timentin
piperacillin + tazobactam = Zosyn

27. 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

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

29. 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 β-lactam antibiotics
Cross-reactivity between penicillins and cephalosporins is between 1% and 18%

30. Penicillins: Adverse Effects (cont’d)
Common adverse effects
Nausea, vomiting, diarrhea, abdominal pain
Other adverse effects are less common

31. Penicillins: Interactions
MANY interactions!
NSAIDs
Oral contraceptives
warfarin
Others

32. Cephalosporins First generation Second generation Third generation
Fourth generation

33. Cephalosporins (cont’d)
Semisynthetic derivatives from a fungus
Structurally and pharmacologically related to penicillins
Bactericidal action
Broad spectrum
Divided into groups according to their antimicrobial activity

34. Cephalosporins: First Generation
cefadroxil
cephradine
Good gram-positive coverage
Poor gram-negative coverage
Parenteral and PO forms
cefazolin
cephradine

35. Cephalosporins: First Generation (cont’d)
Used for surgical prophylaxis, URIs, otitis media
cefazolin (Ancef and Kefzol): IV or IM
cephalexin (Keflex): PO

36. Cephalosporins: Second Generation
Good gram-positive coverage
Better gram-negative coverage than first generation
cefaclor
Cefprozil
Cefmetazole
cefoxitin
cefuroxime
loracarbef
cefotetan

37. Cephalosporins: Second Generation (cont’d)
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

38. Cephalosporins: Third Generation
Most potent group against gram-negative
Less active against gram-positive
Ceftibuten
cefpodoxime proxetil
cefoperazone
ceftizoxime
ceftriaxone
ceftazidime

39. Cephalosporins: Third Generation (cont’d)
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

40. Cephalosporins: Third Generation (cont’d)
ceftazidime (Fortaz, Tazidime)
IV and IM forms
Excellent gram-negative coverage
Used for difficult-to-treat organisms such as Pseudomonas spp.
Eliminated renally instead of biliary route
Excellent spectrum of coverage

41. Cephalosporins: Fourth Generation
Newest cephalosporin drugs
Broader spectrum of antibacterial activity than third generation, especially against gram-positive bacteria
cefepime (Maxipime)
cefdinir
cefditoren pivoxil

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

43. Carbapenems Very broad-spectrum antibacterial action
Reserved for complicated body cavity and connective tissue infections
May cause drug-induced seizure activity
All given parenterally

44. Carbapenems imipenem-cilastatin (Primaxin) meropenem (Merrem)
Used for treatment of bone, joint, skin, and soft tissue infections; many other uses
Cilastatin inhibits an enzyme that breaks down imipenem
meropenem (Merrem)
ertapenem (Invanz)

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

46. Macrolides erythromycin (E-mycin, E.E.S, others)
azithromycin (Zithromax)
clarithromycin (Biaxin)

47. Macrolides: Mechanism of Action
Prevent protein synthesis within bacterial cells
Considered bacteriostatic
Bacteria will eventually die
In high enough concentrations, may also be bactericidal

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

49. Macrolides: Indications (cont’d)
azithromycin and clarithromycin
Recently approved for mycobacterium avium-intracellular complex infection (opportunistic infection associated with HIV/AIDS)
clarithromycin
Recently approved for use in combination with omeprazole for treatment of active ulcer disease associated with Helicobacter pylori infection

50. Macrolides: 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

51. 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

52. Ketolide: telithromycin (Ketek)
Indicated for:
Community-acquired pneumonia, acute bacterial sinusitis, bacterial exacerbations of chronic bronchitis
Adverse reactions include:
Headache, dizziness, GI discomfort, altered potassium levels, prolonged QT intervals

53. Ketolide: telithromycin (Ketek) (cont’d)
Contraindications
Cardiac disease (with prolonged QT) or bradycardia, others
Several drug interactions

54. Tetracyclines demeclocycline (Declomycin) oxytetracycline tetracycline
doxycycline (Doryx, Vibramycin)
minocycline

55. Tetracyclines (cont’d)
Natural and semisynthetic
Obtained from cultures of Streptomyces
Bacteriostatic—inhibit bacterial growth
Inhibit protein synthesis
Stop many essential functions of the bacteria

56. Tetracyclines (cont’d)
Bind (chelate) to Ca2+ and Mg2+ and Al3+ ions to form insoluble complexes
Thus, dairy products, antacids, and iron salts reduce oral absorption of tetracyclines
Should not be used in children under age 8 or in pregnant/lactating women because tooth discoloration will occur if the drug binds to the calcium in the teeth

57. Tetracyclines: Indications
Wide spectrum
Gram-negative and gram-positive organisms, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease, acne, others
Demeclocycline is also used to treat SIADH, and pleural and pericardial effusions

58. 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

59. Tetracyclines: Adverse Effects (cont'd)
Alteration in intestinal flora may result in:
Superinfection (overgrowth of nonsusceptible organisms such as Candida)
Diarrhea
Pseudomembranous colitis

60. Tetracyclines: Adverse Effects (cont'd)
May also cause:
Vaginal candidiasis
Gastric upset
Enterocolitis
Maculopapular rash
Other effects

61. Nursing Implications
Before beginning therapy, assess drug allergies; renal, liver, and cardiac function; and other lab studies
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

62. Nursing Implications (cont’d)
It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy

63. Nursing Implications (cont’d)
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

64. Nursing Implications (cont’d)
For safety reasons, check the name of the medication carefully because there are many drugs that sound alike or have similar spellings

65. Nursing Implications (cont’d)
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

66. Nursing Implications (cont’d)
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

67. Nursing Implications (cont’d)
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

68. Nursing Implications (cont’d)
Cephalosporins
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

69. Nursing Implications (cont’d)
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

70. Nursing Implications (cont’d)
Tetracyclines
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

71. Nursing Implications (cont’d)
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