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Antibiotics: Part 1 (Chapter 38)
A. Antibiotics: Overview a. Medications used to treat bacterial infections b. Ideally, before beginning antibiotic therapy, the suspected areas of infection should be cultured to identify the causative organism and potential antibiotic susceptibilities c. Antibiotic therapy begins with a clinical assessment of the patient to determine common signs and symptoms of infection (fever, chills, sweats, redness, pain, swelling, fatigue, weight loss, increased WBC, pus) B. Antibiotics: Therapy a. Empiric therapy à treatment of an infection before specific culture information has been reported or obtained b. Prophylactic therapy à treatment with antibiotics to prevent an infection, as in intraabdominal surgery i. To be effective, prophylactic antibiotics need to be give n before the procedure, generally 30 minutes before the incision to ensure adequate tissue penetration c. Therapeutic response à decrease in specific signs and symptoms of infection compared with the baseline findings (fever, elevated WBC count, redness, inflammation, drainage, pus) d. Sub-therapeutic response à signs and symptoms do not improve e. Superinfection à occur when antibiotics reduce or completely eliminate the normal bacterial flora i. Examples: vaginal yeast infections and C. diff f. Antibiotic resistance à when many easily treatable bacterial infections become resistant to antibiotic therapy i. May be caused by the overprescribing of antibiotics and/or tendency of a patient to not complete antibiotic regimen g. Host factors à factors that pertain specifically to a given patient. Important on the success or failure of antibiotic therapy i. Age, allergy history, kidney and liver function (aging decreases this), pregnancy status, genetic characteristic, site of infection, and host defenses h. Genetic host factors à i. G6PD deficiency
- Administration of antibiotics such as sulfonamides may result in the destruction of RBCs ii. Slow acetylator metabolic status
- Cause certain drugs to be metabolized more slowly leading to toxicity from drug accumulation i. Allergic Reactions à
i. Symptoms of anaphylaxis include flushing, itching, hives, anxiety, fast irregular pulse, throat/tongue swelling ii. Many patients will say that they are “allergic” to a med when they experienced common side effect such as stomach upset or nausea C. Antibiotics: Mechanism of Action a. 1) interference with bacterial cell wall synthesis b. 2) interference with protein synthesis c. 3) interference with replication of nucleic acids (DNA/RNA) d. 4) antimetabolite action that disrupts critical metabolic reactions inside the bacterial cell e. Bactericidal: kill bacteria f. Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately. Eventually leads to bacterial death
SULFONAMIDES
D. Sulfonamides: Overview a. Bacteriostatic (inhibit growth rather than kill bacteria) b. One of the first groups of antibiotics c. Includes: sulfadiazine, sulfamethoxazole, sulfisoxazole E. Mechanism of Action and Drug Effects a. Inhibit the growth of susceptible bacteria by preventing bacterial synthesis of folic acid b. Compete with PABA for the bacterial enzyme tetrahydropteroic acid synthetase c. Considered antimetabolites because they are capable of blocking a specific step in a biosynthetic pathway d. These drugs do not affect folic acid metabolism in human cells F. Indications a. Used against both gram-positive and gram-negative organisms b. Achieve very high concentrations in the kidneys c. Treatment of UTIs caused by susceptible strains of: i. Enterobacter spp., E. coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, S. aureus d. Pneumocystis carinii pneumonia (PCP) e. Upper respiratory tract and pharynx infections f. Prophylaxis and treatment of opportunistic infections in patients with HIV, especially Pneumocystis jirovecii G. Indications: Combination Products a. Sulfamethoxazole/trimethoprim (Bactrim, Septra) à i. Commonly used in clinical settings ii. Used to treat UTIs, PCP, otitis media, Stenotrophomonas
