Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 38 Antibiotics Part 1

2 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Infections: Sites of Origin  Community-associated infections  An infection that is acquired by a person who has not been hospitalized or had a medical procedure (such as dialysis, surgery, catheterization) within the past year

3 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Infections: Sites of Origin (cont’d)  Healthcare-associated infections  Contracted in a hospital or institutional setting  Were not present or incubating in the patient on admission to the facility  More difficult to treat because causative microorganisms are often drug resistant and the most virulent  One of top ten leading causes of death in the U.S.  MRSA most common  Previously known as nosocomial

4 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Healthcare-Associated Infections: Prevention  Hand washing  Antiseptics  Disinfectants

5 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Healthcare-Associated Infections: Prevention (cont’d)  Disinfectant  Kills organisms  Used only on nonliving objects  Antiseptic  Generally only inhibits the growth of microorganisms but does not necessarily kill them  Applied exclusively to living tissue

6 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antibiotics  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

7 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

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11 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

12 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

13 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antibiotic Therapy (cont’d)  Superinfection  Pseudomembranous colitis  Host factors  Genetic host factors  G6PD deficiency  Slow acetylation  Allergic reactions

14 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antibiotics: Classes  Sulfonamides  Penicillins  Cephalosporins  Macrolides  Quinolones  Aminoglycosides  Tetracyclines  Others

15 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antibiotic Therapy: Mechanism 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

16 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Actions of Antibiotics  Bactericidal: kill bacteria  Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately; will eventually lead to bacterial death

17 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Antibiotics: Sulfonamides  One of the first groups of antibiotics  Sulfadiazine  Sulfamethoxazole  Sulfisoxazole  Often combined with another antibiotic  Sulfamethoxazole combined with trimethoprim (a nonsulfonamide antibiotic), known as Bactrim, Septra, or co-trimoxazole (SMX-TMP)  This combination is used commonly

18 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

19 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Sulfonamides: Indications  Effective against both gram-positive and gram-negative bacteria gram-negative bacteria  Treatment of UTIs caused by susceptible strains of: strains of:  Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus

20 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Sulfonamides: Indications (cont’d)  Pneumocystis jirovecii pneumonia (PJP)  Co-trimoxazole  Upper respiratory tract infections  Other uses

21 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Sulfonamides: Adverse Effects Body SystemAdverse Effects BloodHemolytic and aplastic anemia, agranulocytosis, thrombocytopenia IntegumentaryPhotosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, epidermal necrolysis

22 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Sulfonamides: Adverse Effects (cont’d) Body SystemAdverse Effects GINausea, vomiting, diarrhea, pancreatitis OtherConvulsions, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria

23 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Beta-Lactam Antibiotics  Penicillins  Cephalosporins  Carbapenems  Monobactams

24 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins  Natural penicillins  Penicillinase-resistant penicillins  Aminopenicillins  Extended-spectrum penicillins

25 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins (cont’d)  Natural penicillins  penicillin G, penicillin V potassium  Penicillinase-resistant drugs  cloxacillin, dicloxacillin, nafcillin, oxacillin

26 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins (cont’d)  Aminopenicillins  amoxicillin, ampicillin  Extended-spectrum drugs  piperacillin, ticarcillin, carbenicillin  Usually used with other drugs; rarely used alone

27 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins (cont’d)  First introduced in the 1940s  Bactericidal: inhibit cell wall synthesis  Kill a wide variety of bacteria  Bacteria produce enzymes capable of destroying penicillins  These enzymes are known as beta-lactamases  As a result, the medication is not effective

28 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins (cont’d)  Chemicals have been developed to inhibit these enzymes:  Clavulanic acid  Tazobactam  Sulbactam  These chemicals bind with beta-lactamase and prevent the enzyme from breaking down the penicillin, thus making the drug more effective

29 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins (cont’d)  Penicillin–beta-lactamase inhibitor combination drugs  Ampicillin + sulbactam = Unasyn  Amoxicillin + clavulanic acid = Augmentin  Ticarcillin + clavulanic acid = Timentin  Piperacillin + tazobactam = Zosyn

30 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

31 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins: Indications  Prevention and treatment of infections caused by susceptible bacteria, such as:  Gram-positive bacteria  Streptococcus spp., Enterococcus spp., Staphylococcus spp.

