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Antibiotics: Definition • Medications used to treat bacterial • Ideally, before beginning antibiotic NDEG 26 A – Pharmacology I therapy, the suspected areas of Eliza Rivera-Mitu, RN, MSN infection should be cultured to identify the causative organism and potential antibiotic susceptibilities Mosby items and derived items 2005, 2002 by Mosby, Inc. 1
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Antibiotics: Classes • Aminoglycosides • Cephalosporins• Tetracyclines• Macrolides Figure 37-03 Gram-stain morphology of bacteria. The crystal violet of Gram stain is precipitated by Gram iodine and is trapped in the thick peptidoglycan layer in gram-positive bacteria. The decolorizer disperses the gram-negative outer membrane and washes the crystal violet from the thin layer of peptidoglycan. Gram-negative bacteria are visualized by the red counterstain. (From Murray PR et al: Medical microbiology, St. Louis, 2002, Mosby.) Mosby items and derived items 2005, 2002 by Mosby, Inc. 3
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Gram-negative bacterial infections are harder to treat because drug Signs and symptoms of infection molecules have a harder time penetrating the more complex gram- negative cell wall.
• Ï WBC (normal = 4300-10,800 or 5- • Pain and swelling Mosby items and derived items 2005, 2002 by Mosby, Inc. 5
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Antibiotic Therapy Antibiotic Therapy (cont'd) • Empiric therapy: treatment of an Four common mechanisms of action infection before specific culture • Interference with cell wall synthesis information has been reported or • Interference with protein synthesis • Interference with DNA replication • Prophylactic therapy: treatment with antibiotics to prevent an infection, as in • Acting as a metabolite to disrupt critical intraabdominal surgery metabolic reactions inside the bacterial cell Mosby items and derived items 2005, 2002 by Mosby, Inc. 7
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Actions of Antibiotics • Bactericidal: kill bacteria• Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately; will eventually lead to bacterial death Figure 37-6 Molecules on the surface of gram-negative and gram-positive bacteria involved in pathogenesis. Not shown is the type 3 secretory apparatus of gram-negative bacteria. (From Cotran RS, Kumar V, Collins T: Robbins pathologic basis of disease, ed 6, Philadelphia, 1999, WB Saunders.) Mosby items and derived items 2005, 2002 by Mosby, Inc. 9
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Mechanism of Action One of the first groups of antibiotics • Bacteriostatic action • Prevent synthesis of folic acid required for synthesis of purines and nucleic acid • sulfamethoxazole – FOLATE ANTAGONIST • sulfisoxazole • Do not affect human cells or certain bacteria—they can use preformed folic Mosby items and derived items 2005, 2002 by Mosby, Inc. 11
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Sulfonamides: Distribution and Route Mosby items and derived items 2005, 2002 by Mosby, Inc. 13
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Sulfonamides: Side Effects Combination Products • trimethoprim/sulfamethoxazole (Bactrim, Hemolytic and aplastic – Used to treat UTIs, PCP, otitis media, other • erythromycin/sulfisoxazole (Pediazole) Photosensitivity, – Used to treat otitis media exfoliative dermatitis, • sulfisoxazole (Gantrisin) – Used to treat otitis media, UTIs, other conditions syndrome, epidermal necrolysis Mosby items and derived items 2005, 2002 by Mosby, Inc. 15
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Sulfonamides: Side Effects Side Effects (cont'd) Nausea, vomiting, diarrhea, pancreatitis Convulsions, crystalluria,toxic nephrosis, headache, peripheral neuritis, urticaria Mosby items and derived items 2005, 2002 by Mosby, Inc. 17
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BETA-LACTAM
Table 37-02 Penicillins classification Mosby items and derived items 2005, 2002 by Mosby, Inc. 19
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Penicillins (cont'd) • Bacteria produce enzymes capable of • Chemicals have been developed to destroying penicillins inhibit these enzymes: • These enzymes are known as – Clavulanic acid • As a result, the medication is not • These chemicals bind with beta- lactamase and prevent the enzyme from breaking down the penicillin Mosby items and derived items 2005, 2002 by Mosby, Inc. 21