b. Most commonly destroyed by penicillins are gram-positive bacteria, including Streptococcus spp., Enterococcus spp., and Staphylococcus spp. c. Extended-spectrum à used to treat pneumonia, intraabdominal infections, and sepsis d. Limited bactericidal action against gram-negative bacteria Q. Contraindications a. KDA b. Small incidence of cross-reactivity between cephalosporins and penicillins R. Interactions a. Aminoglycosides (IV) and clavulanic acid b. Methotrexate c. NSAIDs d. Oral contraceptives e. Probenecid f. Rifampin g. Warfarin S. Adverse Effects a. Most common adverse effects involve GI system (N/V/D, abdominal pain) b. Less common adverse effects à Stevens Johnson, exfoliative dermatitis, eosinophilia c. Central nervous à lethargy, anxiety, depression, seizures d. GI à N/V/D, taste alterations, oral candidiasis e. Hematologic à anemia, bone marrow depression, granulocytopenia f. Metabolic à hyperkalemia, hypernatremia, alkalosis g. Skin à pruritus, hives, rash h. Doses must be adjusted for patients with renal dysfunction due to IV forms containing large amounts of sodium and/or potassium i. Allergic reactions à urticaria, pruritus, angioedema T. Natural Penicillins a. Penicillin G i. Benzathine (Bicillin L) – IM only (thick, white, paste-like material)
- Tx of syphilis ii. Potassium (Pfizerpen) – IV only b. Penicillin V i. Potassium (Pen VK) – PO only ii. Used primarily for infection with gram-positive organisms such as Streptococcus U. Penicillinase-Resistant Penicillins a. Resist breakdown by the penicillin-destroying enzyme (penicillinase) commonly produced by bacteria such as staphylococci b. Referred as “anti-staphylococcal penicillins” c. nafcillin (Nallpen, Unipen) i. only available in injectable form
ii. used for infection with penicillinase-producing staphylococci V. Aminopenicillins a. Amoxicillin i. Used to treat infections caused by susceptible organisms in the ears, nose, throat, GU tract, skin, and skin structures ii. Indications: otitis media, sinusitis, various susceptible respiratory, skin, and urinary tract infections, dental prophylaxis for bacterial endocarditis, H. pylori iii. PO form only iv. Can be given with or without food b. Ampicillin i. Available in three different salt forms: anhydrous, trihydrate, and sodium ii. Anhydrous and trihydrate are given PO iii. Sodium is given parenterally iv. Used for: primary infection with gram-negative organisms such as Shigella, Salmonella, Escherichia; Haemophilus, Proteus, and Neisseria spp.; infection with some gram-positive organisms W. Extended-spectrum penicillins a. Piperacillin b. Ticarcillin (Ticar) c. Carbenicillin (Geocillin)
CEPHALOSPORINS
A. Beta-lactam antibiotic B. Semi-synthetic antibiotics that are structurally and pharmacologically related to the penicillins C. Bactericidal and work by interfering with bacterial cell wall synthesis D. Also bind to the same penicillin-binding proteins inside the bacteria E. Can destroy a broad spectrum of bacteria. Active against gram-positive, gram- negative, and anaerobic bacteria. Not active against fungi, viruses, or enterococci F. Level of gram-negative coverage increased with each successive generation G. Contraindications: KDA and allergy to penicillins H. Interactions: alcohol, antacids, iron, probenecid, oral contraceptives I. Adverse effects a. Mild diarrhea, abdominal cramps, rash, pruritus, redness, and edema b. Cross-reactivity between cephalosporins and penicillins J. First generation: Active against gram-positive bacteria, limited activity against gram-negative bacteria. Used for surgical prophylaxis, URIs, otitis media a. Cephalexin (Keflex)
MACROLIDES
A. Bacteriostatic B. Mechanism of action and drug effects: a. Inhibit protein synthesis by binding reversibly to the 50S ribosomal subunits of susceptible microorganisms. Bacteria will eventually die b. Effective in tx of upper and lower respiratory tract, skin, and soft tissue infections; spirochetal infections such as syphilis and Lyme disease; gonorrhea; Chlamydia, Mycoplasma, and Corynebacterium infections C. Indications a. Infections caused by Strep, mild to moderate upper and lower RTIs, syphilis, Lyme disease, Chlamydia and Mycoplasma infections b. Therapeutic effect of erythromycin: ability to irritate the GI tract, stimulating smooth muscle and GI motility (Beneficial to diabetic gastroparesis) c. Azithromycin and clarithromycin: prevention and Tx of MAC complex infections in patients with HIV/AIDS d. Treatment of H. pylori D. Contraindications: KDA E. Adverse effects: a. Cardiovascular à palpitations, chest pain, QT prolongation b. CNS à headache, dizziness, vertigo c. GI à