32 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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 beta- lactam antibiotics  Cross-reactivity between penicillins and cephalosporins is between 1% and 4%

33 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins: Adverse Effects (cont’d)  Common adverse effects  Nausea, vomiting, diarrhea, abdominal pain  Other adverse effects are less common

34 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Penicillins: Interactions  MANY interactions!  NSAIDs  Oral contraceptives  Warfarin  Others

35 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins  First generation  Second generation  Third generation  Fourth generation  Fifth generation (not yet marketed)

36 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins (cont’d)  Semisynthetic derivatives  Structurally and pharmacologically related to penicillins  Bactericidal action  Broad spectrum  Divided into groups according to their antimicrobial activity

37 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: First Generation  Good gram-positive coverage  Poor gram-negative coverage  Parenteral and PO forms  Examples  cefadroxil  cephradine  cefazolin  cephalexin

38 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: First Generation (cont’d)  Used for surgical prophylaxis, and for susceptible staphylococcal infections  cefazolin (Ancef and Kefzol): IV or IM  cephalexin (Keflex): PO

39 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: Second Generation  Good gram-positive coverage  Better gram-negative coverage than first generation  Examples:  cefaclor  cefprozil  cefoxitin  cefuroxime  loracarbef  cefotetan

40 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: Second Generation (cont’d)  cefoxitin (Mefoxin): IV and IM  Used prophylactically for abdominal or colorectal surgeries  Also kills anaerobes  cefuroxime  Zinacef is parenteral form; Ceftin is PO  Surgical prophylaxis  Does not kill anaerobes

41 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: Third Generation  Most potent group against gram-negative bacteria  Less active against gram-positive bacteria  Examples  ceftibuten  cefotaxime  ceftazidime  cefdinir  ceftizoxime  ceftriaxone  ceftazidime

42 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

43 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: Third Generation (cont’d)  ceftazidime (Ceptaz)  IV and IM forms  Excellent gram-negative coverage  Used for difficult-to-treat organisms such as Pseudomonas spp.  Eliminated by renal instead of biliary route  Excellent spectrum of coverage  Resistance is limiting usefulness

44 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: Fourth Generation  Broader spectrum of antibacterial activity than third generation, especially against gram-positive bacteria  Uncomplicated and complicated UTI  cefepime (Maxipime)

45 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: Fifth Generation  Ceftobipriole (not available)  Broader spectrum of antibacterial activity  Effective against a wide variety of organisms  MRSA  Pseudomonas spp.

46 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cephalosporins: Adverse Effects  Similar to penicillins  Mild diarrhea, abdominal cramps, rash, pruritus, redness, edema  Potential cross-sensitivity with penicillins if allergies exist

47 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Carbapenems  Very broad-spectrum antibacterial action  Reserved for complicated body cavity and connective tissue infections  May cause drug-induced seizure activity  This risk can be reduced with proper dosage  All given parenterally

48 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Carbapenems  imipenem/cilastatin (Primaxin)  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)  doripenem (Doribax)

49 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Monobactams  aztreonam (Azactam)  Synthetic beta-lactam antibiotic  Primarily active against aerobic gram-negative bacteria (E. coli, Klebsiella spp., Pseudomonas spp.)  Bactericidal  Parenteral use only  Used for moderately severe systemic infections and UTIs

50 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Macrolides  erythromycin (E-mycin, E.E.S, others)  azithromycin (Zithromax)  clarithromycin (Biaxin)  dirithromycin

51 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Macrolides: Mechanism of Action  Prevent protein synthesis within bacterial cells  Considered bacteriostatic  Bacteria will eventually die  In high enough concentrations, may also be bactericidal

52 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Macrolides: Indications  Strep infections  Streptococcus pyogenes (group A beta-hemolytic streptococci)  Mild to moderate URI and LRI  Haemophilus influenzae  Spirochetal infections  Syphilis and Lyme disease  Gonorrhea, Chlamydia, Mycoplasma

53 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

54 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

55 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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  Associated with severe liver disease  Use is limited

56 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Tetracyclines  demeclocycline (Declomycin)  oxytetracycline  tetracycline  doxycycline (Doryx, Vibramycin)  minocycline  tigecycline (Tygacil)

57 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

58 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Tetracyclines (cont’d)  Bind (chelate) to Ca 2+ and Mg 2+ and Al 3+ 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

59 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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 by inhibiting the action of ADH

60 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

61 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Tetracyclines: Adverse Effects (cont’d)  Alteration in intestinal flora may result in:  Superinfection (overgrowth of nonsusceptible organisms such as Candida)  Diarrhea  Pseudomembranous colitis

62 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Tetracyclines: Adverse Effects (cont’d)  May also cause:  Vaginal candidiasis  Gastric upset  Enterocolitis  Maculopapular rash  Other effects

63 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

64 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy

65 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Instruct patients 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

66 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

67 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d) 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

68 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Sulfonamides  Take with 2000 to 3000 mL of fluid/24 hr  Assess RBCs prior to beginning therapy  Take oral doses with food

69 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Penicillins  Take oral doses with water (not juices) as acidic fluids may nullify drug’s antibacterial action  Monitor patients taking penicillin for an allergic reaction for at least 30 minutes after administration

70 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  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

71 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

72 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Tetracyclines  Avoid milk products, iron preparations, antacids, and other dairy products because of the chelation and drug-binding that occurs  Take all medications with 6 to 8 ounces of fluid, preferably water  Because of photosensitivity, avoid sunlight and tanning beds

73 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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