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Penicillins (cont'd) Mechanism of Action • Penicillins enter the • Penicillin-beta-lactamase inhibitor bacteria via the cell wall combination drugs • Inside the cell they bind to – ampicillin + sulbactam = Unasyn – amoxicillin + clavulanic acid = Augmentin • Once bound, normal cell wall synthesis is disrupted – ticarcillin + clavulanic acid = Timentin • Result: bacteria cells die – piperacillin + tazobactam = Zosyn • Penicillins do not kill other cells in the body Mosby items and derived items 2005, 2002 by Mosby, Inc. 23
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Penicillins: Adverse Effects • Allergic reactions occur in 0.7% to 8% – Urticaria, pruritus, angioedema • 10% of allergic reactions are life – 10% of these are fatal Mosby items and derived items 2005, 2002 by Mosby, Inc. 25
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Penicillins: Side Effects • Common side effects • Semisynthetic derivatives from a fungus – Nausea, vomiting, diarrhea, abdominal • Structurally and pharmacologically related to penicillins • Other side effects are less common • Bactericidal action• Broad spectrum• Divided into groups according to their antimicrobial activity Mosby items and derived items 2005, 2002 by Mosby, Inc. 27
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• Good gram-positive coverage •1st generation • Poor gram-negative coverage •2nd generation First Generation (cont'd) •3rd generation • Used for surgical prophylaxis, URIs, •4th generation – cefazoline (Ancef and Kefzol): IV or PO– cephalexin (Keflex): PO Mosby items and derived items 2005, 2002 by Mosby, Inc. 29
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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 •Good gram-positive coverage•Better gram-negative coverage than first generation Mosby items and derived items 2005, 2002 by Mosby, Inc. 31
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Third Generation (cont'd) cefixime (Suprax)• Only oral third-generation agent• Best of available oral cephalosporins against gram- • Tablet and suspensionceftriaxone (Rocephin) •Most potent group against gram-negative • IV and IM, long half-life, once-a-day dosing •Less active against gram-positive • Easily passes meninges and diffused into CSF to treat CNS infections Mosby items and derived items 2005, 2002 by Mosby, Inc. 33
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Third Generation (cont'd) Fourth Generation • ceftazidime (Ceptaz, Fortaz, Tazidime, • cefepime (Maxipime) – Newest cephalosporin agents – IV and IM forms – Broader spectrum of antibacterial activity – Excellent gram-negative coverage than third generation, especially against – Used for difficult-to-treat organisms such gram-positive bacteria as Pseudomonas spp.
– Eliminated renally instead of biliary route • cefditoren pivoxil – Excellent spectrum of coverage Mosby items and derived items 2005, 2002 by Mosby, Inc. 35
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Cephalosporins: Side Effects Similar to penicillins • Very broad-spectrum antibacterial action• Reserved for complicated body cavity and connective tissue infections • May cause drug-induced seizure activityimipenem-cilastatin (Primaxin)• Used for treatment of bone, joint, skin, and soft tissue infections; many other uses Mosby items and derived items 2005, 2002 by Mosby, Inc. 37
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aztreonam (Azactam) • erythromycin (E-mycin, E.E.S, others) • azithromycin (Zithromax) • Primarily active against aerobic gram- • clarithromycin (Biaxin) negative bacteria (E. coli, Klebsiella, Pseudomonas) • Bactericidal• Used for severe systemic infections and UTIs Mosby items and derived items 2005, 2002 by Mosby, Inc. 39
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Mechanism of Action • Prevent protein synthesis within bacterial cells • Bacteria will eventually die Mosby items and derived items 2005, 2002 by Mosby, Inc. 41
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Macrolides: Indications Macrolides: Side Effects • Strep infections – Streptococcus pyogenes GI effects, primarily with erythromycin (group A beta-hemolytic streptococci) • nausea, vomiting, diarrhea, hepatotoxicity, • Mild to moderate URI flatulence, jaundice, anorexia – Haemophilus influenzae • Newer agents, azithromycin and clarithromycin: fewer side effects, longer • Spirochetal infections duration of action, better efficacy, better – Syphilis and Lyme disease tissue penetration • Gonorrhea, Chlamydia, Mycoplasma Mosby items and derived items 2005, 2002 by Mosby, Inc. 43