N/V/D, hepatotoxicity, heartburn, flatulence, cholestasis jaundice, anorexia, abnormal taste d. Integumentary à rash, urticaria, phlebitis at IV site e. Other à hearing loss, tinnitus f. Erythromycin causes more GI-related adverse effects than azithromycin and clarithromycin (N/V/D, hepatotoxicity, flatulence, jaundice, anorexia) F. Interactions: a. Drugs with cytochrome P-450 complex such as carbamazepine, cyclosporine, theophylline, warfarin b. Reduce efficacy of oral contraceptives c. Moxifloxacin, pimozide, thiroidazine, and other drugs that prolong the QT interval causing malignant dysrhythmias G. Types: a. Erythromycin i. Oral, IV, topical, ophthalmic forms ii. Indications: infections of respiratory and GI tracts and skin caused by various gram-positive, gram-negative, and miscellaneous organisms iii. Absorption of oral form is enhanced if taken on empty stomach, but because of high incidence of stomach irritation, oral form is taken with a meal or snack
iv. Strong inhibitor of cytochrome P450 enzymes – many drug interactions because of this b. Azithromycin and Clarithromycin i. Better adverse-effect profiles, including less GI tract irritation, and more favorable pharmacokinetic properties compared to erythromycin ii. Used to treat upper and lower RTIs, skin structure infections iii. Azithromycin à
- oral and injectable
- long duration of action, dosed once daily taking the drug with food decreased both the rate and extent of GI absorption
TETRACYCLINES
A. Bacteriostatic drugs that inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome. Stop many essential functions of the bacteria B. Co-administration with milk, antacids, or iron salts causes a considerable reduction in the oral absorption of the tetracycline (binds to Ca, Mg, and Al ions to form insoluble complexes) C. Not to be used to patients younger than 8 years of age, pregnant women, and nursing mothers because of strong affinity for calcium resulting in tooth discoloration D. Mechanism of Action and Drug Effects a. Inhibit protein synthesis in susceptible bacteria b. Inhibit the growth of and kill a very wide range of Rickettsia, Chlamydia, and Mycoplasma organisms, as well as gram-negative and gram-positive c. Useful in the Tx of spirochetal infections (syphilis and Lime disease), pelvic inflammatory disease E. Indications a. Inhibit the growth of many gram-negative and gram-positive organisms, protozoans, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease b. Used to treat acne F. Contraindications a. KDA b. Must be avoided in pregnant and nursing women and in children younger than 8 years of age G. Adverse effects a. Discoloration of the permanent teeth b. Tooth enamel hypoplasia in fetuses and children c. Possibly retard fetal skeletal development if taken during pregnancy d. Photosensitivity e. Alteration of intestinal and vaginal flora (resulting in Candida, diarrhea, C. diff)
- Some penicillin preps can lead to exacerbation of these problems (hypernatremia or hyperkalemia) g. For cephalosporins: i. Assess allergies, including penicillin allergies h. For carbapenems: i. Assess history of seizure activity i. For macrolides: i. Assessment of baseline cardiac function, hearing status, liver function j. For tetracyclines: i. Assess for any whitish sore patches on the oral mucosa, vaginal itching ii. Use of antacids, antidiarrheal drugs, dairy products, calcium, enteral feedings, and iron preparation may reduce absorption iii. May decrease effectiveness of oral contraceptives B. Implementation a. Oral antibiotics are not to be given at the same time as antacids, calcium supplements, iron products, laxatives containing magnesium, or some of the antilipemic drugs b. Monitor for allergic reactions. Immediate reactions may not occur for up to 30 minutes, accelerated reactions may occur within 1 to 72 hours, and delayed reactions may occur after 72 hours i. Wheezing, SOB, swelling of the face/tongue/hands, itching, rash ii. If hypersensitivity occurs, first thing to do is stop the dosage form immediately, contact the prescriber, and monitor the patient c. Sulfonamides: i. Need to be avoided in patients with G6PD and slow acetylation ii. Encourage an increase in fluids (2000 to 3000 mL/24 hr) iii. Oral dosage forms are to be taken with food to minimize GI upset iv. Avoid sunlight and tanning beds v. Reduce effectiveness of oral contraceptives d. Penicillins: i. C. diff may overgrow ii. Advise patients to take oral penicillins with at least 6 ounces of water (not juices);
