Pharmacokinetics

Clarithromycin and erythromycin are readily absorbed from the GI tract, mainly by the duodenum. Azithromycin is incompletely absorbed from the GI tract, and only 37% reaches systemic circulation. Azithromycin and erythromycin are available IV, but intermittent infusions should be diluted in normal saline (NS) or in 5% dextrose in water (D₅W) to prevent phlebitis or burning sensations at the injection site. Azithromycin 500 mg should be diluted in 250 to 500 mL of fluid, and erythromycin lactobionate 1 g should be diluted in 200 to 1000 mL. Macrolides are excreted in bile, feces, and urine. Because only a small amount is excreted in urine, renal insufficiency is not a contraindication for macrolide use.

Pharmacodynamics

Macrolides suppress bacterial protein synthesis. The onset of action of oral preparations of erythromycin is 1 hour, peak concentration time is 4 hours, and duration of action is 6 hours. Newer macrolides have a longer half-life and are administered less frequently. Clarithromycin (Biaxin) is administered twice a day, and Biaxin XL is administered once a day. Azithromycin (Zithromax) has up to a 40- to 68-hour half-life and is prescribed to be taken only once a day for 5 days.

Side Effects and Adverse Reactions

Side effects and adverse reactions to macrolides include GI disturbances such as nausea, vomiting, diarrhea, and abdominal cramping. Conjunctivitis may develop as a side effect of azithromycin. The patient should avoid wearing contact lenses if this occurs. Allergic reactions to erythromycin are rare. Hepatotoxicity (liver toxicity) can occur when erythromycin and azithromycin are taken in high doses with other hepatotoxic drugs, such as acetaminophen (high doses), phenothiazines, and sulfonamides. Liver damage is usually reversible when the drug is discontinued. Erythromycin should not be taken with clindamycin or lincomycin because they compete for receptor sites.

Drug Interactions

Macrolides can increase serum levels of theophylline (bronchodilator), carbamazepine (anticonvulsant), and warfarin (anticoagulant). If these drugs are given with macrolides, their drug serum levels should be closely monitored. To avoid severe toxic effects, erythromycin should not be used with other macrolides. Antacids may reduce zithromycin peak levels when taken at the same time.

Extended Macrolide Group

Derivatives of erythromycin have been effective in the treatment of numerous organisms. Like erythromycin, they inhibit protein synthesis. Many of these macrolides have a longer half-life and are administered once a day. The first extended macrolide group developed after the introduction of erythromycin was clarithromycin (Biaxin), which has been effective against many bacterial infections. Clarithromycin is administered twice a day and the XL formulation is given once a day. Another extended macrolide is azithromycin (Zithromax). This drug has a long half-life of up to 40 to 68 hours; therefore it is only prescribed once a day for 5 days.

Elimination of these drugs is via bile and feces. Azithromycin is frequently prescribed for upper and lower respiratory tract infections, STIs, and uncomplicated skin infections.

Side Effects and Adverse Reactions

Side effects and adverse reactions to clindamycin and lincomycin include GI irritation, which may manifest as nausea, vomiting, and stomatitis. Rash may also occur. Severe adverse reactions include colitis and anaphylactic shock.

Drug Interactions

Clindamycin and lincomycin are incompatible with aminophylline, phenytoin (Dilantin), barbiturates, and ampicillin.

Pharmacokinetics

Vancomycin is given orally for treatment of staphylococcal enterocolitis and antibiotic-associated pseudomembranous colitis due to Clostridium difficile. When vancomycin is given orally, it is not absorbed systemically and is excreted in the feces. Vancomycin is given IV for severe infections due to MRSA; septicemia; and bone, skin, and lower respiratory tract infections that do not respond or are resistant to other antibiotics. Intermittent vancomycin doses should be diluted in 100 mL for 500 mg and 200 mL for 1 g of D₅W, NS, or LR and administered at a rate of 10 mg/min or a minimum of 60 minutes. Vancomycin is excreted in the urine when given IV. It is 30% protein-bound, and the half-life is 6 hours.

Pharmacodynamics

Vancomycin inhibits bacterial cell wall synthesis and is active against several gram-positive microorganisms. The peak action is 30 minutes after the end of the infusion.

Side Effects and Adverse Reactions

Vancomycin may cause nephrotoxicity and ototoxicity. Ototoxicity results in damage to the auditory or vestibular branch of cranial nerve VIII. Such damage can result in permanent hearing loss (auditory branch) or temporary or permanent loss of balance (vestibular branch). Side effects may include chills, dizziness, fever, rashes, nausea, vomiting, and thrombophlebitis at the injection site. Too rapid an IV injection of vancomycin can cause a condition known as “red man” syndrome or red neck syndrome. Characterized by red blotching of the face, neck, and chest, this is a toxic effect rather than an allergic reaction. Other adverse effects include eosinophilia, neutropenia, and Stevens-Johnson syndrome. Severe hypotension, tachycardia, generalized tingling, and, rarely, cardiac arrest are also adverse reactions.

Drug Interactions

Dimenhydrinate (Dramamine) can mask ototoxicity when taken with vancomycin. The risk of nephrotoxicity and ototoxicity may be potentiated when vancomycin is taken with furosemide, aminoglycosides, amphotericin B, colistin, cisplatin, and cyclosporine. Vancomycin may inhibit methotrexate excretion and increase methotrexate toxicity. The absorption of oral vancomycin may be decreased when given with cholestyramine and colestipol.

Pharmacodynamics

Telithromycin inhibits protein synthesis in microorganisms by binding to the bacterial ribosomal RNA site of the 50S subunit, resulting in bacterial cell death. The peak action is 1 hour.

Side Effects and Adverse Reactions

Side effects and adverse reactions to telithromycin include visual disturbances (blurred vision and diplopia), headache, dizziness, altered taste, nausea, vomiting, diarrhea, and liver failure. Telithromycin may also lead to an exacerbation of myasthenia gravis.

Drug Interactions

Telithromycin levels are increased when taken concurrently with antilipidemics (simvastatin, lovastatin, and atorvastatin), itraconazole, ketoconazole, and benzodiazepines. Class 1A or class III antidysrhythmics may lead to life-threatening dysrhythmias. Blood levels of telithromycin are decreased when taken with rifampin, phenytoin, carbamazepine, or phenobarbital, producing a subtherapeutic level. Telithromycin can increase levels of cisapride and pimozide, leading to toxicity; therefore, these two drugs are contraindicated for the patient taking telithromycin. Digoxin, metoprolol, midazolam, ritonavir, sirolimus, and tacrolimus levels are increased when taken concurrently with telithromycin. Concurrent use of telithromycin with ergot alkaloid derivatives leads to ergot toxicity (severe peripheral vasospasm and impaired sensation).