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Tetracyclines (cont'd) • Broad-spectrum • Bind to Ca2+ and Mg2 + and Al3 + ions • Obtained from cultures of Streptomyces to form insoluble complexes • Bacteriostatic—inhibit bacterial growth • Thus, dairy products, antacids, and iron • protein synthesis inhibitor salts reduce absorption of tetracyclines • Stop many essential functions of the Mosby items and derived items 2005, 2002 by Mosby, Inc. 45
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• demeclocycline (Declomycin) • Wide spectrum • oxytetracycline – Gram-negative, gram-positive, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease • doxycycline (Doryx, Vibramycin) • demeclocycline is also used to treat SIADH, and pleural and pericardial effusions Mosby items and derived items 2005, 2002 by Mosby, Inc. 47
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Tetracyclines: Side Effects Strong affinity for • Discoloration of permanent teeth and tooth enamel in fetuses and children • May retard fetal skeletal development if taken during pregnancy Mosby items and derived items 2005, 2002 by Mosby, Inc. 49
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Tetracyclines: Side Effects Tetracyclines: Side Effects Alteration in intestinal flora may result in: • Superinfection (overgrowth of nonsusceptible • Vaginal moniliasis organisms such as Candida) • Gastric upset • Enterocolitis• Maculopapular rash • Pseudomembranous colitis Mosby items and derived items 2005, 2002 by Mosby, Inc. 51
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• gentamicin (Garamycin)• kanamycin• neomycin• streptomycin• tobramycin• amikacin (Amikin)• netilmicin Table 37-10 Available aminoglycoside antibiotics Mosby items and derived items 2005, 2002 by Mosby, Inc. 53
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• Natural and semisynthetic • Used to kill gram-negative bacteria such • Produced from Streptomyces as Pseudomonas spp., E. coli, Proteus • Poor oral absorption; no PO forms spp., Klebsiella spp., Serratia spp.
• Very potent antibiotics with serious • Often used in combination with other antibiotics for synergistic effect • Bactericidal; prevents protein synthesis• Kill mostly gram-negative; some gram-positive also Mosby items and derived items 2005, 2002 by Mosby, Inc. 55
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Aminoglycosides: Indications (cont'd) • All aminoglycosides are poorly absorbed through the GI tract, and given parenterally • Exception: neomycin – Given orally to decontaminate the GI tract before surgical procedures – Also used as an enema for this purpose Mosby items and derived items 2005, 2002 by Mosby, Inc. 57
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Aminoglycosides: Agents Aminoglycosides: Side Effects • Ototoxicity and nephrotoxicity are the • Three most common (systemic): gentamicin, tobramycin, amikacin • Cause serious toxicities – Nephrotoxicity (renal failure) – Neuromuscular blockade – Ototoxicity (auditory impairment and vestibular [eighth cranial nerve]) • Must monitor drug levels to prevent Mosby items and derived items 2005, 2002 by Mosby, Inc. 59
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• ciprofloxacin (Cipro) • Excellent oral absorption • lomefloxacin (Maxaquin) • Absorption reduced by antacids • norfloxacin (Noroxin) • First oral antibiotics effective against • ofloxacin (Floxin) gram-negative bacteria • levofloxacin (Levaquin)• gatifloxacin (Tequin) Mosby items and derived items 2005, 2002 by Mosby, Inc. 61
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Quinolones: Indications Mechanism of Action • Lower respiratory tract infections • Effective against gram-negative • Bone and joint infections organisms and some gram-positive • Infectious diarrhea • Urinary tract infections • Alter DNA of bacteria, causing death • Skin infections • Do not affect human DNA • Sexually transmitted diseases• Anthrax Mosby items and derived items 2005, 2002 by Mosby, Inc. 63
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Quinolones: Side Effects Quinolones: Side Effects (cont'd) Headache, dizziness, Rash, pruritus, urticaria, fatigue, depression, flushing, photosensitivity (with lomefloxacin) Nausea, vomiting, diarrhea, constipation, Fever, chills, blurred thrush, increased liver Mosby items and derived items 2005, 2002 by Mosby, Inc. 65
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Other Antibiotics Other Antibiotics (cont'd) • clindamycin (Cleocin) – Natural, bactericidal antibiotic • linezolid (Zyvox) – Destroys cell wall • metronidazole (Flagyl) – Treatment of choice for MRSA, and other gram-positive infections • nitrofurantoin (Macrodantin) – Must monitor blood levels to ensure • quinupristin and dalfopristin (Synercid) therapeutic levels and prevent toxicity – May cause ototoxicity and nephrotoxicity Mosby items and derived items 2005, 2002 by Mosby, Inc. 67
