Antimicrobial Drugs

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M34_ADAM9811_03_SE_CH34.QXD 12/30/09 1:16 PM Page 491 Chapter 34 <strong>Drugs</strong> for Bacterial Infections 491 Prototype Drug Therapeutic Class: Antibacterial ❘ Gentamicin (Garamycin, others) Pharmacologic Class: Aminoglycoside; protein synthesis inhibitor ACTIONS AND USES ADVERSE EFFECTS Gentamicin is a broad-spectrum, bacteriocidal antibiotic usually prescribed for serious urinary, respiratory, nervous, or GI infections when less toxic antibiotics are contraindicated. Activity includes Enterobacter, E. Coli, Klebsiella, Citrobacter, Pseudomonas, and Serratia. Gentamicin is effective against a few gram-positive bacteria, including some strains of methicillin-resistant Staphylococcus aureus (MRSA). It is often used in combination with other antibiotics. A topical formulation (Genoptic) is available for infections of the external eye. ADMINISTRATION ALERTS ■ For IM administration, give deep into a large muscle. ■ Use only IM and IV drug solutions that are clear and colorless or slightly yellow. Discard discolored solutions or those that contain particulate matter. ■ Withhold the drug if the peak serum level lies above the normal range of 5–10 mcg/mL. ■ Pregnancy category C PHARMACOKINETICS Onset: Rapid Peak: 1–2 h Half-life: 3–4 h Duration: 8–12 h Rash, nausea, vomiting, and fatigue are the most frequent adverse effects. As with other aminoglycosides, certain adverse effects may be severe. Ototoxicity can produce a loss of hearing or balance, which may become permanent with continued use.Tinnitus, vertigo, and persistent headaches are early signs of ototoxicity.Nephrotoxicity is of particular concern to patients with pre-existing kidney impairment, and may limit pharmacotherapy. Signs of reduced kidney function include oliguria, proteinuria, and elevated BUN and creatinine levels. Resistance to gentamicin is increasing,and some cross resistance among aminoglycosides has been reported. Contraindications: Gentamicin is contraindicated in patients with hypersensitivity to drugs in the aminoglycoside class. Drug therapy must be monitored carefully in patients with impaired renal function, or those with pre-existing hearing loss. INTERACTIONS Drug–Drug: The risk of ototoxicity increases if the patient is currently taking amphotericin B, furosemide, aspirin, bumetanide, ethacrynic acid, cisplatin, or paromomycin. Concurrent use with amphotericin B, capreomycin, cisplatin, polymyxin B, or vancomycin increases the risk of nephrotoxicity. Lab Tests: Gentamicin may increase values of the following: serum bilirubin, serum creatinine, serum lactate dehydrogenase (LDH), BUN, AST, or ALT; may decrease values for the following: serum calcium, sodium, or potassium. Herbal/Food: Unknown Treatment of Overdose: There is no specific treatment for overdose. Refer to MyNursingKit for a Nursing Process Focus specific to this drug. The clinical applications of the aminoglycosides are limited by their potential to cause serious adverse effects. The degree and types of potential toxicity are similar for all drugs in this class. Of greatest concern are their effects on the inner ear and the kidneys. Damage to the inner ear, or ototoxicity, is recognized by hearing impairment, dizziness, loss of balance, persistent headache, and ringing in the ears. Because permanent deafness may occur, aminoglycosides are usually discontinued when symptoms of hearing impairment first appear. Aminoglycoside nephrotoxicity may be severe, affecting up to 26% of patients receiving these antibiotics. Nephrotoxicity is recognized by abnormal urinary function tests, such as elevated serum creatinine or BUN. Nephrotoxicity is usually reversible. See Nursing Process Focus: Patients Receiving Antibacterial Therapy on page 496 for the Nursing Process applied to all antibacterials. Fluoroquinolones Fluoroquinolones were once reserved only for UTIs because of their toxicity. Development of safer drugs in this class began in the late 1980s and has continued to the present day. Newer fluoroquinolones have a broad spectrum of activity and are used for a variety of infections. The fluoroquinolones are listed in Table 34.7. 34.13 Pharmacotherapy with Fluoroquinolones Although the first drug in this class, nalidixic acid (Neg- Gram), was approved by the FDA in 1962, it had a narrow spectrum of activity, and its use was restricted to UTIs. Nalidixic acid is still used for the pharmacotherapy of UTI, although it is not a preferred drug for this infection. Since then, four generations of fluoroquinolones have become available. All fluoroquinolones have activity against gramnegative pathogens; the newer ones are significantly more effective against gram-positive microbes, such as staphylococci, streptococci, and enterococci. The fluoroquinolones are bacteriocidal and affect DNA synthesis by inhibiting two bacterial enzymes: DNA gyrase and topoisomerase IV. These antibiotics are infrequently first-line drugs, although they are extensively used as alternatives to other antibiotics. Clinical applications include infections of the respiratory, GI, and genitourinary tracts, and some skin and soft-tissue infections. The most widely used drug in this class, ciprofloxacin (Cipro), is an agent of choice for the postexposure prophylaxis of Bacillus anthracis, the organism responsible for causing anthrax. Moxifloxacin (Avelox) is a newer drug that is highly effective against anaerobes. Recent studies suggest that some fluoroquinolones may be effective against M. tuberculosis. # 102887 Cust: PE/NJ/CHET Au: ADAMS Pg. No. 491 Title: Pharmacology for Nurses Server: Jobs2 C/M/Y/K Short / Normal DESIGN SERVICES OF S4CARLISLE Publishing Services
