Miscellaneous antibacterial drugs: fluoroquinolones, metronidazole, daptomycin, rifampin, rifaximin, bacitracin, and polymyxins

CHAPTER 91


Miscellaneous antibacterial drugs: fluoroquinolones, metronidazole, daptomycin, rifampin, rifaximin, bacitracin, and polymyxins




Fluoroquinolones


The fluoroquinolones are fluorinated analogs of nalidixic acid, a narrow-spectrum quinolone antibiotic used only for urinary tract infections (UTIs). However, unlike nalidixic acid, the fluoroquinolones are broad-spectrum agents that have multiple applications. Benefits derive from disrupting DNA replication and cell division. Fluoroquinolones do not disrupt synthesis of proteins or the cell wall. All of the systemic fluoroquinolones can be administered orally. As a result, these drugs are attractive alternatives for people who might otherwise require intravenous antibacterial therapy. Although side effects are generally mild, all fluoroquinolones can cause tendinitis and tendon rupture, usually of the Achilles tendon. Fortunately, the risk is low. Bacterial resistance develops slowly, but has become common in Neisseria gonorrhoeae, and hence these drugs are no longer recommended for this infection. Six fluoroquinolones are currently available for systemic therapy. Six others—gatifloxacin, enoxacin, lomefloxacin, sparfloxacin, trovafloxacin, and alatrofloxacin—were withdrawn in recent years. Fluoroquinolones used solely for topical treatment of the eye are listed in Table 104–7, Chapter 104.



Ciprofloxacin


Ciprofloxacin [Cipro, Proquin XR] was among the first fluoroquinolones available and will serve as our prototype for the group. The drug is active against a broad spectrum of bacterial pathogens, and may be administered PO or IV. Ciprofloxacin has been used as an alternative to parenteral antibiotics for treatment of several serious infections. Because it can be administered by mouth, patients receiving ciprofloxacin can be treated at home, rather than going to the hospital for IV antibacterial therapy.



Mechanism of action

Ciprofloxacin inhibits two bacterial enzymes: DNA gyrase and topoisomerase IV. Both are needed for DNA replication and cell division. DNA gyrase converts closed circular DNA into a supercoiled configuration. In the absence of supercoiling, DNA replication cannot take place. Topoisomerase IV helps separate daughter DNA strands during cell division. Since the mammalian equivalents of DNA gyrase and topoisomerase IV are largely insensitive to fluoroquinolones, cells of the host are spared. Ciprofloxacin is rapidly bactericidal.











Therapeutic uses

Ciprofloxacin is approved for a wide variety of infections. Among these are infections of the respiratory tract, urinary tract, GI tract, bones, joints, skin, and soft tissues. Also, ciprofloxacin is a preferred drug for preventing anthrax in people who have inhaled anthrax spores. Because ciprofloxacin is active against a variety of pathogens and can be given orally, the drug represents an alternative to parenteral treatment for many serious infections. Owing to high rates of resistance, ciprofloxacin is a poor choice for staphylococcal infections. The drug is not useful against infections caused by anaerobes.


Because of concerns about tendon injury (see below), systemic ciprofloxacin is generally avoided in children under 18 years old. Nonetheless, the drug does have two approved pediatric uses: (1) treatment of complicated urinary tract and kidney infections caused by E. coli, and (2) postexposure treatment of inhalational anthrax. Ciprofloxacin is the only systemic fluoroquinolone approved for pediatric use.



Adverse effects

Ciprofloxacin can induce a variety of mild adverse effects, including GI reactions (nausea, vomiting, diarrhea, abdominal pain) and central nervous system (CNS) effects (dizziness, headache, restlessness, confusion). Candida infections of the pharynx and vagina may develop during treatment. Very rarely, seizures have occurred. In the elderly, ciprofloxacin poses a significant risk of confusion, somnolence, psychosis, and visual disturbances.


Rarely, ciprofloxacin and other fluoroquinolones have caused tendon rupture, usually of the Achilles tendon. The incidence is 1 in 10,000 or less. People at highest risk are those 60 and older, those taking glucocorticoids, and those who have undergone heart, lung, or kidney transplantation. How do fluoroquinolones damage tendons? When given to immature animals, fluoroquinolones disrupt the extracellular matrix of cartilage. A similar mechanism may underlie tendon rupture in humans. Since tendon injury is reversible if diagnosed early, fluoroquinolones should be discontinued at the first sign of tendon pain, swelling, or inflammation. In addition, patients should refrain from exercise until tendinitis has been ruled out. Although there are no controlled studies on the use of ciprofloxacin during pregnancy or lactation, available data indicate that such use poses little or no risk of tendon damage to either the fetus or nursing infant.