- Fruit juices, caffeine, cola beverages, and tomato juice may nullify the drug’s antibacterial action iii. Penicillin V, amoxicillin, and amoxicillin/clavulanate are given with water and 1 hour before or 2 hours after meals to maximize absorption; however, theses meds need to be taken with a snack or meal to avoid GI upset iv. Procaine and benzathine salt penicillins are thick solutions; give them IM, using at least a 21-gauge needle v. Reconstitute IM imipenem/cilastin in sterile saline with plain lidocaine
vi. If the patient experiences an anaphylactic reaction, give epi. Have support equipment available at all times e. Cephalosporins: i. May be given with food to decrease GI upset ii. Alcohol and alcohol-containing products are to be avoided (can cause acute alcohol tolerance) f. Macrolides: i. Are not to be given with or immediately before or after fruit juices to avoid interaction with the drug ii. Highly protein-bound and will cause severe interactions with other protein-bound drugs iii. Absorption of oral erythromycin is enhanced when taken on an empty stomach, but because of GI upset, many agents are taken after a meal or snack g. Tetracyclines: i. Causes photosensitivity à avoid sun exposure and tanning bed use ii. Encourage patient to take oral doses with at least 8 ounces of fluids and foods to minimize GI upset iii. Do not take with calcium, mag, or iron iv. Take interacting foods and drugs (dairy products, antacids, iron) 2 hours before or 3 hours after to avoid interaction
Antibiotics: Part 2 (Chapter 39)
A. Aminoglycosides: Overview a. Natural and semisynthetic antibiotics that are classified as bactericidal drugs b. Potent antibiotics, so the drug of choice for the treatment of particularly virulent infections c. Not given orally because of their poor oral absorption (except for neomycin) d. Serum levels of these drugs are routinely monitored in patient’s blood samples i. Trough levels above 2 mcg/mL are associated with a greater risk for both ototoxicity and nephrotoxicity ii. Trough levels are normally monitored initially, and then once every 5 to 7 days until drug therapy is discontinued iii. Patient’s serum creatinine level is measured at least every 3 days iv. Desirable to keep gentamicin and tobramycin trough levels below 2 e. Associated with nephrotoxicity and ototoxicity f. Produced from Streptomyces g. Prevents protein synthesis
i. Uses: pre-op bowel cleansing, hepatic encephalopathy ii. Commonly used for bacterial decontamination of the GI tract before surgical procedures iii. Skin infections, bladder irrigation, treatment of E. coli diarrhea, hepatic encephalopathy, eye infections iv. Not available in injectable forms. Available in tablets, solutions, and powders
QUINOLONES
A. Overview a. Very potent bactericidal broad-spectrum antibiotic b. Excellent oral absorption c. Absorption reduced by antacids d. First oral antibiotic effective against gram-negative bacteria B. Mechanism of Action a. Destroy bacteria by altering their DNA b. Interferes with the bacterial enzymes DNA gyrase and topoisomerase IV c. Do not inhibit the production of human DNA d. Kill susceptible strains of mostly gram-negative and some gram-positive organisms C. Indications a. Most are excreted by the kidneys which makes them suitable for treating complicated UTIs b. Also used to treat respiratory, skin, GI, and bone/joint infections c. Infectious diarrhea d. STDs e. Anthrax D. Contraindications a. KDA E. Adverse Effects a. CNS à headache, dizziness, insomnia, depression, restlessness, convulsions, neuropathy, seizures have been reported b. GI à Nausea, constipation, increased AST and ALT levels, flatulence, heartburn, vomiting, diarrhea, coral candidiasis, dysphagia c. Integumentary à rash, pruritus, urticaria, flushing d. Other à ruptured tendons and tendonitis, fever, chills, blurred vision, tinnitus e. Most worrisome is a cardiac effect that involved prolongation of the QT interval on the ECG f. Tendinitis and tendon rupture à more likely to occur in older adult patients, patients with renal failure, and those receiving concurrent glucocorticoid therapy