M34_ADAM9811_03_SE_CH34.QXD 12/30/09 1:16 PM Page 492 492 Unit 5 The Immune System TABLE 34. 7 Fluoroquinolones Drug Route and Adult Dose (max dose where indicated) Adverse Effects FIRST GENERATION cinoxacin (Cinobac) PO; 250–500 mg bid–qid Nausea, diarrhea, vomiting, rash, headache, nalidixic acid (NegGram) PO; Acute therapy: 1 g qid restlessness, pain and inflammation at injection site, local burning, stinging and corneal irritation PO; Chronic therapy: 500 mg qid (ophthalmic) SECOND GENERATION Anaphylaxis, tendon rupture, superinfections, ciprofloxacin (Cipro) PO; 250–750 mg bid photosensitivity, pseudomembranous colitis, seizure, peripheral neuropathy, hepatotoxicity norfloxacin (Noroxin) ofloxacin (Floxin) THIRD GENERATION PO; 400 mg bid or 800 mg once daily PO; 200–400 mg bid (max: 800 mg/day) gatifloxacin (Zymar) levofloxacin (Levaquin) FOURTH GENERATION Drops (0.3% ophthalmic solution); On days 1 and 2, one drop in each affected eye every 2 hours; on days 3–7, one drop in each affected eye up to four times/day PO; 250–500 mg/day (max: 750 mg/day) gemifloxacin (Factive) PO; 320 mg/day (max: 320 mg/day) moxifloxacin (Avelox) PO/IV; 400 mg/day (max: 400 mg/day) Italics indicate common adverse effects; underlining indicates serious adverse effects. A major advantage of the fluoroquinolones is that most are well absorbed orally and may be administered either once or twice a day. Although they may be taken with food, they should not be taken concurrently with multivitamins or mineral supplements because calcium, magnesium, iron, or zinc ions can reduce the absorption of some fluoroquinolones by as much as 90%. Fluoroquinolones are well tolerated by most patients, with nausea, vomiting, and diarrhea being the most common adverse effects. The most serious adverse effects are dysrhythmias (gatifloxacin and moxifloxacin) and potential hepatotoxicity. Central nervous system effects such as dizziness, headache, and sleep disturbances affect 1% to 8% of patients. Most recently, fluoroquinolones have been associated with an increased risk of tendonitis and tendon rupture, particularly of the Achilles tendon. The risk of tendon rupture is increased in patients over age 60 and those receiving concurrent corticosteroids. Because animal studies have suggested that fluoroquinolones affect cartilage development, these drugs are not approved for children under age 18. Use in pregnancy or in lactating patients should be avoided. See Nursing Process Focus: Patients Receiving Antibacterial Therapy on page 496 for the Nursing Process applied to all antibacterials. Sulfonamides Sulfonamides are older drugs that have been prescribed for a variety of infections over the past 70 years. Although their use has declined, sulfonamides are still useful in treating susceptible UTIs. The sulfonamides are listed in Table 34.8. 34.14 Pharmacotherapy with Sulfonamides The discovery of the sulfonamides in the 1930s heralded a new era in the treatment of infectious disease.With their wide spectrum of activity against both gram-positive and gramnegative bacteria, the sulfonamides significantly reduced mortality from susceptible microbes and earned their discoverer a Nobel Prize in Medicine. Sulfonamides are bacteriostatic and active against a broad spectrum of microorganisms. Sulfonamides suppress bacterial growth by inhibiting the synthesis of folic acid, or folate. These drugs are sometimes referred to as folic acid inhibitors. In human physiology, folic acid is a B-complex vitamin that is essential during periods of rapid growth, especially during childhood and pregnancy. Bacteria also require this substance during periods of rapid cell division and growth. Although initially very effective, several factors led to a significant decline in the use of sulfonamides. Their widespread availability for over 60 years resulted in a substantial number of resistant strains. The discovery of the penicillins, cephalosporins, and macrolides gave physicians larger choices of safer agents. Approval of the combination antibiotic sulfamethoxazole–trimethoprim (Bactrim, Septra, TMP-SMZ) marked a resurgence in the use of sulfonamides in treating UTIs. In communities with high resistance rates, however, TMP-SMZ is no longer a drug of first choice, unless C&S testing determines it to be the most effective drug for the specific pathogen. Sulfonamides are also prescribed for the treatment of Pneumocystis carinii pneumonia and shigella infections of the small bowel. Sulfasalazine (Azulfidine) is a # 102887 Cust: PE/NJ/CHET Au: ADAMS Pg. No. 492 Title: Pharmacology for Nurses Server: Jobs2 C/M/Y/K Short / Normal DESIGN SERVICES OF S4CARLISLE Publishing Services
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Antimicrobial Drugs

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