Ciprofloxacin and other fluoroquinolones pose a risk of phototoxicity (severe sunburn), characterized by burning, erythema, exudation, vesicles, blistering, and edema. These can occur following exposure to direct sunlight, indirect sunlight, and sunlamps—even if a sunscreen has been applied. Patients should be warned about phototoxicity and advised to avoid sunlight and sunlamps. People who must go outdoors should wear protective clothing and apply a sunscreen. Ciprofloxacin should be withdrawn at the first sign of a phototoxic reaction (eg, burning sensation, redness, rash).


Ciprofloxacin and other fluoroquinolones increase the risk of developing Clostridium difficile infection (CDI), a potentially severe infection of the bowel. CDI results from killing off intestinal bacteria that normally keep C. difficile in check.


Ciprofloxacin and other fluoroquinolones can exacerbate muscle weakness in patients with myasthenia gravis. Accordingly, patients with a history of myasthenia gravis should not receive these drugs.



Drug and food interactions



Elevation of drug levels.

Ciprofloxacin can increase plasma levels of several drugs, including theophylline (used for asthma), warfarin (an anticoagulant), and tinidazole (an antifungal drug). Toxicity could result. For patients taking theophylline, drug levels should be monitored and the dosage adjusted accordingly. For patients taking warfarin, prothrombin time should be monitored and the dosage of warfarin reduced as appropriate.







Preparations, dosage, and administration




Dosage and administration. 






Other systemic fluoroquinolones



Ofloxacin



Basic pharmacology.


Ofloxacin [Floxin] is similar to ciprofloxacin in mechanism of action, antimicrobial spectrum, therapeutic applications, and adverse effects. Like ciprofloxacin, the drug may be administered PO or IV. Bioavailability is high (90%) in the absence of food, and greatly reduced in the presence of food. Ofloxacin is widely distributed to tissues and excreted in the urine. Like ciprofloxacin, ofloxacin can cause a variety of mild adverse effects, including nausea, vomiting, headache, and dizziness. In addition, ofloxacin may intensify sensitivity to sunlight, thereby increasing the risk of severe sunburn. Like other fluoroquinolones, ofloxacin can (1) exacerbate muscle weakness in patients with myasthenia gravis, (2) increase the risk of CDI, and (3) cause tendinitis and tendon rupture, especially among those over age 60, those taking glucocorticoids, and those who have undergone a heart, lung, or kidney transplantation. Ofloxacin elevates plasma levels of warfarin, but, in contrast to ciprofloxacin, has little effect on levels of theophylline. Absorption of oral ofloxacin is reduced by cationic substances: milk, milk products, sucralfate, iron and zinc salts, and magnesium- and aluminum-containing antacids.




Moxifloxacin



Basic pharmacology.


Moxifloxacin [Avelox] is a broad-spectrum fluoroquinolone indicated for respiratory tract infections (community-acquired pneumonia [CAP], acute sinusitis, acute exacerbations of chronic bronchitis), intra-abdominal infections, and infections of the skin and skin structures. Administration is oral or IV. The drug is well absorbed from the GI tract, undergoes wide distribution, and is eliminated by hepatic metabolism and renal excretion. Side effects are generally mild, the most common being nausea, vomiting, diarrhea, stomach pain, dizziness, and altered sense of taste. Like other fluoroquinolones, moxifloxacin can promote development of CDI, exacerbate muscle weakness in patients with myasthenia gravis, and cause tendinitis and tendon rupture. The drug may also pose a risk of phototoxicity. Moxifloxacin does not increase levels of warfarin or digoxin, but does prolong the QT interval, and hence may pose a risk of serious dysrhythmias. Accordingly, the drug should be used with great caution, if at all, in patients taking prodysrhythmic drugs or in those with hypokalemia or pre-existing QT prolongation.




Norfloxacin


Norfloxacin [Noroxin] is a fluoroquinolone antibiotic with an antimicrobial spectrum like that of ciprofloxacin. The drug is used for oral therapy of UTIs and prostatitis.




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Jul 24, 2016 | Posted by in NURSING | Comments Off on Miscellaneous antibacterial drugs: fluoroquinolones, metronidazole, daptomycin, rifampin, rifaximin, bacitracin, and polymyxins

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