F. Interactions a. Antacids, calcium, mag, iron, zinc preparations, daily products, enteral tub feedings, or sucralfate à decreased absorption i. Patients need to take the interacting drugs at least 1 hour before or after G. Types a. Ciprofloxacin i. Uses: anthrax, RTIs, UTIs, prostate infections, skin infections, intraabdominal infections, GI infections, bone/joint infections, typhoid fever, health-care associated pneumonias ii. Injectable, ophthalmic, oral, otic iii. Excellent bioavailability so it can work orally as well as many IV forms iv. Capable of killing a wide range of gram-negative bacteria, as well as anaerobic bacterial and atypical organisms v. Drug of choice for anthrax
MISCELLANEOUS
A. Clindamycin a. Semisynthetic that can be either bactericidal or bacteriostatic b. Inhibits protein synthesis in bacteria c. Indicated for the treatment of chronic bone infections, GU tract infections, intraabdominal infections, anaerobic pneumonia, septicemia caused by staph and strep, and serious skin and soft-tissue infections caused by susceptible bacteria d. Contraindicated in patients with KDA, ulcerative colitis, or enteritis e. Adverse effects: GI tract such as N/V/D, abdominal pain, C. diff, anorexia f. C. diff often associated with clindamycin therapy B. Linezolid a. First drug in a class of antibiotics known as oxazolidinones b. Uses: VRE infections, skin and respiratory infections caused by Staph and Strep, MRSA c. Adverse effects: headache, N/V/D, decrease platelet count d. Excellent oral absorption – allows pts to continue oral therapy at home e. Interactions: Increase vasopressor effects of vasopressive drugs, SSRI antidepressants, tyramine-containing foods (aged cheese or wine, soy sauce, smoked meats or fish, sauerkraut. Can raise BP) C. Metronidazole a. Used against anaerobic organisms, to treat intraabdominal and gynecologic infections, treat protozoal infections such as amebiasis and trichomoniasis b. Used orally to treat antibiotic-associated colitis
iii. Assess LFTs d. With clindamycin: i. Not to be used in patients with UC or in those younger than 1 month of age ii. Perform a thorough assessment of GI disorders iii. Ventilator support is needed is patient is using neuromuscular blocking drugs e. With linezolid: i. Assess for use of SSRIs ii. Assess intake of tyramine-containing foods (aged cheese, wine, soy sauce, smoked fish, meat) à can raise BP f. With metronidazole: i. Inquire about alcohol intake g. With vancomycin: i. Assess Hx of preexisting renal disease or hearing loss ii. Trough levels will be drawn immediately before the next dose iii. Note color of patient’s skin iv. Assess BP for hypotension B. Implementation a. Encourage fluid intake up to 3000 mL/day b. Special considerations for gentamicin: 1) IM: give deeply and slowly into muscle mass 2) IV: give only clear or very slightly yellow solutions that have been diluted with either NS or D5W c. Instruct patient not to taken meds with antacids, iron, zinc preparations, multivitamins, or sucralfate à absorption decresed i. If patient needs to take Ca or Mag, instruct to take 1 hour before or after d. With clindamycin à oral form must be taken with 8 oz of water e. Clindamycin must never be given via IV push (too rapid an IV infusion can lead to severe hypotension and possible cardiac arrest) f. Linezolid à give with food or milk to decrease GI upset, protect IV forms from light, infuse over 30-120 mintues g. Metronidazole à give with food to decrease GI upset, avoid alcohol, intravaginal doses are given at bedtime h. Vanco à infuse over 60 minutes, adequate hydration to avoid nephrotoxicity (2L/day), trough levels need to be ordered prior to the third or fourth dose C. Patient Teaching a. Aminoglycosides i. Report any change in hearing ii. Increase fluids up to 3000 mL/day b. Quinolones i. Educate about photosensitivity à can cause burns or blisters. Avoid sun/UV rays/tanning beds. Wear sunglasses and sunscreen ii. Take Ca and Mag supplements at least 1 hours before or after quinolone
iii. Oral anticoagulants must be used with caution c. Clindamycin i. Do not engage in sexual intercourse when vaginal dosage forms are used d. Linezolid i. Avoid tyramine-containing foods e. Metronidazole i. Avoid alcohol and any alcohol containing products (cough preparations and elixirs) f. Vanco i. Report any changes in hearing, nausea, vomiting, unsteady gait, dizziness, generalized tingling, chills, fever, rash, hives ii. Monitor serum levels throughout therapy