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Other Antibiotics Antibiotics: Nursing Implications • vancomycin (cont'd) • Before beginning therapy, assess drug – Should be infused over 60 minutes allergies; hepatic, liver, and cardiac function; – Monitor IV site closely and other lab studies – Redman's syndrome may occur • Be sure to obtain thorough patient health • Decreased BP, flushing of neck and face history, including immune status • Antihistamine may be ordered to reduce these • Assess for conditions that may be contraindications to antibiotic use or that may – Ensure adequate hydration (2 L fluids/24 indicate cautious use hr) if not contraindicated to prevent • Assess for potential drug interactions Mosby items and derived items 2005, 2002 by Mosby, Inc. 69
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Nursing Implications Nursing Implications • Patients should be instructed to take It is ESSENTIAL to obtain cultures from antibiotics exactly as prescribed and for the length of time prescribed; they should not appropriate sites BEFORE beginning stop taking the medication early when they antibiotic therapy • Assess for signs and symptoms of superinfection: fever, perineal itching, cough, lethargy, or any unusual discharge Mosby items and derived items 2005, 2002 by Mosby, Inc. 71
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Nursing Implications Nursing Implications For safety reasons, check the name of the • Each class of antibiotics has specific side medication carefully because there are effects and drug interactions that must be many agents that sound alike or have carefully assessed and monitored similar spellings • The most common side 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 Mosby items and derived items 2005, 2002 by Mosby, Inc. 73
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Nursing Implications Nursing Implications • Should be taken with at least 2000 mL of fluid • Any patient taking a penicillin should be per day, unless contraindicated carefully monitored for an allergic reaction for • Due to photosensitivity, avoid sunlight and at least 30 minutes after its administration • The effectiveness of oral penicillins is • These agents reduce the effectiveness of decreased when taken with caffeine, citrus oral contraceptives fruit, cola beverages, fruit juices, or tomato • Oral forms should be taken with food or milk to reduce GI upset Mosby items and derived items 2005, 2002 by Mosby, Inc. 75
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Nursing Implications Nursing Implications • Orally administered forms should be given • These agents are highly protein-bound and with food to decrease GI upset, even though will cause severe interactions with other this will delay absorption protein-bound drugs • Some of these agents may cause a disulfiram • The absorption of oral erythromycin is (Antabuse)-like reaction when taken with enhanced when taken on an empty stomach, but because of the high incidence of GI upset, many agents are taken after a meal or snack Mosby items and derived items 2005, 2002 by Mosby, Inc. 77
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Nursing Implications Nursing Implications • Milk products, iron preparations, antacids, • Monitor peak and trough blood levels of these and other dairy products should be avoided agents to prevent nephrotoxicity and because of the chelation and drug-binding • Symptoms of ototoxicity include dizziness, • All medications should be taken with 6 to 8 tinnitus, and hearing loss ounces of fluid, preferably water • Symptoms of nephrotoxicity include urinary • Due to photosensitivity, avoid sunlight and casts, proteinuria, and increased BUN and serum creatinine levels Mosby items and derived items 2005, 2002 by Mosby, Inc. 79
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Nursing Implications Nursing Implications Monitor for therapeutic effects • Should be taken with at least 3 L of fluid per • Improvement of signs and symptoms of day, unless otherwise specified • Intake of alkaline foods and drugs, such as • Return to normal vital signs antacids, dairy products, peanuts, and • Negative culture and sensitivity tests sodium bicarbonate should be limited • Disappearance of fever, lethargy, drainage, Monitor for adverse reactions Mosby items and derived items 2005, 2002 by Mosby, Inc. 81
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